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Sample records for broad-spectrum antibiotic enrofloxacin

  1. Broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model.

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    Strzępa, Anna; Majewska-Szczepanik, Monika; Lobo, Francis M; Wen, Li; Szczepanik, Marian

    2017-07-01

    Medical advances in the field of infection therapy have led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice. Natural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with trinitrophenyl chloride followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification. Oral treatment with enrofloxacin suppresses CS and production of anti-trinitrophenyl chloride IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCR αβ + CD4 + CD25 + FoxP3 + Treg, CD19 + B220 + CD5 + IL-10 + , IL-10 + Tr1, and IL-10 + TCR γδ + cells. Treatment with the antibiotic induces dysbiosis characterized by increased proportion of Clostridium coccoides (cluster XIVa), C coccoides-Eubacterium rectale (cluster XIVab), Bacteroidetes, and Bifidobacterium spp, but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals. Oral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology

  2. Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes

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    Clausen, Tine D; Bergholt, Thomas; Bouaziz, Olivier

    2016-01-01

    of childhood type 1 diabetes and the potential effect-modification by mode of delivery. MATERIALS AND METHODS: A Danish nationwide cohort study including all singletons born during 1997-2010. End of follow-up by December 2012. Four national registers provided information on antibiotic redemptions, outcome...... and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow-spectrum or broad-spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox...... regression. A total of 858,201 singletons contributed 5,906,069 person-years, during which 1,503 children developed type 1 diabetes. RESULTS: Redemption of broad-spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years...

  3. Surveillance of broad-spectrum antibiotic prescription in Singaporean hospitals: a 5-year longitudinal study.

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    Yi-Xin Liew

    Full Text Available BACKGROUND: Inappropriate prescription of antibiotics may contribute towards higher levels antimicrobial resistance. A key intervention for improving appropriate antibiotic prescription is surveillance of prescription. This paper presents the results of a longitudinal surveillance of broad-spectrum antibiotic prescription in 5 public-sector hospitals in Singapore from 2006 to 2010. METHODOLOGY/PRINCIPAL FINDINGS: Quarterly antibiotic prescription data were obtained and converted to defined daily doses (DDDs per 1,000 inpatient-days. The presence of significant trends in antibiotic prescription over time for both individual and combined hospitals was tested by regression analysis and corrected for autocorrelation between time-points. Excluding fluoroquinolones, there was a significant increase in prescription of all monitored antibiotics from an average of 233.12 defined daily doses (DDD/1,000 inpatient-days in 2006 to 254.38 DDD/1,000 inpatient-days in 2010 (Coefficient = 1.13, 95%CI: 0.16-2.09, p = 0.025. Increasing utilization of carbapenems, piperacillin/tazobactam, and Gram-positive agents were seen in the majority of the hospitals, while cephalosporins were less prescribed over time. The combined expenditure for 5 hospitals increased from USD9.9 million in 2006 to USD16.7 million in 2010. CONCLUSIONS/SIGNIFICANCE: The rate of prescription of broad-spectrum antibiotics in Singaporean hospitals is much higher compared to those of European hospitals. This may be due to high rates of antimicrobial resistance. The increase in expenditure on monitored antibiotics over the past 5 years outstripped the actual increase in DDD/1,000 inpatient-days of antibiotics prescribed. Longitudinal surveillance of antibiotic prescription on a hospital and countrywide level is important for detecting trends for formulating interventions or policies. Further research is needed to understand the causes for the various prescription trends and to act on these where

  4. Identification and Structural Characterization of Naturally-Occurring Broad-Spectrum Cyclic Antibiotics Isolated from Paenibacillus

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    Knolhoff, Ann M.; Zheng, Jie; McFarland, Melinda A.; Luo, Yan; Callahan, John H.; Brown, Eric W.; Croley, Timothy R.

    2015-08-01

    The rise of antimicrobial resistance necessitates the discovery and/or production of novel antibiotics. Isolated strains of Paenibacillus alvei were previously shown to exhibit antimicrobial activity against a number of pathogens, such as E. coli, Salmonella, and methicillin-resistant Staphylococcus aureus (MRSA). The responsible antimicrobial compounds were isolated from these Paenibacillus strains and a combination of low and high resolution mass spectrometry with multiple-stage tandem mass spectrometry was used for identification. A group of closely related cyclic lipopeptides was identified, differing primarily by fatty acid chain length and one of two possible amino acid substitutions. Variation in the fatty acid length resulted in mass differences of 14 Da and yielded groups of related MSn spectra. Despite the inherent complexity of MS/MS spectra of cyclic compounds, straightforward analysis of these spectra was accomplished by determining differences in complementary product ion series between compounds that differ in molecular weight by 14 Da. The primary peptide sequence assignment was confirmed through genome mining; the combination of these analytical tools represents a workflow that can be used for the identification of complex antibiotics. The compounds also share amino acid sequence similarity to a previously identified broad-spectrum antibiotic isolated from Paenibacillus. The presence of such a wide distribution of related compounds produced by the same organism represents a novel class of broad-spectrum antibiotic compounds.

  5. Trends in broad-spectrum antibiotic prescribing for children with acute otitis media in the United States, 1998–2004

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    Gambler Angela S

    2009-06-01

    Full Text Available Abstract Background Overuse of broad-spectrum antibiotics is associated with antibiotic resistance. Acute otitis media (AOM is responsible for a large proportion of antibiotics prescribed for US children. Rates of broad-spectrum antibiotic prescribing for AOM are unknown. Methods Analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, 1998 to 2004 (N = 6,878. Setting is office-based physicians, hospital outpatient departments, and emergency departments. Patients are children aged 12 years and younger prescribed antibiotics for acute otitis media. Main outcome measure is percentage of broad-spectrum antibiotics, defined as amoxicillin/clavulanate, macrolides, cephalosporins and quinolones. Results Broad-spectrum prescribing for acute otitis media increased from 34% of visits in 1998 to 45% of visits in 2004 (P Conclusion Prescribing of broad-spectrum antibiotics for acute otitis media has steadily increased from 1998 to 2004. Associations with non-clinical factors suggest potential for improvement in prescribing practice.

  6. Pharmacy sales data versus ward stock accounting for the surveillance of broad-spectrum antibiotic use in hospitals

    Science.gov (United States)

    2011-01-01

    Background Antibiotic consumption in hospitals is commonly measured using the accumulated amount of drugs delivered from the pharmacy to ward held stocks. The reliability of this method, particularly the impact of the length of the registration periods, has not been evaluated and such evaluation was aim of the study. Methods During 26 weeks, we performed a weekly ward stock count of use of broad-spectrum antibiotics - that is second- and third-generation cephalosporins, carbapenems, and quinolones - in five hospital wards and compared the data with corresponding pharmacy sales figures during the same period. Defined daily doses (DDDs) for antibiotics were used as measurement units (WHO ATC/DDD classification). Consumption figures obtained with the two methods for different registration intervals were compared by use of intraclass correlation analysis and Bland-Altman statistics. Results Broad-spectrum antibiotics accounted for a quarter to one-fifth of all systemic antibiotics (ATC group J01) used in the hospital and varied between wards, from 12.8 DDDs per 100 bed days in a urological ward to 24.5 DDDs in a pulmonary diseases ward. For the entire study period of 26 weeks, the pharmacy and ward defined daily doses figures for all broad-spectrum antibiotics differed only by 0.2%; however, for single wards deviations varied from -4.3% to 6.9%. The intraclass correlation coefficient, pharmacy versus ward data, increased from 0.78 to 0.94 for parenteral broad-spectrum antibiotics with increasing registration periods (1-4 weeks), whereas the corresponding figures for oral broad-spectrum antibiotics (ciprofloxacin) were from 0.46 to 0.74. For all broad-spectrum antibiotics and for parenteral antibiotics, limits of agreement between the two methods showed, according to Bland-Altman statistics, a deviation of ± 5% or less from average mean DDDs at 3- and 4-weeks registration intervals. Corresponding deviation for oral antibiotics was ± 21% at a 4-weeks interval

  7. Pharmacy sales data versus ward stock accounting for the surveillance of broad-spectrum antibiotic use in hospitals.

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    Haug, Jon B; Myhr, Randi; Reikvam, Asmund

    2011-12-13

    Antibiotic consumption in hospitals is commonly measured using the accumulated amount of drugs delivered from the pharmacy to ward held stocks. The reliability of this method, particularly the impact of the length of the registration periods, has not been evaluated and such evaluation was aim of the study. During 26 weeks, we performed a weekly ward stock count of use of broad-spectrum antibiotics--that is second- and third-generation cephalosporins, carbapenems, and quinolones--in five hospital wards and compared the data with corresponding pharmacy sales figures during the same period. Defined daily doses (DDDs) for antibiotics were used as measurement units (WHO ATC/DDD classification). Consumption figures obtained with the two methods for different registration intervals were compared by use of intraclass correlation analysis and Bland-Altman statistics. Broad-spectrum antibiotics accounted for a quarter to one-fifth of all systemic antibiotics (ATC group J01) used in the hospital and varied between wards, from 12.8 DDDs per 100 bed days in a urological ward to 24.5 DDDs in a pulmonary diseases ward. For the entire study period of 26 weeks, the pharmacy and ward defined daily doses figures for all broad-spectrum antibiotics differed only by 0.2%; however, for single wards deviations varied from -4.3% to 6.9%. The intraclass correlation coefficient, pharmacy versus ward data, increased from 0.78 to 0.94 for parenteral broad-spectrum antibiotics with increasing registration periods (1-4 weeks), whereas the corresponding figures for oral broad-spectrum antibiotics (ciprofloxacin) were from 0.46 to 0.74. For all broad-spectrum antibiotics and for parenteral antibiotics, limits of agreement between the two methods showed, according to Bland-Altman statistics, a deviation of ± 5% or less from average mean DDDs at 3- and 4-weeks registration intervals. Corresponding deviation for oral antibiotics was ± 21% at a 4-weeks interval. There is a need for caution in

  8. Comparison between pathogen directed antibiotic treatment and empirical broad spectrum antibiotic treatment in patients with community acquired pneumonia: a prospective randomised study

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    van der Eerden, M. M.; Vlaspolder, F.; de Graaff, C. S.; Groot, T.; Bronsveld, W.; Jansen, H. M.; Boersma, W. G.

    2005-01-01

    Background: There is much controversy about the ideal approach to the management of community acquired pneumonia ( CAP). Recommendations differ from a pathogen directed approach to an empirical strategy with broad spectrum antibiotics. Methods: In a prospective randomised open study performed

  9. Acute mastoiditis in children: Middle ear cultures may help in reducing use of broad spectrum antibiotics.

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    Garcia, Catarina; Salgueiro, Ana Bárbara; Luís, Catarina; Correia, Paula; Brito, Maria João

    2017-01-01

    Acute mastoiditis (AM) is a suppurative infection of the mastoid air cells, representing the most frequent complication of acute otitis media. AM remains an important entity in children due to its potential complications and sequelae. We aim to describe the cases of AM admitted at our department, identify risk factors potentially associated with complications and analyse the changes in clinical approach of AM over time. Case review of clinical files of children admitted with acute mastoiditis from June 1996 to May 2013 at a Lisbon metropolitan area hospital. Data was divided into two groups (prior and after May 2005) in order to evaluate changes in AM approach over the years. 135 AM episodes were included. The median age was 3.8 years and 42% children were less than 24 months of age. Symptoms at presentation included fever (69%), ear pain (56%) and otorrhea (40%). Complications occurred in 22% patients and were more common in children under 24 months (33% vs 15%, p ≤ 0.01). Leukocyte count was significantly higher in children with complications (16.7 vs 14.5 × 10 9 /μL, p ≤ 0.05) as was C-Reactive Protein value (13 vs 6.3 mg/dL, p ≤ 0.001). There was a significant association between the development of complications and C-Reactive Protein value at admission (OR 1.892; IC95%: 1.018-2.493, p ≤ 0.01). The optimal cut-off value was 7.21 mg/dL. Over time there was a significant increase in middle ear cultures obtained by tympanocentesis during surgery (2% vs 16%, p ≤ 0,01) and also a decrease in the use of broad spectrum antibiotherapy as initial treatment (52% vs 25%,p ≤ 0,001). Children under 24 months, with high leukocyte count or with high C-Reactive Protein value should be monitored closely since complications tend to be more frequent. A CRP value of 7.21 mg/dL at admission seems to be a good cut-off to monitor children for potential complications. Throughout the period analysed more cultures were performed allowing identification of

  10. Antibiotic combination therapy can select for broad-spectrum multidrug resistance in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm; Marvig, Rasmus L.

    2016-01-01

    with the resistance evolved after single-drug exposure. Combination therapy selected for mutants that displayed broad-spectrum resistance, and a major resistance mechanism was mutational inactivation of the repressor gene mexR that regulates the multidrug efflux operon mexAB–oprM. Deregulation of this operon led...... to a broad-spectrum resistance phenotype that decreased susceptibility to the combination of drugs applied during selection as well as to unrelated antibiotic classes. Mutants isolated after single-drug exposure displayed narrow-spectrum resistance and carried mutations in the MexCD–OprJ efflux pump...... regulator gene nfxB conferring ciprofloxacin resistance, or in the gene encoding the non-essential penicillin-binding protein DacB conferring ceftazidime resistance. Reconstruction of resistance mutations by allelic replacement and in vitro fitness assays revealed that in contrast to single antibiotic use...

  11. Role of bronchoalveolar lavage in immunocompromised patients with pneumonia treated with a broad spectrum antibiotic and antifungal regimen

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    Hohenadel, I; Kiworr, M; Genitsariotis, R; Zeidler, D; Lorenz, J

    2001-01-01

    BACKGROUND—In a retrospective study the value of bronchoalveolar lavage (BAL) in the diagnosis of pneumonia was investigated in 95 immunocompromised patients suffering from haematological disorders and receiving a regimen of broad spectrum antibiotics and antifungal agents (BSAR).
METHODS—With the exception of four afebrile patients, all had fever, raised C reactive protein (CRP) levels, and new infiltrates visible on chest radiography. All patients underwent BAL to identify the organism causing the pneumonia and surveillance cultures were performed regularly for pathogens at different sites. Following classification of the isolates, patients with positive cultures were subdivided into two groups, pathogenic or contaminated. We investigated whether relevant pathogens were cultured only from the BAL fluid and whether they were susceptible to BSAR.
RESULTS—Although 77 of the 95 patients were thrombocytopenic, bleeding during BAL occurred in only 15% of all patients. Ten days after the procedure the fever improved in 88% of patients, radiographic findings improved in 71%, and CRP levels improved in 75% of patients; 22% of patients died within 28 days. Pathologically relevant isolates were found in 65% of all patients. Respiratory pathogens were detected only in the BAL fluid of 29 of the 95 patients (35% Gram positive species, 40% Gram negative species, 11% Mycobacterium, 11% fungi, and 3% cytomegalovirus). In 16 of these 29 patients (55%) the pathogens cultured only from the BAL fluid were resistant to treatment. Pathogens detected only in the BAL fluid were not susceptible to a standard broad spectrum antibiotic and antifungal regimen including teicoplanin, ceftriaxon, tobramycin, and amphotericin B in 12 of the 29 patients (41%).
CONCLUSIONS—Our data suggest that 12 patients were treated with broad spectrum antimicrobial agents which were not directed at the appropriate organism on in vitro sensitivity tests without BAL. BAL is a relatively safe

  12. The Probiotic Compound VSL#3 Modulates Mucosal, Peripheral, and Systemic Immunity Following Murine Broad-Spectrum Antibiotic Treatment

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    Ira Ekmekciu

    2017-05-01

    Full Text Available There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. Bulgaricus in reversing immunological effects of microbiota depletion as compared to reassociation with a complex murine microbiota. To address this, conventional mice were subjected to broad-spectrum antibiotic therapy for 8 weeks and perorally reassociated with either VSL#3 bacteria or a complex murine microbiota. VSL#3 recolonization resulted in restored CD4+ and CD8+ cell numbers in the small and large intestinal lamina propria as well as in B220+ cell numbers in the former, whereas probiotic intervention was not sufficient to reverse the antibiotic induced changes of respective cell populations in the spleen. However, VSL#3 application was as efficient as complex microbiota reassociation to attenuate the frequencies of regulatory T cells, activated dendritic cells and memory/effector T cells in the small intestine, colon, mesenteric lymph nodes, and spleen. Whereas broad-spectrum antibiotic treatment resulted in decreased production of cytokines such as IFN-γ, IL-17, IL-22, and IL-10 by CD4+ cells in respective immunological compartments, VSL#3 recolonization was sufficient to completely recover the expression of the anti-inflammatory cytokine IL-10 without affecting pro-inflammatory mediators. In summary, the probiotic compound VSL#3 has an extensive impact on mucosal, peripheral, and

  13. Kidney failure related to broad-spectrum antibiotics in critically ill patients

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    Jensen, Jens-Ulrik Stæhr; Hein, Lars; Lundgren, Bettina

    2012-01-01

    To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients.......To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients....

  14. Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group.

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    Kenyon, S L; Taylor, D J; Tarnow-Mordi, W

    2001-03-31

    Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue. 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection. This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.

  15. The effect of broad-spectrum antibiotics on warfarin excretion and metabolism in the rat

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    Remmel, R.P.; Elmer, G.W.

    1981-01-01

    The excretion and metabolism of 14 C-warfarin in rats was examined in a crossover experiment, the first phase consisting of treatment with normal saline, the second phase using the same animals given neomycin, bacitracin, and tetracycline orally. Urine and feces were collected every 24 hours for 72 hours and examined for warfarin and its metabolites, both unconjugated and conjugated. Significantly more radioactivity was eliminated in th feces of antibiotic-treated rats. The feces of antibiotic-treated rats contained only trace amounts of beta-glucuronidase activity. Urine contained a similar ratio of unconjugated to conjugated radioactivity in both treatment groups, but the antibiotic-treated animals had significantly larger amount of conjugates in their feces. Examination of metabolic profiles of conjugated and unconjugated fractions revealed significantly fewer hydroxylated metabolites in antibiotic-treated rats, especially in the feces. The lower amount of hydroxylative metabolism in attributed to a reduction in gut flora-medicated interohepatic recycling caused by the antibiotics

  16. Use of artificial intelligence in the design of small peptide antibiotics effective against a broad spectrum of highly antibiotic-resistant superbugs.

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    Cherkasov, Artem; Hilpert, Kai; Jenssen, Håvard; Fjell, Christopher D; Waldbrook, Matt; Mullaly, Sarah C; Volkmer, Rudolf; Hancock, Robert E W

    2009-01-16

    Increased multiple antibiotic resistance in the face of declining antibiotic discovery is one of society's most pressing health issues. Antimicrobial peptides represent a promising new class of antibiotics. Here we ask whether it is possible to make small broad spectrum peptides employing minimal assumptions, by capitalizing on accumulating chemical biology information. Using peptide array technology, two large random 9-amino-acid peptide libraries were iteratively created using the amino acid composition of the most active peptides. The resultant data was used together with Artificial Neural Networks, a powerful machine learning technique, to create quantitative in silico models of antibiotic activity. On the basis of random testing, these models proved remarkably effective in predicting the activity of 100,000 virtual peptides. The best peptides, representing the top quartile of predicted activities, were effective against a broad array of multidrug-resistant "Superbugs" with activities that were equal to or better than four highly used conventional antibiotics, more effective than the most advanced clinical candidate antimicrobial peptide, and protective against Staphylococcus aureus infections in animal models.

  17. Effect of healthcare associated infections and broad spectrum antibiotic use in newborn period on development of asthma, allergic rhinitis and atopic dermatitis in early childhood

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    Hacer Yapicioglu Yildizdas

    2017-03-01

    Full Text Available Purpose: The iam of this study was to investigate the effect of healthcare associated infections (HAIs and broad spectrum antibiotic use in newborn period on asthma, allergic rhinitis and atopic dermatitis. Material and Methods: Seventy three children treated for HAIs in newborn period in Neonatal Intesive Care Unitin a 6 years period, and their 41 siblings who were healthy in newborn period were included in the study. Parents answered a detailed questionnaire, children were examined and complete blood count, serum total Ig E and specific Ig E levels were studied. Results: Ventilator associated pneumonia was observed in 32 (45.2%, blood stream infection in 28 (38.4% and clinic sepsis in 12 (16.4% of 73 children with HAIs. Asthma was significantly higher in HAIs group compared to sibling group (32.9% vs. 4.9, whereas there was no significant difference in allergic rhinitis (4.1% vs.2.4% and atopic dermatitis (6.8% vs. 0% among groups. When non-allergic 85 subjects and allergic 29 children compared, children who had been hospitalised and treated with broad-spectrum antibiotics in newborn period were almost 11.5 times as likely to have an allergic disease. Conclusion: Asthma was significantly higher in HAI group, and allergic disease risk seems to increase in children treated with broad-spectrum antibiotics for HAIs in newborn period. [Cukurova Med J 2017; 42(1.000: 132-139

  18. Broad-spectrum antibiotic or G-CSF as potential countermeasures for impaired control of bacterial infection associated with an SPE exposure during spaceflight.

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    Minghong Li

    Full Text Available A major risk for astronauts during prolonged space flight is infection as a result of the combined effects of microgravity, situational and confinement stress, alterations in food intake, altered circadian rhythm, and radiation that can significantly impair the immune system and the body's defense systems. We previously reported a massive increase in morbidity with a decrease in the ability to control a bacterial challenge when mice were maintained under hindlimb suspension (HS conditions and exposed to solar particle event (SPE-like radiation. HS and SPE-like radiation treatment alone resulted in a borderline significant increase in morbidity. Therefore, development and testing of countermeasures that can be used during extended space missions in the setting of exposure to SPE radiation becomes a serious need. In the present study, we investigated the efficacy of enrofloxacin (an orally bioavailable antibiotic and Granulocyte colony stimulating factor (G-CSF (Neulasta on enhancing resistance to Pseudomonas aeruginosa infection in mice subjected to HS and SPE-like radiation. The results revealed that treatment with enrofloxacin or G-CSF enhanced bacterial clearance and significantly decreased morbidity and mortality in challenged mice exposed to suspension and radiation. These results establish that antibiotics, such as enrofloxacin, and G-CSF could be effective countermeasures to decrease the risk of bacterial infections after exposure to SPE radiation during extended space flight, thereby reducing both the risk to the crew and the danger of mission failure.

  19. Microbiota Disruption Induced by Early Use of Broad-Spectrum Antibiotics Is an Independent Risk Factor of Outcome after Allogeneic Stem Cell Transplantation.

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    Weber, Daniela; Jenq, Robert R; Peled, Jonathan U; Taur, Ying; Hiergeist, Andreas; Koestler, Josef; Dettmer, Katja; Weber, Markus; Wolff, Daniel; Hahn, Joachim; Pamer, Eric G; Herr, Wolfgang; Gessner, André; Oefner, Peter J; van den Brink, Marcel R M; Holler, Ernst

    2017-05-01

    In allogeneic stem cell transplantation (ASCT), systemic broad-spectrum antibiotics are frequently used for treatment of infectious complications, but their effect on microbiota composition is still poorly understood. This retrospective analysis of 621 patients who underwent ASCT at the University Medical Center of Regensburg and Memorial Sloan Kettering Cancer Center in New York assessed the impact of timing of peritransplant antibiotic treatment on intestinal microbiota composition as well as transplant-related mortality (TRM) and overall survival. Early exposure to antibiotics was associated with lower urinary 3-indoxyl sulfate levels (P antibiotic treatment, which was particularly significant (P = .005) for Clostridium cluster XIVa in the Regensburg group. Earlier antibiotic treatment before ASCT was further associated with a higher TRM (34%, 79/236) compared with post-ASCT (21%, 62/297, P = .001) or no antibiotics (7%, 6/88, P antibiotic treatment was the dominant independent risk factor for TRM (HR, 2.0; P ≤ .001) in multivariate analysis besides increase age (HR, 2.15; P = .004), reduced Karnofsky performance status (HR, 1.47; P = .03), and female donor-male recipient sex combination (HR, 1.56; P = .02) A competing risk analysis revealed the independent effect of early initiation of antibiotics on graft-versus-host disease-related TRM (P = .004) in contrast to infection-related TRM and relapse (not significant). The poor outcome associated with early administration of antibiotic therapy that is active against commensal organisms, and specifically the possibly protective Clostridiales, calls for the use of Clostridiales-sparing antibiotics and rapid restoration of microbiota diversity after cessation of antibiotic treatment. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  20. Antimicrobial resistance in the Bacteroides fragilis group in faecal samples from patients receiving broad-spectrum antibiotics

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    Møller Hansen, Kia Cirkeline; Ferløv-Schwensen, Simon Andreas; Henriksen, Daniel Pilsgaard

    2017-01-01

    Members of the Bacteroides fragilis group are opportunistic pathogens and cause severe infections including bacteraemia. As increased levels of antimicrobial resistance in B. fragilis group bacteria can be detected years after administration of specific antibiotics, monitoring antimicrobial...... susceptibility in the gut microbiota could be important. The objectives of this study were to 1) investigate the distribution of species and the occurrence of reduced antimicrobial susceptibility in the B. fragilis group from patients treated at departments with a high level of antibiotic use, 2) to determine...... the prevalence of the carbapenem resistance gene cfiA in B. fragilis in this patient group, and 3) to determine the association between previous antibiotic treatment and reduced susceptibility to clindamycin, meropenem, metronidazole, and piperacillin-tazobactam. Consecutive faecal samples (n = 197) were...

  1. Candida albicans and bacterial microbiota interactions in the cecum during recolonization following broad-spectrum antibiotic therapy.

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    Mason, Katie L; Erb Downward, John R; Mason, Kelly D; Falkowski, Nicole R; Eaton, Kathryn A; Kao, John Y; Young, Vincent B; Huffnagle, Gary B

    2012-10-01

    Candida albicans is a normal member of the gastrointestinal (GI) tract microbiota of healthy humans, but during host immunosuppression or alterations in the bacterial microbiota, C. albicans can disseminate and cause life-threatening illness. The bacterial microbiome of the GI tract, including lactic acid bacteria (LAB), plays a vital role in preventing fungal invasion. However, little is known about the role of C. albicans in shaping the bacterial microbiota during antibiotic recovery. We investigated the fungal burdens in the GI tracts of germfree mice and mice with a disturbed microbiome to demonstrate the role of the microbiota in preventing C. albicans colonization. Histological analysis demonstrated that colonization with C. albicans during antibiotic treatment does not trigger overt inflammation in the murine cecum. Bacterial diversity is reduced long term following cefoperazone treatment, but the presence of C. albicans during antibiotic recovery promoted the recovery of bacterial diversity. Cefoperazone diminishes Bacteroidetes populations long term in the ceca of mice, but the presence of C. albicans during cefoperazone recovery promoted Bacteroidetes population recovery. However, the presence of C. albicans resulted in a long-term reduction in Lactobacillus spp. and promoted Enterococcus faecalis populations. Previous studies have focused on the ability of bacteria to alter C. albicans; this study addresses the ability of C. albicans to alter the bacterial microbiota during nonpathogenic colonization.

  2. Effects of the antibiotic enrofloxacin on the ecology of tropical eutrophic freshwater microcosms

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    Rico, A.; Rocha Dimitrov, M.; Wijngaarden, van R.P.A.; Satapornvanit, K.; Smidt, H.; Brink, van den P.J.

    2014-01-01

    The main objective of the present study was to assess the ecological impacts of the fluoroquinolone antibiotic enrofloxacin on the structure and functioning of tropical freshwater ecosystems. Enrofloxacin was applied at a concentration of 1, 10, 100 and 1000µg/L for 7 consecutive days in 600-L

  3. Biogenic nanoparticles bearing antibacterial activity and their synergistic effect with broad spectrum antibiotics: Emerging strategy to combat drug

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    Syed Baker

    2017-01-01

    Full Text Available The present study emphasizes on synthesis of bimetallic silver–gold nanoparticles from cell free supernatant of Pseudomonas veronii strain AS41G inhabiting Annona squamosa L. The synthesized nanoparticles were characterized using hyphenated techniques with UV–Visible spectra ascertained absorbance peak between 400 and 800 nm. Possible interaction of biomolecules in mediating and stabilization of nanoparticles was depicted with Fourier transform infrared spectroscopy (FTIR. X-ray diffraction (XRD displayed Bragg’s peak conferring the 100, 111, 200, and 220 facets of the face centered cubic symmetry of nanoparticles suggesting that these nanoparticles were crystalline in nature. Size and shape of the nanoparticles were determined using Transmission electron microscopy (TEM microgram with size ranging from 5 to 50 nm forming myriad shapes. Antibacterial activity of nanoparticles against significant human pathogens was conferred with well diffusion assay and its synergistic effect with standard antibiotics revealed 87.5% fold increased activity with antibiotic “bacitracin” against bacitracin resistant strains Bacillus subtilis, Escherichia coli and Klebsiella pneumoniae followed by kanamycin with 18.5%, gentamicin with 11.15%, streptomycin with 10%, erythromycin with 9.7% and chloramphenicol with 9.4%. Thus the study concludes with biogenic and ecofriendly route for synthesizing nanoparticles with antibacterial activity against drug resistant pathogens and attributes growing interest on endophytes as an emerging source for synthesis of nanoparticles.

  4. In Vitro and In Vivo Antibacterial Activities of OPC-20011, a Novel Parenteral Broad-Spectrum 2-Oxaisocephem Antibiotic

    Science.gov (United States)

    Matsumoto, Makoto; Tamaoka, Hisashi; Ishikawa, Hiroshi; Kikuchi, Mikio

    1998-01-01

    OPC-20011, a new parenteral 2-oxaisocephem antibiotic, has an oxygen atom at the 2- position of the cephalosporin frame. OPC-20011 had the best antibacterial activities against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae: MICs at which 90% of the isolates were inhibited were 6.25, 6.25, and 0.05 μg/ml, respectively. Its activity is due to a high affinity of the penicillin-binding protein 2′ in MRSA, an affinity which was approximately 1,050 times as high as that for flomoxef. Against gram-negative bacteria, OPC-20011 also showed antibacterial activities similar to those of ceftazidime. The in vivo activities of OPC-20011 were comparable to or greater than those of reference compounds in murine models of systemic infection caused by gram-positive and -negative pathogens. OPC-20011 was up to 10 times as effective as vancomycin against MRSA infections in mice. This better in vivo efficacy is probably due to the bactericidal activity of OPC-20011, while vancomycin showed bacteriostatic activity against MRSA. OPC-20011 produced a significant decrease of viable counts in lung tissue at a dose of 2.5 mg/kg of body weight, an efficacy similar to that of ampicillin at a dose of 10 to 20 mg/kg on an experimental murine model of respiratory tract infection caused by non-ampicillin-susceptible S. pneumoniae T-0005. The better therapeutic efficacy of OPC-20011 was considered to be due to its potent antibacterial activity and low affinity for serum proteins of experimental animals (29% in mice and 6.4% in rats). PMID:9797230

  5. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group.

    Science.gov (United States)

    Kenyon, S L; Taylor, D J; Tarnow-Mordi, W

    2001-03-31

    Preterm, prelabour rupture of the fetal membranes (pPROM) is the commonest antecedent of preterm birth, and can lead to death, neonatal disease, and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. We did a randomised multicentre trial to try to resolve this issue. 4826 women with pPROM were randomly assigned 250 mg erythromycin (n=1197), 325 mg co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid; n=1212), both (n=1192), or placebo (n=1225) four times daily for 10 days or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. Two women were lost to follow-up, and there were 15 protocol violations. Among all 2415 infants born to women allocated erythromycin only or placebo, fewer had the primary composite outcome in the erythromycin group (151 of 1190 [12.7%] vs 186 of 1225 [15.2%], p=0.08) than in the placebo group. Among the 2260 singletons in this comparison, significantly fewer had the composite primary outcome in the erythromycin group (125 of 1111 [11.2%] vs 166 of 1149 [14.4%], p=0.02). Co-amoxiclav only and co-amoxiclav plus erythromycin had no benefit over placebo with regard to this outcome in all infants or in singletons only. Use of erythromycin was also associated with prolongation of pregnancy, reductions in neonatal treatment with surfactant, decreases in oxygen dependence at 28 days of age and older, fewer major cerebral abnormalities on ultrasonography before discharge, and fewer positive blood cultures. Although co-amoxiclav only and co-amoxiclav plus erythromycin were associated with prolongation of pregnancy, they were also associated with a significantly higher rate of neonatal necrotising enterocolitis. Erythromycin for women with pPROM is associated with a range of health

  6. Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy and reduces the overall use of antimicrobial agents during induction therapy for acute leukaemia: A single-centre study.

    Science.gov (United States)

    Hallböök, Helene; Lidström, Anna-Karin; Pauksens, Karlis

    2016-01-01

    Due to an outbreak of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.

  7. Broad spectrum bioactive sunscreens.

    Science.gov (United States)

    Velasco, Maria Valéria Robles; Sarruf, Fernanda Daud; Salgado-Santos, Idalina Maria Nunes; Haroutiounian-Filho, Carlos Alberto; Kaneko, Telma Mary; Baby, André Rolim

    2008-11-03

    The development of sunscreens containing reduced concentration of chemical UV filters, even though, possessing broad spectrum effectiveness with the use of natural raw materials that improve and infer UV absorption is of great interest. Due to the structural similarities between polyphenolic compounds and organic UV filters, they might exert photoprotection activity. The objective of the present research work was to develop bioactive sunscreen delivery systems containing rutin, Passiflora incarnata L. and Plantago lanceolata extracts associated or not with organic and inorganic UV filters. UV transmission of the sunscreen delivery system films was performed by using diffuse transmittance measurements coupling to an integrating sphere. In vitro photoprotection efficacy was evaluated according to the following parameters: estimated sun protection factor (SPF); Boot's Star Rating category; UVA/UVB ratio; and critical wavelength (lambda(c)). Sunscreen delivery systems obtained SPF values ranging from 0.972+/-0.004 to 28.064+/-2.429 and bioactive compounds interacted with the UV filters positive and negatively. This behavior may be attributed to: the composition of the delivery system; the presence of inorganic UV filter and quantitative composition of the organic UV filters; and the phytochemical composition of the P. incarnata L. and P. lanceolata extracts. Among all associations of bioactive compounds and UV filters, we found that the broad spectrum sunscreen was accomplished when 1.68% (w/w) P. incarnata L. dry extract was in the presence of 7.0% (w/w) ethylhexyl methoxycinnamate, 2.0% (w/w) benzophenone-3 and 2.0% (w/w) TiO(2). It was demonstrated that this association generated estimated SPF of 20.072+/-0.906 and it has improved the protective defense against UVA radiation accompanying augmentation of the UVA/UVB ratio from 0.49 to 0.52 and lambda(c) from 364 to 368.6nm.

  8. Effects of the antibiotic enrofloxacin on the ecology of tropical eutrophic freshwater microcosms.

    Science.gov (United States)

    Rico, Andreu; Dimitrov, Mauricio R; Van Wijngaarden, René P A; Satapornvanit, Kriengkrai; Smidt, Hauke; Van den Brink, Paul J

    2014-02-01

    The main objective of the present study was to assess the ecological impacts of the fluoroquinolone antibiotic enrofloxacin on the structure and functioning of tropical freshwater ecosystems. Enrofloxacin was applied at a concentration of 1, 10, 100 and 1,000 μg/L for 7 consecutive days in 600-L outdoor microcosms in Thailand. The ecosystem-level effects of enrofloxacin were monitored on five structural (macroinvertebrates, zooplankton, phytoplankton, periphyton and bacteria) and two functional (organic matter decomposition and nitrogen cycling) endpoint groups for 4 weeks after the last antibiotic application. Enrofloxacin was found to dissipate relatively fast from the water column (half-dissipation time: 11.7h), and about 11% of the applied dose was transformed into its main by-product ciprofloxacin after 24h. Consistent treatment-related effects on the invertebrate and primary producer communities and on organic matter decomposition could not be demonstrated. Enrofloxacin significantly affected the structure of leaf-associated bacterial communities at the highest treatment level, and reduced the abundance of ammonia-oxidizing bacteria and ammonia-oxidizing archaea in the sediments, with calculated NOECs of 10 and enrofloxacin are not likely to result in direct or indirect toxic effects on the invertebrate and primary producer communities, nor on important microbially mediated functions such as nitrification. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Toxicity of the fluoroquinolone antibiotics enrofloxacin and ciprofloxacin to photoautotrophic aquatic organisms.

    Science.gov (United States)

    Ebert, Ina; Bachmann, Jean; Kühnen, Ute; Küster, Anette; Kussatz, Carola; Maletzki, Dirk; Schlüter, Christoph

    2011-12-01

    The present study investigated the growth inhibition effect of the fluoroquinolone antibiotics enrofloxacin and ciprofloxacin on four photoautotrophic aquatic species: the freshwater microalga Desmodesmus subspicatus, the cyanobacterium Anabaena flos-aquae, the monocotyledonous macrophyte Lemna minor, and the dicotyledonous macrophyte Myriophyllum spicatum. Both antibiotics, which act by inhibiting the bacterial DNA gyrase, demonstrated high toxicity to A. flos-aquae and L. minor and moderate to slight toxicity to D. subspicatus and M. spicatum. The cyanobacterium was the most sensitive species with median effective concentration (EC50) values of 173 and 10.2 µg/L for enrofloxacin and ciprofloxacin, respectively. Lemna minor proved to be similarly sensitive, with EC50 values of 107 and 62.5 µg/L for enrofloxacin and ciprofloxacin, respectively. While enrofloxacin was more toxic to green algae, ciprofloxacin was more toxic to cyanobacteria. Calculated EC50s for D. subspicatus were 5,568 µg/L and >8,042 µg/L for enrofloxacin and ciprofloxacin, respectively. These data, as well as effect data from the literature, were compared with predicted and reported environmental concentrations. For two of the four species, a risk was identified at ciprofloxacin concentrations found in surface waters, sewage treatment plant influents and effluents, as well as in hospital effluents. For ciprofloxacin the results of the present study indicate a risk even at the predicted environmental concentration. In contrast, for enrofloxacin no risk was identified at predicted and measured concentrations. Copyright © 2011 SETAC.

  10. Mechanisms of antibiotic resistance to enrofloxacin in uropathogenic Escherichia coli in dog.

    Science.gov (United States)

    Piras, Cristian; Soggiu, Alessio; Greco, Viviana; Martino, Piera Anna; Del Chierico, Federica; Putignani, Lorenza; Urbani, Andrea; Nally, Jarlath E; Bonizzi, Luigi; Roncada, Paola

    2015-09-08

    Escherichia coli (E. coli) urinary tract infections (UTIs) are becoming a serious problem both for pets and humans (zoonosis) due to the close contact and to the increasing resistance to antibiotics. This study has been performed in order to unravel the mechanism of induced enrofloxacin resistance in canine E. coli isolates that represent a good tool to study this pathology. The isolated E. coli has been induced with enrofloxacin and studied through 2D DIGE and shotgun MS. Discovered differentially expressed proteins are principally involved in antibiotic resistance and linked to oxidative stress response, to DNA protection and to membrane permeability. Moreover, since enrofloxacin is an inhibitor of DNA gyrase, the overexpression of DNA starvation/stationary phase protection protein (Dsp) could be a central point to discover the mechanism of this clone to counteract the effects of enrofloxacin. In parallel, the dramatic decrease of the synthesis of the outer membrane protein W, which represents one of the main gates for enrofloxacin entrance, could explain additional mechanism of E. coli defense against this antibiotic. All 2D DIGE and MS data have been deposited into the ProteomeXchange Consortium with identifier PXD002000 and DOI http://dx.doi.org/10.6019/PXD002000. This article is part of a Special Issue entitled: HUPO 2014. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. A novel method to depurate β-lactam antibiotic residues by administration of a broad-spectrum β-lactamase enzyme in fish tissues

    Directory of Open Access Journals (Sweden)

    Young-Sik Choe

    2016-12-01

    Full Text Available Abstract As a novel strategy to remove β-lactam antibiotic residues from fish tissues, utilization of β-lactamase, enzyme that normally degrades β-lactam structure-containing drugs, was explored. The enzyme (TEM-52 selectively degraded β-lactam antibiotics but was completely inactive against tetracycline-, quinolone-, macrolide-, or aminoglycoside-structured antibacterials. After simultaneous administration of the enzyme with cefazolin (a β-lactam antibiotic to the carp, significantly lowered tissue cefazolin levels were observed. It was confirmed that the enzyme successfully reached the general circulation after intraperitoneal administration, as the carp serum obtained after enzyme injection could also degrade cefazolin ex vivo. These results suggest that antibiotics-degrading enzymes can be good candidates for antibiotic residue depuration.

  12. Occurrence and Dissipation of the Antibiotics Sulfamethoxazole, Sulfadiazine, Trimethoprim, and Enrofloxacin in the Mekong Delta, Vietnam

    Science.gov (United States)

    Nguyen Dang Giang, Chau; Sebesvari, Zita; Renaud, Fabrice; Rosendahl, Ingrid; Hoang Minh, Quang; Amelung, Wulf

    2015-01-01

    The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews) for antibiotic use. Different water sources, including surface water, groundwater and piped water (164 water samples) were systematically screened for antibiotic residues. To better understand antibiotic fate under tropical conditions, the dissipation behavior of selected antibiotics in the aquatic environment was investigated for the first time in mesocosm experiments. None of the investigated antibiotics were detected in groundwater and piped water samples. Surface water, which is still often used for drinking and domestic purposes by local populations, contained median concentrations of 21 ng L-1 sulfamethoxazole (SMX), 4 ng L-1 sulfadiazine (SDZ), 17 ng L-1 trimethoprim (TRIM), and 12 ng L-1 enrofloxacin (ENRO). These concentrations were lower than the predicted no effect concentrations (PNECs) and minimum inhibitory concentrations (MICs), suggesting limited antibiotic-related risk to aquatic ecosystems in the monitored systems. The dissipation half-lives of the studied antibiotics ranged from aquatic environment, yet the persistence of these antibiotics is of concern and might lead to chronic exposure of aquatic organisms as well as humans. PMID:26135396

  13. Ecological risk assessment of the antibiotic enrofloxacin applied to Pangasius catfish farms in the Mekong delta, Vietnam

    NARCIS (Netherlands)

    Rico Artero, A.; Phu, T.M.; Huong, D.T.T.; Phuong, N.T.; Brink, van den P.J.

    2015-01-01

    Antibiotics applied in aquaculture production may be released into the environment and contribute to the deterioration of surrounding aquatic ecosystems. In the present study, we assessed the ecological risks posed by the use of the antibiotic enrofloxacin (ENR), and its main metabolite

  14. Occurrence and Dissipation of the Antibiotics Sulfamethoxazole, Sulfadiazine, Trimethoprim, and Enrofloxacin in the Mekong Delta, Vietnam.

    Directory of Open Access Journals (Sweden)

    Chau Nguyen Dang Giang

    Full Text Available The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews for antibiotic use. Different water sources, including surface water, groundwater and piped water (164 water samples were systematically screened for antibiotic residues. To better understand antibiotic fate under tropical conditions, the dissipation behavior of selected antibiotics in the aquatic environment was investigated for the first time in mesocosm experiments. None of the investigated antibiotics were detected in groundwater and piped water samples. Surface water, which is still often used for drinking and domestic purposes by local populations, contained median concentrations of 21 ng L-1 sulfamethoxazole (SMX, 4 ng L-1 sulfadiazine (SDZ, 17 ng L-1 trimethoprim (TRIM, and 12 ng L-1 enrofloxacin (ENRO. These concentrations were lower than the predicted no effect concentrations (PNECs and minimum inhibitory concentrations (MICs, suggesting limited antibiotic-related risk to aquatic ecosystems in the monitored systems. The dissipation half-lives of the studied antibiotics ranged from <1 to 44 days, depending on the availability of sunlight and sediment. Among the studied antibiotics TRIM was the most persistent in water systems. TRIM was not susceptible to photodegradation, while the dissipation of ENRO and SDZ was influenced by photolysis. The recorded dissipation models gave good predictions of the occurrence and concentrations of TRIM, ENRO and SDZ in surface water. In summary, the currently measured concentrations of the investigated antibiotics are unlikely to cause immediate risks

  15. Occurrence and Dissipation of the Antibiotics Sulfamethoxazole, Sulfadiazine, Trimethoprim, and Enrofloxacin in the Mekong Delta, Vietnam.

    Science.gov (United States)

    Nguyen Dang Giang, Chau; Sebesvari, Zita; Renaud, Fabrice; Rosendahl, Ingrid; Hoang Minh, Quang; Amelung, Wulf

    2015-01-01

    The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews) for antibiotic use. Different water sources, including surface water, groundwater and piped water (164 water samples) were systematically screened for antibiotic residues. To better understand antibiotic fate under tropical conditions, the dissipation behavior of selected antibiotics in the aquatic environment was investigated for the first time in mesocosm experiments. None of the investigated antibiotics were detected in groundwater and piped water samples. Surface water, which is still often used for drinking and domestic purposes by local populations, contained median concentrations of 21 ng L-1 sulfamethoxazole (SMX), 4 ng L-1 sulfadiazine (SDZ), 17 ng L-1 trimethoprim (TRIM), and 12 ng L-1 enrofloxacin (ENRO). These concentrations were lower than the predicted no effect concentrations (PNECs) and minimum inhibitory concentrations (MICs), suggesting limited antibiotic-related risk to aquatic ecosystems in the monitored systems. The dissipation half-lives of the studied antibiotics ranged from antibiotics TRIM was the most persistent in water systems. TRIM was not susceptible to photodegradation, while the dissipation of ENRO and SDZ was influenced by photolysis. The recorded dissipation models gave good predictions of the occurrence and concentrations of TRIM, ENRO and SDZ in surface water. In summary, the currently measured concentrations of the investigated antibiotics are unlikely to cause immediate risks to the aquatic environment, yet the persistence of these antibiotics is of concern and might lead to

  16. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis

    Directory of Open Access Journals (Sweden)

    Rima eMoghnieh

    2015-02-01

    Full Text Available Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO-associated bacteremia.This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012.It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR and MDRO-associated bacteremia. Out of 75 bacteremias, 42.7% were gram-positive (GP, and 57.3% were gram-negative (GN. GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias. Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms and Klebsiellapneumoniae(13.3% of total, 23.3% of GN organisms were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/ tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p value<0.05.

  17. Effects of temperature, genetic variation and species competition on the sensitivity of algae populations to the antibiotic enrofloxacin.

    Science.gov (United States)

    Rico, Andreu; Zhao, Wenkai; Gillissen, Frits; Lürling, Miquel; Van den Brink, Paul J

    2018-02-01

    Primary producers are amongst the most sensitive organisms to antibiotic pollution in aquatic ecosystems. To date, there is little information on how different environmental conditions may affect their sensitivity to antibiotics. In this study we assessed how temperature, genetic variation and species competition may affect the sensitivity of the cyanobacterium Microcystis aeruginosa and the green-algae Scenedesmus obliquus to the antibiotic enrofloxacin. First, we performed single-species tests to assess the toxicity of enrofloxacin under different temperature conditions (20°C and 30°C) and to assess the sensitivity of different species strains using a standard temperature (20°C). Next, we investigated how enrofloxacin contamination may affect the competition between M. aeruginosa and S. obliquus. A competition experiment was performed following a full factorial design with different competition treatments, defined as density ratios (i.e. initial bio-volume of 25/75%, 10/90% and 1/99% of S. obliquus/M. aeruginosa, respectively), one 100% S. obliquus treatment and one 100% M. aeruginosa treatment, and four different enrofloxacin concentrations (i.e. control, 0.01, 0.05 and 0.10mg/L). Growth inhibition based on cell number, bio-volume, chlorophyll-a concentration as well as photosynthetic activity were used as evaluation endpoints in the single-species tests, while growth inhibition based on measured chlorophyll-a was primarily used in the competition experiment. M. aeruginosa photosynthetic activity was found to be the most sensitive endpoint to enrofloxacin (EC50-72h =0.02mg/L), followed by growth inhibition based on cell number. S. obliquus was found to be slightly more sensitive at 20°C than at 30°C (EC50-72h cell number growth inhibition of 38 and 41mg/L, respectively), whereas an opposite trend was observed for M. aeruginosa (0.047 and 0.037mg/L, respectively). Differences in EC50-72h values between algal strains of the same species were within a factor

  18. Feasibility study of silica sol as the carrier of a hydrophobic drug in aqueous solution using enrofloxacin as the model

    International Nuclear Information System (INIS)

    Song Meirong; Song Junling; Ning Aimin; Cui Baoan; Cui Shumin; Zhou Yaobing; An Wankai; Dong Xuesong; Zhang Gege

    2010-01-01

    The aim of this study was to determine the feasibility of using silica sol to carry a hydrophobic drug in aqueous solution. Enrofloxacin, which was selected as the model drug because it is a broad-spectrum antibiotic drug with poor solubility in water, was adsorbed onto silica sol in aqueous solution during cooling from 60 deg. C to room temperature. The drug-loaded silica sol was characterized by transmission electron microscopy, Fourier transform infrared spectrum, thermal gravimetric analysis and ultraviolet-visible light spectroscopy. The results showed that enrofloxacin was adsorbed by silica sol without degradation at a loading of 15.23 wt.%. In contrast to the rapid release from pure enrofloxacin, the drug-loaded silica sol showed a slower release over a longer time. Kinetics analysis suggested the drug release from silica sol was mainly a diffusion-controlled process. Therefore, silica sol can be used to carry a hydrophobic drug in aqueous solution for controlled drug delivery.

  19. Occurrence and Dissipation of the Antibiotics Sulfamethoxazole, Sulfadiazine, Trimethoprim, and Enrofloxacin in the Mekong Delta, Vietnam

    OpenAIRE

    Nguyen Dang Giang, Chau; Sebesvari, Zita; Renaud, Fabrice; Rosendahl, Ingrid; Hoang Minh, Quang; Amelung, Wulf

    2015-01-01

    The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews) for antibiotic use. Different water ...

  20. Occurrence and dissipation of the antibiotics sulfamethoxazole, sulfadiazine, trimethoprim, and enrofloxacin in the Mekong Delta, Vietnam

    OpenAIRE

    Das, Surajit; Nguyen Dang Giang, Chau; Sebesvari, Zita; Renaud, Fabrice; Rosendahl, Ingrid; Hoang Minh, Quang; Amelung, Wulf

    2015-01-01

    The Mekong Delta in Vietnam has seen a rapid development and intensification of aquaculture in the last decades, with a corresponding widespread use of antibiotics. This study provides information on current antibiotic use in freshwater aquaculture, as well as on resulting antibiotic concentrations in the aquatic environment of the Mekong Delta. Two major production steps, fish hatcheries and mature fish cultivation, were surveyed (50 fish farm interviews) for antibiotic use. Different water ...

  1. Mechanisms of antibiotic resistance to enrofloxacin in uropathogenic Escherichia coli in dog

    Science.gov (United States)

    Escherichia coli (E. coli) urinary tract infections (UTIs) are becoming a serious problem both for pets and humans (zoonosis) due to the close contact and to the increasing resistance to antibiotics. Canine E. coli represents a good experimental model useful to study this pathology. Moreover, as des...

  2. Broad Spectrum Sanitizing Wipes with Food Additives, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Microcide proposes to develop novel multipurpose non-toxic sanitizing wipes that are aqueous based, have shelf life of 3-5 years, have broad spectrum microbicidal...

  3. Experimental study on effect of roasting, boiling and microwave cooking methods on enrofloxacin antibiotic residues in edible poultry tissues

    Directory of Open Access Journals (Sweden)

    A Javadi

    2011-11-01

    Full Text Available The purpose of this study was to determine the effects of different cooking processes such as boiling, roasting and microwaving on enrofloxacin residues in muscle, liver and gizzard tissues of broiler chickens. Each of chicks was fed by routine diet and water with %0.05 of enrofloxacine for consecutive 5 days .Then; three locations including breast muscle, liver and gizzard were sampled aseptically from each carcass. Enrofloxacin residue was analyzed using microbial method by plates seeded with Escherichia coli. After doing different phases of the test on raw samples, the positive raw samples cooked by various cooking procedures and we surveyed cooked samples with similar method again for present of residue. The results were show reduction in concentration of enrofloxacin residue after different cooking processes. The most reduction of the residue in cooked meat and gizzard samples related to boiling process and roasting process for cooked liver samples and the highest detectable amount of residue belonged to microwaving process in all cooked samples. Regarding to the results of this study, we can conclude that cooking processes can’t annihilate total amounts of these drug and it can only decrease their amounts and the most of residue in boiling process excreted from tissue to cooking fluid.

  4. Effect of an organic acids based feed additive and enrofloxacin on the prevalence of antibiotic-resistant E. coli in cecum of broilers.

    Science.gov (United States)

    Roth, Nataliya; Mayrhofer, Sigrid; Gierus, Martin; Weingut, Christine; Schwarz, Christiane; Doupovec, Barbara; Berrios, Roger; Domig, Konrad J

    2017-09-01

    Increasing antibiotic resistance is a major public health concern. Fluoroquinolones are used to treat and prevent poultry diseases worldwide. Fluoroquinolone resistance rates are high in their countries of use. The aim of this study was to evaluate the effect of an acids-based feed additive, as well as fluoroquinolone antibiotics, on the prevalence of antibiotic-resistant E. coli. A total of 480 broiler chickens (Ross 308) were randomly assigned to 3 treatments: a control group receiving a basal diet; a group receiving a feed additive (FA) based on formic acid, acetic acid and propionic acid; and an antibiotic enrofloxacin (AB) group given the same diet, but supplemented with enrofloxacin in water. A pooled fecal sample of one-day-old chicks was collected upon arrival at the experimental farm. On d 17 and d 38 of the trial, cecal samples from each of the 8 pens were taken, and the count of E. coli and antibiotic-resistant E. coli was determined.The results of the present study show a high prevalence of antibiotic-resistant E. coli in one-day-old chicks. Supplementation of the diet with FA and treatment of broilers with AB did not have a significant influence on the total number of E. coli in the cecal content on d 17 and d 38 of the trial. Supplementation with FA contributed to better growth performance and to a significant decrease (P ≤ 0.05) in E. coli resistant to ampicillin and tetracycline compared to the control and AB groups, as well as to a decrease (P ≤ 0.05) in sulfamethoxazole and ciprofloxacin-resistant E. coli compared to the AB group. Treatment with AB increased (P ≤ 0.05) the average daily weight compared to the control group and increased (P ≤ 0.05) the number of E. coli resistant to ciprofloxacin, streptomycin, sulfamethoxazole and tetracycline; it also decreased (P ≤ 0.05) the number of E. coli resistant to cefotaxime and extended spectrum beta-lactamase- (ESBL-) producing E. coli in the ceca of broilers. © 2017 Poultry Science

  5. MOLECULAR PATHOBIOLOGICAL AND SCANNING ELECTRON MICROSCOPIC CHANGES IN HORSE TENDON CELLS TREA TED WITH ENROFLOXACIN

    Directory of Open Access Journals (Sweden)

    A. Khan1 and J. Halper

    2003-12-01

    Full Text Available Fluoroquinolone (FQNL antibiotics have been used widely in horses because of their broad-spectrum bactericidal activity and relative safety, however, their use is not without risk. Tendonitis and spontaneous tendon rupture have been reported in people during or following therapy with FQNLs. To evaluate the potential damage of enrofloxacin (ENRO on the equine superficial digital flexor tendon (SOFT, an equine cell culture system as an in vitro model of equine tendon injury and repair was developed. The effects of ENRO on tendon cell cultures established from equine SOFT were studied. The data thus collected demonstrated that ENRO inhibited cell proliferation, induced morphological changes and altered proteoglycan synthesis in equine tendon cell cultures. Interestingly, these effects were more pronounced in juvenile tendon cells as compared to adult horses, It. is hypothesized that morphological changes and inhibition of cell proliferation is a result of impaired production of proteoglycans and other glycoproteins in the extracellular matrix of ENRO-treated tendon cells.

  6. The precipitation synthesis of broad-spectrum UV absorber nanoceria

    International Nuclear Information System (INIS)

    Nurhasanah, Iis; Sutanto, Heri; Puspaningrum, Nurul Wahyu

    2013-01-01

    In this paper the possibility of nanoceria as broad-spectrum UV absorber was evaluated. Nanoceria were synthesized by precipitation process from cerium nitrate solution and ammonium hydroxide as precipitant agent. Isopropanol was mixed with water as solvent to prevent hard agglomeration. The structure of resulting nanoceria was characterized by x-ray diffractometer (XRD). The transparency in the visible light and efficiency of protection in UV A region were studied using ultraviolet-visible (UV - Vis) spectrophotometer. The results show that nanoceria possess good tranparency in visible light and high UV light absorption. The critical absorption wavelenght of 368 nm was obtained which is desirable for excellent broad-spectrum protection absorbers. Moreover, analysis of photodegradation nanoceria to methylene blue solution shows poor photocatalytic activity. It indicates that nanoceria suitable for used as UV absorber in personal care products

  7. Broad spectrum antiangiogenic treatment for ocular neovascular diseases.

    Directory of Open Access Journals (Sweden)

    Ofra Benny

    2010-09-01

    Full Text Available Pathological neovascularization is a hallmark of late stage neovascular (wet age-related macular degeneration (AMD and the leading cause of blindness in people over the age of 50 in the western world. The treatments focus on suppression of choroidal neovascularization (CNV, while current approved therapies are limited to inhibiting vascular endothelial growth factor (VEGF exclusively. However, this treatment does not address the underlying cause of AMD, and the loss of VEGF's neuroprotective can be a potential side effect. Therapy which targets the key processes in AMD, the pathological neovascularization, vessel leakage and inflammation could bring a major shift in the approach to disease treatment and prevention. In this study we have demonstrated the efficacy of such broad spectrum antiangiogenic therapy on mouse model of AMD.Lodamin, a polymeric formulation of TNP-470, is a potent broad-spectrum antiangiogenic drug. Lodamin significantly reduced key processes involved in AMD progression as demonstrated in mice and rats. Its suppressive effects on angiogenesis, vascular leakage and inflammation were studied in a wide array of assays including; a Matrigel, delayed-type hypersensitivity (DTH, Miles assay, laser-induced CNV and corneal micropocket assay. Lodamin significantly suppressed the secretion of various pro-inflammatory cytokines in the CNV lesion including monocyte chemotactic protein-1 (MCP-1/Ccl2. Importantly, Lodamin was found to regress established CNV lesions, unlike soluble fms-like tyrosine kinase-1 (sFlk-1. The drug was found to be safe in mice and have little toxicity as demonstrated by electroretinography (ERG assessing retinal and by histology.Lodamin, a polymer formulation of TNP-470, was identified as a first in its class, broad-spectrum antiangiogenic drug that can be administered orally or locally to treat corneal and retinal neovascularization. Several unique properties make Lodamin especially beneficial for ophthalmic

  8. Brevibacillus laterosporus, a Pathogen of Invertebrates and a Broad-Spectrum Antimicrobial Species

    Directory of Open Access Journals (Sweden)

    Luca Ruiu

    2013-09-01

    Full Text Available Brevibacillus laterosporus, a bacterium characterized by the production of a unique canoe-shaped lamellar body attached to one side of the spore, is a natural inhabitant of water, soil and insects. Its biopesticidal potential has been reported against insects in different orders including Coleoptera, Lepidoptera, Diptera and against nematodes and mollusks. In addition to its pathogenicity against invertebrates, different B. laterosporus strains show a broad-spectrum antimicrobial activity including activity against phytopathogenic bacteria and fungi. A wide variety of molecules, including proteins and antibiotics, have been associated with the observed pathogenicity and mode of action. Before being considered as a biological control agent against plant pathogens, the antifungal and antibacterial properties of certain B. laterosporus strains have found medical interest, associated with the production of antibiotics with therapeutic effects. The recent whole genome sequencing of this species revealed its potential to produce polyketides, nonribosomal peptides, and toxins. Another field of growing interest is the use of this bacterium for bioremediation of contaminated sites by exploiting its biodegradation properties. The aim of the present review is to gather and discuss all recent findings on this emerging entomopathogen, giving a wider picture of its complex and broad-spectrum biocontrol activity.

  9. Effects of temperature, genetic variation and species competition on the sensitivity of algae populations to the antibiotic enrofloxacin

    NARCIS (Netherlands)

    Rico, Andreu; Zhao, Wenkai; Gillissen, Frits; Lürling, Miquel; Brink, van den Paul J.

    2018-01-01

    Primary producers are amongst the most sensitive organisms to antibiotic pollution in aquatic ecosystems. To date, there is little information on how different environmental conditions may affect their sensitivity to antibiotics. In this study we assessed how temperature, genetic variation and

  10. The relationship between blood and muscle samples to monitor for residues of the antibiotic enrofloxacin in chickens

    Science.gov (United States)

    Use of antibiotics in food animals has generated concern as the presence of these residues in food may contribute to increased microbial resistance in humans. Fluoroquinolone antibiotics are thus now no longer allowed by the U.S. Food and Drug Administration for use in poultry and monitoring of the...

  11. Impact of broad-spectrum antimicrobial treatment on the ecology of intestinal flora.

    Science.gov (United States)

    Yang, Jen-Jia; Wang, Jann-Tay; Cheng, Aristine; Chuang, Yu-Chung; Sheng, Wang-Huei

    2017-06-28

    Suppression of intestinal flora by broad-spectrum antimicrobial agents facilitated risk of colonization or infection with resistant pathogen. We aimed to investigate the changes in bowel carriage of target resistant microorganisms (TRO) among patients treated with three different classes of Pseudomonas-sparing broad-spectrum antimicrobial agents (ertapenem, moxifloxacin and flomoxef) with anaerobic coverage. Risk factors for developing colonization of TRO were also analyzed. We prospectively enrolled the adult hospitalized patients (>20 years old) who were indicated for at least 7-day course with either of ertapenem, moxifloxacin or flomoxef. Rectal swabs were performed for the patients who received at least 1-day course of study antibiotics during the treatment duration. The TROs included Pseudomonas aeruginosa, Enterobacteriaceae, and Acinetobacter baumannii. MacConkey agars with study antibiotics were used to isolate the TROs and evaluate the antimicrobial resistance. The mean age of our study population was 61.6 years, and 58.8% were males. The rates of rectal colonization for Pseudomonas aeruginosa was similar among the study medications (ertapenem 13.2%, flomoxef 20%, moxifloxacin 14.3%, p = 0.809). Compared with ertapenem, flomoxef (odds ratio [OR], 4.30; 95% confidence interval [95% CI], 1.28-14.48, p = 0.019) and moxifloxacin (OR, 6.95; 95% CI, 1.36-35.52, p = 0.019) had higher risk for colonization of ertapenem-resistant Escherichiacoli colonization. The patients who received treatment of ertapenem may have a lower risk of rectal colonization for ertapenem resistant Escherichia coli than those who received flomoxef or moxifloxacin. The rate of Pseudomonas colonization did not differ between the three study Pseudomonas-sparing agents. Copyright © 2017. Published by Elsevier B.V.

  12. Isolation of a new broad spectrum antifungal polyene from Streptomyces sp. MTCC 5680.

    Science.gov (United States)

    Vartak, A; Mutalik, V; Parab, R R; Shanbhag, P; Bhave, S; Mishra, P D; Mahajan, G B

    2014-06-01

    A new polyene macrolide antibiotic PN00053 was isolated from the fermentation broth of Streptomyces sp. wild-type strain MTCC-5680. The producer strain was isolated from fertile mountain soil of Naldehra region, Himachal Pradesh, India. The compound PN00053 was purified through various steps of chromatographic techniques and bio-activity guided fractionation followed by its characterization using physiochemical properties, spectral data ((1) H-NMR, (13) C-NMR, HMBC, HSQC, and COSY) and MS analysis. PN00053 exhibited broad spectrum in vitro antifungal activity against strains of Aspergillus fumigatus (HMR), A. fumigatus ATCC 16424, Candida albicans (I.V.), C. albicans ATCC 14503, C. krusei GO6, C. glabrata HO4, Cryptococcus neoformans, Trichophyton sp. as well as fluconazole resistant strains C. krusei GO3 and C. glabrata HO5. It did not inhibit growth of gram positive and gram-negative bacteria, displaying its specificity against fungi. PN00053 is a novel polyene macrolide isolated from a wild strain of Streptomyces sp. PM0727240 (MTCC5680), an isolate from the mountainous rocky regions of Himachal Pradesh, India. The compound is a new derivative of the antibiotic Roflamycoin [32, 33-didehydroroflamycoin (DDHR)]. It displayed broad spectrum antifungal activity against yeast and filamentous fungi. However, it did not show any antibacterial activity. The in vitro study revealed that PN00053 has better potency as compared to clinical gold standard fluconazole. The development of pathogenic resistance against the polyenes has been seldom reported. Hence, we envisage PN00053 could be a potential antifungal lead. © 2014 The Society for Applied Microbiology.

  13. Transcriptome differences between enrofloxacin-resistant and enrofloxacin-susceptible strains of Aeromonas hydrophila

    OpenAIRE

    Zhu, Fengjiao; Yang, Zongying; Zhang, Yiliu; Hu, Kun; Fang, Wenhong

    2017-01-01

    Enrofloxacin is the most commonly used antibiotic to control diseases in aquatic animals caused by A. hydrophila. This study conducted de novo transcriptome sequencing and compared the global transcriptomes of enrofloxacin-resistant and enrofloxacin-susceptible strains. We got a total of 4,714 unigenes were assembled. Of these, 4,122 were annotated. A total of 3,280 unigenes were assigned to GO, 3,388 unigenes were classified into Cluster of Orthologous Groups of proteins (COG) using BLAST an...

  14. A Broad-Spectrum Inhibitor of CRISPR-Cas9.

    Science.gov (United States)

    Harrington, Lucas B; Doxzen, Kevin W; Ma, Enbo; Liu, Jun-Jie; Knott, Gavin J; Edraki, Alireza; Garcia, Bianca; Amrani, Nadia; Chen, Janice S; Cofsky, Joshua C; Kranzusch, Philip J; Sontheimer, Erik J; Davidson, Alan R; Maxwell, Karen L; Doudna, Jennifer A

    2017-09-07

    CRISPR-Cas9 proteins function within bacterial immune systems to target and destroy invasive DNA and have been harnessed as a robust technology for genome editing. Small bacteriophage-encoded anti-CRISPR proteins (Acrs) can inactivate Cas9, providing an efficient off switch for Cas9-based applications. Here, we show that two Acrs, AcrIIC1 and AcrIIC3, inhibit Cas9 by distinct strategies. AcrIIC1 is a broad-spectrum Cas9 inhibitor that prevents DNA cutting by multiple divergent Cas9 orthologs through direct binding to the conserved HNH catalytic domain of Cas9. A crystal structure of an AcrIIC1-Cas9 HNH domain complex shows how AcrIIC1 traps Cas9 in a DNA-bound but catalytically inactive state. By contrast, AcrIIC3 blocks activity of a single Cas9 ortholog and induces Cas9 dimerization while preventing binding to the target DNA. These two orthogonal mechanisms allow for separate control of Cas9 target binding and cleavage and suggest applications to allow DNA binding while preventing DNA cutting by Cas9. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Application of broad-spectrum resequencing microarray for genotyping rhabdoviruses.

    Science.gov (United States)

    Dacheux, Laurent; Berthet, Nicolas; Dissard, Gabriel; Holmes, Edward C; Delmas, Olivier; Larrous, Florence; Guigon, Ghislaine; Dickinson, Philip; Faye, Ousmane; Sall, Amadou A; Old, Iain G; Kong, Katherine; Kennedy, Giulia C; Manuguerra, Jean-Claude; Cole, Stewart T; Caro, Valérie; Gessain, Antoine; Bourhy, Hervé

    2010-09-01

    The rapid and accurate identification of pathogens is critical in the control of infectious disease. To this end, we analyzed the capacity for viral detection and identification of a newly described high-density resequencing microarray (RMA), termed PathogenID, which was designed for multiple pathogen detection using database similarity searching. We focused on one of the largest and most diverse viral families described to date, the family Rhabdoviridae. We demonstrate that this approach has the potential to identify both known and related viruses for which precise sequence information is unavailable. In particular, we demonstrate that a strategy based on consensus sequence determination for analysis of RMA output data enabled successful detection of viruses exhibiting up to 26% nucleotide divergence with the closest sequence tiled on the array. Using clinical specimens obtained from rabid patients and animals, this method also shows a high species level concordance with standard reference assays, indicating that it is amenable for the development of diagnostic assays. Finally, 12 animal rhabdoviruses which were currently unclassified, unassigned, or assigned as tentative species within the family Rhabdoviridae were successfully detected. These new data allowed an unprecedented phylogenetic analysis of 106 rhabdoviruses and further suggest that the principles and methodology developed here may be used for the broad-spectrum surveillance and the broader-scale investigation of biodiversity in the viral world.

  16. Application of Broad-Spectrum Resequencing Microarray for Genotyping Rhabdoviruses▿

    Science.gov (United States)

    Dacheux, Laurent; Berthet, Nicolas; Dissard, Gabriel; Holmes, Edward C.; Delmas, Olivier; Larrous, Florence; Guigon, Ghislaine; Dickinson, Philip; Faye, Ousmane; Sall, Amadou A.; Old, Iain G.; Kong, Katherine; Kennedy, Giulia C.; Manuguerra, Jean-Claude; Cole, Stewart T.; Caro, Valérie; Gessain, Antoine; Bourhy, Hervé

    2010-01-01

    The rapid and accurate identification of pathogens is critical in the control of infectious disease. To this end, we analyzed the capacity for viral detection and identification of a newly described high-density resequencing microarray (RMA), termed PathogenID, which was designed for multiple pathogen detection using database similarity searching. We focused on one of the largest and most diverse viral families described to date, the family Rhabdoviridae. We demonstrate that this approach has the potential to identify both known and related viruses for which precise sequence information is unavailable. In particular, we demonstrate that a strategy based on consensus sequence determination for analysis of RMA output data enabled successful detection of viruses exhibiting up to 26% nucleotide divergence with the closest sequence tiled on the array. Using clinical specimens obtained from rabid patients and animals, this method also shows a high species level concordance with standard reference assays, indicating that it is amenable for the development of diagnostic assays. Finally, 12 animal rhabdoviruses which were currently unclassified, unassigned, or assigned as tentative species within the family Rhabdoviridae were successfully detected. These new data allowed an unprecedented phylogenetic analysis of 106 rhabdoviruses and further suggest that the principles and methodology developed here may be used for the broad-spectrum surveillance and the broader-scale investigation of biodiversity in the viral world. PMID:20610710

  17. Broad spectrum microarray for fingerprint-based bacterial species identification

    Directory of Open Access Journals (Sweden)

    Frey Jürg E

    2010-02-01

    Full Text Available Abstract Background Microarrays are powerful tools for DNA-based molecular diagnostics and identification of pathogens. Most target a limited range of organisms and are based on only one or a very few genes for specific identification. Such microarrays are limited to organisms for which specific probes are available, and often have difficulty discriminating closely related taxa. We have developed an alternative broad-spectrum microarray that employs hybridisation fingerprints generated by high-density anonymous markers distributed over the entire genome for identification based on comparison to a reference database. Results A high-density microarray carrying 95,000 unique 13-mer probes was designed. Optimized methods were developed to deliver reproducible hybridisation patterns that enabled confident discrimination of bacteria at the species, subspecies, and strain levels. High correlation coefficients were achieved between replicates. A sub-selection of 12,071 probes, determined by ANOVA and class prediction analysis, enabled the discrimination of all samples in our panel. Mismatch probe hybridisation was observed but was found to have no effect on the discriminatory capacity of our system. Conclusions These results indicate the potential of our genome chip for reliable identification of a wide range of bacterial taxa at the subspecies level without laborious prior sequencing and probe design. With its high resolution capacity, our proof-of-principle chip demonstrates great potential as a tool for molecular diagnostics of broad taxonomic groups.

  18. bioequivalence study on two 10% enrofloxacin oral formulations

    African Journals Online (AJOL)

    AONDOVER

    sampled before and after drug administration for 24 hours. Plasma enrofloxacin ... Pharmacokinetic studies have indicated ... variation of the inhibitory effect of antibiotics on .... These factors determine .... dependent, the in vivo performance of.

  19. Discovery of potent broad spectrum antivirals derived from marine actinobacteria.

    Directory of Open Access Journals (Sweden)

    Avi Raveh

    Full Text Available Natural products provide a vast array of chemical structures to explore in the discovery of new medicines. Although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. In this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characterize antiviral compounds produced by marine microbes. We isolated a compound from Streptomyces kaviengensis, a novel actinomycetes isolated from marine sediments obtained off the coast of New Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound displays potent activity against western equine encephalitis virus in cultured cells with half-maximal inhibitory concentrations of less than 4 nM and a selectivity index of greater than 550. Our efforts also revealed that several antimycin A analogues display antiviral activity, and mechanism of action studies confirmed that these Streptomyces-derived secondary metabolites function by inhibiting the cellular mitochondrial electron transport chain, thereby suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A functions as a broad spectrum agent with activity against a wide range of RNA viruses in cultured cells, including members of the Togaviridae, Flaviviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we demonstrate that antimycin A reduces central nervous system viral titers, improves clinical disease severity, and enhances survival in mice given a lethal challenge with western equine encephalitis virus. Our results provide conclusive validation for using natural product resources derived from marine microbes as source material for antiviral drug discovery, and they indicate that host mitochondrial electron transport is a viable

  20. The broad spectrum revisited: evidence from plant remains.

    Science.gov (United States)

    Weiss, Ehud; Wetterstrom, Wilma; Nadel, Dani; Bar-Yosef, Ofer

    2004-06-29

    The beginning of agriculture is one of the most important developments in human history, with enormous consequences that paved the way for settled life and complex society. Much of the research on the origins of agriculture over the last 40 years has been guided by Flannery's [Flannery, K. V. (1969) in The Domestication and Exploitation of Plants and Animals, eds. Ucko, P. J. & Dimbleby, G. W. (Duckworth, London), pp. 73-100] "broad spectrum revolution" (BSR) hypothesis, which posits that the transition to farming in southwest Asia entailed a period during which foragers broadened their resource base to encompass a wide array of foods that were previously ignored in an attempt to overcome food shortages. Although these resources undoubtedly included plants, nearly all BSR hypothesis-inspired research has focused on animals because of a dearth of Upper Paleolithic archaeobotanical assemblages. Now, however, a collection of >90,000 plant remains, recently recovered from the Stone Age site Ohalo II (23,000 B.P.), Israel, offers insights into the plant foods of the late Upper Paleolithic. The staple foods of this assemblage were wild grasses, pushing back the dietary shift to grains some 10,000 years earlier than previously recognized. Besides the cereals (wild wheat and barley), small-grained grasses made up a large component of the assemblage, indicating that the BSR in the Levant was even broader than originally conceived, encompassing what would have been low-ranked plant foods. Over the next 15,000 years small-grained grasses were gradually replaced by the cereals and ultimately disappeared from the Levantine diet.

  1. Reverse engineering truncations of an antimicrobial peptide dimer to identify the origins of potency and broad spectrum of action.

    Science.gov (United States)

    Anantharaman, Aparna; Sahal, Dinkar

    2010-08-26

    Antimicrobial peptides hold promise against antibiotic resistant pathogens. Here, to find the physicochemical origins of potency and broad spectrum antimicrobial action, we report the structure-activity relationships of synthetic intermediates (peptides A-D) of a potent lysine branched dimeric antibacterial peptide DeltaFd. Our studies show that a tetracationic character in a weak helical fold (peptide C) elicits potent but narrow spectrum antimicrobial activity [Minimum inhibitory concentrations (MICs) E. coli 10 microM, S. aureus>100 microM]. In contrast, a hexacationic character in a strong, amphipathic helix (DeltaFd) confers potent and broad spectrum action [MICs E. coli 2.5 microM, S. aureus 5 microM]. While DeltaFd caused rapid and potent permeabilization of the E. coli membranes, the less helical intermediates (peptides A-D) showed slow and weak to no responses. Two seminal findings that may aid future drug design are (a) at identical helicity, increasing charge enhanced outer membrane permeabilization, and (b) at identical charge, increasing helicity stimulated rate of outer membrane permeabilization and kill kinetics besides enhancing potency leading to broad spectrum action.

  2. Risk Factors for Emergence of Resistance to Broad-Spectrum Cephalosporins among Enterobacter spp.

    Science.gov (United States)

    Kaye, Keith S.; Cosgrove, Sara; Harris, Anthony; Eliopoulos, George M.; Carmeli, Yehuda

    2001-01-01

    Among 477 patients with susceptible Enterobacter spp., 49 subsequently harbored third-generation cephalosporin-resistant Enterobacter spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk [OR] = 2.3, P = 0.01); quinolone therapy was protective (OR = 0.4, P = 0.03). There were trends toward decreased risk for resistance among patients receiving broad-spectrum cephalosporins and either aminoglycosides or imipenem. Of the patients receiving broad-spectrum cephalosporins, 19% developed resistance. PMID:11502540

  3. Broad spectrum probiotic (Sakhabactisubtil recovered from Yakutia permafrost soil

    Directory of Open Access Journals (Sweden)

    Mikhail Petrovich Neustroev

    2011-10-01

    Full Text Available Probiotic “Sakhabactisubtil” has been developed, it has unique biological properties: frank antagonistic effect against pathogen and opportunistic microorganisms (bacteria, fungi and viruses, interferon-evoke activity, immune system enhancing effect, producing a range of ferments, beneficial microflora formation's stimulation, resistance to a number of antibiotics. [Vet. World 2011; 4(5.000: 222-224

  4. Transcriptome differences between enrofloxacin-resistant and enrofloxacin-susceptible strains of Aeromonas hydrophila.

    Science.gov (United States)

    Zhu, Fengjiao; Yang, Zongying; Zhang, Yiliu; Hu, Kun; Fang, Wenhong

    2017-01-01

    Enrofloxacin is the most commonly used antibiotic to control diseases in aquatic animals caused by A. hydrophila. This study conducted de novo transcriptome sequencing and compared the global transcriptomes of enrofloxacin-resistant and enrofloxacin-susceptible strains. We got a total of 4,714 unigenes were assembled. Of these, 4,122 were annotated. A total of 3,280 unigenes were assigned to GO, 3,388 unigenes were classified into Cluster of Orthologous Groups of proteins (COG) using BLAST and BLAST2GO software, and 2,568 were mapped onto pathways using the Kyoto Encyclopedia of Gene and Genomes Pathway database. Furthermore, 218 unigenes were deemed to be DEGs. After enrofloxacin treatment, 135 genes were upregulated and 83 genes were downregulated. The GO terms biological process (126 genes) and metabolic process (136 genes) were the most enriched, and the terms for protein folding, response to stress, and SOS response were also significantly enriched. This study identified enrofloxacin treatment affects multiple biological functions of A. hydrophila. Enrofloxacin resistance in A. hydrophila is closely related to the reduction of intracellular drug accumulation caused by ABC transporters and increased expression of topoisomerase IV.

  5. Potential Adverse Effects of Broad-Spectrum Antimicrobial Exposure in the Intensive Care Unit.

    Science.gov (United States)

    Wiens, Jenna; Snyder, Graham M; Finlayson, Samuel; Mahoney, Monica V; Celi, Leo Anthony

    2018-02-01

    The potential adverse effects of empiric broad-spectrum antimicrobial use among patients with suspected but subsequently excluded infection have not been fully characterized. We sought novel methods to quantify the risk of adverse effects of broad-spectrum antimicrobial exposure among patients admitted to an intensive care unit (ICU). Among all adult patients admitted to ICUs at a single institution, we selected patients with negative blood cultures who also received ≥1 broad-spectrum antimicrobials. Broad-spectrum antimicrobials were categorized in ≥1 of 5 categories based on their spectrum of activity against potential pathogens. We performed, in serial, 5 cohort studies to measure the effect of each broad-spectrum category on patient outcomes. Exposed patients were defined as those receiving a specific category of broad-spectrum antimicrobial; nonexposed were all other patients in the cohort. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital and ICU stay and nosocomial acquisition of antimicrobial-resistant bacteria (ARB) or Clostridium difficile within 30 days of admission. Among the study cohort of 1918 patients, 316 (16.5%) died within 30 days, 821 (42.8%) had either a length of hospital stay >7 days or an ICU length of stay >3 days, and 106 (5.5%) acquired either a nosocomial ARB or C. difficile . The short-term use of broad-spectrum antimicrobials in any of the defined broad-spectrum categories was not significantly associated with either primary or secondary outcomes. The prompt and brief empiric use of defined categories of broad-spectrum antimicrobials could not be associated with additional patient harm.

  6. In vitro activities of doxycycline and enrofloxacin against European Chlamydia psittaci strains from turkeys.

    OpenAIRE

    Butaye, P; Ducatelle, R; De Backer, P; Vermeersch, H; Remon, J P; Haesebrouck, F

    1997-01-01

    The in vitro susceptibility of 14 European Chlamydia psittaci strains from turkeys to the antibiotics doxycycline and enrofloxacin was tested. For doxycycline the MIC ranged from 0.05 to 0.2 microg/ml, with an average of 0.1 microg/ml. For enrofloxacin the MIC was 0.25 microg/ml. Acquired resistance was not detected against doxycycline and enrofloxacin.

  7. Broad spectrum antimicrobial activity of melimine covalently bound to contact lenses.

    Science.gov (United States)

    Dutta, Debarun; Cole, Nerida; Kumar, Naresh; Willcox, Mark D P

    2013-01-07

    To develop a stable antimicrobial contact lens, which is effective against the International Organization for Standardization (ISO) panel microorganisms, Acanthamoeba castellanii and drug resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. Melimine was covalently incorporated into etafilcon A lenses. The amount of peptide present on the lens surface was quantified using amino acid analysis. After coating, the heat stability (121°C), lens surface hydrophobicity (by captive bubble), and in vitro cytotoxicity to mouse L929 cells of the lenses were investigated. Antimicrobial activity against the micro-organisms was evaluated by viable plate count and fluorescence microscopy, measuring the proportion of cell death compared with control lenses with no melimine. The most effective concentration was determined to be 152 ± 44 μg lens(-1) melimine on the lens surface. After coating, lenses were relatively hydrophilic and were nontoxic to mammalian cells. The activity remained high after autoclaving (e.g., 3.1, 3.9, 1.2, and 1.0 log inhibition against P. aeruginosa, S. aureus, A. castellanii, and Fusarium solani, respectively). Fluorescence microscopy confirmed significantly reduced (P bacteria to melimine contact lenses. Viable count confirmed that lenses were active against all the bacteria and fungi from the ISO panel, Acanthamoeba and gave at least 2 log inhibition against all the multidrug resistant S. aureus and P. aeruginosa strains. Melimine may offer excellent potential for development as a broad spectrum antimicrobial coating for contact lenses, showing activity against all the bacterial and fungal ISO panel microorganisms, Acanthamoeba, and antibiotic resistant strains of P. aeruginosa and S. aureus.

  8. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

    DEFF Research Database (Denmark)

    Taylor, Jenny C; Martin, Hilary C; Lise, Stefano

    2015-01-01

    To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the numb...

  9. Novel water-based antiseptic lotion demonstrates rapid, broad-spectrum kill compared with alcohol antiseptic.

    Science.gov (United States)

    Czerwinski, Steven E; Cozean, Jesse; Cozean, Colette

    2014-01-01

    A novel alcohol-based antiseptic and a novel water-based antiseptic lotion, both with a synergistic combination of antimicrobial ingredients containing 0.2% benzethonium chloride, were evaluated using the standard time-kill method against 25 FDA-specified challenge microorganisms. The purpose of the testing was to determine whether a non-alcohol product could have equivalent rapid and broad-spectrum kill to a traditional alcohol sanitizer. Both the alcohol- and water-based products showed rapid and broad-spectrum antimicrobial activity. The average 15-s kill was 99.999% of the challenge organism for the alcohol-based antiseptic and 99.971% for the water-based antiseptic. The alcohol-based product demonstrated 100% of peak efficacy (60s) within the first 15s, whereas the water-based product showed 99.97%. The novel alcohol-based antiseptic reduced concentrations of 100% of organisms by 99.999%, whereas the water-based antiseptic lotion showed the same reduction for 96% of organisms. A novel water-based antiseptic product demonstrated equivalent rapid, broad-spectrum antimicrobial activity to an alcohol-based sanitizer and provided additional benefits of reduced irritation, persistent effect, and greater efficacy against common viruses. The combination of rapid, broad-spectrum immediate kill and persistent efficacy against pathogens may have significant clinical benefit in limiting the spread of disease. Copyright © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  10. Enrofloxacin enhances the formation of neutrophil extracellular traps in bovine granulocytes

    Science.gov (United States)

    Jerjomiceva, Natalja; Seri, Hisham; Völlger, Lena; Wang, Yanming; Zeitouni, Nathalie; Naim, Hassan Y.; von Köckritz-Blickwede, Maren

    2014-01-01

    Several antibiotics are known for their ability to accumulate in neutrophils and thereby modulate the antimicrobial functions of those cells. This manuscript demonstrates for the first time that an antibiotic, namely the fluoroquinolone enrofloxacin, enhances the formation of bovine neutrophil extracellular traps (NETs). When pharmacologically inactivating NADPH oxidase or peptidylarginine deiminase-4, enrofloxacin-induced NET-formation was distinctly reduced. Additionally, when treating the cells with cytochalasin D or nocodazole, the enrofloxacin-mediated NET-induction was abolished, indicating that besides oxidative burst and histone citrullination also the actin and microtubule polymerization are involved in this process. PMID:24642685

  11. A novel alkaloid from marine-derived actinomycete Streptomyces xinghaiensis with broad-spectrum antibacterial and cytotoxic activities.

    Directory of Open Access Journals (Sweden)

    Wence Jiao

    Full Text Available Due to the increasing emergence of drug-resistant bacteria and tumor cell lines, novel antibiotics with antibacterial and cytotoxic activities are urgently needed. Marine actinobacteria are rich sources of novel antibiotics, and here we report the discovery of a novel alkaloid, xinghaiamine A, from a marine-derived actinomycete Streptomyces xinghaiensis NRRL B24674(T. Xinghaiamine A was purified from the fermentation broth, and its structure was elucidated based on extensive spectroscopic analysis, including 1D and 2D NMR spectrum as well as mass spectrometry. Xinghaiamine A was identified to be a novel alkaloid with highly symmetric structure on the basis of sulfoxide functional group, and sulfoxide containing compound has so far never been reported in microorganisms. Biological assays revealed that xinghaiamine A exhibited broad-spectrum antibacterial activities to both Gram-negative persistent hospital pathogens (e.g. Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli and Gram-positive ones, which include Staphylococcus aureus and Bacillus subtilis. In addition, xinghaiamine A also exhibited potent cytotoxic activity to human cancer cell lines of MCF-7 and U-937 with the IC50 of 0.6 and 0.5 µM, respectively.

  12. Tricyclic GyrB/ParE (TriBE inhibitors: a new class of broad-spectrum dual-targeting antibacterial agents.

    Directory of Open Access Journals (Sweden)

    Leslie W Tari

    Full Text Available Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. However, growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highly conserved ATP-binding subunits of DNA gyrase (GyrB and topoisomerase IV (ParE have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD, we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models.

  13. Effects of Enrofloxacin on Porcine Phagocytic Function

    OpenAIRE

    Schoevers, E. J.; van Leengoed, L. A. M. G.; Verheijden, J. H. M.; Niewold, T. A.

    1999-01-01

    The interaction between enrofloxacin and porcine phagocytes was studied with clinically relevant concentrations of enrofloxacin. Enrofloxacin accumulated in phagocytes, with cellular concentration/extracellular concentration ratios of 9 for polymorphonuclear leukocytes (PMNs) and 5 for alveolar macrophages (AMs). Cells with accumulated enrofloxacin brought into enrofloxacin-free medium released approximately 80% (AMs) to 90% (PMNs) of their enrofloxacin within the first 10 min, after which no...

  14. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

    OpenAIRE

    Taylor, Jenny C; Martin, Hilary C; Lise, Stefano; Broxholme, John; Cazier, Jean-Baptiste; Rimmer, Andy; Kanapin, Alexander; Lunter, Gerton; Fiddy, Simon; Allan, Chris; Aricescu, A. Radu; Attar, Moustafa; Babbs, Christian; Becq, Jennifer; Beeson, David

    2015-01-01

    To assess factors influencing the success of whole genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases across a broad spectrum of disorders in whom prior screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritisation. We found that jointly calling variants across samples, filtering against both local and e...

  15. Elution of Clindamycin and Enrofloxacin From Calcium Sulfate Hemihydrate Beads In Vitro.

    Science.gov (United States)

    Phillips, Heidi; Boothe, Dawn M; Bennett, R Avery

    2015-11-01

    To compare the in vitro elution characteristics of clindamycin and enrofloxacin from calcium sulfate hemihydrate beads containing a single antibiotic, both antibiotics, and each antibiotic incubated in the same eluent well. Experimental in vitro study. Calcium sulfate hemihydrate beads were formed by mixing with clindamycin and/or enrofloxacin to create 4 study groups: (1) 160 mg clindamycin/10 beads; (2) 160 mg enrofloxacin/10 beads; (3) 160 mg clindamycin + 160 mg enrofloxacin/10 beads; and (4) 160 mg clindamycin/5 beads and 160 mg enrofloxacin/5 beads. Chains of beads were formed in triplicate and placed in 5 mL phosphate buffered saline (PBS; pH 7.4 and room temperature) with constant agitation. Antibiotic-conditioned PBS was sampled at 14 time points from 1 hour to 30 days. Clindamycin and enrofloxacin concentrations in PBS were determined using high-performance liquid chromatography. Eluent concentrations from clindamycin-impregnated beads failed to remain sufficiently above minimum inhibitory concentration (MIC) for common infecting bacteria over the study period. Enrofloxacin eluent concentrations remained sufficiently above MIC for common wound pathogens of dogs and cats and demonstrated an atypical biphasic release pattern. No significant differences in elution occurred as a result of copolymerization of the antibiotics into a single bead or from individual beads co-eluting in the same eluent well. Clindamycin-impregnated beads cannot be recommended for treatment of infection at the studied doses; however, use of enrofloxacin-impregnated beads may be justified when susceptible bacteria are cultured. © Copyright 2015 by The American College of Veterinary Surgeons.

  16. Therapeutic administration of enrofloxacin in mice does not select for fluoroquinolone resistance in Campylobacter jejuni.

    Science.gov (United States)

    Inglis, G Douglas; Zaytsoff, S J M; Selinger, L Brent; Taboada, Eduardo N; Uwiera, R R E

    2018-05-11

    Enrofloxacin is registered for therapeutic use in beef cattle to treat bovine respiratory disease in Canada. A murine model was used to experimentally examine the impact of therapeutic administration of enrofloxacin on fluoroquinolone resistance development in Campylobacter jejuni. Administration of enrofloxacin to mice via subcutaneous injection or per os routes resulted in equivalent levels of bioactive enrofloxacin within the intestine, but bioactivity was short-lived (Enrofloxacin administration did not affect densities of total bacteria, Firmicutes, or Bacteroidetes in digesta, and had modest impacts on densities of Enterobacteriaceae. All mice inoculated with C. jejuni NCTC 11168 became persistently colonized by the bacterium. Enrofloxacin reduced C. jejuni cell densities within the cecal and colonic digesta for all treatments, and densities shed in feces as a function of antibiotic duration. None of the C. jejuni isolates recovered from mice after administration of enrofloxacin (n=260) developed resistance to ciprofloxacin regardless of method or duration of administration. Furthermore, only modest shifts in the minimum inhibitory concentration of the isolates by treatment were noted. The study findings indicate that the risk posed by short-term subcutaneous administration of enrofloxacin for the development of fluoroquinolone resistance in mammals is low.

  17. Selection of target mutation in rat gastrointestinal tract E. coli by minute dosage of enrofloxacin.

    Science.gov (United States)

    Lin, Dachuan; Chen, Kaichao; Li, Ruichao; Liu, Lizhang; Guo, Jiubiao; Yao, Wen; Chen, Sheng

    2014-01-01

    It has been suggested that bacterial resistance is selected within a mutation selection window of antibiotics. More recent studies showed that even extremely low concentration of antibiotic could select resistant bacteria in vitro. Yet little is known about the exact antibiotic concentration range that can effectively select for resistant organisms in animal gastrointestinal (GI) tract. In this study, the effect of different dosages of enrofloxacin on resistance and mutation development in rat GI tract E. coli was investigated by determining the number of resistant E. coli recoverable from rat fecal samples. Our data showed that high dose antibiotic treatment could effectively eliminate E. coli with single gyrA mutation in the early course of treatment, yet the eradication effects diminished upon prolonged treatment. Therapeutic and sub-therapeutic dose (1/10 and 1/100 of therapeutic doses) of enrofloxacin could effectively select for mutation in GI tract E. coli at the later course of enrofloxacin treatment and during the cessation periods. Surprisingly, very low dose of enrofloxacin (1/1000 therapeutic dose) could also select for mutation in GI tract E. coli at the later course of enrofloxacin treatment, only with slightly lower efficiency. No enrofloxacin-resistant E. coli could be selected at all test levels of enrofloxacin during long term treatment and the strength of antibiotic treatment does not alter the overall level of E. coli in rat GI tract. This study demonstrated that long term antibiotic treatment seems to be the major trigger for the development of target mutations in GI tract E. coli, which provided insight into the rational use of antibiotics in animal husbandry.

  18. 21 CFR 522.812 - Enrofloxacin.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enrofloxacin. 522.812 Section 522.812 Food and... Enrofloxacin. (a) Specifications. Each milliliter (mL) of solution contains: (1) 22.7 milligrams (mg) enrofloxacin or (2) 100 mg enrofloxacin. (b) Sponsor. See No. 000859 in § 510.600(c) of this chapter. (c...

  19. Gamma-irradiated scrub typhus immunogens: broad-spectrum immunity with combinations of rickettsial strains

    International Nuclear Information System (INIS)

    Eisenberg, G.H. Jr.; Osterman, J.V.

    1979-01-01

    Scrub typhus immunogens were prepared from Rickettsia tsutsugamushi strains Karp, Kato, Gilliam, Kostival, and Buie by exposing frozen infected yolk sac suspensions to 300 krad of gamma radiation. Mouse protection tests showed that each of the irradiated immunogens protected C3H/HeDub mice against high challenge levels of Karp and Gilliam, but that none of these single-strain immunogens were capable of protecting against all five of the challenge strains. Broad-spectrum protection was achieved by using combinations of three strains of irradiated rickettsiae in a vaccination regimen of three injections at 5-day intervals

  20. Biological activity of sedaxane---a novel broad-spectrum fungicide for seed treatment.

    Science.gov (United States)

    Zeun, Ronald; Scalliet, Gabriel; Oostendorp, Michael

    2013-04-01

    Sedaxane is a new broad-spectrum seed treatment fungicide developed by Syngenta Crop Protection for control of seed- and soil-borne diseases in a broad range of crops. Its physicochemical properties and activity spectrum have been optimised for use as a seed treatment providing both local and systemic protection of the seed and roots of target crops. Sedaxane inhibits respiration by binding to the succinate dehydrogenase complex in the fungal mitochondrium. Its activity spectrum covers seed-borne fungi such as Ustilago nuda, Tilletia caries, Monographella nivalis and Pyrenophora graminea, as well as the soil-borne fungi Rhizoctonia solani, R. cerealis and Typhula incarnata. Under greenhouse conditions, sedaxane showed high levels and consistent protection against U. nuda, P. graminea and Rhizoctonia spp. Under field conditions, efficacy against Rhizoctonia spp. resulted in increased yield compared with the untreated check. Efficacy against snow mould has been shown under very high disease pressure conditions. The combination of sedaxane plus fludioxonil against snow mould can provide resistance management for sustainable use. The broad spectrum and high level of activity in combination with excellent crop tolerance allow the use of sedaxane as a seed treatment in a wide variety of crops. It is a potential tool for precautionary resistance management when combined with other fungicides, especially against pathogens showing a potential for resistance development, such as M. nivalis. © 2012 Society of Chemical Industry.

  1. Nanomedicine for Infectious Disease Applications: Innovation towards Broad-Spectrum Treatment of Viral Infections.

    Science.gov (United States)

    Jackman, Joshua A; Lee, Jaywon; Cho, Nam-Joon

    2016-03-02

    Nanomedicine enables unique diagnostic and therapeutic capabilities to tackle problems in clinical medicine. As multifunctional agents with programmable properties, nanomedicines are poised to revolutionize treatment strategies. This promise is especially evident for infectious disease applications, for which the continual emergence, re-emergence, and evolution of pathogens has proven difficult to counter by conventional approaches. Herein, a conceptual framework is presented that envisions possible routes for the development of nanomedicines as superior broad-spectrum antiviral agents against enveloped viruses. With lipid membranes playing a critical role in the life cycle of medically important enveloped viruses including HIV, influenza, and Ebola, cellular and viral membrane interfaces are ideal elements to incorporate into broad-spectrum antiviral strategies. Examples are presented that demonstrate how nanomedicine strategies inspired by lipid membranes enable a wide range of targeting opportunities to gain control of critical stages in the virus life cycle through either direct or indirect approaches involving membrane interfaces. The capabilities can be realized by enabling new inhibitory functions or improving the function of existing drugs through nanotechnology-enabled solutions. With these exciting opportunities, due attention is also given to the clinical translation of nanomedicines for infectious disease applications, especially as pharmaceutical drug-discovery pipelines demand new routes of innovation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Antibiotics can ameliorate circulatory complications of liver cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn Stæhr; Schaffalitzky de Muckadell, Ove B

    2011-01-01

    . This review focuses on how broad spectrum antibiotics can ameliorate the haemodynamic consequences of bacterial translocation. It is possible that the use of broad spectrum antibiotics in the future may be used to prevent other complications of liver cirrhosis than spontaneous bacterial peritonitis...

  3. Enrofloxacin Permeation Pathways across the Porin OmpC.

    Science.gov (United States)

    Prajapati, Jigneshkumar Dahyabhai; Solano, Carlos José Fernández; Winterhalter, Mathias; Kleinekathöfer, Ulrich

    2018-02-01

    In Gram-negative bacteria, the lack or quenching of antibiotic translocation across the outer membrane is one of the main factors for acquiring antibiotic resistance. An atomic-level comprehension of the key features governing the transport of drugs by outer-membrane protein channels would be very helpful in developing the next generation of antibiotics. In a previous study [ J. D. Prajapati et al. J. Chem. Theory Comput. 2017 , 13 , 4553 ], we characterized the diffusion pathway of a ciprofloxacin molecule through the outer membrane porin OmpC of Escherichia coli by combining metadynamics and a zero-temperature string method. Here, we evaluate the diffusion route through the OmpC porin for a similar fluoroquinolone, that is, the enrofloxacin molecule, using the previously developed protocol. As a result, it was found that the lowest-energy pathway was similar to that for ciprofloxacin; namely, a reorientation was required on the extracellular side with the carboxyl group ahead before enrofloxacin reached the constriction region. In turn, the free-energy basins for both antibiotics are located at similar positions in the space defined by selected reaction coordinates, and their affinity sites share a wide number of porin residues. However, there are some important deviations due to the chemical differences of these two drugs. On the one hand, a slower diffusion process is expected for enrofloxacin, as the permeation pathway exhibits higher overall energy barriers, mainly in the constriction region. On the other hand, enrofloxacin needs to replace some polar interactions in its affinity sites with nonpolar ones. This study demonstrates how minor chemical modifications can qualitatively affect the translocation mechanism of an antibiotic molecule.

  4. Production and characterization of a monoclonal antibody against enrofloxacin.

    Science.gov (United States)

    Chusri, Manaspong; Wongphanit, Pitikarn; Palaga, Tanapat; Puthong, Songchan; Sooksai, Sarintip; Komolpis, Kittinan

    2013-01-01

    Enrofloxacin is a fluoroquinolone antibiotic approved for the treatment of infections in animals. Because of the side effects to consumers of animal products, the maximum residue limits (MRLs) of enrofloxacin in animal tissues for consumption are regulated. In this study, a monoclonal antibody (mAb) against enrofloxacin was prepared and characterized for the development of a direct competitive enzyme-linked immunosorbent assay (ELISA). The obtained mAb, Enro44, was highly specific for enrofloxacin and had a 50% inhibition concentration (IC(50)) of 1.99 ng/ml in a competitive ELISA, and the limit of detection (LOD) was 0.50 ng/ml. The cross-reactivity of the mAb with other quinolones and fluoroquinolones was lower than 0.01%. The subclass of the mAb Enro44 was identified as IgG1. The antigen (Ag)-captured direct competitive ELISA using the mAb Enro44 was tested on different spiked samples, including chicken muscle, cattle milk, and cattle urine, and the assay demonstrated recoveries of 82-112%, 80-125%, and 78-124%, respectively. Furthermore, the quantitation of enrofloxacin obtained from the ELISA and from high-performance liquid chromatography (HPLC) was in good agreement, with the linear regression coefficient between 0.933 and 1.056. The cDNAs encoding a heavy-chain Fd fragment (VH and CH1) and a light chain of the mAb Enro44 were cloned and sequenced. Taken together, the results obtained reveal a potential use of this mAb in an ELISA for the detection of enrofloxacin in food samples. The information of amino acid sequence of this mAb will be useful for further modification and production of the mAb in a bioreactor.

  5. The broad-spectrum antiviral compound ST-669 restricts chlamydial inclusion development and bacterial growth and localizes to host cell lipid droplets within treated cells.

    Science.gov (United States)

    Sandoz, Kelsi M; Valiant, William G; Eriksen, Steven G; Hruby, Dennis E; Allen, Robert D; Rockey, Daniel D

    2014-07-01

    Novel broad-spectrum antimicrobials are a critical component of a strategy for combating antibiotic-resistant pathogens. In this study, we explored the activity of the broad-spectrum antiviral compound ST-669 for activity against different intracellular bacteria and began a characterization of its mechanism of antimicrobial action. ST-669 inhibits the growth of three different species of chlamydia and the intracellular bacterium Coxiella burnetii in Vero and HeLa cells but not in McCoy (murine) cells. The antichlamydial and anti-C. burnetii activity spectrum was consistent with those observed for tested viruses, suggesting a common mechanism of action. Cycloheximide treatment in the presence of ST-669 abrogated the inhibitory effect, demonstrating that eukaryotic protein synthesis is required for tested activity. Immunofluorescence microscopy demonstrated that different chlamydiae grow atypically in the presence of ST-669, in a manner that suggests the compound affects inclusion formation and organization. Microscopic analysis of cells treated with a fluorescent derivative of ST-669 demonstrated that the compound localized to host cell lipid droplets but not to other organelles or the host cytosol. These results demonstrate that ST-669 affects intracellular growth in a host-cell-dependent manner and interrupts proper development of chlamydial inclusions, possibly through a lipid droplet-dependent process. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  6. Impact of enrofloxacin on the human intestinal microbiota revealed by comparative molecular analysis.

    Science.gov (United States)

    Kim, Bong-Soo; Kim, Jong Nam; Yoon, Seok-Hwan; Chun, Jongsik; Cerniglia, Carl E

    2012-06-01

    The indigenous human intestinal microbiota could be disrupted by residues of antibiotics in foods as well as therapeutically administered antibiotics to humans. These disruptions may lead to adverse health outcomes. To observe the possible impact of residues of antibiotics at concentrations below therapeutic levels on human intestinal microbiota, we performed studies using in vitro cultures of fecal suspensions from three individuals with 10 different concentrations (0, 0.1, 0.5, 1, 5, 10, 15, 25, 50 and 150 μg/ml) of the fluoroquinolone, enrofloxacin. The bacterial communities of the control and enrofloxacin dosed fecal samples were analyzed by denaturing gradient gel electrophoresis (DGGE) and pyrosequencing. In addition, changes of functional gene expression were analyzed by a pyrosequencing-based random whole-community mRNA sequencing method. Although each individual had a unique microbial composition, the communities of all individuals were affected by enrofloxacin. The proportions of two phyla, namely, Bacteroidetes and Proteobacteria, were significantly reduced with increasing concentrations of enrofloxacin exposure, while the proportion of Firmicutes increased. Principal Coordinate Analysis (PCoA) using the Fast UniFrac indicated that the community structures of intestinal microbiota were shifted by enrofloxacin. Most of the mRNA transcripts and the anti-microbial drug resistance genes increased with increasing concentrations of enrofloxacin. 16S rRNA gene pyrosequencing of control and enrofloxacin treated fecal suspensions provided valuable information of affected bacterial taxa down to the species level, and the community transcriptomic analyses using mRNA revealed the functional gene expression responses of the changed bacterial communities by enrofloxacin. Published by Elsevier Ltd.

  7. Development of a broad-spectrum antiviral with activity against Ebola virus.

    Science.gov (United States)

    Aman, M Javad; Kinch, Michael S; Warfield, Kelly; Warren, Travis; Yunus, Abdul; Enterlein, Sven; Stavale, Eric; Wang, Peifang; Chang, Shaojing; Tang, Qingsong; Porter, Kevin; Goldblatt, Michael; Bavari, Sina

    2009-09-01

    We report herein the identification of a small molecule therapeutic, FGI-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including Ebola, Rift Valley and Dengue Fever viruses, in cell-based assays. Using mouse models of Ebola virus, we further demonstrate that FGI-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or therapeutic setting. A single treatment, administered 1 day after infection, is sufficient to protect animals from lethal Ebola virus challenge. Cell-based assays also identified inhibitory activity against divergent virus families, which supports a hypothesis that FGI-106 interferes with a common pathway utilized by different viruses. These findings suggest FGI-106 may provide an opportunity for targeting viral diseases.

  8. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

    Science.gov (United States)

    Lise, Stefano; Broxholme, John; Cazier, Jean-Baptiste; Rimmer, Andy; Kanapin, Alexander; Lunter, Gerton; Fiddy, Simon; Allan, Chris; Aricescu, A. Radu; Attar, Moustafa; Babbs, Christian; Becq, Jennifer; Beeson, David; Bento, Celeste; Bignell, Patricia; Blair, Edward; Buckle, Veronica J; Bull, Katherine; Cais, Ondrej; Cario, Holger; Chapel, Helen; Copley, Richard R; Cornall, Richard; Craft, Jude; Dahan, Karin; Davenport, Emma E; Dendrou, Calliope; Devuyst, Olivier; Fenwick, Aimée L; Flint, Jonathan; Fugger, Lars; Gilbert, Rodney D; Goriely, Anne; Green, Angie; Greger, Ingo H.; Grocock, Russell; Gruszczyk, Anja V; Hastings, Robert; Hatton, Edouard; Higgs, Doug; Hill, Adrian; Holmes, Chris; Howard, Malcolm; Hughes, Linda; Humburg, Peter; Johnson, David; Karpe, Fredrik; Kingsbury, Zoya; Kini, Usha; Knight, Julian C; Krohn, Jonathan; Lamble, Sarah; Langman, Craig; Lonie, Lorne; Luck, Joshua; McCarthy, Davis; McGowan, Simon J; McMullin, Mary Frances; Miller, Kerry A; Murray, Lisa; Németh, Andrea H; Nesbit, M Andrew; Nutt, David; Ormondroyd, Elizabeth; Oturai, Annette Bang; Pagnamenta, Alistair; Patel, Smita Y; Percy, Melanie; Petousi, Nayia; Piazza, Paolo; Piret, Sian E; Polanco-Echeverry, Guadalupe; Popitsch, Niko; Powrie, Fiona; Pugh, Chris; Quek, Lynn; Robbins, Peter A; Robson, Kathryn; Russo, Alexandra; Sahgal, Natasha; van Schouwenburg, Pauline A; Schuh, Anna; Silverman, Earl; Simmons, Alison; Sørensen, Per Soelberg; Sweeney, Elizabeth; Taylor, John; Thakker, Rajesh V; Tomlinson, Ian; Trebes, Amy; Twigg, Stephen RF; Uhlig, Holm H; Vyas, Paresh; Vyse, Tim; Wall, Steven A; Watkins, Hugh; Whyte, Michael P; Witty, Lorna; Wright, Ben; Yau, Chris; Buck, David; Humphray, Sean; Ratcliffe, Peter J; Bell, John I; Wilkie, Andrew OM; Bentley, David; Donnelly, Peter; McVean, Gilean

    2015-01-01

    To assess factors influencing the success of whole genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases across a broad spectrum of disorders in whom prior screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritisation. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease causing variants in 21% of cases, rising to 34% (23/68) for Mendelian disorders and 57% (8/14) in trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, though only four were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis, but also highlight many outstanding challenges. PMID:25985138

  9. Development of an enrofloxacin immunosensor based on label-free electrochemical impedance spectroscopy.

    Science.gov (United States)

    Wu, Ching-Chou; Lin, Chia-Hung; Wang, Way-Shyan

    2009-06-30

    Enrofloxacin is the most widespread antibiotic in the fluoroquinolone family. As such, the development of a rapid and sensitive method for the determination of trace amounts of enrofloxacin is an important issue in the health field. The interaction of the enrofloxacin antigen to a specific antibody (Ab) immobilized on an 11-mercapto-undecanoic acid-coated gold electrode was quantified by electrochemical impedance spectroscopy. Two equivalent circuits were separately used to interpret the obtained impedance spectra. These circuits included one resistor in series with one parallel circuit comprised of a resistor and a capacitor (1R//C), and one resistor in series with two parallel RC circuits (2R//C). The results indicate that the antigen-antibody reaction analyzed using the 1R//C circuit provided a more sensitive resistance increment against the enrofloxacin concentration than that of the 2R//C circuit. However, the 2R//C circuit provided a better fitting for impedance spectra, and therefore supplies more detailed results of the enrofloxacin-antibody interaction, causing the increase of electron transfer resistance selectively to the modified layer, and not the electrical double layer. The antibody-modified electrode allowed for analysis of the dynamic linear range of 1-1000 ng/ml enrofloxacin with a detection limit of 1 ng/ml. The reagentless and label-free impedimetric immunosensors provide a simple and sensitive detection method for the specific determination of enrofloxacin.

  10. Effect of therapeutic doses of enrofloxacin on circulating lymphocyte subpopulations in pigs

    Directory of Open Access Journals (Sweden)

    Pomorska-Mól Małgorzata

    2015-06-01

    Full Text Available Twenty pigs of similar genetics (PIC were used. Pigs were randomly divided into two groups: experimental (ENRO, n = 10 and control (C, n = 10. From day 0 to day 4, pigs from ENRO group received enrofloxacin at the recommended therapeutic dose. Pigs from C group received PBS instead of enrofloxacin. Blood samples were collected on days 0 (before antibiotic administration, 2, 4 (during antibiotic therapy, 9, and 13 of the study (after enrofloxacin administration. Haematological examination and flow cytometry were used to establish the relative and absolute counts of various leukocyte subsets. Lymphocyte subpopulations were measured by fluorochrom-labelled antibodies according to following definitions: CD3+ (T cells, CD21+ (B cells, CD4+CD8- (helper T cells, Th, CD4-CD8+ (cytolytic T cells, CLT, CD4+CD8+ (cytolytic and memory T cells. The present study revealed the modulating effect of enrofloxacin on the composition of circulating lymphocytes in pigs. Concentration and percentage of CD8+ cells decreased significantly after treatment with enrofloxacin and as a result the absolute CD4/CD8 ratio increased significantly as compared to control group (P < 0.05.These findings should prompt further studies on the practical significance of the results obtained in terms of clinical implications. In view of the results, it cannot be excluded that enrofloxacin may also have immunomodulatory effects on host response to infection.

  11. Antibiotics

    Science.gov (United States)

    Antibiotics are powerful medicines that fight bacterial infections. Used properly, antibiotics can save lives. They either kill bacteria or ... natural defenses can usually take it from there. Antibiotics do not fight infections caused by viruses, such ...

  12. Designing a broad-spectrum integrative approach for cancer prevention and treatment.

    Science.gov (United States)

    Block, Keith I; Gyllenhaal, Charlotte; Lowe, Leroy; Amedei, Amedeo; Amin, A R M Ruhul; Amin, Amr; Aquilano, Katia; Arbiser, Jack; Arreola, Alexandra; Arzumanyan, Alla; Ashraf, S Salman; Azmi, Asfar S; Benencia, Fabian; Bhakta, Dipita; Bilsland, Alan; Bishayee, Anupam; Blain, Stacy W; Block, Penny B; Boosani, Chandra S; Carey, Thomas E; Carnero, Amancio; Carotenuto, Marianeve; Casey, Stephanie C; Chakrabarti, Mrinmay; Chaturvedi, Rupesh; Chen, Georgia Zhuo; Chen, Helen; Chen, Sophie; Chen, Yi Charlie; Choi, Beom K; Ciriolo, Maria Rosa; Coley, Helen M; Collins, Andrew R; Connell, Marisa; Crawford, Sarah; Curran, Colleen S; Dabrosin, Charlotta; Damia, Giovanna; Dasgupta, Santanu; DeBerardinis, Ralph J; Decker, William K; Dhawan, Punita; Diehl, Anna Mae E; Dong, Jin-Tang; Dou, Q Ping; Drew, Janice E; Elkord, Eyad; El-Rayes, Bassel; Feitelson, Mark A; Felsher, Dean W; Ferguson, Lynnette R; Fimognari, Carmela; Firestone, Gary L; Frezza, Christian; Fujii, Hiromasa; Fuster, Mark M; Generali, Daniele; Georgakilas, Alexandros G; Gieseler, Frank; Gilbertson, Michael; Green, Michelle F; Grue, Brendan; Guha, Gunjan; Halicka, Dorota; Helferich, William G; Heneberg, Petr; Hentosh, Patricia; Hirschey, Matthew D; Hofseth, Lorne J; Holcombe, Randall F; Honoki, Kanya; Hsu, Hsue-Yin; Huang, Gloria S; Jensen, Lasse D; Jiang, Wen G; Jones, Lee W; Karpowicz, Phillip A; Keith, W Nicol; Kerkar, Sid P; Khan, Gazala N; Khatami, Mahin; Ko, Young H; Kucuk, Omer; Kulathinal, Rob J; Kumar, Nagi B; Kwon, Byoung S; Le, Anne; Lea, Michael A; Lee, Ho-Young; Lichtor, Terry; Lin, Liang-Tzung; Locasale, Jason W; Lokeshwar, Bal L; Longo, Valter D; Lyssiotis, Costas A; MacKenzie, Karen L; Malhotra, Meenakshi; Marino, Maria; Martinez-Chantar, Maria L; Matheu, Ander; Maxwell, Christopher; McDonnell, Eoin; Meeker, Alan K; Mehrmohamadi, Mahya; Mehta, Kapil; Michelotti, Gregory A; Mohammad, Ramzi M; Mohammed, Sulma I; Morre, D James; Muralidhar, Vinayak; Muqbil, Irfana; Murphy, Michael P; Nagaraju, Ganji Purnachandra; Nahta, Rita; Niccolai, Elena; Nowsheen, Somaira; Panis, Carolina; Pantano, Francesco; Parslow, Virginia R; Pawelec, Graham; Pedersen, Peter L; Poore, Brad; Poudyal, Deepak; Prakash, Satya; Prince, Mark; Raffaghello, Lizzia; Rathmell, Jeffrey C; Rathmell, W Kimryn; Ray, Swapan K; Reichrath, Jörg; Rezazadeh, Sarallah; Ribatti, Domenico; Ricciardiello, Luigi; Robey, R Brooks; Rodier, Francis; Rupasinghe, H P Vasantha; Russo, Gian Luigi; Ryan, Elizabeth P; Samadi, Abbas K; Sanchez-Garcia, Isidro; Sanders, Andrew J; Santini, Daniele; Sarkar, Malancha; Sasada, Tetsuro; Saxena, Neeraj K; Shackelford, Rodney E; Shantha Kumara, H M C; Sharma, Dipali; Shin, Dong M; Sidransky, David; Siegelin, Markus David; Signori, Emanuela; Singh, Neetu; Sivanand, Sharanya; Sliva, Daniel; Smythe, Carl; Spagnuolo, Carmela; Stafforini, Diana M; Stagg, John; Subbarayan, Pochi R; Sundin, Tabetha; Talib, Wamidh H; Thompson, Sarah K; Tran, Phuoc T; Ungefroren, Hendrik; Vander Heiden, Matthew G; Venkateswaran, Vasundara; Vinay, Dass S; Vlachostergios, Panagiotis J; Wang, Zongwei; Wellen, Kathryn E; Whelan, Richard L; Yang, Eddy S; Yang, Huanjie; Yang, Xujuan; Yaswen, Paul; Yedjou, Clement; Yin, Xin; Zhu, Jiyue; Zollo, Massimo

    2015-12-01

    Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us

  13. 21 CFR 520.812 - Enrofloxacin tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enrofloxacin tablets. 520.812 Section 520.812 Food... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.812 Enrofloxacin tablets. (a) Specifications. Each tablet contains either 22.7, 68.0, or 136.0 milligrams of enrofloxacin. (b) Sponsor. See No...

  14. 21 CFR 556.226 - Enrofloxacin.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enrofloxacin. 556.226 Section 556.226 Food and... Residues of New Animal Drugs § 556.226 Enrofloxacin. (a) Acceptable daily intake (ADI). The ADI for total residues of enrofloxacin is 3 micrograms per kilogram of body weight per day. (b) Tolerances. The...

  15. The effects of exogenous catalase on broad-spectrum near-UV (300-400nm) treated Escherichia coli cells

    International Nuclear Information System (INIS)

    Sammartano, L.J.; Tuveson, R.W.

    1984-01-01

    Catalase incorporated into plating medium protects against inactivation and mutagenesis by broad-spectrum near-ultraviolet wavelength (300-400nm) (NUV) radiation in strains of Escherichia coli. Plating medium containing catalase does not provide protection against inactivation by wavelengths in the FUV region. Catalase added to the cell suspension during or added immediately after NUV exposure also protects against inactivation. The protection provided by catalase suggests a possible role for hydrogen peroxide in the processes of inactivation and mutagenesis by broad-spectrum NUV. (author)

  16. Dissecting disease entities out of the broad spectrum of bipolar-disorders.

    Science.gov (United States)

    Levine, Joseph; Toker, Lilach; Agam, Galila

    2018-01-01

    The etiopathology of bipolar disorders is yet unraveled and new avenues should be pursued. One such avenue may be based on the assumption that the bipolar broad spectrum includes, among others, an array of rare medical disease entities. Towards this aim we propose a dissecting approach based on a search for rare medical diseases with known etiopathology which also exhibit bipolar disorders symptomatology. We further suggest that the etiopathologic mechanisms underlying such rare medical diseases may also underlie a rare variant of bipolar disorder. Such an assumption may be further reinforced if both the rare medical disease and its bipolar clinical phenotype demonstrate a] a similar mode of inheritance (i.e, autosomal dominant); b] brain involvement; and c] data implicating that the etiopathological mechanisms underlying the rare diseases affect biological processes reported to be associated with bipolar disorders and their treatment. We exemplify our suggested approach by a rare case of autosomal dominant leucodystrophy, a disease entity exhibiting nuclear lamin B1 pathology also presenting bipolar symptomatology. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. XA23 is an executor R protein and confers broad-spectrum disease resistance in rice.

    Science.gov (United States)

    Wang, Chunlian; Zhang, Xiaoping; Fan, Yinglun; Gao, Ying; Zhu, Qinlong; Zheng, Chongke; Qin, Tengfei; Li, Yanqiang; Che, Jinying; Zhang, Mingwei; Yang, Bing; Liu, Yaoguang; Zhao, Kaijun

    2014-11-09

    The majority of plant disease resistance (R) genes encode proteins that share common structural features. However, the transcription activator-like effector (TALE) associated executor type R genes show no considerable sequence homology to any known R genes. We adopted a map-based cloning approach and TALE-based technology to isolate and characterize Xa23, a new executor R gene derived from the wild rice (Oryza rufipogon) that confers an extremely broad spectrum of resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo). Xa23 encodes a 113-amino acid protein that shares 50% identity to the known executor R protein XA10. The predicted transmembrane helices in XA23 also overlap with those of XA10. Unlike Xa10, however, Xa23 transcription is specifically activated by AvrXa23, a TALE present in all examined Xoo field isolates. Moreover, the susceptible xa23 allele has an identical open reading frame of Xa23, but differs in promoter region by lacking the TALE binding-element (EBE) for AvrXa23. XA23 can trigger strong hypersensitive response in rice, tobacco and tomato. Our results provide the first evidence that plant genomes have an executor R gene family in which members execute their function and spectrum of disease resistance by recognizing the cognate TALEs in pathogen. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

  18. Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection

    Directory of Open Access Journals (Sweden)

    Pécheur Eve-Isabelle

    2006-07-01

    Full Text Available Abstract Arbidol (ARB is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 μM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB's affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.

  19. Ceftiofur sodium, a broad-spectrum cephalosporin: evaluation in vitro and in vivo in mice.

    Science.gov (United States)

    Yancey, R J; Kinney, M L; Roberts, B J; Goodenough, K R; Hamel, J C; Ford, C W

    1987-07-01

    Ceftiofur sodium, a broad-spectrum beta-lactamase-resistant cephalosporin, was evaluated in vitro and in vivo in mice. Ceftiofur is the sodium salt of (6R, 7R)-7[( 2-amino-4-thiazolyl)-Z- (methoxyimino)acetyl]amino)-3-[( (2-furanylcarbonyl)thio]methyl)-8-oxo-5- thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylate. Minimal inhibitory concentration values were obtained with 264 strains representing 9 genera and 17 species of bacterial pathogens from cattle, swine, sheep, horses, poultry, dogs, cats, and human beings. Ceftiofur was more active than was ampicillin against all strains tested including beta-lactamase-producing organisms. In mice with systemic infections, ceftiofur was more active than or equivalent to ampicillin, cephalothin, cefamandole, cloxacillin, cefoperazone, or pirlimycin. These protection tests included infections with Escherichia coli, Haemophilus pleuropneumoniae, H somnus, Pasteurella haemolytica, P multocida, Salmonella typhimurium, or Staphylococcus aureus. In infant mice with E coli-induced lethal diarrhea and in mice with S aureus and E coli-induced mastitis, ceftiofur was comparable or more active than was ampicillin.

  20. Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism

    Science.gov (United States)

    Cagno, Valeria; Andreozzi, Patrizia; D'Alicarnasso, Marco; Jacob Silva, Paulo; Mueller, Marie; Galloux, Marie; Le Goffic, Ronan; Jones, Samuel T.; Vallino, Marta; Hodek, Jan; Weber, Jan; Sen, Soumyo; Janeček, Emma-Rose; Bekdemir, Ahmet; Sanavio, Barbara; Martinelli, Chiara; Donalisio, Manuela; Rameix Welti, Marie-Anne; Eleouet, Jean-Francois; Han, Yanxiao; Kaiser, Laurent; Vukovic, Lela; Tapparel, Caroline; Král, Petr; Krol, Silke; Lembo, David; Stellacci, Francesco

    2018-02-01

    Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon dilution, the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral association with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (~190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and molecular dynamics simulations support the proposed mechanism. These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.

  1. Steps toward broad-spectrum therapeutics: discovering virulence-associated genes present in diverse human pathogens

    Directory of Open Access Journals (Sweden)

    de Rochefort Anna

    2009-10-01

    Full Text Available Abstract Background New and improved antimicrobial countermeasures are urgently needed to counteract increased resistance to existing antimicrobial treatments and to combat currently untreatable or new emerging infectious diseases. We demonstrate that computational comparative genomics, together with experimental screening, can identify potential generic (i.e., conserved across multiple pathogen species and novel virulence-associated genes that may serve as targets for broad-spectrum countermeasures. Results Using phylogenetic profiles of protein clusters from completed microbial genome sequences, we identified seventeen protein candidates that are common to diverse human pathogens and absent or uncommon in non-pathogens. Mutants of 13 of these candidates were successfully generated in Yersinia pseudotuberculosis and the potential role of the proteins in virulence was assayed in an animal model. Six candidate proteins are suggested to be involved in the virulence of Y. pseudotuberculosis, none of which have previously been implicated in the virulence of Y. pseudotuberculosis and three have no record of involvement in the virulence of any bacteria. Conclusion This work demonstrates a strategy for the identification of potential virulence factors that are conserved across a number of human pathogenic bacterial species, confirming the usefulness of this tool.

  2. Novel α-MSH peptide analogues with broad spectrum antimicrobial activity.

    Directory of Open Access Journals (Sweden)

    Paolo Grieco

    Full Text Available Previous investigations indicate that α-melanocyte-stimulating hormone (α-MSH and certain synthetic analogues of it exert antimicrobial effects against bacteria and yeasts. However, these molecules have weak activity in standard microbiology conditions and this hampers a realistic clinical use. The aim in the present study was to identify novel peptides with broad-spectrum antimicrobial activity in growth medium. To this purpose, the Gly10 residue in the [DNal(2'-7, Phe-12]-MSH(6-13 sequence was replaced with conventional and unconventional amino acids with different degrees of conformational rigidity. Two derivatives in which Gly10 was replaced by the residues Aic and Cha, respectively, had substantial activity against Candida strains, including C. albicans, C. glabrata, and C. krusei and against gram-positive and gram-negative bacteria. Conformational analysis indicated that the helical structure along residues 8-13 is a key factor in antimicrobial activity. Synthetic analogues of α-MSH can be valuable agents to treat infections in humans. The structural preferences associated with antimicrobial activity identified in this research can help further development of synthetic melanocortins with enhanced biological activity.

  3. Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis

    International Nuclear Information System (INIS)

    Benedictis, P. de; Minola, A.; Rota, E.; Aiello, R.; Zecchin, B.; Salomoni, A.; Foglierini, M.; Agatic, G.; Vanzetta, F.; Lavenir, R.; Lepelletier, A.; Bentley, E.; Weiss, R.; Cattoli, G.

    2016-01-01

    Full text: Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response. (author)

  4. Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.

    Directory of Open Access Journals (Sweden)

    Wai-Leung Ng

    Full Text Available Quorum sensing (QS is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress virulence factor production and biofilm formation. Thus, molecules that activate QS in V. cholerae have the potential to control pathogenicity in this globally important bacterium. Using a whole-cell high-throughput screen, we identified eleven molecules that activate V. cholerae QS: eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. The LuxO inhibitors act by an uncompetitive mechanism by binding to the pre-formed LuxO-ATP complex to inhibit ATP hydrolysis. Genetic analyses suggest that the inhibitors bind in close proximity to the Walker B motif. The inhibitors display broad-spectrum capability in activation of QS in Vibrio species that employ LuxO. To the best of our knowledge, these are the first molecules identified that inhibit the ATPase activity of a NtrC-type response regulator. Our discovery supports the idea that exploiting pro-QS molecules is a promising strategy for the development of novel anti-infectives.

  5. Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.

    Directory of Open Access Journals (Sweden)

    Pan Kyeom Kim

    Full Text Available Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC. Two kinds of chimeric human antibodies (chimeric #7 and #17 were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

  6. Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.

    Science.gov (United States)

    Kim, Pan Kyeom; Keum, Sun Ju; Osinubi, Modupe O V; Franka, Richard; Shin, Ji Young; Park, Sang Tae; Kim, Man Su; Park, Mi Jung; Lee, Soo Young; Carson, William; Greenberg, Lauren; Yu, Pengcheng; Tao, Xiaoyan; Lihua, Wang; Tang, Qing; Liang, Guodong; Shampur, Madhusdana; Rupprecht, Charles E; Chang, Shin Jae

    2017-01-01

    Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

  7. Development of Broad-Spectrum Halomethyl Ketone Inhibitors Against Coronavirus Main Protease 3CL(pro)

    Energy Technology Data Exchange (ETDEWEB)

    Bacha,U.; Barilla, J.; Gabelli, S.; Kiso, Y.; Amzel, L.; Freire, E.

    2008-01-01

    Coronaviruses comprise a large group of RNA viruses with diverse host specificity. The emergence of highly pathogenic strains like the SARS coronavirus (SARS-CoV), and the discovery of two new coronaviruses, NL-63 and HKU1, corroborates the high rate of mutation and recombination that have enabled them to cross species barriers and infect novel hosts. For that reason, the development of broad-spectrum antivirals that are effective against several members of this family is highly desirable. This goal can be accomplished by designing inhibitors against a target, such as the main protease 3CLpro (Mpro), which is highly conserved among all coronaviruses. Here 3CLpro derived from the SARS-CoV was used as the primary target to identify a new class of inhibitors containing a halomethyl ketone warhead. The compounds are highly potent against SARS 3CLpro with Ki's as low as 300 nm. The crystal structure of the complex of one of the compounds with 3CLpro indicates that this inhibitor forms a thioether linkage between the halomethyl carbon of the warhead and the catalytic Cys 145. Furthermore, Structure Activity Relationship (SAR) studies of these compounds have led to the identification of a pharmacophore that accurately defines the essential molecular features required for the high affinity.

  8. Effects of Enrofloxacin on Porcine Phagocytic Function

    Science.gov (United States)

    Schoevers, E. J.; van Leengoed, L. A. M. G.; Verheijden, J. H. M.; Niewold, T. A.

    1999-01-01

    The interaction between enrofloxacin and porcine phagocytes was studied with clinically relevant concentrations of enrofloxacin. Enrofloxacin accumulated in phagocytes, with cellular concentration/extracellular concentration ratios of 9 for polymorphonuclear leukocytes (PMNs) and 5 for alveolar macrophages (AMs). Cells with accumulated enrofloxacin brought into enrofloxacin-free medium released approximately 80% (AMs) to 90% (PMNs) of their enrofloxacin within the first 10 min, after which no further release was seen. Enrofloxacin affected neither the viability of PMNs and AMs nor the chemotaxis of PMNs at concentrations ranging from 0 to 10 μg/ml. Enrofloxacin (0.5 μg/ml) did not alter the capability of PMNs and AMs to phagocytize fluorescent microparticles or Actinobacillus pleuropneumoniae, Pasteurella multocida, and Staphylococcus aureus. Significant differences in intracellular killing were seen with enrofloxacin at 5× the MIC compared with that for controls not treated with enrofloxacin. PMNs killed all S. aureus isolates in 3 h with or without enrofloxacin. Intracellular S. aureus isolates in AMs were less susceptible than extracellular S. aureus isolates to the bactericidal effect of enrofloxacin. P. multocida was not phagocytosed by PMNs. AMs did not kill P. multocida, and similar intra- and extracellular reductions of P. multocida isolates by enrofloxacin were found. Intraphagocytic killing of A. pleuropneumoniae was significantly enhanced by enrofloxacin at 5× the MIC in both PMNs and AMs. AMs are very susceptible to the A. pleuropneumoniae cytotoxin. This suggests that in serologically naive pigs the enhancing effect of enrofloxacin on the bactericidal action of PMNs may have clinical relevance. PMID:10471554

  9. Insight into the mechanism of action of temporin-SHa, a new broad-spectrum antiparasitic and antibacterial agent.

    Directory of Open Access Journals (Sweden)

    Zahid Raja

    Full Text Available Antimicrobial peptides (AMPs are promising drugs to kill resistant pathogens. In contrast to bacteria, protozoan parasites, such as Leishmania, were little studied. Therefore, the antiparasitic mechanism of AMPs is still unclear. In this study, we sought to get further insight into this mechanism by focusing our attention on temporin-SHa (SHa, a small broad-spectrum AMP previously shown to be active against Leishmania infantum. To improve activity, we designed analogs of SHa and compared the antibacterial and antiparasitic mechanisms. [K3]SHa emerged as a highly potent compound active against a wide range of bacteria, yeasts/fungi, and trypanosomatids (Leishmania and Trypanosoma, with leishmanicidal intramacrophagic activity and efficiency toward antibiotic-resistant strains of S. aureus and antimony-resistant L. infantum. Multipassage resistance selection demonstrated that temporins-SH, particularly [K3]SHa, are not prone to induce resistance in Escherichia coli. Analysis of the mode of action revealed that bacterial and parasite killing occur through a similar membranolytic mechanism involving rapid membrane permeabilization and depolarization. This was confirmed by high-resolution imaging (atomic force microscopy and field emission gun-scanning electron microscopy. Multiple combined techniques (nuclear magnetic resonance, surface plasmon resonance, differential scanning calorimetry allowed us to detail peptide-membrane interactions. [K3]SHa was shown to interact selectively with anionic model membranes with a 4-fold higher affinity (KD = 3 x 10-8 M than SHa. The amphipathic α-helical peptide inserts in-plane in the hydrophobic lipid bilayer and disrupts the acyl chain packing via a detergent-like effect. Interestingly, cellular events, such as mitochondrial membrane depolarization or DNA fragmentation, were observed in L. infantum promastigotes after exposure to SHa and [K3]SHa at concentrations above IC50. Our results indicate that these

  10. Enrofloxacin hydrochloride dihydrate

    Directory of Open Access Journals (Sweden)

    Jorge E. Miranda-Calderón

    2014-04-01

    Full Text Available The asymmetric unit of the title compound, C19H23FN3O3+·Cl−·2H2O [systematic name: 4-(3-carboxy-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl-1-ethylpiperazin-1-ium chloride dihydrate], consists of two independent monocations of the protonated enrofloxacin, two chloride anions and four water molecules. In the cations, the piperazinium rings adopt chair conformations and the dihedral angles between the cyclopropyl ring and the 10-membered quinoline ring system are 56.55 (2 and 51.11 (2°. An intramolecular O—H...O hydrogen bond is observed in each cation. In the crystal, the components are connected via O—H...Cl, N—H...Cl and O—H...O hydrogen bonds, and a π–π interaction between the benzene rings [centroid–centroid distance = 3.6726 (13 Å], resulting in a three-dimensional array.

  11. Wild Coastline Birds as Reservoirs of Broad-Spectrum-β-Lactamase-Producing Enterobacteriaceae in Miami Beach, Florida

    Science.gov (United States)

    Potron, Anaïs; De La Cuesta, Carolina; Cleary, Timothy; Nordmann, Patrice; Munoz-Price, L. Silvia

    2012-01-01

    A high rate of broad-spectrum-β-lactamase-producing Escherichia coli isolates was identified from seagull and pelican feces collected in the Miami Beach, Florida, area. The most commonly identified resistance determinants were CMY-2 and CTX-M-15. Those wild birds might be therefore considered vehicles for wide dissemination of multidrug-resistant Enterobacteriaceae in the United States. PMID:22314536

  12. Broad-Spectrum Inhibitors against 3C-Like Proteases of Feline Coronaviruses and Feline Caliciviruses

    Science.gov (United States)

    Shivanna, Vinay; Narayanan, Sanjeev; Prior, Allan M.; Weerasekara, Sahani; Hua, Duy H.; Kankanamalage, Anushka C. Galasiti; Groutas, William C.; Chang, Kyeong-Ok

    2015-01-01

    ABSTRACT Feline infectious peritonitis and virulent, systemic calicivirus infection are caused by certain types of feline coronaviruses (FCoVs) and feline caliciviruses (FCVs), respectively, and are important infectious diseases with high fatality rates in members of the Felidae family. While FCoV and FCV belong to two distinct virus families, the Coronaviridae and the Caliciviridae, respectively, they share a dependence on viral 3C-like protease (3CLpro) for their replication. Since 3CLpro is functionally and structurally conserved among these viruses and essential for viral replication, 3CLpro is considered a potential target for the design of antiviral drugs with broad-spectrum activities against these distinct and highly important viral infections. However, small-molecule inhibitors against the 3CLpro enzymes of FCoV and FCV have not been previously identified. In this study, derivatives of peptidyl compounds targeting 3CLpro were synthesized and evaluated for their activities against FCoV and FCV. The structures of compounds that showed potent dual antiviral activities with a wide margin of safety were identified and are discussed. Furthermore, the in vivo efficacy of 3CLpro inhibitors was evaluated using a mouse model of coronavirus infection. Intraperitoneal administration of two 3CLpro inhibitors in mice infected with murine hepatitis virus A59, a hepatotropic coronavirus, resulted in significant reductions in virus titers and pathological lesions in the liver compared to the findings for the controls. These results suggest that the series of 3CLpro inhibitors described here may have the potential to be further developed as therapeutic agents against these important viruses in domestic and wild cats. This study provides important insights into the structure and function relationships of 3CLpro for the design of antiviral drugs with broader antiviral activities. IMPORTANCE Feline infectious peritonitis virus (FIPV) is the leading cause of death in young cats

  13. Modified lysozymes as novel broad spectrum natural antimicrobial agents in foods.

    Science.gov (United States)

    Aminlari, Ladan; Hashemi, Marjan Mohammadi; Aminlari, Mahmoud

    2014-06-01

    In recent years much attention and interest have been directed toward application of natural antimicrobial agents in foods. Some naturally occurring proteins such as lactoperoxidase, lactoferrin, and lysozyme have received considerable attention and are being considered as potential antimicrobial agents in foods. Lysozyme kills bacteria by hydrolyzing the peptidoglycan layer of the cell wall of certain bacterial species, hence its application as a natural antimicrobial agent has been suggested. However, limitations in the action of lysozyme against only Gram-positive bacteria have prompted scientists to extend the antimicrobial effects of lysozyme by several types of chemical modifications. During the last 2 decades extensive research has been directed toward modification of lysozyme in order to improve its antimicrobial properties. This review will report on the latest information available on lysozyme modifications and examine the applicability of the modified lysozymes in controlling growth of Gram-positive and Gram-negative bacteria in foods. The results of modifications of lysozyme using its conjugation with different small molecule, polysaccharides, as well as modifications using proteolytic enzymes will be reviewed. These types of modifications have not only increased the functional properties of lysozyme (such as solubility and heat stability) but also extended the antimicrobial activity of lysozyme. Many examples will be given to show that modification can decrease the count of Gram-negative bacteria in bacterial culture and in foods by as much as 5 log CFU/mL and in some cases essentially eliminated Escherichia coli. In conclusion this review demonstrates that modified lysozymes are excellent natural food preservatives, which can be used in food industry. The subject described in this review article can lead to the development of methods to produce new broad-spectrum natural antimicrobial agents, based on modification of chicken egg white lysozyme, which

  14. Overexpression of NPR1 in Brassica juncea Confers Broad Spectrum Resistance to Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    Sajad Ali

    2017-10-01

    Full Text Available Brassica juncea (Indian mustard is a commercially important oil seed crop, which is highly affected by many biotic stresses. Among them, Alternaria leaf blight and powdery mildew are the most devastating diseases leading to huge yield losses in B. juncea around the world. In this regard, genetic engineering is a promising tool that may possibly allow us to enhance the B. juncea disease resistance against these pathogens. NPR1 (non-expressor of pathogen-related gene 1 is a bonafide receptor of salicylic acid (SA which modulates multiple immune responses in plants especially activation of induced and systemic acquired resistance (SAR. Here, we report the isolation and characterization of new NPR1 homolog (BjNPR1 from B. juncea. The phylogenetic tree constructed based on the deduced sequence of BjNPR1 with homologs from other species revealed that BjNPR1 grouped together with other known NPR1 proteins of Cruciferae family, and was nearest to B. napus. Furthermore, expression analysis showed that BjNPR1 was upregulated after SA treatment and fungal infection but not by jasmonic acid or abscisic acid. To understand the defensive role of this gene, we generated B. juncea transgenic lines overexpressing BjNPR1, and further confirmed by PCR and Southern blotting. The transgenic lines showed no phenotypic abnormalities, and constitutive expression of BjNPR1 activates defense signaling pathways by priming the expression of antifungal PR genes. Moreover, BjNPR1 transgenic lines showed enhanced resistance to Alternaria brassicae and Erysiphe cruciferarum as there was delay in symptoms and reduced disease severity than non-transgenic plants. In addition, the rate of disease spreading to uninfected or distal parts was also delayed in transgenic plants thus suggesting the activation of SAR. Altogether, the present study suggests that BjNPR1 is involved in broad spectrum of disease resistance against fungal pathogens.

  15. A Broad-Spectrum Integrative Design for Cancer Prevention and Therapy

    Science.gov (United States)

    Block, Keith I.; Gyllenhaal, Charlotte; Lowe, Leroy; Amedei, Amedeo; Amin, A.R.M. Ruhul; Amin, Amr; Aquilano, Katia; Arbiser, Jack; Arreola, Alexandra; Arzumanyan, Alla; Ashraf, S. Salman; Azmi, Asfar S.; Benencia, Fabian; Bhakta, Dipita; Bilsland, Alan; Bishayee, Anupam; Blain, Stacy W.; Block, Penny B.; Boosani, Chandra S.; Carey, Thomas E.; Carnero, Amancio; Carotenuto, Marianeve; Casey, Stephanie C.; Chakrabarti, Mrinmay; Chaturvedi, Rupesh; Chen, Georgia Zhuo; Chen, Helen; Chen, Sophie; Chen, Yi Charlie; Choi, Beom K.; Ciriolo, Maria Rosa; Coley, Helen M.; Collins, Andrew R.; Connell, Marisa; Crawford, Sarah; Curran, Colleen S.; Dabrosin, Charlotta; Damia, Giovanna; Dasgupta, Santanu; DeBerardinis, Ralph J.; Decker, William K.; Dhawan, Punita; Diehl, Anna Mae E.; Dong, Jin-Tang; Dou, Q. Ping; Drew, Janice E.; Elkord, Eyad; El-Rayes, Bassel; Feitelson, Mark A.; Felsher, Dean W.; Ferguson, Lynnette R; Fimognari, Carmela; Firestone, Gary L.; Frezza, Christian; Fujii, Hiromasa; Fuster, Mark M.; Generali, Daniele; Georgakilas, Alexandros G.; Gieseler, Frank; Gilbertson, Michael; Green, Michelle F.; Grue, Brendan; Guha, Gunjan; Halicka, Dorota; Helferich, William G.; Heneberg, Petr; Hentosh, Patricia; Hirschey, Matthew D.; Hofseth, Lorne J.; Holcombe, Randall F.; Honoki, Kanya; Hsu, Hsue-Yin; Huang, Gloria S.; Jensen, Lasse D.; Jiang, Wen G.; Jones, Lee W.; Karpowicz, Phillip A.; Keith, W Nicol; Kerkar, Sid P.; Khan, Gazala N.; Khatami, Mahin; Ko, Young H.; Kucuk, Omer; Kulathinal, Rob J.; Kumar, Nagi B.; Kumara, H.M.C. Shantha; Kwon, Byoung S.; Le, Anne; Lea, Michael A.; Lee, Ho-Young; Lichtor, Terry; Lin, Liang-Tzung; Locasale, Jason W.; Lokeshwar, Bal L.; Longo, Valter D.; Lyssiotis, Costas A.; MacKenzie, Karen L.; Malhotra, Meenakshi; Marino, Maria; Martinez-Chantar, Maria L.; Matheu, Ander; Maxwell, Christopher; McDonnell, Eoin; Meeker, Alan K.; Mehrmohamadi, Mahya; Mehta, Kapil; Michelotti, Gregory A.; Mohammad, Ramzi M.; Mohammed, Sulma I.; Morre, D. James; Muqbil, Irfana; Muralidhar, Vinayak; Murphy, Michael P.; Nagaraju, Ganji Purnachandra; Nahta, Rita; Niccolai, Elena; Nowsheen, Somaira; Panis, Carolina; Pantano, Francesco; Parslow, Virginia R.; Pawelec, Graham; Pedersen, Peter L.; Poore, Brad; Poudyal, Deepak; Prakash, Satya; Prince, Mark; Raffaghello, Lizzia; Rathmell, Jeffrey C.; Rathmell, W. Kimryn; Ray, Swapan K.; Reichrath, Jörg; Rezazadeh, Sarallah; Ribatti, Domenico; Ricciardiello, Luigi; Robey, R. Brooks; Rodier, Francis; Rupasinghe, H.P. Vasantha; Russo, Gian Luigi; Ryan, Elizabeth P.; Samadi, Abbas K.; Sanchez-Garcia, Isidro; Sanders, Andrew J.; Santini, Daniele; Sarkar, Malancha; Sasada, Tetsuro; Saxena, Neeraj K.; Shackelford, Rodney E; Sharma, Dipali; Shin, Dong M.; Sidransky, David; Siegelin, Markus David; Signori, Emanuela; Singh, Neetu; Sivanand, Sharanya; Sliva, Daniel; Smythe, Carl; Spagnuolo, Carmela; Stafforini, Diana M.; Stagg, John; Subbarayan, Pochi R.; Sundin, Tabetha; Talib, Wamidh H.; Thompson, Sarah K.; Tran, Phuoc T.; Ungefroren, Hendrik; Vander Heiden, Matthew G.; Venkateswaran, Vasundara; Vinay, Dass S.; Vlachostergios, Panagiotis J.; Wang, Zongwei; Wellen, Kathryn E.; Whelan, Richard L.; Yang, Eddy S.; Yang, Huanjie; Yang, Xujuan; Yaswen, Paul; Yedjou, Clement; Yin, Xin; Zhu, Jiyue; Zollo, Massimo

    2016-01-01

    Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested; many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to help us address disease relapse, which is a

  16. The use of inexpensive broad spectrum lower toxicity therapeutics in chronic lymphocytic leukemia.

    Science.gov (United States)

    Marjanovic, Goran

    2017-01-01

    The use of new and highly efficient targeted therapies for chronic lymphocytic leukemia (CLL) is costly and out of reach for many health care systems. On the other hand, in recent years, few inexpensive, broad-spectrum low-toxicity therapeutics have proven to be effective both in the preclinical and clinical settings. In early-stage CLL, the use of 2000 mg of epigallocatechin-3-gallate (EGCG) from the green tea extract twice a day was able to reduce the absolute leukocyte count. Supplementation of >2000 IU/day of Vitamin D in early low-risk CLL patients is able to delay disease progression and postpone the moment of initiation of the first treatment. The doses of both vitamin D and EGCG were shown to be safe in older patients. Vitamin D, EGCG and Curcumin, either as monotherapy or in combination, have additive and synergistic effects with conventional chemotherapy. Further observations have identified the improvement of response to rituximab-fludarabine-cyclophosphamide (R-FC) therapy with concomitant administration of statin and aspirin combination in relapsed/refractory CLL. Finally, high dose dexamethasone with 40mg/m 2 /day for 4 days, every 28 days, either alone or with monoclonal antibody, might be used as a salvage therapy or for debulking before transplantation in refractory/resistant cases. Dexamethasone therapy is followed by transient response and high rate of infections, but fluid retention and other toxicities are lower compared to high dose methylprednisolone schedules. The low cost therapeutics discussed in this review could not be a substitute for the more effective targeted therapies, but their use in every day practice might postpone the need for early implementation of new and costly medications.

  17. Isolation and Characterization of a Broad Spectrum Bacteriocin from Bacillus amyloliquefaciens RX7

    Directory of Open Access Journals (Sweden)

    Kong Boon Lim

    2016-01-01

    Full Text Available We isolated a Bacillus strain, RX7, with inhibitory activity against Listeria monocytogenes from soil and identified it as Bacillus amyloliquefaciens based on 16S rRNA gene sequencing. The inhibitory activity was stable over a wide range of pH and was fully retained after 30 min at 80°C, after which it decreased gradually at higher temperatures. The activity was sensitive to the proteolytic action of α-chymotrypsin, proteinase-K, and trypsin, indicating its proteinaceous nature. This bacteriocin was active against a broad spectrum of bacteria and the fungus Candida albicans. Direct detection of antimicrobial activity on a sodium dodecyl sulfate-polyacrylamide gel suggested an apparent molecular mass of approximately 5 kDa. Ammonium sulfate precipitation and anion-exchange and gel permeation chromatography integrated with reverse phase-high-performance liquid chromatography were used for bacteriocin purification. Automated N-terminal Edman degradation of the purified RX7 bacteriocin recognized the first 15 amino acids as NH2-X-Ala-Trp-Tyr-Asp-Ile-Arg-Lys-Leu-Gly-Asn-Lys-Gly-Ala, where the letter X in the sequence indicates an unknown or nonstandard amino acid. Based on BLAST similarity search and multiple alignment analysis, the obtained partial sequence showed high homology with the two-peptide lantibiotic haloduracin (HalA1 from Bacillus halodurans, although at least two amino acids differed between the sequences. A time-kill study demonstrated a bactericidal mode of action of RX7 bacteriocin.

  18. Enrofloxacin is able to control Toxoplasma gondii infection in both in vitro and in vivo experimental models.

    Science.gov (United States)

    Barbosa, Bellisa Freitas; Gomes, Angelica Oliveira; Ferro, Eloisa Amália Vieira; Napolitano, Danielle Reis; Mineo, José Roberto; Silva, Neide Maria

    2012-06-08

    Currently, toxoplasmosis is treated with sulfadiazine and pyrimethamine. However, this treatment presents several adverse side effects; thus, there is a critical need for the development and evaluation of new drugs, which do not present the same problems of the standard therapy. Enrofloxacin is a fluoroquinolone antibiotic known to control infection against several bacteria in veterinary medicine. Recently, this drug has demonstrated protective effects against protozoan parasites such as Neospora caninum. The present study aimed to determine the effect of enrofloxacin in the control of Toxoplasma gondii infection. For this purpose, human foreskin fibroblast (HFF) cells were infected with T. gondii RH strain and treated with sulfadiazine, penicillin/streptomycin, pyrimethamine, or enrofloxacin. Following treatment, we analyzed the infection index, parasite intracellular proliferation and the number of plaques. Additionally, tissue parasitism and histological changes were investigated in the brain of Calomys callosus that were infected with T. gondii (ME49 strain) and treated with either sulfadiazine or enrofloxacin. Enrofloxacin was able to reduce the infection index, intracellular proliferation and the number of plaques in HFF cells infected by T. gondii in comparison with untreated or penicillin/streptomycin-treated ones. Enrofloxacin was more protective against T. gondii in HFF infected cells than sulfadiazine treatment (Penrofloxacin or the associations of sulfadiazine plus pyrimethamine, enrofloxacin plus sulfadiazine or enrofloxacin plus pyrimethamine-treatments were able to reduce the plaque numbers in HFF cells infected by T. gondii when compared to medium, penicillin/streptomycin or sulfadiazine alone. In vivo experiments demonstrated that enrofloxacin diminished significantly the tissue parasitism as well as the inflammatory alterations in the brain of C. callosus infected with T. gondii when compared with untreated animals. Based on our findings, it can

  19. Integrated DNA walking system to characterize a broad spectrum of GMOs in food/feed matrices.

    Science.gov (United States)

    Fraiture, Marie-Alice; Herman, Philippe; Lefèvre, Loic; Taverniers, Isabel; De Loose, Marc; Deforce, Dieter; Roosens, Nancy H

    2015-08-14

    In order to provide a system fully integrated with qPCR screening, usually used in GMO routine analysis, as well as being able to detect, characterize and identify a broad spectrum of GMOs in food/feed matrices, two bidirectional DNA walking methods targeting p35S or tNOS, the most common transgenic elements found in GM crops, were developed. These newly developed DNA walking methods are completing the previously implemented DNA walking method targeting the t35S pCAMBIA element. Food/feed matrices containing transgenic crops (Bt rice or MON863 maize) were analysed using the integrated DNA walking system. First, the newly developed DNA walking methods, anchored on the sequences used for the p35S or tNOS qPCR screening, were tested on Bt rice that contains these two transgenic elements. Second, the methods were assessed on a maize sample containing a low amount of the GM MON863 event, representing a more complex matrix in terms of genome size and sensitivity. Finally, to illustrate its applicability in GMO routine analysis by enforcement laboratories, the entire workflow of the integrated strategy, including qPCR screening to detect the potential presence of GMOs and the subsequent DNA walking methods to characterize and identify the detected GMOs, was applied on a GeMMA Scheme Proficiency Test matrix. Via the characterization of the transgene flanking region between the transgenic cassette and the plant genome as well as of a part of the transgenic cassette, the presence of GMOs was properly confirmed or infirmed in all tested samples. Due to their simple procedure and their short time-frame to get results, the developed DNA walking methods proposed here can be easily implemented in GMO routine analysis by the enforcement laboratories. In providing crucial information about the transgene flanking regions and/or the transgenic cassettes, this DNA walking strategy is a key molecular tool to prove the presence of GMOs in any given food/feed matrix.

  20. Computational approaches for discovery of common immunomodulators in fungal infections: towards broad-spectrum immunotherapeutic interventions.

    Science.gov (United States)

    Kidane, Yared H; Lawrence, Christopher; Murali, T M

    2013-10-07

    newly generated or expanded data sets for further elucidation of additional drug targets. Moreover, identified immunomodulators may be used to generate experimentally testable hypotheses that could help in the discovery of broad-spectrum immunotherapeutic interventions. All of our results are available at the following supplementary website: http://bioinformatics.cs.vt.edu/~murali/supplements/2013-kidane-bmc.

  1. Time-resolved luminescence screening method for enrofloxacin in beef serum

    Science.gov (United States)

    Enrofloxacin is one of only two fluoroquinolone antibiotics approved for use in cattle in the U.S. Microbial screening methods currently used in the U.S. for monitoring veterinary drug residues are not sensitive or selective for fluoroquinolones. In this work, a luminescence-based screening assay ...

  2. Molecular detection of TEM broad spectrum β-lactamase in clinical ...

    African Journals Online (AJOL)

    Resistance to β-lactam antibiotics, along with clinical isolates, frequently results to production of β- lactamase enzymes. In recent years, the production of extended spectrum β-lactamases (ESBLs) among clinical isolates, especially Escherichia coli has greatly increased. On the other hand, β lactamase genes have several ...

  3. Prescribing antibiotics in general practice:

    DEFF Research Database (Denmark)

    Sydenham, Rikke Vognbjerg; Pedersen, Line Bjørnskov; Plejdrup Hansen, Malene

    Objectives The majority of antibiotics are prescribed from general practice. The use of broad-spectrum antibiotics increases the risk of development of bacteria resistant to antibiotic treatment. In spite of guidelines aiming to minimize the use of broad-spectrum antibiotics we see an increase...... in the use of these agents. The overall aim of the project is to explore factors influencing the decision process and the prescribing behaviour of the GPs when prescribing antibiotics. We will study the impact of microbiological testing on the choice of antibiotic. Furthermore the project will explore how...... the GPs’ prescribing behaviour is influenced by selected factors. Method The study consists of a register-based study and a questionnaire study. The register-based study is based on data from the Register of Medicinal Product Statistics (prescribed antibiotics), Statistics Denmark (socio-demographic data...

  4. The secreted fructose 1,6-bisphosphate aldolase as a broad spectrum vaccine candidate against pathogenic bacteria in aquaculture.

    Science.gov (United States)

    Sun, Zhongyang; Shen, Binbing; Wu, Haizhen; Zhou, Xiangyu; Wang, Qiyao; Xiao, Jingfan; Zhang, Yuanxing

    2015-10-01

    The development of aquaculture has been hampered by different aquatic pathogens that can cause edwardsiellosis, vibriosis, or other diseases. Therefore, developing a broad spectrum vaccine against different fish diseases is necessary. In this study, fructose 1,6-bisphosphate aldolase (FBA), a conserved enzyme in the glycolytic pathway, was demonstrated to be located in the non-cytoplasmic components of five aquatic pathogenic bacteria and exhibited remarkable protection and cross-protection against these pathogens in turbot and zebrafish. Further analysis revealed that sera sampled from vaccinated turbot had a high level of specific antibody and bactericidal activity against these pathogens. Meanwhile, the increased expressions of immune response-related genes associated with antigen recognition and presentation indicated that the adaptive immune response was effectively aroused. Taken together, our results suggest that FBA can be utilized as a broad-spectrum vaccine against various pathogenic bacteria of aquaculture in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Broad-spectrum enhanced absorption of graphene-molybdenum disulfide photovoltaic cells in metal-mirror microcavity

    Science.gov (United States)

    Jiang-Tao, Liu; Yun-Kai, Cao; Hong, Tong; Dai-Qiang, Wang; Zhen-Hua, Wu

    2018-04-01

    The optical absorption of graphene-molybdenum disulfide photovoltaic cells (GM-PVc) in wedge-shaped metal-mirror microcavities (w-MMCs) combined with a spectrum-splitting structure was studied. Results showed that the combination of spectrum-splitting structure and w-MMC can enable the light absorption of GM-PVcs to reach about 65% in the broad spectrum. The influence of processing errors on the absorption of GM-PVcs in w-MMCs was 3-14 times lower than that of GM-PVcs in wedge photonic crystal microcavities. The light absorption of GM-PVcs reached 60% in the broad spectrum, even with the processing errors. The proposed structure is easy to implement and may have potentially important applications in the development of ultra-thin and high-efficiency solar cells and optoelectronic devices.

  6. Screening of broad spectrum natural pesticides against conserved target arginine kinase in cotton pests by molecular modeling.

    Science.gov (United States)

    Sakthivel, Seethalakshmi; Habeeb, S K M; Raman, Chandrasekar

    2018-03-12

    Cotton is an economically important crop and its production is challenged by the diversity of pests and related insecticide resistance. Identification of the conserved target across the cotton pest will help to design broad spectrum insecticide. In this study, we have identified conserved sequences by Expressed Sequence Tag profiling from three cotton pests namely Aphis gossypii, Helicoverpa armigera, and Spodoptera exigua. One target protein arginine kinase having a key role in insect physiology and energy metabolism was studied further using homology modeling, virtual screening, molecular docking, and molecular dynamics simulation to identify potential biopesticide compounds from the Zinc natural database. We have identified four compounds having excellent inhibitor potential against the identified broad spectrum target which are highly specific to invertebrates.

  7. 宽光谱太阳能电池%Broad-Spectrum Solar Cell

    Institute of Scientific and Technical Information of China (English)

    李承辉; 王锴; 郑玮; 王致祥; 刘建; 游效曾

    2012-01-01

    太阳能电池的光谱响应特性和光电转换效率与光伏材料的微观能带结构及其宏观组装方式密切相关。无论使用哪种光伏材料,普通单结或单层太阳能电池都只能对部分波段的太阳光进行有效利用。宽光谱研究的目标是要使太阳能电池更好地利用太阳光谱所覆盖的全部波段范围的能量,从而提高太阳能电池光电转换效率。本文从化学角度综述了实现宽光谱太阳能电池的基本方法和当前的研究进展,其中包括叠层太阳能电池、中间带太阳能电池、量子点太阳能电池、热光伏太阳能电池、上转换和下转换、分子基柔性太阳能电池等方法。%Due to the energy crisis, utilization of renewable energy sources has been intensively investigated in recent years. Among a variety of renewable energy sources, solar energy is a sustainable alternative option that can be utilized in various ways and can be used for many applications. Converting directly the sunlight to electricity through solar cells is the most common and effective way to use solar energy. The spectral response and overall photo-to-electric energy conversion efficiency of solar cells are closely correlated to the micro band-gap structure and macro assembly process of photovoltaie materials. A solar cell can effectively utilize photons with energy hu close to the semiconductor band gap E,. Photons with energy smaller than the band gap are not absorbed. On the other hand, photons with energy larger than the band gap are absorbed, but the excess energy hu - Eg is not used effectively due to thermalization. Therefore, a normal single junction or single layer solar cell can only use part of the solar radiation no matter what kind of photovoltaic materials are used. Broad-spectrum solar cell aims to use most of the solar energy effectively via several structures or methods: Tandem solar cells, intermediate-band solar cells, quantum dot solar cells

  8. Broad-spectrum physical fitness benefits of recreational football: a systematic review and meta-analysis.

    Science.gov (United States)

    Milanović, Zoran; Pantelić, Saša; Čović, Nedim; Sporiš, Goran; Mohr, Magni; Krustrup, Peter

    2018-01-25

    participants with mild hypertension (11 and 7 mm Hg decrease, respectively) and participants with prehypertension (10 and 7 mm Hg decrease, respectively). Meta-analysis of recreational football determined the impact on resting heart rate as most likely extremely largely beneficial (ES=6.03 beats/min; 95% CI 4.43 to 7.64) when compared with non-active groups. The observed recreational football effect on fat mass was most likely largely beneficial (ES=1.72 kg; 95% CI 0.86 to 2.58) and the effect on countermovement jump (CMJ) performance was most likely very largely beneficial (ES=2.27 cm; 95% CI 1.29 to 3.25) when compared with non-active groups. Possibly beneficial decreases were found in low-density lipoprotein levels (ES=0.21 mmol/L; 95% CI 0.06 to 0.36). Possibly largely beneficial effect was observed for DBP in comparison with continuous running training. Small harmful and unclear results were noted for SBP, fat and lean body mass, body mass index, as well as muscular fitness when compared with running and Zumba training. The present meta-analysis demonstrated multiple broad-spectrum benefits of recreational football on health-related physical fitness compared with no-exercise controls, including improvements in blood pressure, resting heart rate, fat mass, low-density lipoprotein cholesterol and CMJ performance. Additionally, recreational football is efficient and effective as Zumba and continuous running exercise regimens with highlighted social, motivational and competitive components. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Anti-enrofloxacin antibody production by using enrofloxacin-screened HSA as an immunogen

    Science.gov (United States)

    Liu, Chune; Lin, Hong; Cao, Limin; Jiang, Jie

    2005-07-01

    A two-step zero-length cross-linking procedure using active esters was successfully adopted for conjugating enrofloxacin (EF) to human serum albumin (HSA). The derived conjugate was characterized by UV spectrum and then used for immunization of BALB/C mice. In enzyme-linked immunosorbent assay (ELISA) and competitive inhibition ELISA experiments, the derived antiserum exhibited high antibody titer (greater than 1:250 000) as well as varied cross-reactivity (from 97.8% to 161.7%) to three analogs of EF belonging to fluoroquinolones family. But over the concentration range studied, no significant cross-reactivity was observed to other group of antibiotics (chloramphenicol, oxytetracycline, sulphamethoxazole and nysfungin). It was confirmed that the synthesized immunogen was highly antigenic and elicited specific antibody responses in BALB/C mice against EF.

  10. Efficacy of Enrofloxacin in the Treatment of Recurrent Pyoderma in Dogs

    Directory of Open Access Journals (Sweden)

    B. Sudhakara Reddy

    2014-07-01

    Full Text Available Dogs with a history of more than three episodes of skin infections in a period of one year were selected for a study on recurrent pyoderma. Oral enrofloxacin along with appropriate simultaneous medication for the underlying associated conditions were chosen as therapy for recurrent pyoderma in dogs. Response to therapy was excellent in all the cases. Improvement was noticed by 12 to 20 days and 20 to 26 days in recurrent superficial and deep pyoderma respectively. Relapse occurred in one dog by 45 days due to re-introduction of allergic food. Enrofloxacin proved to be an effective, safe and convenient antibiotic for the treatment of recurrent pyoderma in dogs.

  11. Risks Involved in the Use of Enrofloxacin for Salmonella Enteritidis or Salmonella Heidelberg in Commercial Poultry

    Science.gov (United States)

    Morales-Barrera, Eduardo; Calhoun, Nicole; Lobato-Tapia, Jose L.; Lucca, Vivian; Prado-Rebolledo, Omar; Hernandez-Velasco, Xochitl; Merino-Guzman, Ruben; Petrone-García, Victor M.; Latorre, Juan D.; Mahaffey, Brittany D.; Teague, Kyle D.; Graham, Lucas E.; Wolfenden, Amanda D.; Baxter, Mikayla F. A.; Hargis, Billy M.; Tellez, Guillermo

    2016-01-01

    The objectives of the present study were to evaluate the risks involved in the use of Enrofloxacin for Salmonella Enteritidis (SE) or Salmonella Heidelberg (SH) in commercial poultry and determine the effects of a probiotic as an antibiotic alternative. Two experiments were conducted to evaluate the risks involved in the use of Enrofloxacin for SE or SH in commercial poultry. Experiment 1 consisted of two trials. In each trial, chickens were assigned to one of three groups; control + SE challenged; Enrofloxacin 25 mg/kg + SE; and Enrofloxacin 50 mg/kg + SE. Chickens received Enrofloxacin in the drinking water from days 1 to 5 of age. On day 6, all groups received fresh water without any treatment. All chickens were orally gavaged with 107 cfu/chick of SE at 7 days of age and euthanized on 8 days of age. In Experiment 2, turkey poults were assigned to one of the three groups; control + SH; probiotic + SH; and Enrofloxacin 50 mg/kg + SH. Poults received probiotic or Enrofloxacin in the drinking water from days 1 to 5 of age. On day 6, poults received fresh water without any treatment. Poults were orally gavaged with 107 cfu/poult of SH at 7 days of age. Poults were weighed and humanely killed 24 h post-SH challenge to evaluate serum concentration of fluorescein isothiocyanate-dextran to evaluate intestinal permeability, metagenomics, and SH infection. In both trials of Experiment 1, chickens treated with Enrofloxacin were more susceptible to SE organ invasion and intestinal colonization when compared with control non-treated chickens (P < 0.05). In Experiment 2, poults treated with 50 mg/kg of Enrofloxacin showed an increase in body weight, however, this group also showed an increase in SH susceptibility, intestinal permeability, and lower proportion of Firmicutes and Bacteroidetes, but with control group had the highest proportion of Proteobacteria. By contrast, poults that received the probiotic had the highest

  12. Risks involved in the use of Enrofloxacin for Salmonella Enteritidis or Salmonella Heidelberg in commercial poultry

    Directory of Open Access Journals (Sweden)

    Eduardo Morales-Barrera

    2016-08-01

    Full Text Available The objectives of the present study were to evaluate the risks involved in the use of Enrofloxacin for Salmonella Enteritidis (SE or Salmonella Heidelberg (SH in commercial poultry and determine the effects of a probiotic as an antibiotic alternative. Two experiments were conducted to evaluate the risks involved in the use of Enrofloxacin for SE or SH in commercial poultry. Exp 1 consisted of 2 trials. In each trial, chickens were assigned to one of three groups; control + SE challenged; Enrofloxacin 25 mg/kg + SE; Enrofloxacin 50 mg/kg + SE. Chickens received Enrofloxacin in the drinking water from days 1 to 5 of age. On day 6, all groups received fresh water without any treatment. All chickens were orally gavaged with 107 cfu/chick of SE at 7 days of age and euthanized on 8 days of age. In Exp 2, turkey poults were assigned to one of the three groups; control + SH; probiotic + SH; Enrofloxacin 50 mg/kg + SH. Poults received probiotic or Enrofloxacin in the drinking water from days 1 to 5 of age. On day 6, poults received fresh water without any treatment. Poults were orally gavaged with 107 cfu/poult of SH at 7 days of age. Poults were weighted and humanely killed 24 h post-SH challenge to evaluate serum concentration of FITC-D to evaluate intestinal permeability, metagenomics and SH infection. In both trials of Exp 1, chickens treated with Enrofloxacin were more susceptible to SE organ invasion and intestinal colonization when compared with control non-treated chickens (P < 0.05. In Exp 2, poults treated with 50 mg/kg of Enrofloxacin showed an increase in body weight, however, this group also showed an increase in SH susceptibility, intestinal permeability and lower proportion of Firmicutes and Bacteroidetes, but with control group had the highest proportion of Proteobacteria. In contrast, poults that received the probiotic had the highest proportion of Firmicutes and Bacteroidetes, but lowest Proteobacteria. The results of the present study

  13. Risks Involved in the Use of Enrofloxacin for Salmonella Enteritidis or Salmonella Heidelberg in Commercial Poultry.

    Science.gov (United States)

    Morales-Barrera, Eduardo; Calhoun, Nicole; Lobato-Tapia, Jose L; Lucca, Vivian; Prado-Rebolledo, Omar; Hernandez-Velasco, Xochitl; Merino-Guzman, Ruben; Petrone-García, Victor M; Latorre, Juan D; Mahaffey, Brittany D; Teague, Kyle D; Graham, Lucas E; Wolfenden, Amanda D; Baxter, Mikayla F A; Hargis, Billy M; Tellez, Guillermo

    2016-01-01

    The objectives of the present study were to evaluate the risks involved in the use of Enrofloxacin for Salmonella Enteritidis (SE) or Salmonella Heidelberg (SH) in commercial poultry and determine the effects of a probiotic as an antibiotic alternative. Two experiments were conducted to evaluate the risks involved in the use of Enrofloxacin for SE or SH in commercial poultry. Experiment 1 consisted of two trials. In each trial, chickens were assigned to one of three groups; control + SE challenged; Enrofloxacin 25 mg/kg + SE; and Enrofloxacin 50 mg/kg + SE. Chickens received Enrofloxacin in the drinking water from days 1 to 5 of age. On day 6, all groups received fresh water without any treatment. All chickens were orally gavaged with 10(7) cfu/chick of SE at 7 days of age and euthanized on 8 days of age. In Experiment 2, turkey poults were assigned to one of the three groups; control + SH; probiotic + SH; and Enrofloxacin 50 mg/kg + SH. Poults received probiotic or Enrofloxacin in the drinking water from days 1 to 5 of age. On day 6, poults received fresh water without any treatment. Poults were orally gavaged with 10(7) cfu/poult of SH at 7 days of age. Poults were weighed and humanely killed 24 h post-SH challenge to evaluate serum concentration of fluorescein isothiocyanate-dextran to evaluate intestinal permeability, metagenomics, and SH infection. In both trials of Experiment 1, chickens treated with Enrofloxacin were more susceptible to SE organ invasion and intestinal colonization when compared with control non-treated chickens (P Enrofloxacin showed an increase in body weight, however, this group also showed an increase in SH susceptibility, intestinal permeability, and lower proportion of Firmicutes and Bacteroidetes, but with control group had the highest proportion of Proteobacteria. By contrast, poults that received the probiotic had the highest proportion of Firmicutes and Bacteroidetes, but lowest

  14. Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents

    Czech Academy of Sciences Publication Activity Database

    Seydlová, G.; Pohl, Radek; Zborníková, Eva; Ehn, Marcel; Šimák, Ondřej; Panova, Natalya; Kolář, M.; Bogdanová, K.; Večeřová, R.; Fišer, R.; Šanderová, Hana; Vítovská, Dragana; Sudzinová, Petra; Pospíšil, Jiří; Benada, Oldřich; Křížek, T.; Sedlák, David; Bartůněk, Petr; Krásný, Libor; Rejman, Dominik

    2017-01-01

    Roč. 60, č. 14 (2017), s. 6098-6118 ISSN 0022-2623 R&D Projects: GA MŠk LO1220; GA MŠk LM2015063; GA ČR(CZ) GBP305/12/G034; GA MŠk(CZ) LM2015055; GA MZd(CZ) NV17-29680A Institutional support: RVO:61388963 ; RVO:61388971 ; RVO:68378050 Keywords : resistant Staphylococcus aureus * cationic steroid antibiotics * antimicrobial peptides Subject RIV: EE - Microbiology, Virology; EE - Microbiology, Virology (MBU-M) OBOR OECD: Microbiology; Microbiology (MBU-M) Impact factor: 6.259, year: 2016

  15. Ex-Vivo percutaneous absorption of enrofloxacin: Comparison of LMOG organogel vs. pentravan cream.

    Science.gov (United States)

    Kirilov, Plamen; Tran, Van Hung; Ducrotté-Tassel, Alban; Salvi, Jean-Paul; Perrot, Sébastien; Haftek, Marek; Boulieu, Roselyne; Pirot, Fabrice

    2016-02-10

    The objective of this study was to investigate the percutaneous absorption of enrofloxacin from two base formulations, Pentravan cream and LMOG organogel. Ex-vivo experiments were carried out on pig ear skin. The percutaneous permeation through pig skin of two formulations containing 5 wt% of enrofloxacin was measured and compared using Franz diffusion cells. At appropriate intervals up to 120 h, diffusion samples were taken and analyzed using HPLC assays. Permeation profiles were established and the parameters Tlag and flux values were calculated. In this ex-vivo study, the flux values were 0.35 μgcm(-2)h(-1) for Pentravan and 1.22 μgcm(-2)h(-1) for LMOG organogel, corresponding respectively to 7.9 % and 29.3 % of enrofloxacin absorbed after 120 h by these formulations. The lag time (T lag) of Pentravan and organogel were 6.32 and 0.015 h respectively. The absorption time to reach the antibiotic concentration of enrofloxacin (2 μgmL(-1)) in the receptor was 60 h with Pentravan and 30 h with the organogel, suggesting more effective treatment by the latter. Enrofloxacin contained in organogel could be absorbed through pig ear skin 3.7 times greater than that in Pentravan (commercial formulation). This study demonstrates the perspective of organogel formulations as potential drug delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Use of enrofloxacin in the treatment of canine brucellosis in a dog kennel (clinical trial).

    Science.gov (United States)

    Wanke, M M; Delpino, M V; Baldi, P C

    2006-10-01

    To date, no totally effective antibiotic for the eradication of canine brucellosis has been found. The purpose of this study was to evaluate the efficacy of enrofloxacin in a kennel infected with Brucella canis. Twelve dogs, 2 males and 10 females (including 1 in estrus, 3 pregnant, and 6 in anestrus) infected with B. canis were given 5 mg/kg of enrofloxacin orally every 12 h for 30 days. Females received additional courses of enrofloxacin during the estral and luteal phases of the subsequent cycles (0-2 cycles). They were repeatedly mated by infected males. A serological follow-up was carried out for 38 months. The clinical, serological and bacteriological findings were recorded. In a trial carried out 14 months after the beginning of this study, all dogs were negative on the Rapid Slide Agglutination Test (RSAT). No abortions were observed. All mated female dogs conceived and gave birth to healthy puppies. Cultures of postpartum vaginal discharges (lochia) were negative for B. canis. Similar to other treatments, although enrofloxacin was not completely efficacious in treating canine brucellosis, it maintained fertility and avoided the recurrence of abortions, transmission of the disease to the puppies and dissemination of microorganisms during parturition. We inferred that enrofloxacin could be used as an alternative drug for the treatment of canine brucellosis.

  17. National ambulatory antibiotic prescribing patterns for pediatric urinary tract infection, 1998-2007.

    Science.gov (United States)

    Copp, Hillary L; Shapiro, Daniel J; Hersh, Adam L

    2011-06-01

    The goal of this study was to investigate patterns of ambulatory antibiotic use and to identify factors associated with broad-spectrum antibiotic prescribing for pediatric urinary tract infections (UTIs). We examined antibiotics prescribed for UTIs for children aged younger than 18 years from 1998 to 2007 using the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey. Amoxicillin-clavulanate, quinolones, macrolides, and second- and third-generation cephalosporins were classified as broad-spectrum antibiotics. We evaluated trends in broad-spectrum antibiotic prescribing patterns and performed multivariable logistic regression to identify factors associated with broad-spectrum antibiotic use. Antibiotics were prescribed for 70% of pediatric UTI visits. Trimethoprim-sulfamethoxazole was the most commonly prescribed antibiotic (49% of visits). Broad-spectrum antibiotics were prescribed one third of the time. There was no increase in overall use of broad-spectrum antibiotics (P = .67); however, third-generation cephalosporin use doubled from 12% to 25% (P = .02). Children younger than 2 years old (odds ratio: 6.4 [95% confidence interval: 2.2-18.7, compared with children 13-17 years old]), females (odds ratio: 3.6 [95% confidence interval: 1.6-8.5]), and temperature ≥ 100.4°F (odds ratio: 2.9 [95% confidence interval: 1.0-8.6]) were independent predictors of broad-spectrum antibiotic prescribing. Race, physician specialty, region, and insurance status were not associated with antibiotic selection. Ambulatory care physicians commonly prescribe broad-spectrum antibiotics for the treatment of pediatric UTIs, especially for febrile infants in whom complicated infections are more likely. The doubling in use of third-generation cephalosporins suggests that opportunities exist to promote more judicious antibiotic prescribing because most pediatric UTIs are susceptible to narrower alternatives.

  18. National Ambulatory Antibiotic Prescribing Patterns for Pediatric Urinary Tract Infection, 1998–2007

    Science.gov (United States)

    Shapiro, Daniel J.; Hersh, Adam L.

    2011-01-01

    OBJECTIVE: The goal of this study was to investigate patterns of ambulatory antibiotic use and to identify factors associated with broad-spectrum antibiotic prescribing for pediatric urinary tract infections (UTIs). METHODS: We examined antibiotics prescribed for UTIs for children aged younger than 18 years from 1998 to 2007 using the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey. Amoxicillin-clavulanate, quinolones, macrolides, and second- and third-generation cephalosporins were classified as broad-spectrum antibiotics. We evaluated trends in broad-spectrum antibiotic prescribing patterns and performed multivariable logistic regression to identify factors associated with broad-spectrum antibiotic use. RESULTS: Antibiotics were prescribed for 70% of pediatric UTI visits. Trimethoprim-sulfamethoxazole was the most commonly prescribed antibiotic (49% of visits). Broad-spectrum antibiotics were prescribed one third of the time. There was no increase in overall use of broad-spectrum antibiotics (P = .67); however, third-generation cephalosporin use doubled from 12% to 25% (P = .02). Children younger than 2 years old (odds ratio: 6.4 [95% confidence interval: 2.2–18.7, compared with children 13–17 years old]), females (odds ratio: 3.6 [95% confidence interval: 1.6–8.5]), and temperature ≥100.4°F (odds ratio: 2.9 [95% confidence interval: 1.0–8.6]) were independent predictors of broad-spectrum antibiotic prescribing. Race, physician specialty, region, and insurance status were not associated with antibiotic selection. CONCLUSIONS: Ambulatory care physicians commonly prescribe broad-spectrum antibiotics for the treatment of pediatric UTIs, especially for febrile infants in whom complicated infections are more likely. The doubling in use of third-generation cephalosporins suggests that opportunities exist to promote more judicious antibiotic prescribing because most pediatric UTIs are susceptible to narrower

  19. Efficacy of chloramphenicol, enrofloxacin, and tetracycline for treatment of experimental Rocky Mountain spotted fever in dogs.

    Science.gov (United States)

    Breitschwerdt, E B; Davidson, M G; Aucoin, D P; Levy, M G; Szabados, N S; Hegarty, B C; Kuehne, A L; James, R L

    1991-01-01

    Dogs were experimentally inoculated with Rickettsia rickettsii to characterize the comparative efficacies of chloramphenicol, enrofloxacin, and tetracycline for the treatment of Rocky Mountain spotted fever (RMSF). All three antibiotics were equally effective in abrogating the clinical, hematologic, and vascular indicators of rickettsial infection. Antibiotic treatment for 24 h was sufficient to decrease the rickettsemia to levels below detection by Vero cell culture. Early treatment with all three antibiotics resulted in a similar decrease in antibody titer, but acute and convalescent serum samples taken at appropriate times would have still facilitated an accurate diagnosis of RMSF in all but one dog, which did not seroconvert. We conclude that chloramphenicol, enrofloxacin, and tetracycline are equally efficacious for treating experimental canine RMSF. PMID:1666498

  20. Broad spectrum screening of 463 organic contaminants in rivers in Macedonia.

    Science.gov (United States)

    Stipaničev, Draženka; Dragun, Zrinka; Repec, Siniša; Rebok, Katerina; Jordanova, Maja

    2017-01-01

    Target screening of 463 organic contaminants in surface water using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) with direct injection was performed in spring of 2015 in northern Macedonia, at six sampling sites in four rivers belonging to Vardar basin: Kriva, Zletovska, Bregalnica and Vardar. The aim of the study was to differentiate between various types of organic contamination characteristic for different types of anthropogenic activities, such as mining, agriculture, and urbanization. Depending on the studied river, 9-16% of analyzed compounds were detected. The highest total levels of organic contaminants were recorded in agriculturally impacted Bregalnica River (1839-1962ngL -1 ) and Vardar River downstream from the city of Skopje (1945ngL -1 ), whereas the lowest level was found in the mining impacted Zletovska River (989ngL -1 ). The principal organic contaminants of the Bregalnica River were herbicides (45-55% of all detected compounds; 838-1094ngL -1 ), with the highest concentrations of bentazone (407-530ngL -1 ) and molinate (84-549ngL -1 ), common herbicides in rice cultivation. The main organic contaminants in the other rivers were drugs (70-80% of all detected compounds), with antibiotics as a predominant drug class. The highest drug concentrations were measured in the Vardar River, downstream from Skopje (1544ngL -1 ). Screening of surface water by UHPLC-QTOF-MS was proven as a practical tool for fast collection of comprehensive preliminary information on organic contamination of natural waters, which can present a significant contribution in the monitoring and preservation of good ecological status of freshwater ecosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Enrofloxacin in therapeutic doses alters cytokine production by porcine PBMCs induced by lipopolysaccharide.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Pejsak, Zygmunt

    2017-07-01

    The effect of enrofloxacin on cytokine secretion by porcine peripheral blood mononuclear cells (PBMCs) was studied. Twenty 8-20-week-old pigs were randomly divided into two groups: control (C, n = 10) and experimental (E, n = 10) were used. Pigs from group E received enrofloxacin at therapeutic dose for 5 consecutive days. Blood samples were collected at 0 (before antibiotic administration), 2, 4 (during antibiotic therapy) 6, 9, 14 21, 35, 49, and 63 d of study (after treatment). PBMCs of pigs from both groups were incubated with or without lipopolysaccharide (LPS). Ex vivo production on interleukin (IL)-4, IL-6, IL-10, INF-γ, and TNF-α were analyzed using ELISA assay. Intramuscular administration of enrofloxacin to healthy pigs for 5 consecutive days induced a transitory reduction of the ex vivo response of PBMCs to LPS in terms of IL-6 and TNF-α secretion. The level of IL-6 returned to day 0 level shortly after end of treatment, while the TNF-α production remained reduced 10 d after the end of treatment. Our results indicate that enrofloxacin given in vivo in therapeutic doses has an immunomodulatory effect through its capacity to inhibit ex vivo secretion of IL-6 and TNF-α by porcine PBMC after LPS stimulation.

  2. The investigation of copper-based impregnated activated carbons prepared from water-soluble materials for broad spectrum respirator applications

    International Nuclear Information System (INIS)

    Smith, J.W.H.; Westreich, P.; Abdellatif, H.; Filbee-Dexter, P.; Smith, A.J.; Wood, T.E.; Croll, L.M.; Reynolds, J.H.; Dahn, J.R.

    2010-01-01

    The preparation of impregnated activated carbons (IACs) from aqueous, copper-containing solutions for broad spectrum gas filtration applications is studied here. Several samples were studied to determine the effect that impregnant loading, impregnant distribution and impregnant recipe had on the overall performance. Dynamic flow testing was used to determine the gas filtration capacity of the IAC samples versus a variety of challenge gases. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were used to characterize the impregnant distribution on the carbon as a function of impregnant loading. Oven tests were performed to determine the thermal stability of the IAC samples exposed to elevated temperatures. The role impregnant distribution plays in gas filtration capacity and the overall performance of the IAC samples is discussed. The IAC samples prepared in this work were found to have gas filtration capacities as good as or better than broad spectrum respirator carbon samples prepared from the patent literature. IACs impregnated with an aqueous 2.4 M Cu(NO 3 ) 2 /0.04 M H 3 PO 4 .12MoO 3 /4 M HNO 3 solution that were heated to 200 deg. C under argon were found to have the best overall performance of the samples studied in this work.

  3. An aggregated perylene-based broad-spectrum, efficient and label-free quencher for multiplexed fluorescent bioassays.

    Science.gov (United States)

    Liu, Tao; Hu, Rong; Lv, Yi-Fan; Wu, Yuan; Liang, Hao; Huan, Shuang-Yan; Zhang, Xiao-Bing; Tan, Weihong; Yu, Ru-Qin

    2014-08-15

    Fluorescent sensing systems based on the quenching of fluorophores have found wide applications in bioassays. An efficient quencher will endow the sensing system a high sensitivity. The frequently used quenchers are based on organic molecules or nanomaterials, which usually need tedious synthesizing and modifying steps, and exhibit different quenching efficiencies to different fluorophores. In this work, we for the first time report that aggregated perylene derivative can serve as a broad-spectrum and label-free quencher that is able to efficiently quench a variety of fluorophores, such as green, red and far red dyes labeled on DNA. By choosing nucleases as model biomolecules, such a broad-spectrum quencher was then employed to construct a multiplexed bioassay platform through a label-free manner. Due to the high quenching efficiency of the aggregated perylene, the proposed platform could detect nuclease with high sensitivity, with a detection limit of 0.03U/mL for EcoRV, and 0.05U/mL for EcoRI. The perylene quencher does not affect the activity of nuclease, which makes it possible to design post-addition type bioassay platform. Moreover, the proposed platform allows simultaneous and multicolor analysis of nucleases in homogeneous solution, demonstrating its value of potential application in rapid screening of multiple bio-targets. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Novel engineered cationic antimicrobial peptides display broad-spectrum activity against Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei.

    Science.gov (United States)

    Abdelbaqi, Suha; Deslouches, Berthony; Steckbeck, Jonathan; Montelaro, Ronald; Reed, Douglas S

    2016-02-01

    Broad-spectrum antimicrobials are needed to effectively treat patients infected in the event of a pandemic or intentional release of a pathogen prior to confirmation of the pathogen's identity. Engineered cationic antimicrobial peptides (eCAPs) display activity against a number of bacterial pathogens including multi-drug-resistant strains. Two lead eCAPs, WLBU2 and WR12, were compared with human cathelicidin (LL-37) against three highly pathogenic bacteria: Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei. Both WLBU2 and WR12 demonstrated bactericidal activity greater than that of LL-37, particularly against F. tularensis and Y. pestis. Only WLBU2 had bactericidal activity against B. pseudomallei. WLBU2, WR12 and LL-37 were all able to inhibit the growth of the three bacteria in vitro. Because these bacteria can be facultative intracellular pathogens, preferentially infecting macrophages and dendritic cells, we evaluated the activity of WLBU2 against F. tularensis in an ex vivo infection model with J774 cells, a mouse macrophage cell line. In that model WLBU2 was able to achieve greater than 50% killing of F. tularensis at a concentration of 12.5 μM. These data show the therapeutic potential of eCAPs, particularly WLBU2, as a broad-spectrum antimicrobial for treating highly pathogenic bacterial infections.

  5. Changes in Cell Viability of Wounded Fibroblasts following Laser Irradiation in Broad-Spectrum or Infrared Light

    International Nuclear Information System (INIS)

    Hawkins, D.; Abrahamse, H.

    2007-01-01

    Objective. This study aimed to establish if broad-spectrum or infrared (IR) light in combination with laser therapy can assist phototherapy to improve the cell function of wounded cells. Background. The effect of laser light may be partly or completely reduced by broad-spectrum light. Methods. Wounded human skin fibroblasts were irradiated with 5 J/cm2 using a helium-neon laser, a diode laser, or an Nd:YAG laser in the dark, in the light, or in IR. Changes in cell viability were evaluated by cell morphology, ATP cell viability, LDH membrane integrity, and caspase 3/7 as an early marker of apoptosis. Results. Wounded cells exposed to 5 J/cm2 using 632.8 nm in the dark or 830 nm in the light or 1064 nm in the dark showed an increase in ATP viability, an increase in cytokine expression, and a decrease in LDH cytotoxicity indicating that the metabolic activity of the wounded cells was stimulated. Conclusion. Wounded cells irradiated in IR light showed an undesirable thermal effect that was proportional to the duration of exposure.

  6. The investigation of copper-based impregnated activated carbons prepared from water-soluble materials for broad spectrum respirator applications

    Energy Technology Data Exchange (ETDEWEB)

    Smith, J.W.H.; Westreich, P.; Abdellatif, H.; Filbee-Dexter, P.; Smith, A.J. [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 3J5 (Canada); Wood, T.E. [3M Company, St. Paul, MN, 55144 (United States); Croll, L.M.; Reynolds, J.H. [3M Canada Company, Brockville, Ontario, K6V 5V8 (Canada); Dahn, J.R., E-mail: jeff.dahn@dal.ca [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, B3H 3J5 (Canada); Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4J3 (Canada)

    2010-08-15

    The preparation of impregnated activated carbons (IACs) from aqueous, copper-containing solutions for broad spectrum gas filtration applications is studied here. Several samples were studied to determine the effect that impregnant loading, impregnant distribution and impregnant recipe had on the overall performance. Dynamic flow testing was used to determine the gas filtration capacity of the IAC samples versus a variety of challenge gases. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were used to characterize the impregnant distribution on the carbon as a function of impregnant loading. Oven tests were performed to determine the thermal stability of the IAC samples exposed to elevated temperatures. The role impregnant distribution plays in gas filtration capacity and the overall performance of the IAC samples is discussed. The IAC samples prepared in this work were found to have gas filtration capacities as good as or better than broad spectrum respirator carbon samples prepared from the patent literature. IACs impregnated with an aqueous 2.4 M Cu(NO{sub 3}){sub 2}/0.04 M H{sub 3}PO{sub 4}.12MoO{sub 3}/4 M HNO{sub 3} solution that were heated to 200 deg. C under argon were found to have the best overall performance of the samples studied in this work.

  7. Antibiotic Prescription in Danish General Practice

    DEFF Research Database (Denmark)

    Sydenham, Rikke Vognbjerg; Plejdrup Hansen, Malene; Pedersen, Line Bjørnskov

    2016-01-01

    1. Background & Aim The overall aim of the project is to describe antibiotic consumption in Danish general practice with emphasis on specific types of antibiotics. The project will shed light on the impact of microbiological diagnostic methods (MDM) on the choice of antibiotic and the project...... will explore how the GPs prescription behaviour is influenced by selected factors. Antibiotics are essential when treating potentially lethal infections. An increasing development of resistant bacteria is considered one of the primary threats to public health. The majority of antibiotics (90%) are prescribed...... from general practice. The prescription of broad-spectrum antibiotics can cause unnecessary side effects for the individual and increases the risk of development of bacteria resistant to antibiotic treatment. Both the prescription of broad-spectrum antibiotics and the level of resistant bacteria...

  8. Profil Kinetik dan Efektivitas Enrofloksasin yang Dikombinasikan dengan BioATP dalam Mengatasi Coxiella burnetii (KINETIC PROFILE AND EFFECTIVITY OF ENROFLOXACINE WITH BIO ADENOSIN TRIPHOSPHATE SUPPLEMENTATION AGAINST COXIELLA BURNETII

    Directory of Open Access Journals (Sweden)

    Andriyanto .

    2013-11-01

    Full Text Available Coxiella burnetii belongs to rikettsia group living obligate intracellularly and as the agent of zoonosisQ fever. Enrofloxacine is an antibiotic in quinolon group used to treat infection of C. burnetii in chicken,goat, calve, pig, dog, cat,  and horse. From ruminant practical experience, enrofloxacine if combined withBioATP  can enhance the enrofloxacine activity. Research for the effecivity of enrofloxacine and BioATP totreat C. burnetii has never been carried out. The research was conducted to explore effect of enrofloxacinewith supplementation BioATP against C. burnetii. Enrofloxacine pharmacokinetic study was carried outby using simental beef as an experimental animals. The effectivity of BioATP supplementation onenrofloxacine activity to treat C. burnetii was tested by using Vero cell tissue culture. The results showedthat combination of enrofloxacine and BioATP increased kinetic profile of enrofloxacine in term of onset,duration, pharmacology intensity, and bioavailaibility. Enrofloxacine had activity to treat C. burnetii withvalue of minimal inhibitory concentration (MIC at 1-2 ppm and value of minimal bactericidal concentrationat 4 ppm. Supplementation of BioATP improved the effectivity of enrofloxacine in treating C. burnetii.

  9. Influence of enrofloxacin traces in drinking water to doxycycline tissue pharmacokinetics in healthy and infected by Mycoplasma gallisepticum broiler chickens.

    Science.gov (United States)

    Gbylik-Sikorska, Malgorzata; Posyniak, Andrzej; Sniegocki, Tomasz; Sell, Bartosz; Gajda, Anna; Sawicka, Anna; Olszewska-Tomczyk, Monika; Bladek, Tomasz; Tomczyk, Grzegorz; Zmudzki, Jan

    2016-04-01

    Most of antibiotics, administrated in the treatment of poultry diseases are dissolved in drinking water, and it can lead to water supply systems contamination, especially when the regular cleaning is not using. This situation can lead to unconscious administration of low doses of antibiotics to untreated animals. The aim of this study was to clarify the impact of the exposure of enrofloxacin traces (500 μg l(-1)) to doxycycline pharmacokinetics in healthy and experimentally Mycoplasma gallisepticum infected broiler chickens., Two experimental groups, received of enrofloxacin in water and all groups, received 20 mg kg(-1) bw of doxycycline. The compounds concentrations in muscles and livers were determined by LC-MS/MS. The maximum drug tissue concentration (Cmax) of doxycycline was highest in liver obtained from infected chickens which, received enrofloxacin traces (ENR + DC/MG). It was about 40% higher than in healthy chickens from group I which received only doxycycline. It was found that the concentration-time curve AUC(0-t) values in group ENR + DC/MG were almost 75% higher than in the group (DC) and 35% higher than in group (ENR + DC) which also received enrofloxacin traces. The constant exposure of broiler chickens on enrofloxacin traces as well as infection, may significantly influenced on doxycycline tissue pharmacokinetic profile. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Efficacy of Elimination of Pasteurella pneumotropica from a Mouse Specific Pathogen-Free Barrier Breeding Unit through Treatment with Enrofloxacin

    DEFF Research Database (Denmark)

    Østergaard, Grete; Arnorsdottir, Stefania Embla; Schumacher-Petersen, Camilla

    2010-01-01

    , and enrofloxacin (EF) was chosen as the most appropriate antibiotic to treat this infection. Various doses of EF were tested for toxic effects on NMRI-mice prior to the treatment, and since no negative effects of EF, regardlessof dose tested, were observed, the highest dose of 150 mg/kg body weight was chosen...

  11. Comparative Activity of Pradofloxacin, Enrofloxacin, and Azithromycin against Bartonella henselae Isolates Collected from Cats and a Human ▿

    Science.gov (United States)

    Biswas, Silpak; Maggi, Ricardo G.; Papich, Mark G.; Keil, Daniel; Breitschwerdt, Edward B.

    2010-01-01

    Using Bartonella henselae isolates from cats and a human, the activity of pradofloxacin was compared with those of enrofloxacin and azithromycin. By Etest and disc diffusion assay, pradofloxacin showed greater antimicrobial activity than did other antibiotics. We conclude that pradofloxacin may prove useful for the treatment of B. henselae infections. PMID:20007401

  12. Pentocin MQ1: A Novel, Broad-Spectrum, Pore-Forming Bacteriocin From Lactobacillus pentosus CS2 With Quorum Sensing Regulatory Mechanism and Biopreservative Potential

    Directory of Open Access Journals (Sweden)

    Samson B. Wayah

    2018-03-01

    Full Text Available Micrococcus luteus, Listeria monocytogenes, and Bacillus cereus are major food-borne pathogenic and spoilage bacteria. Emergence of antibiotic resistance and consumer demand for foods containing less of chemical preservatives led to a search for natural antimicrobials. A study aimed at characterizing, investigating the mechanism of action and regulation of biosynthesis and evaluating the biopreservative potential of pentocin from Lactobacillus pentosus CS2 was conducted. Pentocin MQ1 is a novel bacteriocin isolated from L. pentosus CS2 of coconut shake origin. The purification strategy involved adsorption-desorption of bacteriocin followed by RP-HPLC. It has a molecular weight of 2110.672 Da as determined by MALDI-TOF mass spectrometry and a molar extinction value of 298.82 M−1 cm−1. Pentocin MQ1 is not plasmid-borne and its biosynthesis is regulated by a quorum sensing mechanism. It has a broad spectrum of antibacterial activity, exhibited high chemical, thermal and pH stability but proved sensitive to proteolytic enzymes. It is potent against M. luteus, B. cereus, and L. monocytogenes at micromolar concentrations. It is quick-acting and exhibited a bactericidal mode of action against its targets. Target killing was mediated by pore formation. We report for the first time membrane permeabilization as a mechanism of action of the pentocin from the study against Gram-positive bacteria. Pentocin MQ1 is a cell wall-associated bacteriocin. Application of pentocin MQ1 improved the microbiological quality and extended the shelf life of fresh banana. This is the first report on the biopreservation of banana using bacteriocin. These findings place pentocin MQ1 as a potential biopreservative for further evaluation in food and medical applications.

  13. A Strategy for Generating a Broad-Spectrum Monoclonal Antibody and Soluble Single-Chain Variable Fragments against Plant Potyviruses

    Science.gov (United States)

    Liu, Han-Lin; Lin, Wei-Fang; Hu, Wen-Chi; Lee, Yung-An

    2015-01-01

    Potyviruses are major pathogens that often cause mixed infection in calla lilies. To reduce the time and cost of virus indexing, a detection method for the simultaneous targeting of multiple potyviruses was developed by generating a broad-spectrum monoclonal antibody (MAb) for detecting the greatest possible number of potyviruses. The conserved 121-amino-acid core regions of the capsid proteins of Dasheen mosaic potyvirus (DsMV), Konjak mosaic potyvirus (KoMV), and Zantedeschia mild mosaic potyvirus (ZaMMV) were sequentially concatenated and expressed as a recombinant protein for immunization. After hybridoma cell fusion and selection, one stable cell line that secreted a group-specific antibody, named C4 MAb, was selected. In the reaction spectrum test, the C4 MAb detected at least 14 potyviruses by indirect enzyme-linked immunosorbent assay (I-ELISA) and Western blot analysis. Furthermore, the variable regions of the heavy (VH) and light (VL) chains of the C4 MAb were separately cloned and constructed as single-chain variable fragments (scFvs) for expression in Escherichia coli. Moreover, the pectate lyase E (PelE) signal peptide of Erwinia chrysanthemi S3-1 was added to promote the secretion of C4 scFvs into the medium. According to Western blot analysis and I-ELISA, the soluble C4 scFv (VL-VH) fragment showed a binding specificity similar to that of the C4 MAb. Our results demonstrate that a recombinant protein derived from fusion of the conserved regions of viral proteins has the potential to produce a broad-spectrum MAb against a large group of viruses and that the PelE signal peptide can improve the secretion of scFvs in E. coli. PMID:26209665

  14. Mechanisms of Broad-Spectrum Antiemetic Efficacy of Cannabinoids against Chemotherapy-Induced Acute and Delayed Vomiting

    Directory of Open Access Journals (Sweden)

    Nissar A. Darmani

    2010-09-01

    Full Text Available Chemotherapy-induced nausea and vomiting (CINV is a complex pathophysiological condition and consists of two phases. The conventional CINV neurotransmitter hypothesis suggests that the immediate phase is mainly due to release of serotonin (5-HT from the enterochromaffin cells in the gastrointestinal tract (GIT, while the delayed phase is a consequence of release of substance P (SP in the brainstem. However, more recent findings argue against this simplistic neurotransmitter and anatomical view of CINV. Revision of the hypothesis advocates a more complex, differential and overlapping involvement of several emetic neurotransmitters/modulators (e.g. dopamine, serotonin, substance P, prostaglandins and related arachidonic acid derived metabolites in both phases of emesis occurring concomitantly in the brainstem and in the GIT enteric nervous system (ENS [1]. No single antiemetic is currently available to completely prevent both phases of CINV. The standard antiemetic regimens include a 5-HT3 antagonist plus dexamethasone for the prevention of acute emetic phase, combined with an NK1 receptor antagonist (e.g. aprepitant for the delayed phase. Although NK1 antagonists behave in animals as broad-spectrum antiemetics against different emetogens including cisplatin-induced acute and delayed vomiting, by themselves they are not very effective against CINV in cancer patients. Cannabinoids such as D9-THC also behave as broad-spectrum antiemetics against diverse emetic stimuli as well as being effective against both phases of CINV in animals and patients. Potential side effects may limit the clinical utility of direct-acting cannabinoid agonists which could be avoided by the use of corresponding indirect-acting agonists. Cannabinoids (both phyto-derived and synthetic behave as agonist antiemetics via the activation of cannabinoid CB1 receptors in both the brainstem and the ENS emetic loci. An endocannabinoid antiemetic tone may exist since inverse CB1

  15. Polymyxin B in Combination with Enrofloxacin Exerts Synergistic Killing against Extensively Drug-Resistant Pseudomonas aeruginosa.

    Science.gov (United States)

    Lin, Yu-Wei; Yu, Heidi H; Zhao, Jinxin; Han, Mei-Ling; Zhu, Yan; Akter, Jesmin; Wickremasinghe, Hasini; Walpola, Hasini; Wirth, Veronika; Rao, Gauri G; Forrest, Alan; Velkov, Tony; Li, Jian

    2018-06-01

    Polymyxins are increasingly used as a last-resort class of antibiotics against extensively drug-resistant (XDR) Gram-negative bacteria. However, resistance to polymyxins can emerge with monotherapy. As nephrotoxicity is the major dose-limiting factor for polymyxin monotherapy, dose escalation to suppress the emergence of polymyxin resistance is not a viable option. Therefore, novel approaches are needed to preserve this last-line class of antibiotics. This study aimed to investigate the antimicrobial synergy of polymyxin B combined with enrofloxacin against Pseudomonas aeruginosa Static time-kill studies were conducted over 24 h with polymyxin B (1 to 4 mg/liter) and enrofloxacin (1 to 4 mg/liter) alone or in combination. Additionally, in vitro one-compartment model (IVM) and hollow-fiber infection model (HFIM) experiments were performed against P. aeruginosa 12196. Polymyxin B and enrofloxacin in monotherapy were ineffective against all of the P. aeruginosa isolates examined, whereas polymyxin B-enrofloxacin in combination was synergistic against P. aeruginosa , with ≥2 to 4 log 10 kill at 24 h in the static time-kill studies. In both IVM and HFIM, the combination was synergistic, and the bacterial counting values were below the limit of quantification on day 5 in the HFIM. A population analysis profile indicated that the combination inhibited the emergence of polymyxin resistance in P. aeruginosa 12196. The mechanism-based modeling suggests that the synergistic killing is a result of the combination of mechanistic and subpopulation synergy. Overall, this is the first preclinical study to demonstrate that the polymyxin-enrofloxacin combination is of considerable utility for the treatment of XDR P. aeruginosa infections and warrants future clinical evaluations. Copyright © 2018 American Society for Microbiology.

  16. Detection and characterization of broad-spectrum antipathogen activity of novel rhizobacterial isolates and suppression of Fusarium crown and root rot disease of tomato.

    Science.gov (United States)

    Zhang, L; Khabbaz, S E; Wang, A; Li, H; Abbasi, P A

    2015-03-01

    To detect and characterize broad-spectrum antipathogen activity of indigenous bacterial isolates obtained from potato soil and soya bean leaves for their potential to be developed as biofungicides to control soilborne diseases such as Fusarium crown and root rot of tomato (FCRR) caused by Fusarium oxysporum f. sp. radicis-lycopersici (Forl). Thirteen bacterial isolates (Bacillus amyloliquefaciens (four isolates), Paenibacillus polymyxa (three isolates), Pseudomonas chlororaphis (two isolates), Pseudomonas fluorescens (two isolates), Bacillus subtilis (one isolate) and Pseudomonas sp. (one isolate)) or their volatiles showed antagonistic activity against most of the 10 plant pathogens in plate assays. Cell-free culture filtrates (CF) of five isolates or 1-butanol extracts of CFs also inhibited the growth of most pathogen mycelia in plate assays. PCR analysis confirmed the presence of most antibiotic biosynthetic genes such as phlD, phzFA, prnD and pltC in most Pseudomonas isolates and bmyB, bacA, ituD, srfAA and fenD in most Bacillus isolates. These bacterial isolates varied in the production of hydrogen cyanide (HCN), siderophores, β-1,3-glucanases, chitinases, proteases, indole-3-acetic acid, salicylic acid, and for nitrogen fixation and phosphate solubilization. Gas chromatography-mass spectrometry analysis identified 10 volatile compounds from 10 isolates and 18 compounds from 1-butanol extracts of CFs of five isolates. Application of irradiated peat formulation of six isolates to tomato roots prior to transplanting in a Forl-infested potting mix and field soil provided protection of tomato plants from FCRR disease and enhanced plant growth under greenhouse conditions. Five of the 13 indigenous bacterial isolates were antagonistic to eight plant pathogens, both in vitro and in vivo. Antagonistic and plant-growth promotion activities of these isolates might be related to the production of several types of antibiotics, lytic enzymes, phytohormones, secondary

  17. Determination and health risk assessment of enrofloxacin, flumequine and sulfamethoxazole in imported Pangasius catfish products in Thailand.

    Science.gov (United States)

    Jansomboon, Worawat; Boontanon, Suwanna Kitpati; Boontanon, Narin; Polprasert, Chongrak

    2018-02-01

    The goals of this study were to determine the levels of three antibiotics - enrofloxacin, flumequine and sulfamethoxazole - in Pangasius catfish products imported into Thailand and to assess the health risks from consumption. To extract these antibiotic residues, acetonitrile, methanol and a small amount of formic acid were used as solvents. Determination of the antibiotics after extraction steps was carried out by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) technique. The results showed that 14 and 3 samples of Pangasius catfish products were contaminated with enrofloxacin and sulfamethoxazole, respectively. No flumequine residue was found. While the concentration levels of these antibiotics in most contaminated samples were lower than the European Union (EU) standard, one sample was found to contain sulfamethoxazole at 245.91 µg kg -1 , which was higher than the EU standard (100 µg kg -1 ), indicating the likelihood that some contaminated freshwater fish products are widely distributed in Thai markets. Notably, the concentration levels of enrofloxacin in samples of Pangasius catfish with skin were higher than in non-skin products, suggesting that products with skin might retain more antibiotic residues than non-skin products. Although the hazard quotient showed that consuming imported Pangasius catfish products, based on the current consumption rate, will not adversely affect consumer health, antibiotic residues in Pangasius catfish products imported into Thailand should be continually monitored.

  18. Quantitative and qualitative determination of enrofloxacin residues in fish tissues

    OpenAIRE

    Đorđević Vesna; Baltić M.; Ćirković M.; Kilibarda Nataša; Glamočlija Nataša; Stefanović S.; Miščević Mirjana

    2009-01-01

    Presence of enrofloxacin residues in fish liver, kidney and muscle tissue was investigated after per os application of the drug. For the purpose of determination of enrofloxacin, the following analytical methods were used: microbiological method - plate pH 8 with Escherichia coli ATCC 11303 and HPLC method with fluorescence detection. After a 5-day oral treatment of carps, enrofloxacin residues in tissues were determined up to the 10th day after the end of the drug application. Enrofloxacin c...

  19. Enrofloxacin enhances the effects of chemotherapy in canine osteosarcoma cells with mutant and wild-type p53.

    Science.gov (United States)

    York, D; Withers, S S; Watson, K D; Seo, K W; Rebhun, R B

    2017-09-01

    Adjuvant chemotherapy improves survival time in dogs receiving adequate local control for appendicular osteosarcoma, but most dogs ultimately succumb to metastatic disease. The fluoroquinolone antibiotic enrofloxacin has been shown to inhibit survival and proliferation of canine osteosarcoma cells in vitro. Others have reported that fluoroquinolones may modulate cellular responses to DNA damaging agents and that these effects may be differentially mediated by p53 activity. We therefore determined p53 status and activity in three canine osteosarcoma cell lines and examined the effects of enrofloxacin when used alone or in combination with doxorubicin or carboplatin chemotherapy. Moresco and Abrams canine osteosarcoma cell lines contained mutations in p53, while no mutations were identified in the D17 cells or in a normal canine osteoblast cell line. The addition of enrofloxacin to either doxorubicin or carboplatin resulted in further reductions in osteosarcoma cell viability; this effect was apparent regardless of p53 mutational status or downstream activity. © 2016 John Wiley & Sons Ltd.

  20. New insights into broad spectrum communities of the Early Holocene Near East: The birds of Hallan Çemi

    Science.gov (United States)

    Zeder, Melinda A.; Spitzer, Megan D.

    2016-11-01

    The Early Holocene in Near East was a pivotal transitional period that witnessed dramatic changes in climate and environment, human settlement, major changes in subsistence strategies focusing on a broad range of different plant and animal resources, and a radical restructuring of social relations. The remarkable corpus of avifauna from the Early Holocene site of Hallan Çemi in southeastern Turkey sheds new light on key issues about this dynamic period that has been termed the ;Broad Spectrum Revolution;. The avifauna from this important site demonstrate how Hallan Çemi occupants took advantage of the site's strategic location at the junction of multiple environmental zones by extracting a diverse range of seasonally available resources from both near-by and more distant eco-zones to cobble together a stable subsistence economy capable of supporting this small community throughout the year. They give testimony to the impacts of resource utilization over time, especially on species unable to rebound from sustained human hunting. At the same time, they show how Hallan Çemi residents mitigated these impacts by replacing depleted resources with alternative, more resilient ones that could be more sustainably harvested. They open a window onto the growing investment in feasting and ritual activity that helped bind this community together. In so doing they provide a means of empirically evaluating the efficacy of contrasting explanatory frameworks for the Broad Spectrum Revolution that gave rise to the subsequent domestication of plant and animals in the Near East. Contrary to frameworks that cast these developments as responses to resource depression, lessons learned from the Hallan Çemi avifauna lend support to frameworks that emphasize the human capacity to strategically target, capitalize, and improve upon circumscribed resource rich environments in a way that permits more permanent occupation of these niches. And they underscore the degree to which social and

  1. 21 CFR 524.802 - Enrofloxacin, silver sulfadiazine emulsion.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Enrofloxacin, silver sulfadiazine emulsion. 524... ANIMAL DRUGS § 524.802 Enrofloxacin, silver sulfadiazine emulsion. (a) Specifications. Each milliliter contains 5 milligrams (mg) enrofloxacin and 10 mg silver sulfadiazine. (b) Sponsor. See No. 000859 in § 510...

  2. 77 FR 55414 - New Animal Drugs; Enrofloxacin; Tylvalosin

    Science.gov (United States)

    2012-09-10

    ... 556 [Docket No. FDA-2012-N-0002] New Animal Drugs; Enrofloxacin; Tylvalosin AGENCY: Food and Drug...Care BAYTRIL 100 Supplement adding 522.812 yes CE \\1\\ LLC, Animal (enrofloxacin) control of bovine... Enrofloxacin. * * * * * (e) * * * (2) * * * (i) Amount--(A) Single-dose therapy: For treatment of bovine...

  3. 78 FR 19986 - New Animal Drugs; Enrofloxacin; Tilmicosin; Tylosin

    Science.gov (United States)

    2013-04-03

    ... 558 [Docket No. FDA-2013-N-0002] New Animal Drugs; Enrofloxacin; Tilmicosin; Tylosin AGENCY: Food and............ CE \\1\\ Laboratories, (enrofloxacin) as a generic Ltd., Station Injectable copy of NADA 141- Works... introductory text to paragraph (e)(2) to read as follows: Sec. 522.812 Enrofloxacin. * * * * * (b) Sponsors...

  4. The Pharmacokinetics of Enrofloxacin in Adult African Clawed Frogs (Xenopus laevis)

    Science.gov (United States)

    Howard, Antwain M; Papich, Mark G; Felt, Stephen A; Long, Charles T; McKeon, Gabriel P; Bond, Emmitt S; Torreilles, Stéphanie L; Luong, Richard H; Green, Sherril L

    2010-01-01

    Pharmacokinetics of enrofloxacin, a fluoroquinolone antibiotic, was determined in adult female Xenopus laevis after single-dose administration (10 mg/kg) by intramuscular or subcutaneous injection. Frogs were evaluated at various time points until 8 h after injection. Plasma was analyzed for antibiotic concentration levels by HPLC. We computed pharmacokinetic parameters by using noncompartmental analysis of the pooled concentrations (naive pooled samples). After intramuscular administration of enrofloxacin, the half-life was 5.32 h, concentration maximum was 10.85 µg/mL, distribution volume was 841.96 mL/kg, and area under the time–concentration curve was 57.59 µg×h/mL; after subcutaneous administration these parameters were 4.08 h, 9.76 µg/mL, 915.85 mL/kg, and 47.42 µg×h/mL, respectively. According to plasma pharmacokinetics, Xenopus seem to metabolize enrofloxacin in a manner similar to mammals: low levels of the enrofloxacin metabolite, ciprofloxacin, were detected in the frogs’ habitat water and plasma. At necropsy, there were no gross or histologic signs of toxicity after single-dose administration; toxicity was not evaluated for repeated dosing. The plasma concentrations reached levels considered effective against common aquatic pathogens and suggest that a single, once-daily dose would be a reasonable regimen to consider when treating sick frogs. The treatment of sick frogs should be based on specific microbiologic identification of the pathogen and on antibiotic susceptibility testing. PMID:21205443

  5. Endophytic Paraconiothyrium sp. from Zingiber officinale Rosc. Displays Broad-Spectrum Antimicrobial Activity by Production of Danthron.

    Science.gov (United States)

    Anisha, C; Sachidanandan, P; Radhakrishnan, E K

    2018-03-01

    The bioactivity spectrum of fungal endophytes isolated from Zingiber officinale was analyzed against clinical pathogens and against the phytopathogen Pythium myriotylum, which causes Pythium rot in ginger. One of the isolates GFM13 showed broad bioactivity against various pathogens tested including P. myriotylum. The spore suspension as well as the culture filtrate of the endophytic fungal isolate was found to effectively protect ginger rhizomes from Pythium rot. By molecular identification, the fungal endophyte was identified as Paraconiothyrium sp. The bioactive compound produced by the isolate was separated by bioactivity-guided fractionation and was identified by GC-MS as danthron, an anthraquinone derivative. PCR amplification showed the presence of non-reducing polyketide synthase gene (NR-PKS) in the endophyte GFM13, which is reported to be responsible for the synthesis of anthraquinones in fungi. This is the first report of danthron being produced as the biologically active component of Paraconiothyrium sp. Danthron is reported to have wide pharmaceutical and agronomic applications which include its use as a fungicide in agriculture. The broad-spectrum antimicrobial activity of danthron and the endophytic origin of Paraconiothyrium sp. offer immense applications of the study.

  6. A broad-spectrum, efficient and nontransgenic approach to control plant viruses by application of salicylic acid and jasmonic acid.

    Science.gov (United States)

    Shang, Jing; Xi, De-Hui; Xu, Fei; Wang, Shao-Dong; Cao, Sen; Xu, Mo-Yun; Zhao, Ping-Ping; Wang, Jian-Hui; Jia, Shu-Dan; Zhang, Zhong-Wei; Yuan, Shu; Lin, Hong-Hui

    2011-02-01

    Plant viruses cause many diseases that lead to significant economic losses. However, most of the approaches to control plant viruses, including transgenic processes or drugs are plant-species-limited or virus-species-limited, and not very effective. We introduce an application of jasmonic acid (JA) and salicylic acid (SA), a broad-spectrum, efficient and nontransgenic method, to improve plant resistance to RNA viruses. Applying 0.06 mM JA and then 0.1 mM SA 24 h later, enhanced resistance to Cucumber mosaic virus (CMV), Tobacco mosaic virus (TMV) and Turnip crinkle virus (TCV) in Arabidopsis, tobacco, tomato and hot pepper. The inhibition efficiency to virus replication usually achieved up to 80-90%. The putative molecular mechanism was investigated. Some possible factors affecting the synergism of JA and SA have been defined, including WRKY53, WRKY70, PDF1.2, MPK4, MPK2, MPK3, MPK5, MPK12, MPK14, MKK1, MKK2, and MKK6. All genes involving in the synergism of JA and SA were investigated. This approach is safe to human beings and environmentally friendly and shows potential as a strong tool for crop protection against plant viruses.

  7. Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry

    Science.gov (United States)

    2013-01-01

    Background We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry. Results Extensive analysis of the tannins’ mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at μM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses. Conclusions CHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified. PMID:23924316

  8. Novel Hybrid Anticonvulsants Derived from Pyrrolidine-2,5-dione Scaffold with Broad Spectrum of Activity in the Preclinical Studies.

    Science.gov (United States)

    Kaminski, Krzysztof

    2017-01-01

    The multifunctional ligands application is an emerging approach in drug delivery, mainly in the treatment of diseases with complex pathology, such as Alzheimer's, cancer, and epilepsy. Using this method many biomolecules with different properties are combined to form a single unit that can provide a complex broad spectrum activity. Thus, a new type of hybrid anticonvulsants based on the pyrrolidine-2,5-dione frame are detailed with the aim of acquiring more effective antiepileptic drugs (AED) that could suppress various human convulsions. These hybrid molecules attach to the chemical particles of clinically relevant AEDs such as ethosuximide, levetiracetam, and lacosamide. As a result of this hybridization process the compounds obtained were effective in three most important animal epilepsy models, namely the maximal electroshock seizure (MES) test, the subcutaneous pentylenetetrazole (scPTZ) test, and the six-Hertz (6 Hz) model in mice. These substances displayed wider spectrum of protection, more potent efficacy, and better safety profile than the aforementioned AEDs. Several compounds were also active in the formalin model of persistent pain in mice. The in vitro ligand binding studies have proved that the most conceivable molecular mechanism of anticonvulsant and antinociceptive action was the influence on the neuronal voltage-sensitive sodium and L-type calcium channels. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. A universal aptameric biosensor: Multiplexed detection of small analytes via aggregated perylene-based broad-spectrum quencher.

    Science.gov (United States)

    Hu, Rong; Zhang, Xi; Xu, Qiang; Lu, Dan-Qing; Yang, Yun-Hui; Xu, Quan-Qing; Ruan, Qiong; Mo, Liu-Ting; Zhang, Xiao-Bing

    2017-06-15

    A universal aptameric system based on the taking advantage of double-stranded DNA/perylene diimide (dsDNA/PDI) as the signal probe was developed for multiplexed detection of small molecules. Aptamers are single-stranded DNA or RNA oligonucleotides which are selected in vitro by a process known as systematic evolution of ligands by exponential enrichment. In this work, we synthesized a new kind of PDI and reported this aggregated PDI could quench the double-stranded DNA (dsDNA)-labeled fluorophores with a high quenching efficiency. The quenching efficiencies on the fluorescence of FAM, TAMRA and Cy5 could reach to 98.3%±0.9%, 97.2%±0.6% and 98.1%±1.1%, respectively. This broad-spectrum quencher was then adopted to construct a multicolor biosensor via a label-free approach. A structure-switching-triggered enzymatic recycling amplification was employed for signal amplification. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity towards small analytes. For other targets, changing the corresponding aptamer can achieve the goal. The quencher did not interfere with the catalytic activity of nuclease. The biosensor could be manipulated with similar sensitivity no matter in pre-addition or post-addition manner. Moreover, simultaneous and multiplexed analysis of several small molecules in homogeneous solution was achieved, demonstrating its potential application in the rapid screening of multiple biotargets. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Data-driven analysis of biomedical literature suggests broad-spectrum benefits of culinary herbs and spices.

    Science.gov (United States)

    Rakhi, N K; Tuwani, Rudraksh; Mukherjee, Jagriti; Bagler, Ganesh

    2018-01-01

    Spices and herbs are key dietary ingredients used across cultures worldwide. Beyond their use as flavoring and coloring agents, the popularity of these aromatic plant products in culinary preparations has been attributed to their antimicrobial properties. Last few decades have witnessed an exponential growth of biomedical literature investigating the impact of spices and herbs on health, presenting an opportunity to mine for patterns from empirical evidence. Systematic investigation of empirical evidence to enumerate the health consequences of culinary herbs and spices can provide valuable insights into their therapeutic utility. We implemented a text mining protocol to assess the health impact of spices by assimilating, both, their positive and negative effects. We conclude that spices show broad-spectrum benevolence across a range of disease categories in contrast to negative effects that are comparatively narrow-spectrum. We also implement a strategy for disease-specific culinary recommendations of spices based on their therapeutic tradeoff against adverse effects. Further by integrating spice-phytochemical-disease associations, we identify bioactive spice phytochemicals potentially involved in their therapeutic effects. Our study provides a systems perspective on health effects of culinary spices and herbs with applications for dietary recommendations as well as identification of phytochemicals potentially involved in underlying molecular mechanisms.

  11. Data-driven analysis of biomedical literature suggests broad-spectrum benefits of culinary herbs and spices

    Science.gov (United States)

    Mukherjee, Jagriti

    2018-01-01

    Spices and herbs are key dietary ingredients used across cultures worldwide. Beyond their use as flavoring and coloring agents, the popularity of these aromatic plant products in culinary preparations has been attributed to their antimicrobial properties. Last few decades have witnessed an exponential growth of biomedical literature investigating the impact of spices and herbs on health, presenting an opportunity to mine for patterns from empirical evidence. Systematic investigation of empirical evidence to enumerate the health consequences of culinary herbs and spices can provide valuable insights into their therapeutic utility. We implemented a text mining protocol to assess the health impact of spices by assimilating, both, their positive and negative effects. We conclude that spices show broad-spectrum benevolence across a range of disease categories in contrast to negative effects that are comparatively narrow-spectrum. We also implement a strategy for disease-specific culinary recommendations of spices based on their therapeutic tradeoff against adverse effects. Further by integrating spice-phytochemical-disease associations, we identify bioactive spice phytochemicals potentially involved in their therapeutic effects. Our study provides a systems perspective on health effects of culinary spices and herbs with applications for dietary recommendations as well as identification of phytochemicals potentially involved in underlying molecular mechanisms. PMID:29813110

  12. Broad-spectrum detection of H5 subtype influenza A viruses with a new fluorescent immunochromatography system.

    Directory of Open Access Journals (Sweden)

    Akira Sakurai

    Full Text Available Immunochromatography (IC is an antigen-detection assay that plays an important role in the rapid diagnosis of influenza virus because the protocol is short time and easy to use. Despite the usability of IC, the sensitivity is approximately 10(3 pfu per reaction. In addition, antigen-antibody interaction-based method cannot be used for the detection of influenza viruses with major antigenic change. In this study, we established the use of fluorescent immunochromatography (FLIC to detect a broad spectrum of H5 subtype influenza A viruses. This method has improved sensitivity 10-100 fold higher than traditional IC because of the use of fluorescent conjugated beads. Our Type-E FLIC kit detected all of the H5 subtype influenza viruses that were examined, as well as recombinant hemagglutinin (HA proteins (rHAs belonging to the Eurasian H5 subtype viruses and the Type-N diagnosed North American H5 subtype influenza A viruses. Thus, this kit has the improved potential to detect H5 subtype influenza viruses of different clades with both Type-E and Type-N FLIC kits. Compared with PCR-based diagnosis, FLIC has a strong advantage in usability, because the sample preparation required for FLIC is only mix-and-drop without any additional steps such as RNA extraction. Our results can provide new strategies against the spread and transmission of HPAI H5N1 viruses in birds and mammals including humans.

  13. Broad-spectrum health improvements with one year of soccer training in inactive mildly hypertensive middle-aged women.

    Science.gov (United States)

    Krustrup, P; Skoradal, M-B; Randers, M B; Weihe, P; Uth, J; Mortensen, J; Mohr, M

    2017-12-01

    The study tested the hypothesis that long-term soccer training has positive impact on cardiovascular profile, body composition, bone health, and physical capacity in inactive, pre-menopausal women with mild hypertension. The study applied a randomized controlled design in which physically inactive middle-aged women were separated into a soccer training group (n=19; SOC) and a control group (n=12; CON). SOC performed 128±29 (±SD) one-h small-sided soccer training sessions over one year. Blood pressure, body composition, blood lipid profile, and fitness level were determined pre- and post-intervention. Over one year, mean arterial pressure decreased more in SOC than in CON (-5±7 vs +4±5 mmHg; Pendurance level 1 (122±105 vs 2±21%) and 20-m sprint performance (6±6 vs -1±2%) increased more (Ptraining resulted in broad-spectrum improvements in the health profile of untrained, pre-menopausal women with mild hypertension, including cardiovascular, metabolic, and musculo-skeletal benefits. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Choline and Geranate Deep Eutectic Solvent as a Broad-Spectrum Antiseptic Agent for Preventive and Therapeutic Applications.

    Science.gov (United States)

    Zakrewsky, Michael; Banerjee, Amrita; Apte, Sanjana; Kern, Theresa L; Jones, Mattie R; Sesto, Rico E Del; Koppisch, Andrew T; Fox, David T; Mitragotri, Samir

    2016-06-01

    Antiseptic agents are the primary arsenal to disinfect skin and prevent pathogens spreading within the host as well as into the surroundings; however the Food and Drug Administration published a report in 2015 requiring additional validation of nearly all current antiseptic agents before their continued use can be allowed. This vulnerable position calls for urgent identification of novel antiseptic agents. Recently, the ability of a deep eutectic, Choline And Geranate (CAGE), to treat biofilms of Pseudomonas aeruginosa and Salmonella enterica was demonstrated. Here it is reported that CAGE exhibits broad-spectrum antimicrobial activity against a number of drug-resistant bacteria, fungi, and viruses including clinical isolates of Mycobacterium tuberculosis, Staphylococcus aureus, and Candida albicans as well as laboratory strains of Herpes Simplex Virus. Studies in human keratinocytes and mice show that CAGE affords negligible local or systemic toxicity, and an ≈180-14 000-fold improved efficacy/toxicity ratio over currently used antiseptic agents. Further, CAGE penetrates deep into the dermis and treats pathogens located in deep skin layers as confirmed by the ability of CAGE in vivo to treat Propionibacterium acnes infection. In combination, the results clearly demonstrate CAGE holds promise as a transformative platform antiseptic agent for preventive as well as therapeutic applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Weak turbulence and broad-spectrum excitation in a nonmagnetized electron beam via second-harmonic generation

    International Nuclear Information System (INIS)

    Bogdanov, A.T.

    1990-01-01

    The nonlinear evolution of an initially monoenergetic [ν-bar(t = 0) = (0,0,u)] electron beam propagating in a nonmagnetized dielectric medium of permittivity ε > 1, with initial velocity u ≥ c/√ε (where c is the vacuum speed of light) is investigated. The specific instability of the beam under such conditions is the cause of the generation of a broad spectrum of transverse electromagnetic waves coupled to the simultaneous excitation of the second harmonic of the beam's oscillations, both at the expense of the beam's initial kinetic energy. The system of self-consistent nonlinear equations, describing the particle-field dynamics, is treated in the spirit of the weak-turbulence approach. The integrals of the resulting nonlinear system of equations for the amplitudes of the fields of the electron density are used to evaluate the spectral distribution of the amplitudes in the saturation phase, and hence the efficiency of the transformation of the beam's energy into electromagnetic radiation as a function of the width of the spectrum of the initially present electromagnetic fluctuations. A substantial increase in this efficiency is observed in comparison with the single-mode case. (author)

  16. Marker-assisted introgression of broad-spectrum blast resistance genes into the cultivated MR219 rice variety.

    Science.gov (United States)

    Miah, Gous; Rafii, Mohd Y; Ismail, Mohd R; Puteh, Adam B; Rahim, Harun A; Latif, Mohammad A

    2017-07-01

    The rice cultivar MR219 is famous for its better yield and long and fine grain quality; however, it is susceptible to blast disease. The main objective of this study was to introgress blast resistance genes into MR219 through marker-assisted selection (MAS). The rice cultivar MR219 was used as the recurrent parent, and Pongsu Seribu 1 was used as the donor. Marker-assisted foreground selection was performed using RM6836 and RM8225 to identify plants possessing blast resistance genes. Seventy microsatellite markers were used to estimate recurrent parent genome (RPG) recovery. Our analysis led to the development of 13 improved blast resistant lines with Piz, Pi2 and Pi9 broad-spectrum blast resistance genes and an MR219 genetic background. The RPG recovery of the selected improved lines was up to 97.70% with an average value of 95.98%. Selected improved lines showed a resistance response against the most virulent blast pathogen pathotype, P7.2. The selected improved lines did not express any negative effect on agronomic traits in comparison with MR219. The research findings of this study will be a conducive approach for the application of different molecular techniques that may result in accelerating the development of new disease-resistant rice varieties, which in turn will match rising demand and food security worldwide. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  17. Oral treatment with enrofloxacin early in life promotes Th2-mediated immune response in mice.

    Science.gov (United States)

    Strzępa, Anna; Majewska-Szczepanik, Monika; Kowalczyk, Paulina; Woźniak, Dorota; Motyl, Sylwia; Szczepanik, Marian

    2016-02-01

    Th2 lymphocytes play a crucial role in the development of allergy. These pathologies are caused by coordinated production of the cytokines IL-4, IL-5 and IL-13 that regulate the activity of eosinophils, basophils and B cells. According to the 'hygiene hypothesis', the reduced exposure to microorganisms favors allergy occurrence. The advances in medicine in the field of infection therapy promoted an increasing application of antibiotics which, apart from eliminating pathogens, also partially eliminate the microbiota. Epicutaneous (EC) immunization with ovalbumin (OVA) followed by OVA challenge was used to study the influence of partial gut flora depletion by oral treatment with enrofloxacin on type-2 immune response. Current work describes the influence of enrofloxacin application on anti-OVA antibody production and cytokine synthesis in young and adult mice. Immune response in adult mice is less sensitive to modification of natural gut flora. We observed that enrofloxacin treatment of adult mice leads to significant decrease of anti-OVA IgG2a production while synthesis of anti-OVA IgE was not changed. The production of type-1 (IFN-γ), type-2 (IL-4, IL-5, IL-10, IL-13) and Th17-associated (IL-17A) cytokines was inhibited. On the other hand, treatment of young mice with enrofloxacin significantly upregulates the production of anti-OVA IgE and inhibits the secretion of anti-OVA IgG2a antibodies. Additionally, treatment with enrofloxacin early in life prior to OVA immunization results in increased production of type-2 (IL-4, IL-10 and IL-13) cytokines. Our results clearly indicate that the immune system is more vulnerable to decreased bacterial exposure early in life that may promote development of allergy. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Complete Genome Sequence of Bacillus velezensis YJ11-1-4, a Strain with Broad-Spectrum Antimicrobial Activity, Isolated from Traditional Korean Fermented Soybean Paste.

    Science.gov (United States)

    Lee, Hyo Jung; Chun, Byung-Hee; Jeon, Hye Hee; Kim, Yeon Bee; Lee, Se Hee

    2017-11-30

    Bacillus velezensis YJ11-1-4 is a strain that exhibits broad-spectrum antimicrobial activity against various pathogens. It was isolated from doenjang, a traditional Korean fermented soybean paste. The genome comprises a single circular chromosome of 4,006,637 bp with 46.42% G+C content without plasmids. Copyright © 2017 Lee et al.

  19. Naturally occurring broad-spectrum powdery mildw resistance in a central American tomato accession is caused by loss of Mlo function

    NARCIS (Netherlands)

    Bai, Y.; Pavan, S.N.C.; Zheng, Z.; Zappel, N.F.; Reinstadler, A.; Lotti, C.; Giovanni, de C.; Ricciardi, L.; Lindhout, P.; Visser, R.G.F.; Theres, K.; Panstruga, R.

    2008-01-01

    The resistant cherry tomato (Solanum lycopersicum var. cerasiforme) line LC-95, derived from an accession collected in Ecuador, harbors a natural allele (ol-2) that confers broad-spectrum and recessively inherited resistance to powdery mildew (Oidium neolycopersici). As both the genetic and

  20. Durable broad-spectrum powdery mildew resistance in pea er1 plants is conferred by natural loss-of-function mutations in PsMLO1

    NARCIS (Netherlands)

    Humphry, M.; Reinstädler, A.; Ivanov, S.; Bisseling, T.; Panstruga, R.

    2011-01-01

    Loss-of-function alleles of plant-specific MLO (Mildew Resistance Locus O) genes confer broad-spectrum powdery mildew resistance in monocot (barley) and dicot (Arabidopsis thaliana, tomato) plants. Recessively inherited powdery mildew resistance in pea (Pisum sativum) er1 plants is, in many aspects,

  1. Draft Genome Sequence of Streptomyces sp. Strain Wb2n-11, a Desert Isolate with Broad-Spectrum Antagonism against Soilborne Phytopathogens

    Energy Technology Data Exchange (ETDEWEB)

    Köberl, Martina; White, Richard A.; Erschen, Sabine; El-Arabi, Tarek F.; Jansson, Janet K.; Berg, Gabriele

    2015-08-06

    Streptomyces sp. strain Wb2n-11, isolated from native desert soil, exhibited broad-spectrum antagonism against plant pathogenic fungi, bacteria and nematodes. The 8.2 Mb draft genome reveals genes putatively responsible for its promising biocontrol activity and genes which enable the soil bacterium to directly interact beneficially with plants.

  2. A highly sensitive, multiplex broad-spectrum PCR-DNA-enzyme immunoassay and reverse hybridization assay for rapid detection and identification of Chlamydia trachomatis serovars.

    NARCIS (Netherlands)

    Quint, K.D.; Doorn, L.J. van; Kleter, B.; Koning, M.N. de; Munckhof, H.A. van den; Morre, S.A.; Harmsel, B. ter; Weiderpass, E.; Harbers, G.; Melchers, W.J.G.; Quint, W.G.V.

    2007-01-01

    Chlamydia trachomatis (Ct) comprises distinct serogroups and serovars. The present study evaluates a novel Ct amplification, detection, and genotyping method (Ct-DT assay). The Ct-DT amplification step is a multiplex broad-spectrum PCR for the cryptic plasmid and the VD2-region of ompl. The Ct-DT

  3. Spectral properties of plant leaves pertaining to urban landscape design of broad-spectrum solar ultraviolet radiation reduction

    Science.gov (United States)

    Yoshimura, Haruka; Zhu, Hui; Wu, Yunying; Ma, Ruijun

    2010-03-01

    Human exposure to harmful ultraviolet (UV) radiation has important public health implications. Actual human exposure to solar UV radiation depends on ambient UV irradiance, and the latter is influenced by ground reflection. In urban areas with higher reflectivity, UV exposure occurs routinely. To discover the solar UV radiation regulation mechanism of vegetation, the spectral reflectance and transmittance of plant leaves were measured with a spectrophotometer. Typically, higher plants have low leaf reflectance (around 5%) and essentially zero transmittance throughout the UV region regardless of plant species and seasonal change. Accordingly, incident UV radiation decreases to 5% by being reflected and is reduced to zero by passing through a leaf. Therefore, stratified structures of vegetation are working as another terminator of UV rays, protecting whole terrestrial ecosystems, while vegetation at waterfronts contributes to protect aquatic ecosystems. It is possible to protect the human population from harmful UV radiation by urban landscape design of tree shade and the botanical environment. Even thin but uniformly distributed canopy is effective in attenuating UV radiation. To intercept diffuse radiation, UV screening by vertical structures such as hedges should be considered. Reflectivity of vegetation is around 2%, as foliage surfaces reduce incident UV radiation via reflection, while also eliminating it by transmittance. Accordingly, vegetation reduces incident UV radiation to around 2% by reflection. Vegetation influence on ambient UV radiation is broad-spectrum throughout the UV region. Only trees provide cool UV protective shade. Urban landscapes aimed at abating urban heat islands integrated with a reduction of human UV over-exposure would contribute to mitigation of climate change.

  4. Broad spectrum reactivity versus subtype specificity-trade-offs in serodiagnosis of influenza A virus infections by competitive ELISA.

    Science.gov (United States)

    Postel, A; Ziller, M; Rudolf, M; Letzel, T; Ehricht, Ralf; Pourquier, P; Dauber, M; Grund, C; Beer, Martin; Harder, T C

    2011-04-01

    Avian influenza viruses (AIVs) of the H5 and H7 subtypes can cause substantial economic losses in the poultry industry and are a potential threat to public health. Serosurveillance of poultry populations is an important monitoring tool and can also be used for control of vaccination campaigns. The purpose of this study was to develop broadly reactive, yet subtype-specific competitive ELISAs (cELISAs) for the specific detection of antibodies to the notifiable AIV subtypes H5 and H7 as an alternative to the gold standard haemagglutination inhibition assay (HI). Broadly reacting monoclonal competitor antibodies (mAbs) and genetically engineered subtype H5 or H7 haemagglutinin antigen, expressed and in vivo biotinylated in insect cells, were used to develop the cELISAs. Sera from galliform species and water fowl (n=793) were used to evaluate the performance characteristics of the cELISAs. For the H5 specific cELISA, 98.1% test sensitivity and 91.5% test specificity (97.7% and 90.2% for galliforms; 98.9% and 92.6% for waterfowl), and for the H7 cELISA 97.3% sensitivity and 91.8% specificity (95.3% and 98.9% for galliforms; 100% and 82.7% for waterfowl) were reached when compared to HI. The use of competitor mAbs with broad spectrum reactivity within an AIV haemagglutinin subtype allowed for homogenous detection with high sensitivity of subtype-specific antibodies induced by antigenically widely distinct isolates including antigenic drift variants. However, a trade-off regarding sensitivity versus nonspecific detection of interfering antibodies induced by phylo- and antigenically closely related subtypes, e.g., H5 versus H2 and H7 versus H15, must be considered. The observed intersubtype antibody cross-reactivity remains a disturbance variable in AIV subtype-specific serodiagnosis which negatively affects specificity. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Application of the broad-spectrum bacteriocin enterocin AS-48 to inhibit Bacillus coagulans in canned fruit and vegetable foods.

    Science.gov (United States)

    Lucas, R; Grande, M A J; Abriouel, H; Maqueda, M; Ben Omar, N; Valdivia, E; Martínez-Cañamero, M; Gálvez, A

    2006-10-01

    The enterococcal bacteriocin (enterocin) AS-48 is a broad-spectrum cyclic peptide. Enterocin AS-48 was tested against Bacillus coagulans in three vegetable canned foods: tomato paste (pH 4.64), syrup from canned peaches (pH 3.97), and juice from canned pineapple (pH 3.65). When vegetative cells of B. coagulans CECT (Spanish Type Culture Collection) 12 were inoculated in tomato paste supplemented with 6 microg/ml AS-48 and stored at different temperatures, viable cell counts were reduced by approximately 2.37 (4 degrees C), 4.3 (22 degrees C) and 3.0 (37 degrees C) log units within 24 h storage. After 15-days storage, no viable cells were detected in any sample. Strain B. coagulans CECT 561 showed a poor survival in tomato paste, but surviving cells were also killed by AS-48. The bacteriocin was also very active against B. coagulans CECT 12 vegetative cells in juice from canned pineapple stored at 22 degrees C, and slightly less active in syrup from canned peaches. In food samples supplemented with 1.5% lactic acid, enterocin AS-48 (6 microg/ml) rapidly reduced viable counts of vegetative cells below detection limits within 24 h storage. Addition of glucose and sucrose (10% and 20%) significantly increased bacteriocin activity against vegetative cells of B. coagulans CECT 12. Enterocin AS-48 had no significant effect on B. coagulans CECT 12 spores. However, the combined application of AS-48 and heat (80-95 degrees C for 5 min) significantly increased the effect of thermal treatments on spores.

  6. Exoproteome and Secretome Derived Broad Spectrum Novel Drug and Vaccine Candidates in Vibrio cholerae Targeted by Piper betel Derived Compounds

    Science.gov (United States)

    Barh, Debmalya; Barve, Neha; Gupta, Krishnakant; Chandra, Sudha; Jain, Neha; Tiwari, Sandeep; Leon-Sicairos, Nidia; Canizalez-Roman, Adrian; Rodrigues dos Santos, Anderson; Hassan, Syed Shah; Almeida, Síntia; Thiago Jucá Ramos, Rommel; Augusto Carvalho de Abreu, Vinicius; Ribeiro Carneiro, Adriana; de Castro Soares, Siomar; Luiz de Paula Castro, Thiago; Miyoshi, Anderson; Silva, Artur; Kumar, Anil; Narayan Misra, Amarendra; Blum, Kenneth; Braverman, Eric R.; Azevedo, Vasco

    2013-01-01

    Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC) for most of the pathogenic Vibrio strains. Two targets (uppP and yajC) are novel to Vibrio, and two targets (uppP and ompU) can be used to develop both drugs and vaccines (dual targets) against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species. PMID:23382822

  7. Exoproteome and secretome derived broad spectrum novel drug and vaccine candidates in Vibrio cholerae targeted by Piper betel derived compounds.

    Directory of Open Access Journals (Sweden)

    Debmalya Barh

    Full Text Available Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC for most of the pathogenic Vibrio strains. Two targets (uppP and yajC are novel to Vibrio, and two targets (uppP and ompU can be used to develop both drugs and vaccines (dual targets against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species.

  8. Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor.

    Directory of Open Access Journals (Sweden)

    Yunjeong Kim

    2016-03-01

    Full Text Available Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP, can arise through mutation of FECV to FIP virus (FIPV. The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for

  9. Broad-spectrum sunscreens prevent the secretion of proinflammatory cytokines in human keratinocytes exposed to ultraviolet A and phototoxic lomefloxacin

    International Nuclear Information System (INIS)

    Reinhardt, P.; Cybulski, M.; Miller, S.M.; Ferrarotto, C.; Wilkins, R.; Deslauriers, Y.

    2006-01-01

    The combination of phototoxic drugs and ultraviolet (UV) radiation can trigger the release of proinflammatory cytokines. The present study measured the ability of sunscreens to prevent cytokine secretion in human keratinocytes following cotreatment of these cells with a known photoreactive drug and UVA. Keratinocytes were treated for 1 h with increasing concentrations of lomefloxacin (LOM) or norfloxacin (NOR), exposed to 15 J/cm 2 UVA, and incubated for 24 h. NOR, owing to the absence of a fluorine atom in position 8, was non-phototoxic and used as a negative control. Cell viability and the release of 3 cytokines were assessed, namely interleukin-1α (IL-1α), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). The measurement of these cytokines may be a useful tool for detecting photoreactive compounds. To measure their ability to prevent cytokine secretion, various sunscreens were inserted between the UVA source and the cells. Treatment with NOR, NOR plus UVA, or LOM had no effect on the cells. LOM plus UVA, however, had an effect on cell viability and on cytokine secretion. IL-1α levels increased with LOM concentration. The release of TNF-α and IL-6 followed the same pattern at lower concentrations of LOM but peaked at 15 μmol/L and decreased at higher concentrations. Sunscreens protected the cells from the effects of LOM plus UVA, as cell viability and levels of cytokines remained the same as in the control cells. In conclusion, the application of broad-spectrum sunscreen by individuals exposed to UVA radiation may prevent phototoxic reactions initiated by drugs such as LOM. (author)

  10. A Novel, Broad-Spectrum Inhibitor of Enterovirus Replication That Targets Host Cell Factor Phosphatidylinositol 4-Kinase IIIβ

    Science.gov (United States)

    van der Schaar, Hilde M.; Leyssen, Pieter; Thibaut, Hendrik J.; de Palma, Armando; van der Linden, Lonneke; Lanke, Kjerstin H. W.; Lacroix, Céline; Verbeken, Erik; Conrath, Katja; MacLeod, Angus M.; Mitchell, Dale R.; Palmer, Nicholas J.; van de Poël, Hervé; Andrews, Martin

    2013-01-01

    Despite their high clinical and socioeconomic impacts, there is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections. Here we report on a novel inhibitor of enterovirus replication, compound 1, 2-fluoro-4-(2-methyl-8-(3-(methylsulfonyl)benzylamino)imidazo[1,2-a]pyrazin-3-yl)phenol. This compound exhibited a broad spectrum of antiviral activity, as it inhibited all tested species of enteroviruses and rhinoviruses, with 50% effective concentrations ranging between 4 and 71 nM. After a lengthy resistance selection process, coxsackievirus mutants resistant to compound 1 were isolated that carried substitutions in their 3A protein. Remarkably, the same substitutions were recently shown to provide resistance to inhibitors of phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ), a lipid kinase that is essential for enterovirus replication, suggesting that compound 1 may also target this host factor. Accordingly, compound 1 directly inhibited PI4KIIIβ in an in vitro kinase activity assay. Furthermore, the compound strongly reduced the PI 4-phosphate levels of the Golgi complex in cells. Rescue of coxsackievirus replication in the presence of compound 1 by a mutant PI4KIIIβ carrying a substitution in its ATP-binding pocket revealed that the compound directly binds the kinase at this site. Finally, we determined that an analogue of compound 1, 3-(3-fluoro-4-methoxyphenyl)-2-methyl-N-(pyridin-4-ylmethyl)imidazo[1,2-a]pyrazin-8-amine, is well tolerated in mice and has a dose-dependent protective activity in a coxsackievirus serotype B4-induced pancreatitis model. PMID:23896472

  11. Antibiotic-Induced Gut Microbiota Disruption Decreases TNF-alpha Release by Mononuclear Cells in Healthy Adults

    NARCIS (Netherlands)

    Lankelma, Jacqueline M.; Belzer, Clara; Hoogendijk, Arie J.; de Vos, Alex F.; de Vos, Willem M.; van der Poll, Tom; Wiersinga, W. Joost

    2016-01-01

    OBJECTIVES: Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however,

  12. Antibiotics resistance of Stenotrophomonas maltophilia strains ...

    African Journals Online (AJOL)

    Introduction. Stenotrophomonas maltophilia is a resistant pathogen that can cause bacteremia, endocarditis, respiratory system, central nervous system and urinary tract infections in patients with risk factors like malignancy or neutrope- nia, use of broad-spectrum antibiotics like carbapenem or long-term hospitalization1,2.

  13. Feather segmentation to discriminate between different enrofloxacin treatments in order to monitor off-label use in the poultry sector.

    Science.gov (United States)

    Jansen, Larissa J M; Bolck, Yvette J C; Berendsen, Bjorn J A

    2016-01-01

    Antibiotics are commonly used in the poultry industry to treat bacterial infections. In the combat against bacterial resistance, policies require, besides a reduction of antibiotic usage in humans and animals, an up-to-date farmer registration mentioning all treatments. For enforcement of such policies, tests are needed to antedate administration and to determine the type of treatment so as to prevent off-label use and the supervacaneous use of last-resort antibiotics like cephalosporins and fluoroquinolones. After poultry treatment, high amounts of enrofloxacin and its metabolite ciprofloxacin are deposited in chicken feathers. A method is presented to discriminate different treatments based on differentiating extractable and non-extractable enrofloxacin and ciprofloxacin in chicken feathers. With this approach, we show it is possible to distinguish between a registered therapeutic oral treatment, an off-label spray treatment and an illegal prolonged sub-therapeutic treatment with enrofloxacin. This approach is a new and strong tool in the enforcement of new policies in the fight against off-label and supervacaneous antibiotic use.

  14. In vitro development of resistance to enrofloxacin, erythromycin, tylosin, tiamulin and oxytetracycline in Mycoplasma gallisepticum, Mycoplasma iowae and Mycoplasma synoviae.

    Science.gov (United States)

    Gautier-Bouchardon, A V; Reinhardt, A K; Kobisch, M; Kempf, I

    2002-08-02

    The in vitro emergence of resistance to enrofloxacin, erythromycin, tylosin, tiamulin, and oxytetracycline in three avian Mycoplasma species, Mycoplasma gallisepticum, Mycoplasma synoviae and Mycoplasma iowae was studied. Mutants were selected stepwise and their MICs were determined after 10 passages in subinhibitory concentrations of antibiotic. High-level resistance to erythromycin and tylosin developed within 2-6 passages in the three Mycoplasma species. Resistance to enrofloxacin developed more gradually. No resistance to tiamulin or oxytetracycline could be evidenced in M. gallisepticum or M. synoviae after 10 passages whereas, resistant mutants were obtained with M. iowae. Cross-sensitivity tests performed on mutants demonstrated that mycoplasmas made resistant to tylosin were also resistant to erythromycin, whereas mutants made resistant to erythromycin were not always resistant to tylosin. Some M. iowae tiamulin-resistant mutants were also resistant to both macrolide antibiotics. Enrofloxacin and oxytetracycline did not induce any cross-resistance to the other antibiotics tested. These results show that Mycoplasma resistance to macrolides can be quickly selected in vitro, and thus, providing that similar results could be obtained under field conditions, that development of resistance to these antibiotics in vivo might also be a relatively frequent event.

  15. A Broad-Spectrum Infection Diagnostic that Detects Pathogen-Associated Molecular Patterns (PAMPs in Whole Blood

    Directory of Open Access Journals (Sweden)

    Mark Cartwright

    2016-07-01

    Conclusion: The FcMBL ELLecSA-based PAMP assay offers a rapid, simple, sensitive and specific method for diagnosing infections, even when blood cultures are negative and antibiotic therapy has been initiated. It may help to triage patients with suspected systemic infections, and serve as a companion diagnostic to guide administration of emerging dialysis-like sepsis therapies.

  16. Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites.

    Science.gov (United States)

    Kevin Ii, Dion A; Meujo, Damaris Af; Hamann, Mark T

    2009-02-01

    As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic infections. Despite the long history of use of this class of drugs, very limited medicinal chemistry and drug optimization studies have been reported, thus leaving the door open to these opportunities in the future. Scifinder and PubMed were the main search engines used to locate articles relevant to the topic presented in the present review. Keywords used in our search were specific names of each of the 88 compounds presented in the review as well as more general terms such as polyethers, ionophores, carboxylic polyethers and polyether antibiotics.

  17. Detection of a Mixed Infection in a Culture-Negative Brain Abscess by Broad-Spectrum Bacterial 16S rRNA Gene PCR ▿ †

    Science.gov (United States)

    Keller, Peter M.; Rampini, Silvana K.; Bloemberg, Guido V.

    2010-01-01

    We describe the identification of two bacterial pathogens from a culture-negative brain abscess by the use of broad-spectrum 16S rRNA gene PCR. Simultaneous detection of Fusobacterium nucleatum and Porphyromonas endodontalis was possible due to a 24-bp length difference of their partially amplified 16S rRNA genes, which allowed separation by high-resolution polyacrylamide gel electrophoresis. PMID:20392909

  18. Antibiotic rezistance genes in soil actinobacteria

    OpenAIRE

    Patrmanová, Tereza

    2016-01-01

    Actinobacteria are important members of the soil ecosystems, where they are involved in organic matter decomposition. It is worth mentioning that their secondary metabolism allows them to produce a variety of different compounds. These compounds include antibiotics, among them aminoglycosides have a place in clinical practice. These antibiotics are significant due to a broad spectrum of activities against both gram-negative and gram-positive bacteria. However, their use currently carries a ri...

  19. Efficacy of Enrofloxacin in a Mouse Model of Sepsis

    OpenAIRE

    Slate, Andrea R; Bandyopadhyay, Sheila; Francis, Kevin P; Papich, Mark G; Karolewski, Brian; Hod, Eldad A; Prestia, Kevin A

    2014-01-01

    We examined the efficacy of enrofloxacin administered by 2 different routes in a mouse model of sepsis. Male CD1 mice were infected with a bioluminescent strain of enteropathogenic Escherichia coli and treated with enrofloxacin either by injection or in drinking water. Peak serum levels were evaluated by using HPLC. Mice were monitored for signs of clinical disease, and infections were monitored by using bioluminescence imaging. Serum levels of enrofloxacin and the active metabolite ciproflox...

  20. A broad-spectrum sunscreen prevents cumulative damage from repeated exposure to sub-erythemal solar ultraviolet radiation representative of temperate latitudes.

    Science.gov (United States)

    Seité, S; Christiaens, F; Bredoux, C; Compan, D; Zucchi, H; Lombard, D; Fourtanier, A; Young, A R

    2010-02-01

    We have previously shown the detrimental effects of 19 sub-erythemal exposures to daily ultraviolet radiation (DUVR, which mimics non-extreme exposure conditions), delivered over 4 weeks to volunteers. This source had UVA (320-400 nm) to UVB (290-320 nm) irradiance ratio of 25, instead of that close to 10 that is typically the case with solar-simulated radiation (SSR) that represents summer global sunlight with a clear sky and quasi-zenith solar irradiance. Here, we report on an extension of this previous study, in which we evaluated the photoprotection afforded by a broad-spectrum daily-care product with a low-sun protection factor (SPF 8, UVA-PF 7 and 3* rated UVA protection). We assessed cellular and molecular markers of photodamage that are relevant to skin cancer and photoageing. This study shows that biological effects of repeated exposure to DUVR can be prevented by a broad-spectrum daily-care product and that the level of protection afforded varies with the studied endpoint. Efficient daily UVR protection, as provided by a broad-spectrum daily-care product, is necessary to prevent the 'silent' sub-erythemal cumulative effects of UVR from inadvertent sun exposure.

  1. Targeted Treatment for Bacterial Infections: Prospects for Pathogen-Specific Antibiotics Coupled with Rapid Diagnostics

    OpenAIRE

    Maxson, Tucker; Mitchell, Douglas A.

    2015-01-01

    Antibiotics are a cornerstone of modern medicine and have significantly reduced the burden of infectious diseases. However, commonly used broad-spectrum antibiotics can cause major collateral damage to the human microbiome, causing complications ranging from antibiotic-associated colitis to the rapid spread of resistance. Employing narrower spectrum antibiotics targeting specific pathogens may alleviate this predicament as well as provide additional tools to expand an antibiotic repertoire th...

  2. Effect of probiotics on enrofloxacin disposition in gastrointestinal tract of poultry.

    Science.gov (United States)

    Pavlova, I; Danova, S; Naidenski, H; Tropcheva, R; Milanova, A

    2015-12-01

    Probiotics are routinely used in poultry husbandry due to health benefit on the host. The gut microbiota is now recognized to exert an important influence on the absorption and pharmacokinetics of many compounds. Therefore, this study was designed to evaluate the effect of candidate probiotics belonging to the species Lactobacillus brevis, L. plantarum and L. bulgaricus on pharmacokinetics of enrofloxacin in healthy chickens. The probiotic administration leads to higher degree of metabolism of enrofloxacin to ciprofloxacin in liver. The antibacterial drug was significantly faster absorbed (kab of 0.61 ± 0.54 h(-1) and Tmax 7.81 ± 3.52 h) at lower concentrations (Cmax of 1.34 ± 0.18 μg·g(-1)) during the first 24 h of treatment in the probiotic's group. The values of kab , Tmax , and Cmax for the group, treated solely with enrofloxacin, were 0.10 ± 0.065 h(-1), 15.42 ± 3.07 h, and 1.61 ± 0.24 μg·g(-1), respectively. A significantly higher concentration of enrofloxacin and its metabolite ciprofloxacin in the liver was observed in the group with the probiotic treatment. Disposition of both drugs was not significantly changed in the duodenum and in the jejunum. The selected dose is appropriate for treatment of infections caused by pathogens with MIC < 0.06 μg·mL(-1) irrespective of antibiotic administration alone or in combination with probiotics. © 2015 John Wiley & Sons Ltd.

  3. Microbial Shifts in the Intestinal Microbiota of Salmonella Infected Chickens in Response to Enrofloxacin.

    Science.gov (United States)

    Li, Jun; Hao, Haihong; Cheng, Guyue; Liu, Chunbei; Ahmed, Saeed; Shabbir, Muhammad A B; Hussain, Hafiz I; Dai, Menghong; Yuan, Zonghui

    2017-01-01

    Fluoroquinolones (FQs) are important antibiotics used for treatment of Salmonella infection in poultry in many countries. However, oral administration of fluoroquinolones may affect the composition and abundance of a number of bacterial taxa in the chicken intestine. Using 16S rRNA gene sequencing, the microbial shifts in the gut of Salmonella infected chickens in response to enrofloxacin treatments at different dosages (0, 0.1, 4, and 100 mg/kg b.w.) were quantitatively evaluated. The results showed that the shedding levels of Salmonella were significantly reduced in the high dosage group as demonstrated by both the culturing method and 16S rRNA sequencing method. The average values of diversity indices were higher in the control group than in the three medicated groups. Non-metric multidimensional scaling (NMDS) analysis results showed that the microbial community of high dosage group was clearly separated from the other three groups. In total, 25 genera were significantly enriched (including 6 abundant genera: Lactococcus , Bacillus , Burkholderia , Pseudomonas , Rhizobium , and Acinetobacter ) and 23 genera were significantly reduced in the medicated groups than in the control group for the treatment period, but these bacterial taxa recovered to normal levels after therapy withdrawal. Additionally, 5 genera were significantly reduced in both treatment and withdrawal periods (e.g., Blautia and Anaerotruncus ) and 23 genera (e.g., Enterobacter and Clostridium ) were significantly decreased only in the withdrawal period, indicating that these genera might be the potential targets for the fluoroquinolones antimicrobial effects. Specially, Enterococcus was significantly reduced under high dosage of enrofloxacin treatment, while significantly enriched in the withdrawal period, which was presumably due to the resistance selection. Predicted microbial functions associated with genetic information processing were significantly decreased in the high dosage group. Overall

  4. Microbial Shifts in the Intestinal Microbiota of Salmonella Infected Chickens in Response to Enrofloxacin

    Directory of Open Access Journals (Sweden)

    Jun Li

    2017-09-01

    Full Text Available Fluoroquinolones (FQs are important antibiotics used for treatment of Salmonella infection in poultry in many countries. However, oral administration of fluoroquinolones may affect the composition and abundance of a number of bacterial taxa in the chicken intestine. Using 16S rRNA gene sequencing, the microbial shifts in the gut of Salmonella infected chickens in response to enrofloxacin treatments at different dosages (0, 0.1, 4, and 100 mg/kg b.w. were quantitatively evaluated. The results showed that the shedding levels of Salmonella were significantly reduced in the high dosage group as demonstrated by both the culturing method and 16S rRNA sequencing method. The average values of diversity indices were higher in the control group than in the three medicated groups. Non-metric multidimensional scaling (NMDS analysis results showed that the microbial community of high dosage group was clearly separated from the other three groups. In total, 25 genera were significantly enriched (including 6 abundant genera: Lactococcus, Bacillus, Burkholderia, Pseudomonas, Rhizobium, and Acinetobacter and 23 genera were significantly reduced in the medicated groups than in the control group for the treatment period, but these bacterial taxa recovered to normal levels after therapy withdrawal. Additionally, 5 genera were significantly reduced in both treatment and withdrawal periods (e.g., Blautia and Anaerotruncus and 23 genera (e.g., Enterobacter and Clostridium were significantly decreased only in the withdrawal period, indicating that these genera might be the potential targets for the fluoroquinolones antimicrobial effects. Specially, Enterococcus was significantly reduced under high dosage of enrofloxacin treatment, while significantly enriched in the withdrawal period, which was presumably due to the resistance selection. Predicted microbial functions associated with genetic information processing were significantly decreased in the high dosage group

  5. Chemosensitization of Trypanosoma congolense strains resistant to isometamidium chloride by tetracyclines and enrofloxacin.

    Directory of Open Access Journals (Sweden)

    Vincent Delespaux

    Full Text Available BACKGROUND: Because of the development of resistance in trypanosomes to trypanocidal drugs, the livelihood of millions of livestock keepers in sub-Saharan Africa is threatened now more than ever. The existing compounds have become virtually useless and pharmaceutical companies are not keen on investing in the development of new trypanocides. We may have found a breakthrough in the treatment of resistant trypanosomal infections, through the combination of the trypanocide isometamidium chloride (ISM with two affordable veterinary antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: In a first experiment, groups of mice were inoculated with Trypanosoma congolense strains resistant to ISM and either left untreated or treated with (i tetracycline, (ii ISM or (iii the combination of the antibiotic and the trypanocide. Survival analysis showed that there was a significant effect of treatment and resistance to treatment on the survival time. The groups treated with ISM (with or without antibiotic survived significantly longer than the groups that were not treated with ISM (P<0.01. The group treated with the combination trypanocide/antibiotic survived significantly longer than the group treated with ISM (P<0.01. In a second experiment, groups of cattle were inoculated with the same resistant trypanosome strain and treated with (i ISM, (ii ISM associated with oxytetracycline or (iii ISM associated with enrofloxacine. All animals treated with ISM became parasitaemic. In the groups treated with ISM-oxytetracycline and ISM-enrofloxacine, 50% of the animals were cured. Animals from the groups treated with a combination trypanocide/antibiotic presented a significantly longer prepatent period than animals treated with ISM (p<0.001. The impact of the disease on the haematocrit was low in all ISM treated groups. Yet, it was lower in the groups treated with the combination trypanocide/antibiotic (p<0.01. CONCLUSIONS/SIGNIFICANCE: After optimization of the administration

  6. A Novel Mechanism of High-Level, Broad-Spectrum Antibiotic Resistance Caused by a Single Base Pair Change in Neisseria gonorrhoeae

    Science.gov (United States)

    2011-09-20

    respect, Eisenstein and Sparling noted that a single base pair deletion in the inverted repeat in the mtrR promoter, a mutation which also confers high...Regulation of the MtrC-MtrD-MtrE efflux-pump system modulates the in vivo fitness of Neisseria gonorrhoeae. J. Infect. Dis. 196:1804 –1812. 21. Eisenstein BI

  7. Comparison of direct sampling and brochoalveolar lavage for determining active drug concentrations in the pulmonary epithelial lining fluid of calves injected with enrofloxacin or tilmicosin.

    Science.gov (United States)

    Foster, D M; Sylvester, H J; Papich, M G

    2017-12-01

    Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril ® 100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil ® 300) was administered at a dose of 20 mg/kg SC. PELF, sampled by two different methods-bronchoalveolar lavage (BAL) and direct sampling (DS)-plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by AUC in DS samples was 137 ± 72% higher than in plasma, but in BAL samples, this value was 535 ± 403% (p enrofloxacin/ciprofloxacin concentrations collected by DS were significantly different than those collected by BAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine respiratory disease pathogens but tilmicosin did not reach MIC levels for these pathogens in any fluids. © 2017 John Wiley & Sons Ltd.

  8. A Broad-Spectrum Infection Diagnostic that Detects Pathogen-Associated Molecular Patterns (PAMPs) in Whole Blood.

    Science.gov (United States)

    Cartwright, Mark; Rottman, Martin; Shapiro, Nathan I; Seiler, Benjamin; Lombardo, Patrick; Gamini, Nazita; Tomolonis, Julie; Watters, Alexander L; Waterhouse, Anna; Leslie, Dan; Bolgen, Dana; Graveline, Amanda; Kang, Joo H; Didar, Tohid; Dimitrakakis, Nikolaos; Cartwright, David; Super, Michael; Ingber, Donald E

    2016-07-01

    Blood cultures, and molecular diagnostic tests that directly detect pathogen DNA in blood, fail to detect bloodstream infections in most infected patients. Thus, there is a need for a rapid test that can diagnose the presence of infection to triage patients, guide therapy, and decrease the incidence of sepsis. An Enzyme-Linked Lectin-Sorbent Assay (ELLecSA) that uses magnetic microbeads coated with an engineered version of the human opsonin, Mannose Binding Lectin, containing the Fc immunoglobulin domain linked to its carbohydrate recognition domain (FcMBL) was developed to quantify pathogen-associated molecular patterns (PAMPs) in whole blood. This assay was tested in rats and pigs to explore whether it can detect infections and monitor disease progression, and in prospectively enrolled, emergency room patients with suspected sepsis. These results were also compared with data obtained from non-infected patients with or without traumatic injuries. The FcMBL ELLecSA was able to detect PAMPS present on, or released by, 85% of clinical isolates representing 47 of 55 different pathogen species, including the most common causes of sepsis. The PAMP assay rapidly (animals, even when blood cultures were negative and bacteriocidal antibiotics were administered. In patients with suspected sepsis, the FcMBL ELLecSA detected infection in 55 of 67 patients with high sensitivity (>81%), specificity (>89%), and diagnostic accuracy of 0·87. It also distinguished infection from trauma-related inflammation in the same patient cohorts with a higher specificity than the clinical sepsis biomarker, C-reactive Protein. The FcMBL ELLecSA-based PAMP assay offers a rapid, simple, sensitive and specific method for diagnosing infections, even when blood cultures are negative and antibiotic therapy has been initiated. It may help to triage patients with suspected systemic infections, and serve as a companion diagnostic to guide administration of emerging dialysis-like sepsis therapies

  9. Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections.

    Science.gov (United States)

    Gerber, Jeffrey S; Ross, Rachael K; Bryan, Matthew; Localio, A Russell; Szymczak, Julia E; Wasserman, Richard; Barkman, Darlene; Odeniyi, Folasade; Conaboy, Kathryn; Bell, Louis; Zaoutis, Theoklis E; Fiks, Alexander G

    2017-12-19

    Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment. To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children. A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts. Broad-spectrum antibiotics vs narrow-spectrum antibiotics. In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events. Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868

  10. Susceptibility Breakpoint for Enrofloxacin against Swine Salmonella spp.

    Science.gov (United States)

    Hao, Haihong; Pan, Huafang; Ahmad, Ijaz; Cheng, Guyue; Wang, Yulian; Dai, Menghong; Tao, Yanfei; Chen, Dongmei; Peng, Dapeng; Liu, Zhenli

    2013-01-01

    Susceptibility breakpoints are crucial for prudent use of antimicrobials. This study has developed the first susceptibility breakpoint (MIC ≤ 0.25 μg/ml) for enrofloxacin against swine Salmonella spp. based on wild-type cutoff (COWT) and pharmacokinetic-pharmacodynamic (PK-PD) cutoff (COPD) values, consequently providing a criterion for susceptibility testing and clinical usage of enrofloxacin. PMID:23784134

  11. INVESTIGATION OF ENROFLOXACIN-ASSOCIATED RETINAL TOXICITY IN NONDOMESTIC FELIDS.

    Science.gov (United States)

    Newkirk, Kim M; Beard, L Kathryn; Sun, Xiaocun; Ramsay, Edward C

    2017-06-01

    Enrofloxacin is known to cause retinal toxicity in domestic cats. The hallmark lesion of enrofloxacin-associated retinal toxicity in domestic cats is thinning of the outer nuclear layer of the retina. Enrofloxacin is commonly used to treat bacterial infections in nondomestic felids because of its action against a wide spectrum of bacteria and the ability for it to be given orally. No previous studies have investigated the potential retinal toxicity of enrofloxacin in nondomestic felids. This retrospective study evaluated 81 eyes from 14 lions ( Panthera leo ) and 33 tigers ( Panthera tigris ) that had been enucleated or collected postmortem. The thickness of the outer nuclear retina was assessed in two separate sites in each eye by counting the rows of nuclei and by using digital image analysis software to determine the area of the nuclei at each site. Medical records were reviewed to determine the enrofloxacin dose for each cat. Cats that had not received enrofloxacin (n = 11) were compared with treated animals (n = 36). The outer nuclear layer thickness or area in treated versus untreated cats was not significantly different. Additionally, no clinical blindness was reported in any of the cats. This study showed no evidence of enrofloxacin-associated thinning of the outer nuclear layer in the lions and tigers evaluated, suggesting that enrofloxacin can be used safely in these animals.

  12. Bioequivalence study on two brands of 10% enrofloxacin oral ...

    African Journals Online (AJOL)

    A bioequivalence of two brands of 10% enrofloxacin was tested in broiler chickens using a parallel design at 20 mg/kg bodyweight orally. Blood was sampled before and after drug administration for 24 hours. Plasma enrofloxacin concentrations were analyzed using microbiological assay. Peak plasma concentrations ...

  13. Effect of doxycycline concentrations in chicken tissues as a consequence of permanent exposure to enrofloxacin traces in drinking water

    Directory of Open Access Journals (Sweden)

    Gbylik-Sikorska Małgorzata

    2016-09-01

    Full Text Available Introduction: The main problem in poultry farming is the difficulty in producing food of animal origin without using antibacterial agents. Because most antibacterial compounds are dispensed in water, some water supply systems can be contaminated by antibiotics which are then administered to the animals unintentionally. This can lead to unexpected increases in antibiotic residues in food of animal origin. The aim of the present study was to determine whether the constant exposure of chicken broilers to enrofloxacin affects the withdrawal time of a therapeutic doxycycline that is intentionally administered to the chickens.

  14. Recent updates of carbapenem antibiotics.

    Science.gov (United States)

    El-Gamal, Mohammed I; Brahim, Imen; Hisham, Noorhan; Aladdin, Rand; Mohammed, Haneen; Bahaaeldin, Amany

    2017-05-05

    Carbapenems are among the most commonly used and the most efficient antibiotics since they are relatively resistant to hydrolysis by most β-lactamases, they target penicillin-binding proteins, and generally have broad-spectrum antibacterial effect. In this review, we described the initial discovery and development of carbapenems, chemical characteristics, in vitro/in vivo activities, resistance studies, and clinical investigations for traditional carbapenem antibiotics in the market; imipenem-cilastatin, meropenem, ertapenem, doripenem, biapenem, panipenem/betamipron in addition to newer carbapenems such as razupenem, tebipenem, tomopenem, and sanfetrinem. We focused on the literature published from 2010 to 2016. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Plasmid-mediated AmpC-type beta-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum beta-lactams, including moxalactam.

    Science.gov (United States)

    Horii, T; Arakawa, Y; Ohta, M; Ichiyama, S; Wacharotayankun, R; Kato, N

    1993-01-01

    Klebsiella pneumoniae NU2936 was isolated from a patient and was found to produce a plasmid-encoded beta-lactamase (MOX-1) which conferred resistance to broad spectrum beta-lactams, including moxalactam, flomoxef, ceftizoxime, cefotaxime, and ceftazidime. Resistance could be transferred from K. pneumoniae NU2936 to Escherichia coli CSH2 by conjugation with a transfer frequency of 5 x 10(-7). The structural gene of MOX-1 (blaMOX-1) was cloned and expressed in E. coli HB101. The MIC of moxalactam for E. coli HB101 producing MOX-1 was > 512 micrograms/ml. The apparent molecular mass and pI of this enzyme were calculated to be 38 kDa and 8.9, respectively. Hg2+ and Cu2+ failed to block enzyme activity, and the presence of EDTA in the reaction buffer did not reduce the enzyme activity. However, clavulanate and cloxacillin, serine beta-lactamase inhibitors, inhibited the enzyme activity competitively (Kis = 5.60 and 0.35 microM, respectively). The kinetic study of MOX-1 suggested that it effectively hydrolyzed broad-spectrum beta-lactams. A hybridization study confirmed that blaMOX-1 is encoded on a large resident plasmid (pRMOX1; 180 kb) of strain NU2936. By deletion analysis, the functional region was localized within a 1.2-kb region of the plasmid. By amino acid sequencing, 18 of 33 amino acid residues at the N terminus of MOX-1 were found to be identical to those of Pseudomonas aeruginosa AmpC. These findings suggest that MOX-1 is a plasmid-mediated AmpC-type beta-lactamase that provides enteric bacteria resistance to broad-spectrum beta-lactams, including moxalactam. Images PMID:8517725

  16. Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

    Directory of Open Access Journals (Sweden)

    Denong Wang

    2015-03-01

    Full Text Available Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA, for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV, and human cytomegalovirus (HCMV. In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn. These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.

  17. Novel Clostridium difficile Anti-Toxin (TcdA and TcdB Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model.

    Directory of Open Access Journals (Sweden)

    Hongyu Qiu

    Full Text Available Clostridium difficile (C. difficile infection (CDI is the main cause of nosocomial antibiotic-associated colitis and increased incidence of community-associated diarrhea in industrialized countries. At present, the primary treatment of CDI is antibiotic administration, which is effective but often associated with recurrence, especially in the elderly. Pathogenic strains produce enterotoxin, toxin A (TcdA, and cytotoxin, toxin B (TcdB, which are necessary for C. difficile induced diarrhea and gut pathological changes. Administration of anti-toxin antibodies provides an alternative approach to treat CDI, and has shown promising results in preclinical and clinical studies. In the current study, several humanized anti-TcdA and anti-TcdB monoclonal antibodies were generated and their protective potency was characterized in a hamster infection model. The humanized anti-TcdA (CANmAbA4 and anti-TcdB (CANmAbB4 and CANmAbB1 antibodies showed broad spectrum in vitro neutralization of toxins from clinical strains and neutralization in a mouse toxin challenge model. Moreover, co-administration of humanized antibodies (CANmAbA4 and CANmAbB4 cocktail provided a high level of protection in a dose dependent manner (85% versus 57% survival at day 22 for 50 mg/kg and 20 mg/kg doses, respectively in a hamster gastrointestinal infection (GI model. This study describes the protective effects conferred by novel neutralizing anti-toxin monoclonal antibodies against C. difficile toxins and their potential as therapeutic agents in treating CDI.

  18. Effect of enrofloxacin on Haemophilus parasuis infection, disease and immune response.

    Science.gov (United States)

    Macedo, Nubia; Cheeran, Maxim C J; Rovira, Albert; Holtcamp, Andrew; Torremorell, Montserrat

    2017-02-01

    Haemophilus parasuis, the causative agent of Glasser's disease, is a pathogen that colonizes the upper respiratory tract (URT) of pigs, invades the bloodstream and causes polyserositis. Because antimicrobials are highly effective against H. parasuis, we hypothesized that they could have a detrimental effect on the establishment of an immune response if given at the time of URT colonization. In this study, we characterized clinical outcomes and antibody and IFN-γ responses to H. parasuis in pigs treated with enrofloxacin before or after low dose inoculation with a pathogenic H. parasuis strain. Pigs that were only inoculated with the agent (EXP group) and pigs that were treated with enrofloxacin and then inoculated (ABT/EXP group) developed signs of disease starting at 4days post inoculation (DPI), presented a significant increase in serum IgG and were protected against a subsequent homologous challenge. In contrast, pigs treated with antibiotic after inoculation (EXP/ABT group) neither showed signs of disease nor seroconverted (IgG) after low dose inoculation. EXP/ABT pigs as well as naïve control pigs [enrofloxacin only (ABT) and challenge only (CHA)] were susceptible to challenge. Variable levels of antibodies in bronchioalveolar fluid and IFN-γ in peripheral blood mononuclear cells were observed after H. parasuis inoculation, but were not associated with protection. In summary, only pigs treated before low dose H. parasuis inoculation seroconverted and were protected against subsequent challenge. Results from this study can help determine timing of antimicrobial use and contribute to our current understanding of judicious antibiotic use. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Pharmacokinetic behavior of enrofloxacin and its metabolite ciprofloxacin in urutu pit vipers (Bothrops alternatus) after intramuscular administration.

    Science.gov (United States)

    Waxman, Samanta; Prados, Ana Paula; de Lucas, José Julio; San Andrés, Manuel Ignacion; Regner, Pablo; de Oliveira, Vanesa Costa; de Roodt, Adolfo; Rodríguez, Casilda

    2014-03-01

    Enrofloxacin is widely used in veterinary medicine and is an important alternative to treating bacterial infections, which play an important role as causes of disease and death in captive snakes. Its extralabel use in nontraditional species has been related to its excellent pharmacokinetic and antimicrobial characteristics. This can be demonstrated by its activity against gram-negative organisms implicated in serious infectious diseases of reptile species with a rapid and concentration-dependent bactericidal effect and a large volume of distribution. Pharmacokinetic parameters for enrofloxacin were investigated in seven urutu pit vipers (Bothrops alternatus), following intramuscular injections of 10 mg/kg. The plasma concentrations of enrofloxacin and its metabolite, ciprofloxacin, were measured using high-performance liquid chromatography. Blood samples were collected from the ventral coccygeal veins at 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 108, and 168 hr. The kinetic behavior was characterized by a relatively slow absorption (time of maximal plasma concentration = 4.50 +/- 3.45 hr) with peak plasma concentration of 4.81 +/- 1.12 microg/ml. The long half-life during the terminal elimination phase (t1/2 lambda = 27.91 +/- 7.55 hr) of enrofloxacin after intramuscular administration, calculated in the present study, could suggest that the antibiotic is eliminated relatively slowly and/or the presence of a slow absorption in urutu pit vipers. Ciprofloxacin reached a peak plasma concentration of 0.35 microg/ml at 13.45 hr, and the fraction of enrofloxacin metabolized to ciprofloxacin was 13.06%. If enrofloxacin's minimum inhibitory concentration (MIC90) values of 0.5 microg/ml were used, the ratios AUC(e+c): MIC90 (276 +/- 67 hr) and Cmax(e+c): MIC90 (10 +/- 2) reach the proposed threshold values (125 hr and 10, respectively) for optimized efficacy and minimized resistance development when treating infections caused by Pseudomonas. The administration of 10 mg/kg of

  20. TOC-39, a novel parenteral broad-spectrum cephalosporin with excellent activity against methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Hanaki, H; Akagi, H; Masaru, Y; Otani, T; Hyodo, A; Hiramatsu, K

    1995-01-01

    TOC-39, a new parenteral cephalosporin, is a hydroxyimino-type cephem antibiotic with vinylthio-pyridyl moiety at the 3 position. TOC-39 was evaluated for antibacterial activity against various clinically isolated strains. TOC-39 had excellent activity, stronger than that of methicillin, oxacillin, the cephalosporins tested, imipenem, gentamicin, minocycline, tobramycin, ofloxacin, and ciprofloxacin against methicillin-resistant Staphylococcus aureus (MRSA) and had an MIC comparable to that of vancomycin (the MICs of TOC-39 and vancomycin for 90% of the strains tested were 3.13 and 1.56 micrograms/ml, respectively). Against Enterococcus faecalis strains, which are resistant to cephalosporins, TOC-39 was twice as active as ampicillin. Against methicillin-susceptible S. aureus, coagulase-negative Staphylococcus spp., and Streptococcus pneumoniae, TOC-39 was twice as active as or more active than cefotiam, ceftazidime, flomoxef, and cefpirome. Against Streptococcus pyogenes, TOC-39 was superior to cefotiam, ceftazidime, and flomoxef and was similar to cefpirome. In addition, the activity of TOC-39 was equal to or greater than that of cefotiam, ceftazidime, flomoxef, and cefpirome against Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii. In terms of bactericidal effect against MRSA, TOC-39 was superior to vancomycin. No mutant resistant to TOC-39 or vancomycin was obtained from susceptible MRSA strains. In murine systemic infection models, TOC-39 showed potent activity against S. aureus and E. coli. Against highly MRSA, the activity of TOC-39 was comparable to that of vancomycin. PMID:7625799

  1. Prophylactic administration of a combined prebiotic and probiotic, or therapeutic administration of enrofloxacin, to reduce the incidence of bacterial chondronecrosis with osteomyelitis in broilers.

    Science.gov (United States)

    Wideman, R F; Al-Rubaye, A; Kwon, Y M; Blankenship, J; Lester, H; Mitchell, K N; Pevzner, I Y; Lohrmann, T; Schleifer, J

    2015-01-01

    with enrofloxacin, indicating that probiotics potentially can provide effective alternatives to antibiotics for reducing BCO lameness attributable to bacterial translocation and hematogenous distribution. © 2015 Poultry Science Association Inc.

  2. Different effect of doxycycline and enrofloxacin on ca¬thelicidin-3 mRNA expression in chickens with or without probiotics supplementati

    Directory of Open Access Journals (Sweden)

    I. Pavlova

    2017-12-01

    Full Text Available The function of immune system of poultry has a significant impact on poultry husbandry sustainabi¬lity. Therefore the aim of this study was to investigate the effect of lactic acid bacteria administered with enrofloxacin or doxycycline on expression levels of antimicrobial peptide cathelicidin-3 (CATH3 at mRNA level in the duodenum, jejunum and liver of broilers. A day-old Ross (n=24 and Duc (n=24 chickens were included in experiments with enrofloxacin and doxycycline, respectively. They were divided into four groups (n=6 for each experiment: control, supplemented with probiotics (15 days via feed, 5 days after hatching, treated with either enrofloxacin or doxycycline (10 mg.kg-1 for 5 days, via drinking water and treated with antibiotic and probiotics. Expression levels of CATH3 mRNA in liver, duodenum and jejunum were determined by RT-PCR and were statistically evaluated by Mann-Whitney test.Administration of probiotics led to insignificant down-regulation of CATH3 mRNA in the investigated tissues. The combination of doxycycline with probiotics led to statistically significant down-regulation of CATH3 mRNA in the duodenum (P<0.01. Statistically significant up-regulation of mRNA of the studied gene was found in the jejunum of enrofloxacin treated Ross chickens. The data suggest the existence of an interaction between antibiotics and innate immunity. Further evaluation in infected poultry would shed more light on the pharmacodynamics of antibacterials.

  3. Broad spectrum antibacterial and antifungal polymeric paint materials: synthesis, structure-activity relationship, and membrane-active mode of action.

    Science.gov (United States)

    Hoque, Jiaul; Akkapeddi, Padma; Yadav, Vikas; Manjunath, Goutham B; Uppu, Divakara S S M; Konai, Mohini M; Yarlagadda, Venkateswarlu; Sanyal, Kaustuv; Haldar, Jayanta

    2015-01-28

    Microbial attachment and subsequent colonization onto surfaces lead to the spread of deadly community-acquired and hospital-acquired (nosocomial) infections. Noncovalent immobilization of water insoluble and organo-soluble cationic polymers onto a surface is a facile approach to prevent microbial contamination. In the present study, we described the synthesis of water insoluble and organo-soluble polymeric materials and demonstrated their structure-activity relationship against various human pathogenic bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and beta lactam-resistant Klebsiella pneumoniae as well as pathogenic fungi such as Candida spp. and Cryptococcus spp. The polymer coated surfaces completely inactivated both bacteria and fungi upon contact (5 log reduction with respect to control). Linear polymers were more active and found to have a higher killing rate than the branched polymers. The polymer coated surfaces also exhibited significant activity in various complex mammalian fluids such as serum, plasma, and blood and showed negligible hemolysis at an amount much higher than minimum inhibitory amounts (MIAs). These polymers were found to have excellent compatibility with other medically relevant polymers (polylactic acid, PLA) and commercial paint. The cationic hydrophobic polymer coatings disrupted the lipid membrane of both bacteria and fungi and thus showed a membrane-active mode of action. Further, bacteria did not develop resistance against these membrane-active polymers in sharp contrast to conventional antibiotics and lipopeptides, thus the polymers hold great promise to be used as coating materials for developing permanent antimicrobial paint.

  4. Diversity and natural functions of antibiotics produced by beneficial and plant pathogenic bacteria

    NARCIS (Netherlands)

    Raaijmakers, J.M.; Mazzola, M.

    2012-01-01

    Soil- and plant-associated environments harbor numerous bacteria that produce antibiotic metabolites with specific or broad-spectrum activities against coexisting microorganisms. The function and ecological importance of antibiotics have long been assumed to yield a survival advantage to the

  5. Broad-spectrum inhibition of HIV-1 by a monoclonal antibody directed against a gp120-induced epitope of CD4.

    Science.gov (United States)

    Burastero, Samuele E; Frigerio, Barbara; Lopalco, Lucia; Sironi, Francesca; Breda, Daniela; Longhi, Renato; Scarlatti, Gabriella; Canevari, Silvana; Figini, Mariangela; Lusso, Paolo

    2011-01-01

    To penetrate susceptible cells, HIV-1 sequentially interacts with two highly conserved cellular receptors, CD4 and a chemokine receptor like CCR5 or CXCR4. Monoclonal antibodies (MAbs) directed against such receptors are currently under clinical investigation as potential preventive or therapeutic agents. We immunized Balb/c mice with molecular complexes of the native, trimeric HIV-1 envelope (Env) bound to a soluble form of the human CD4 receptor. Sera from immunized mice were found to contain gp120-CD4 complex-enhanced antibodies and showed broad-spectrum HIV-1-inhibitory activity. A proportion of MAbs derived from these mice preferentially recognized complex-enhanced epitopes. In particular, a CD4-specific MAb designated DB81 (IgG1Κ) was found to preferentially bind to a complex-enhanced epitope on the D2 domain of human CD4. MAb DB81 also recognized chimpanzee CD4, but not baboon or macaque CD4, which exhibit sequence divergence in the D2 domain. Functionally, MAb DB81 displayed broad HIV-1-inhibitory activity, but it did not exert suppressive effects on T-cell activation in vitro. The variable regions of the heavy and light chains of MAb DB81 were sequenced. Due to its broad-spectrum anti-HIV-1 activity and lack of immunosuppressive effects, a humanized derivative of MAb DB81 could provide a useful complement to current preventive or therapeutic strategies against HIV-1.

  6. Broad-spectrum inhibition of HIV-1 by a monoclonal antibody directed against a gp120-induced epitope of CD4.

    Directory of Open Access Journals (Sweden)

    Samuele E Burastero

    Full Text Available To penetrate susceptible cells, HIV-1 sequentially interacts with two highly conserved cellular receptors, CD4 and a chemokine receptor like CCR5 or CXCR4. Monoclonal antibodies (MAbs directed against such receptors are currently under clinical investigation as potential preventive or therapeutic agents. We immunized Balb/c mice with molecular complexes of the native, trimeric HIV-1 envelope (Env bound to a soluble form of the human CD4 receptor. Sera from immunized mice were found to contain gp120-CD4 complex-enhanced antibodies and showed broad-spectrum HIV-1-inhibitory activity. A proportion of MAbs derived from these mice preferentially recognized complex-enhanced epitopes. In particular, a CD4-specific MAb designated DB81 (IgG1Κ was found to preferentially bind to a complex-enhanced epitope on the D2 domain of human CD4. MAb DB81 also recognized chimpanzee CD4, but not baboon or macaque CD4, which exhibit sequence divergence in the D2 domain. Functionally, MAb DB81 displayed broad HIV-1-inhibitory activity, but it did not exert suppressive effects on T-cell activation in vitro. The variable regions of the heavy and light chains of MAb DB81 were sequenced. Due to its broad-spectrum anti-HIV-1 activity and lack of immunosuppressive effects, a humanized derivative of MAb DB81 could provide a useful complement to current preventive or therapeutic strategies against HIV-1.

  7. Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses.

    Science.gov (United States)

    Hu, Yanmei; Zhang, Jiantao; Musharrafieh, Rami Ghassan; Ma, Chunlong; Hau, Raymond; Wang, Jun

    2017-09-01

    The emergence of multidrug-resistant influenza viruses poses a persistent threat to public health. The current prophylaxis and therapeutic interventions for influenza virus infection have limited efficacy due to the continuous antigenic drift and antigenic shift of influenza viruses. As part of our ongoing effort to develop the next generation of influenza antivirals with broad-spectrum antiviral activity and a high genetic barrier to drug resistance, in this study we report the discovery of dapivirine, an FDA-approved HIV nonnucleoside reverse transcriptase inhibitor, as a broad-spectrum antiviral against multiple strains of influenza A and B viruses with low micromolar efficacy. Mechanistic studies revealed that dapivirine inhibits the nuclear entry of viral ribonucleoproteins at the early stage of viral replication. As a result, viral RNA and protein synthesis were inhibited. Furthermore, dapivirine has a high in vitro genetic barrier to drug resistance, and its antiviral activity is synergistic with oseltamivir carboxylate. In summary, the in vitro antiviral results of dapivirine suggest it is a promising candidate for the development of the next generation of dual influenza and HIV antivirals. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Biogenic synthesis of Zinc oxide nanostructures from Nigella sativa seed: Prospective role as food packaging material inhibiting broad-spectrum quorum sensing and biofilm.

    Science.gov (United States)

    Al-Shabib, Nasser A; Husain, Fohad Mabood; Ahmed, Faheem; Khan, Rais Ahmad; Ahmad, Iqbal; Alsharaeh, Edreese; Khan, Mohd Shahnawaz; Hussain, Afzal; Rehman, Md Tabish; Yusuf, Mohammad; Hassan, Iftekhar; Khan, Javed Masood; Ashraf, Ghulam Md; Alsalme, Ali Mohammed; Al-Ajmi, Mohamed F; Tarasov, Vadim V; Aliev, Gjumrakch

    2016-12-05

    Bacterial spoilage of food products is regulated by density dependent communication system called quorum sensing (QS). QS control biofilm formation in numerous food pathogens and Biofilms formed on food surfaces act as carriers of bacterial contamination leading to spoilage of food and health hazards. Agents inhibiting or interfering with bacterial QS and biofilm are gaining importance as a novel class of next-generation food preservatives/packaging material. In the present study, Zinc nanostructures were synthesised using Nigella sativa seed extract (NS-ZnNPs). Synthesized nanostructures were characterized hexagonal wurtzite structure of size ~24 nm by UV-visible, XRD, FTIR and TEM. NS-ZnNPs demonstrated broad-spectrum QS inhibition in C. violaceum and P. aeruginosa biosensor strains. Synthesized nanostructures inhibited QS regulated functions of C. violaceum CVO26 (violacein) and elastase, protease, pyocyanin and alginate production in PAO1 significantly. NS-ZnNPs at sub-inhibitory concentrations inhibited the biofilm formation of four-food pathogens viz. C. violaceum 12472, PAO1, L. monocytogenes, E. coli. Moreover, NS-ZnNPs was found effective in inhibiting pre-formed mature biofilms of the four pathogens. Therefore, the broad-spectrum inhibition of QS and biofilm by biogenic Zinc oxide nanoparticles and it is envisaged that these nontoxic bioactive nanostructures can be used as food packaging material and/or as food preservative.

  9. Modulation of enrofloxacin binding in OmpF by Mg2+ as revealed by the analysis of fast flickering single-porin current

    Science.gov (United States)

    Brauser, Annemarie; Schroeder, Indra; Gutsmann, Thomas; Cosentino, Cristian; Moroni, Anna; Winterhalter, Mathias

    2012-01-01

    One major determinant of the efficacy of antibiotics on Gram-negative bacteria is the passage through the outer membrane. During transport of the fluoroquinolone enrofloxacin through the trimeric outer membrane protein OmpF of Escherichia coli, the antibiotic interacts with two binding sites within the pore, thus partially blocking the ionic current. The modulation of one affinity site by Mg2+ reveals further details of binding sites and binding kinetics. At positive membrane potentials, the slow blocking events induced by enrofloxacin in Mg2+-free media are converted to flickery sojourns at the highest apparent current level (all three pores flickering). This indicates weaker binding in the presence of Mg2+. Analysis of the resulting amplitude histograms with β distributions revealed the rate constants of blocking (kOB) and unblocking (kBO) in the range of 1,000 to 120,000 s−1. As expected for a bimolecular reaction, kOB was proportional to blocker concentration and kBO independent of it. kOB was approximately three times lower for enrofloxacin coming from the cis side than from the trans side. The block was not complete, leading to a residual conductivity of the blocked state being ∼25% of that of the open state. Interpretation of the results has led to the following model: fast flickering as caused by interaction of Mg2+ and enrofloxacin is related to the binding site at the trans side, whereas the cis site mediates slow blocking events which are also found without Mg2+. The difference in the accessibility of the binding sites also explains the dependency of kOB on the side of enrofloxacin addition and yields a means of determining the most plausible orientation of OmpF in the bilayer. The voltage dependence suggests that the dipole of the antibiotic has to be adequately oriented to facilitate binding. PMID:22689827

  10. Efficacy of enrofloxacin in a mouse model of sepsis.

    Science.gov (United States)

    Slate, Andrea R; Bandyopadhyay, Sheila; Francis, Kevin P; Papich, Mark G; Karolewski, Brian; Hod, Eldad A; Prestia, Kevin A

    2014-07-01

    We examined the efficacy of enrofloxacin administered by 2 different routes in a mouse model of sepsis. Male CD1 mice were infected with a bioluminescent strain of enteropathogenic Escherichia coli and treated with enrofloxacin either by injection or in drinking water. Peak serum levels were evaluated by using HPLC. Mice were monitored for signs of clinical disease, and infections were monitored by using bioluminescence imaging. Serum levels of enrofloxacin and the active metabolite ciprofloxacin were greater in the group treated by injection than in controls or the groups treated by administration in drinking water. Survival of the group treated with enrofloxacin injection was greater than that of controls and groups treated with enrofloxacin in the drinking water. Bioluminescence in the group treated with enrofloxacin injection was less than that in the groups treated with oral administration at 12 h and in the groups treated orally and the control group at 16 h. According to these findings, we recommend the use of injectable enrofloxacin at 5 mg/kg SC for mice with systemic infections.

  11. Excretion pattern of enrofloxacin after oral treatment of chicken broilers.

    Science.gov (United States)

    Slana, M; Pahor, V; Cvitkovič Maričič, L; Sollner-Dolenc, M

    2014-12-01

    The metabolism and excretion of enrofloxacin were studied when applied as oral solution to chicken broilers for five consecutive days. Sixty 9-day-old broilers were isolated within an intensively rearing poultry farm during enrofloxacin therapy (15.5 mg/kg per day). The excreta of the isolated broilers were collected daily, 9 days after therapy termination, for 13 consecutive days, and analyzed for the presence of enrofloxacin and its metabolites [ciprofloxacin, desethylene-enrofloxacin (DES-EF) and desethylene-ciprofloxacin (DES-CF)]. Enrofloxacin was excreted predominantly in the form of the parent compound between days 1 and 13. Ciprofloxacin was detected in the excreta between days 1 and 6, whereas minor amounts of DES-EF and DES-CF were excreted only between days 1-7 and 1-6, respectively. In conclusion, the analysis of the excreta showed that approximately 74% of orally applied enrofloxacin was excreted as the parent compound, approximately 25% as the main metabolite ciprofloxacin, and approximately 1% as the minor metabolites desethylene-enrofloxacin and desethylene-ciprofloxacin. © 2014 John Wiley & Sons Ltd.

  12. Use of antibiotics in children

    DEFF Research Database (Denmark)

    Pottegård, Anton; Broe, A.; Aabenhus, R.

    2015-01-01

    Background: We aimed to describe the use of systemic antibiotics among children in Denmark. Methods: National data on drug use in Denmark were extracted from the Danish National Prescription Database. We used prescription data for all children in Denmark aged 0 to 11 years from January 1, 2000...... to December 31, 2012. Results: We obtained data on 5,884,301 prescriptions for systemic antibiotics issued to 1,206,107 children. The most used single substances were phenoxymethylpenicillin (45%), amoxicillin (34%) and erythromycin (6%). The highest incidence rate of antibiotic treatment episodes......-1. There was little evidence of heavy users. Conclusion: Prescribing rate of antibiotics to children in Denmark remained stable at a high level from 2000 to 2012. An increase in the use of broad-spectrum beta-lactam penicillin was noted, but otherwise the prescribing pattern adhered well to National guidelines...

  13. Novel, broad-spectrum anticonvulsants containing a sulfamide group: advancement of N-((benzo[b]thien-3-yl)methyl)sulfamide (JNJ-26990990) into human clinical studies.

    Science.gov (United States)

    Parker, Michael H; Smith-Swintosky, Virginia L; McComsey, David F; Huang, Yifang; Brenneman, Douglas; Klein, Brian; Malatynska, Ewa; White, H Steve; Milewski, Michael E; Herb, Mark; Finley, Michael F A; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Iannucci, Robert; Leclercq, Laurent; Cuyckens, Filip; Reitz, Allen B; Maryanoff, Bruce E

    2009-12-10

    In seeking broad-spectrum anticonvulsants to treat epilepsy and other neurological disorders, we synthesized and tested a group of sulfamide derivatives (4a-k, 5), which led to the clinical development of 4a (JNJ-26990990). This compound exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures, with very weak inhibition of human carbonic anhydrase-II (IC(50) = 110 microM). The pharmacological profile for 4a supports its potential in the treatment of multiple forms of epilepsy, including pharmacoresistant variants. Mechanistically, 4a inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels but was not effective as a K(+) channel opener. The pharmacokinetics and metabolic properties of 4a are discussed.

  14. Bio-Inspired Wide-Angle Broad-Spectrum Cylindrical Lens Based on Reflections from Micro-Mirror Array on a Cylindrical Elastomeric Membrane

    Directory of Open Access Journals (Sweden)

    Chi-Chieh Huang

    2014-06-01

    Full Text Available We present a wide-angle, broad-spectrum cylindrical lens based on reflections from an array of three-dimensional, high-aspect-ratio micro-mirrors fabricated on a cylindrical elastomeric substrate, functionally inspired by natural reflecting superposition compound eyes. Our device can perform one-dimensional focusing and beam-shaping comparable to conventional refraction-based cylindrical lenses, while avoiding chromatic aberration. The focal length of our cylindrical lens is 1.035 mm, suitable for micro-optical systems. Moreover, it demonstrates a wide field of view of 152° without distortion, as well as modest spherical aberrations. Our work could be applied to diverse applications including laser diode collimation, barcode scanning, holography, digital projection display, microlens arrays, and optical microscopy.

  15. Genetic analysis of a novel broad-spectrum powdery mildew resistance gene from the wheat-Agropyron cristatum introgression line Pubing 74.

    Science.gov (United States)

    Lu, Yuqing; Yao, Miaomiao; Zhang, Jinpeng; Song, Liqiang; Liu, Weihua; Yang, Xinming; Li, Xiuquan; Li, Lihui

    2016-09-01

    A novel broad-spectrum powdery mildew resistance gene PmPB74 was identified in wheat- Agropyron cristatum introgression line Pubing 74. Development of wheat cultivars with broad-spectrum, durable resistance to powdery mildew has been restricted by lack of superior genetic resources. In this study, a wheat-A. cristatum introgression line Pubing 74, originally selected from a wide cross between the common wheat cultivar Fukuhokomugi (Fukuho) and Agropyron cristatum (L.) Gaertn (2n = 4x = 28; genome PPPP), displayed resistance to powdery mildew at both the seedling and adult stages. The putative alien chromosomal fragment in Pubing 74 was below the detection limit of genomic in situ hybridization (GISH), but evidence for other non-GISH-detectable introgressions was provided by the presence of three STS markers specific to A. cristatum. Genetic analysis indicated that Pubing 74 carried a single dominant gene for powdery mildew resistance, temporarily designated PmPB74. Molecular mapping showed that PmPB74 was located on wheat chromosome arm 5DS, and flanked by markers Xcfd81 and HRM02 at genetic distances of 2.5 and 1.7 cM, respectively. Compared with other lines with powdery mildew resistance gene(s) on wheat chromosome arm 5DS, Pubing 74 was resistant to all 28 Blumeria graminis f. sp tritici (Bgt) isolates from different wheat-producing regions of northern China. Allelism tests indicated that PmPB74 was not allelic to PmPB3558 or Pm2. Our work showed that PmPB74 is a novel gene with broad resistance to powdery mildew, and hence will be helpful in broadening the genetic basis of powdery mildew resistance in wheat.

  16. Enrofloxacin degradation in broiler chicken manure under various laboratory conditions.

    Science.gov (United States)

    Slana, Marko; Sollner-Dolenc, Marija

    2016-03-01

    The rate of degradation of enrofloxacin in broiler chicken manure has been characterized in the laboratory according to the CVMP guideline on determining the fate of veterinary medicinal products in manure. Degradation was followed in a flow-through system under aerobic and anaerobic conditions, in the dark and in the presence of light. The rate of degradation of enrofloxacin and the formation of its degradation products are dependent on laboratory conditions. A rapid degradation of enrofloxacin in the dark was noticed, where a shorter degradation half-life under aerobic (DT50 = 59.1 days), comparing to anaerobic conditions (DT50 = 88.9 days), was determined. The presence of light slowed down the enrofloxacin degradation half-life, which was significantly shorter under aerobic (DT50 = 115.0 days), comparing to anaerobic conditions (DT50 = 190.8 days). Desethylene-enrofoxacin was the only degradation product formed, its concentrations ranged from 2.5 to 14.9 %. The concentration of the degradation product was approximately 2.5-fold higher under aerobic conditions. Enrofloxacin degradation in sterile manure incubated under sterile conditions was marginal comparing to non-sterile conditions; after 120 days of incubation, approximately 80 % of enrofloxacin was still present in manure and only 1 % of desethylene-enrofloxacin was formed. The present work demonstrates that enrofloxacin degradation in chicken manure is relatively fast when incubated in the dark under aerobic conditions which is the recommended incubation system for chicken manure according to CVMP guideline.

  17. Enrofloxacin and Toltrazuril Are Able to Reduce Toxoplasma gondii Growth in Human BeWo Trophoblastic Cells and Villous Explants from Human Third Trimester Pregnancy

    Directory of Open Access Journals (Sweden)

    Rafaela J. da Silva

    2017-07-01

    Full Text Available Classical treatment for congenital toxoplasmosis is based on combination of sulfadiazine and pyrimethamine plus folinic acid. Due to teratogenic effects and bone marrow suppression caused by pyrimethamine, the establishment of new therapeutic strategies is indispensable to minimize the side effects and improve the control of infection. Previous studies demonstrated that enrofloxacin and toltrazuril reduced the incidence of Neospora caninum and Toxoplasma gondii infection. The aim of the present study was to evaluate the efficacy of enrofloxacin and toltrazuril in the control of T. gondii infection in human trophoblast cells (BeWo line and in human villous explants from the third trimester. BeWo cells and villous were treated with several concentrations of enrofloxacin, toltrazuril, sulfadiazine, pyrimethamine, or combination of sulfadiazine+pyrimethamine, and the cellular or tissue viability was verified. Next, BeWo cells were infected by T. gondii (2F1 clone or the ME49 strain, whereas villous samples were only infected by the 2F1 clone. Then, infected cells and villous were treated with all antibiotics and the T. gondii intracellular proliferation as well as the cytokine production were analyzed. Finally, we evaluated the direct effect of enrofloxacin and toltrazuril in tachyzoites to verify possible changes in parasite structure. Enrofloxacin and toltrazuril did not decrease the viability of cells and villous in lower concentrations. Both drugs were able to significantly reduce the parasite intracellular proliferation in BeWo cells and villous explants when compared to untreated conditions. Regardless of the T. gondii strain, BeWo cells infected and treated with enrofloxacin or toltrazuril induced high levels of IL-6 and MIF. In villous explants, enrofloxacin induced high MIF production. Finally, the drugs increased the number of unviable parasites and triggered damage to tachyzoite structure. Taken together, it can be concluded that

  18. Enrofloxacin and Toltrazuril Are Able to Reduce Toxoplasma gondii Growth in Human BeWo Trophoblastic Cells and Villous Explants from Human Third Trimester Pregnancy.

    Science.gov (United States)

    da Silva, Rafaela J; Gomes, Angelica O; Franco, Priscila S; Pereira, Ariane S; Milian, Iliana C B; Ribeiro, Mayara; Fiorenzani, Paolo; Dos Santos, Maria C; Mineo, José R; da Silva, Neide M; Ferro, Eloisa A V; de Freitas Barbosa, Bellisa

    2017-01-01

    Classical treatment for congenital toxoplasmosis is based on combination of sulfadiazine and pyrimethamine plus folinic acid. Due to teratogenic effects and bone marrow suppression caused by pyrimethamine, the establishment of new therapeutic strategies is indispensable to minimize the side effects and improve the control of infection. Previous studies demonstrated that enrofloxacin and toltrazuril reduced the incidence of Neospora caninum and Toxoplasma gondii infection. The aim of the present study was to evaluate the efficacy of enrofloxacin and toltrazuril in the control of T. gondii infection in human trophoblast cells (BeWo line) and in human villous explants from the third trimester. BeWo cells and villous were treated with several concentrations of enrofloxacin, toltrazuril, sulfadiazine, pyrimethamine, or combination of sulfadiazine+pyrimethamine, and the cellular or tissue viability was verified. Next, BeWo cells were infected by T. gondii (2F1 clone or the ME49 strain), whereas villous samples were only infected by the 2F1 clone. Then, infected cells and villous were treated with all antibiotics and the T. gondii intracellular proliferation as well as the cytokine production were analyzed. Finally, we evaluated the direct effect of enrofloxacin and toltrazuril in tachyzoites to verify possible changes in parasite structure. Enrofloxacin and toltrazuril did not decrease the viability of cells and villous in lower concentrations. Both drugs were able to significantly reduce the parasite intracellular proliferation in BeWo cells and villous explants when compared to untreated conditions. Regardless of the T. gondii strain, BeWo cells infected and treated with enrofloxacin or toltrazuril induced high levels of IL-6 and MIF. In villous explants, enrofloxacin induced high MIF production. Finally, the drugs increased the number of unviable parasites and triggered damage to tachyzoite structure. Taken together, it can be concluded that enrofloxacin and

  19. Integrated pharmacokinetics/pharmacodynamics parameters-based dosing guidelines of enrofloxacin in grass carp Ctenopharyngodon idella to minimize selection of drug resistance.

    Science.gov (United States)

    Xu, Lijuan; Wang, Hao; Yang, Xianle; Lu, Liqun

    2013-06-25

    Antibiotic resistance has become a serious global problem and is steadily increasing worldwide in almost every bacterial species treated with antibiotics. In aquaculture, the therapeutic options for the treatment of A. hydrophila infection were only limited to several antibiotics, which contributed for the fast-speed emergence of drug tolerance. Accordingly, the aim of this study was to establish a medication regimen to prevent drug resistant bacteria. To determine a rational therapeutic guideline, integrated pharmacodynamics and pharmacokinetics parameters were based to predict dose and dosage interval of enrofloxacin in grass carp Ctenopharyngodon idella infected by a field-isolated A. hydrophila strain. The pathogenic A. hydrophila strain (AH10) in grass carp was identified and found to be sensitive to enrofloxacin. The mutant selection window (MSW) of enrofloxacin on isolate AH10 was determined to be 0.5-3 μg/mL based on the mutant prevention concentration (MPC) and minimum inhibitory concentration (MIC) value. By using high-performance liquid chromatography (HPLC) system, the Pharmacokinetic (PK) parameters of enrofloxacin and its metabolite ciprofloxacin in grass carp were monitored after a single oral gavage of 10, 20, 30 μg enrofloxacin per g body weight. Dosing of 30 μg/g resulted in serum maximum concentration (Cmax) of 7.151 μg/mL, and concentration in serum was above MPC till 24 h post the single dose. Once-daily dosing of 30 μg/g was determined to be the rational choice for controlling AH10 infection and preventing mutant selection in grass carp. Data of mean residue time (MRT) and body clearance (CLz) indicated that both enrofloxacin and its metabolite ciprofloxacin present similar eliminating rate and pattern in serum, muscle and liver. A withdraw time of more than 32 d was suggested based on the drug eliminating rate and pharmacokinetic model described by a polyexponential equation. Based on integrated PK/PD parameters (AUC/MIC, Cmax/MIC, and T

  20. A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chang, So Young; Park, Ji Hoon [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of); Kim, Young Ho; Kang, Jong Seong [College of Pharmacy, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Min, Ji-Young, E-mail: jiyoung.min@ip-korea.org [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of)

    2016-03-04

    The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. - Highlights: • The plant-derived natural product TGBG has broad-spectrum antiviral activity against seasonal influenza A and B viruses. • TGBG has a novel anti-viral mechanism of action that from differs from the currently available anti-influenza drugs. • TGBG hinders nuclear export of the influenza virus ribonucleoprotein (v

  1. A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein

    International Nuclear Information System (INIS)

    Chang, So Young; Park, Ji Hoon; Kim, Young Ho; Kang, Jong Seong; Min, Ji-Young

    2016-01-01

    The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. - Highlights: • The plant-derived natural product TGBG has broad-spectrum antiviral activity against seasonal influenza A and B viruses. • TGBG has a novel anti-viral mechanism of action that from differs from the currently available anti-influenza drugs. • TGBG hinders nuclear export of the influenza virus ribonucleoprotein (v

  2. Transgenic Brassica rapa plants over-expressing eIF(iso)4E variants show broad-spectrum Turnip mosaic virus (TuMV) resistance.

    Science.gov (United States)

    Kim, Jinhee; Kang, Won-Hee; Hwang, Jeena; Yang, Hee-Bum; Dosun, Kim; Oh, Chang-Sik; Kang, Byoung-Cheorl

    2014-08-01

    The protein-protein interaction between VPg (viral protein genome-linked) of potyviruses and eIF4E (eukaryotic initiation factor 4E) or eIF(iso)4E of their host plants is a critical step in determining viral virulence. In this study, we evaluated the approach of engineering broad-spectrum resistance in Chinese cabbage (Brassica rapa) to Turnip mosaic virus (TuMV), which is one of the most important potyviruses, by a systematic knowledge-based approach to interrupt the interaction between TuMV VPg and B. rapa eIF(iso)4E. The seven amino acids in the cap-binding pocket of eIF(iso)4E were selected on the basis of other previous results and comparison of protein models of cap-binding pockets, and mutated. Yeast two-hybrid assay and co-immunoprecipitation analysis demonstrated that W95L, K150L and W95L/K150E amino acid mutations of B. rapa eIF(iso)4E interrupted its interaction with TuMV VPg. All eIF(iso)4E mutants were able to complement an eIF4E-knockout yeast strain, indicating that the mutated eIF(iso)4E proteins retained their function as a translational initiation factor. To determine whether these mutations could confer resistance, eIF(iso)4E W95L, W95L/K150E and eIF(iso)4E wild-type were over-expressed in a susceptible Chinese cabbage cultivar. Evaluation of the TuMV resistance of T1 and T2 transformants demonstrated that the over-expression of the eIF(iso)4E mutant forms can confer resistance to multiple TuMV strains. These data demonstrate the utility of knowledge-based approaches for the engineering of broad-spectrum resistance in Chinese cabbage. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  3. 77 FR 76862 - New Animal Drugs; Enrofloxacin; Melengestrol; Meloxicam; Pradofloxacin; Tylosin

    Science.gov (United States)

    2012-12-31

    ..., and 558 [Docket No. FDA-2012-N-0002] New Animal Drugs; Enrofloxacin; Melengestrol; Meloxicam... (enrofloxacin) adding treatment and Health Division, Injectable control of swine P.O. Box 390, Solution... Enrofloxacin. * * * * * (e) * * * (3) * * * (ii) Indications for use. For the treatment and control of swine...

  4. 76 FR 22610 - Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin

    Science.gov (United States)

    2011-04-22

    .... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin AGENCY: Food... the indications for use of enrofloxacin solution in cattle, as a single injection, for the treatment... supplement to NADA 141-068 for BAYTRIL 100 (enrofloxacin), an injectable solution. The supplemental NADA...

  5. 78 FR 30197 - Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin

    Science.gov (United States)

    2013-05-22

    ...-0002] Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin AGENCY: Food and Drug Administration...- Tallaght, Dublin Oral Drops. 940. 24, Ireland. 200-551........ Putney, Inc., 400 Enrofloxacin Original....812 Enrofloxacin. (a) Specifications. Each tablet contains 22.7, 68.0, or 136.0 milligrams (mg) of...

  6. 78 FR 52852 - New Animal Drugs; Carprofen; Enrofloxacin; Florfenicol; Tildipirosin; Zilpaterol

    Science.gov (United States)

    2013-08-27

    ..., 556, and 558 [Docket No. FDA-2013-N-0002] New Animal Drugs; Carprofen; Enrofloxacin; Florfenicol..., (enrofloxacin) approval as a Inc., 3200 Flavored generic copy Northline Ave., Antibacterial of NADA 140- suite...) to read as follows: Sec. 520.812 Enrofloxacin. (a) Specifications. Each tablet contains: (1) 22.7, 68...

  7. Efficacy of oral E1210, a new broad-spectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis.

    Science.gov (United States)

    Hata, Katsura; Horii, Takaaki; Miyazaki, Mamiko; Watanabe, Nao-Aki; Okubo, Miyuki; Sonoda, Jiro; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto

    2011-10-01

    E1210 is a first-in-class, broad-spectrum antifungal with a novel mechanism of action-inhibition of fungal glycosylphosphatidylinositol biosynthesis. In this study, the efficacies of E1210 and reference antifungals were evaluated in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. Oral E1210 demonstrated dose-dependent efficacy in infections caused by Candida species, Aspergillus spp., and Fusarium solani. In the treatment of oropharyngeal candidiasis, E1210 and fluconazole each caused a significantly greater reduction in the number of oral CFU than the control treatment (P candidiasis model, mice treated with E1210, fluconazole, caspofungin, or liposomal amphotericin B showed significantly higher survival rates than the control mice (P candidiasis caused by azole-resistant Candida albicans or Candida tropicalis. A 24-h delay in treatment onset minimally affected the efficacy outcome of E1210 in the treatment of disseminated candidiasis. In the Aspergillus flavus pulmonary aspergillosis model, mice treated with E1210, voriconazole, or caspofungin showed significantly higher survival rates than the control mice (P candidiasis, pulmonary aspergillosis, and disseminated fusariosis. These data suggest that further studies to determine E1210's potential for the treatment of disseminated fungal infections are indicated.

  8. Protease-sensitive conformers in broad spectrum of distinct PrPSc structures in sporadic Creutzfeldt-Jakob disease are indicator of progression rate.

    Directory of Open Access Journals (Sweden)

    Chae Kim

    2011-09-01

    Full Text Available The origin, range, and structure of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD, are largely unknown. To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD, we analyzed the conformational characteristics of protease-sensitive and protease-resistant fractions of the pathogenic prion protein (PrP(Sc using novel conformational methods derived from a conformation-dependent immunoassay (CDI. In 46 brains of patients homozygous for polymorphisms in the PRNP gene and exhibiting either Type 1 or Type 2 western blot pattern of the PrP(Sc, we identified an extensive array of PrP(Sc structures that differ in protease sensitivity, display of critical domains, and conformational stability. Surprisingly, in sCJD cases homozygous for methionine or valine at codon 129 of the PRNP gene, the concentration and stability of protease-sensitive conformers of PrP(Sc correlated with progression rate of the disease. These data indicate that sCJD brains exhibit a wide spectrum of PrP(Sc structural states, and accordingly argue for a broad spectrum of prion strains coding for different phenotypes. The link between disease duration, levels, and stability of protease-sensitive conformers of PrP(Sc suggests that these conformers play an important role in the pathogenesis of sCJD.

  9. Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control (FSC) platform

    Science.gov (United States)

    Liu, Qi; Zhang, Cheng; Ding, Xianting; Deng, Hui; Zhang, Daming; Cui, Wei; Xu, Hongwei; Wang, Yingwei; Xu, Wanhai; Lv, Lei; Zhang, Hongyu; He, Yinghua; Wu, Qiong; Szyf, Moshe; Ho, Chih-Ming; Zhu, Jingde

    2015-06-01

    Therapeutic outcomes of combination chemotherapy have not significantly advanced during the past decades. This has been attributed to the formidable challenges of optimizing drug combinations. Testing a matrix of all possible combinations of doses and agents in a single cell line is unfeasible due to the virtually infinite number of possibilities. We utilized the Feedback System Control (FSC) platform, a phenotype oriented approach to test 100 options among 15,625 possible combinations in four rounds of assaying to identify an optimal tri-drug combination in eight distinct chemoresistant bladder cancer cell lines. This combination killed between 82.86% and 99.52% of BCa cells, but only 47.47% of the immortalized benign bladder epithelial cells. Preclinical in vivo verification revealed its markedly enhanced anti-tumor efficacy as compared to its bi- or mono-drug components in cell line-derived tumor xenografts. The collective response of these pathways to component drugs was both cell type- and drug type specific. However, the entire spectrum of pathways triggered by the tri-drug regimen was similar in all four cancer cell lines, explaining its broad spectrum killing of BCa lines, which did not occur with its component drugs. Our findings here suggest that the FSC platform holdspromise for optimization of anti-cancer combination chemotherapy.

  10. The sun protection factor (SPF) inadequately defines broad spectrum photoprotection: demonstration using skin reconstructed in vitro exposed to UVA, UVBor UV-solar simulated radiation.

    Science.gov (United States)

    Bernerd, Françoise; Vioux, Corinne; Lejeune, François; Asselineau, Daniel

    2003-01-01

    Wavelength specific biological damage has been previously identified in human skin reconstructed in vitro. Sunburn cell and pyrimidine dimers were found after UVB exposure, and alterations of dermal fibroblasts after UVA exposure. These damages permitted us to discriminate UVB and UVA single absorbers. The present study shows that these biological effects can be obtained simultaneously by a combined UVB + UVA exposure using ultraviolet solar simulated light (UV-SSR), which represents a relevant UV source. In addition, the protection afforded by two broad spectrum sunscreen complex formulations was assessed after topical application. These two formulations displayed the same sun protection factor but different UVA protection factors determined by the persistent pigment darkening (PPD) method. Dose response experiments of UVA or UV-SSR showed that the preparation with the highest PF-UVA provided a better protection with regard to dermal damage compared to the other formulation. Using an original UVB source to obtain the UVB portion of SSR spectrum, the preparations provided the same protection. This study strikingly illustrates the fact that the photoprotection afforded by two sunscreen formulations having similar SPF values is not equal with regard to dermal damage related to photoaging.

  11. Ectopic expression of Arabidopsis broad-spectrum resistance gene RPW8.2 improves the resistance to powdery mildew in grapevine (Vitis vinifera).

    Science.gov (United States)

    Hu, Yang; Li, Yajuan; Hou, Fengjuan; Wan, Dongyan; Cheng, Yuan; Han, Yongtao; Gao, Yurong; Liu, Jie; Guo, Ye; Xiao, Shunyuan; Wang, Yuejin; Wen, Ying-Qiang

    2018-02-01

    Powdery mildew is the most economically important disease of cultivated grapevines worldwide. Here, we report that the Arabidopsis broad-spectrum disease resistance gene RPW8.2 could improve resistance to powdery mildew in Vitis vinifera cv. Thompson Seedless. The RPW8.2-YFP fusion gene was stably expressed in grapevines from either the constitutive 35S promoter or the native promoter (NP) of RPW8.2. The grapevine shoots and plantlets transgenic for 35S::RPW8.2-YFP showed reduced rooting and reduced growth at later development stages in the absence of any pathogens. Infection tests with an adapted grapevine powdery mildew isolate En NAFU1 showed that hyphal growth and sporulation were significantly restricted in transgenic grapevines expressing either of the two constructs. The resistance appeared to be attributable to the ectopic expression of RPW8.2, and associated with the enhanced encasement of the haustorial complex (EHC) and onsite accumulation of H 2 O 2 . In addition, the RPW8.2-YFP fusion protein showed focal accumulation around the fungal penetration sites. Transcriptome analysis revealed that ectopic expression of RPW8.2 in grapevines not only significantly enhanced salicylic acid-dependent defense signaling, but also altered expression of other phytohormone-associated genes. Taken together, our results indicate that RPW8.2 could be utilized as a transgene for improving resistance against powdery mildew in grapevines. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Efficacy of Oral E1210, a New Broad-Spectrum Antifungal with a Novel Mechanism of Action, in Murine Models of Candidiasis, Aspergillosis, and Fusariosis▿

    Science.gov (United States)

    Hata, Katsura; Horii, Takaaki; Miyazaki, Mamiko; Watanabe, Nao-aki; Okubo, Miyuki; Sonoda, Jiro; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto

    2011-01-01

    E1210 is a first-in-class, broad-spectrum antifungal with a novel mechanism of action—inhibition of fungal glycosylphosphatidylinositol biosynthesis. In this study, the efficacies of E1210 and reference antifungals were evaluated in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. Oral E1210 demonstrated dose-dependent efficacy in infections caused by Candida species, Aspergillus spp., and Fusarium solani. In the treatment of oropharyngeal candidiasis, E1210 and fluconazole each caused a significantly greater reduction in the number of oral CFU than the control treatment (P candidiasis model, mice treated with E1210, fluconazole, caspofungin, or liposomal amphotericin B showed significantly higher survival rates than the control mice (P candidiasis caused by azole-resistant Candida albicans or Candida tropicalis. A 24-h delay in treatment onset minimally affected the efficacy outcome of E1210 in the treatment of disseminated candidiasis. In the Aspergillus flavus pulmonary aspergillosis model, mice treated with E1210, voriconazole, or caspofungin showed significantly higher survival rates than the control mice (P candidiasis, pulmonary aspergillosis, and disseminated fusariosis. These data suggest that further studies to determine E1210's potential for the treatment of disseminated fungal infections are indicated. PMID:21788462

  13. Dissemination and genetic support of broad-spectrum beta-lactam-resistant Escherichia coli strain isolated from two Tunisian hospitals during 2004-2012.

    Science.gov (United States)

    Ayari, Khaoula; Bourouis, Amel; Chihi, Hela; Mahrouki, Sihem; Naas, Thierry; Belhadj, Omrane

    2017-06-01

    The dissemination of extended-spectrum β-lactamase (ESBL)-producing bacteria presented a great concern worldwide. Gram-negative organisms such as Escherichia coli and Klebsiella pneumoniae are the most frequently isolated pathogens responsible for nosocomial infections. The aim of this study was to investigate and to follow the emergence of resistance and the characterization of Extended-Spectrum Beta-Lactamases (ESBL) among broad-spectrum beta-lactam- Escherichia coli clinical isolates recovered from the military hospital and Habib Thameur hospital in Tunisia. A total of 113 E.coli isolates obtained during the period 2004 through 2012 showed a significant degree of multi-resistance. Among these strains, the double-disk synergy test confirmed the ESBL phenotype in 46 isolates. These included 32(70%) strains from Hospital A and 14(30%) from Hospital B. The ESBL was identified as CTX-M-15. The ESBL resistance was transferred by a 60 kb plasmid CTXM-15-producing isolates were unrelated according to the PFGE analysis and characterization of the regions surrounding the blaCTX-M-15 showed the ISEcp1 elements located in the upstream region of the bla gene and 20 of them truncated by IS26. ESBL producing E. coli strains are a serious threat in the community in Tunisia and we should take into consideration any possible spread of such epidemiological resistance.

  14. An application in cheddar cheese manufacture for a strain of Lactococcus lactis producing a novel broad-spectrum bacteriocin, lacticin 3147.

    Science.gov (United States)

    Ryan, M P; Rea, M C; Hill, C; Ross, R P

    1996-01-01

    Lactococcus lactis DPC3147, a strain isolated from an Irish kefir grain, produces a bacteriocin with a broad spectrum of inhibition. The bacteriocin produced is heat stable, particularly at a low pH, and inhibits nisin-producing (Nip+) lactococci. On the basis of the observation that the nisin structural gene (nisA) does not hybridize to DPC3147 genomic DNA, the bacteriocin produced was considered novel and designated lacticin 3147. The genetic determinants which encode lacticin 3147 are contained on a 63-kb plasmid, which was conjugally mobilized to a commercial cheese starter, L. lactis subsp. cremoris DPC4268. The resultant transconjugant, DPC4275, both produces and is immune to lacticin 3147. The ability of lacticin 3147-producing lactococci to perform as cheddar cheese starters was subsequently investigated in cheesemaking trials. Bacteriocin-producing starters (which included the transconjugant strain DPC4275) produced acid at rates similar to those of commercial strains. The level of lacticin 3147 produced in cheese remained constant over 6 months of ripening and correlated with a significant reduction in the levels of nonstarter lactic acid bacteria. Such results suggest that these starters provide a means of controlling developing microflora in ripened fermented products. PMID:8593062

  15. CRA-026440: a potent, broad-spectrum, hydroxamic histone deacetylase inhibitor with antiproliferative and antiangiogenic activity in vitro and in vivo.

    Science.gov (United States)

    Cao, Z Alexander; Bass, Kathryn E; Balasubramanian, Sriram; Liu, Liang; Schultz, Brian; Verner, Erik; Dai, Yuqin; Molina, Rafael A; Davis, Jack R; Misialek, Shawn; Sendzik, Martin; Orr, Christine J; Leung, Ling; Callan, Ondine; Young, Peter; Dalrymple, Stacie A; Buggy, Joseph J

    2006-07-01

    CRA-026440 is a novel, broad-spectrum, hydroxamic acid-based inhibitor of histone deacetylase (HDAC) that shows antitumor and antiangiogenic activities in vitro and in vivo preclinically. CRA-026440 inhibited pure recombinant isozymes HDAC1, HDAC2, HDAC3/SMRT, HDAC6, HDAC8, and HDAC10 in the nanomolar range. Treatment of cultured tumor cell lines grown in vitro with CRA-026440 resulted in the accumulation of acetylated histone and acetylated tubulin, leading to an inhibition of tumor cell growth and the induction of apoptosis. CRA-026440 inhibited ex vivo angiogenesis in a dose-dependent manner. CRA-026440 parenterally given to mice harboring HCT116 or U937 human tumor xenografts resulted in a statistically significant reduction in tumor growth. CRA-026440, when used in combination with Avastin, achieved greater preclinical efficacy in HCT 116 colorectal tumor model. Inhibition of tumor growth was accompanied by an increase in the acetylation of alpha-tubulin in peripheral blood mononuclear cells and an alteration in the expression of many genes in the tumors, including several involved in angiogenesis, apoptosis, and cell growth. These results reveal CRA-026440 to be a novel HDAC inhibitor with potent antitumor activity.

  16. A P25/(NH4)xWO3 hybrid photocatalyst with broad spectrum photocatalytic properties under UV, visible, and near-infrared irradiation.

    Science.gov (United States)

    Yang, Linfen; Liu, Bin; Liu, Tongyao; Ma, Xinlong; Li, Hao; Yin, Shu; Sato, Tsugio; Wang, Yuhua

    2017-04-03

    In this study, a series of hybrid nanostructured photocatalysts P25/(NH 4 ) x WO 3 nanocomposites with the average crystallite size of P25 and (NH 4 ) x WO 3 of the sample was calculated to be about 30 nm and 130 nm, were successfully synthesized via a simple one-step hydrothermal method. The as-obtained samples was characterized by transmission electron microscopy (TEM), which implies that the P25/(NH 4 ) x WO 3 nanocomposites are fabricated with favourable nanosizd interfacial. The XPS results confirmed that the obtained sample consists of mixed chemical valences of W 5+ and W 6+ , the low-valance W 5+ sites could be the origin of NIR absorption. As revealed by optical absorption results, P25/(NH 4 ) x WO 3 nanocomposites possess high optical absorption in the whole solar spectrum of 200-2500 nm. Benefiting from this unique photo-absorption property and the synergistic effect of P25 and (NH 4 ) x WO 3 , broad spectrum response photocatalytic activities covering UV, visible and near infrared regions on degradation of Rhodamine B have been realized by P25/(NH 4 ) x WO 3 nanocomposites. Meanwhile, the stability of photocatalysts was examined by the XRD and XPS of the photocatalysts after the reaction. The results show that P25/(NH 4 ) x WO 3 photocatalysts has a brilliant application prospect in the energy utilization to solve deteriorating environmental issues.

  17. Oldest human occupation of Wallacea at Laili Cave, Timor-Leste, shows broad-spectrum foraging responses to late Pleistocene environments

    Science.gov (United States)

    Hawkins, Stuart; O'Connor, Sue; Maloney, Tim Ryan; Litster, Mirani; Kealy, Shimona; Fenner, Jack N.; Aplin, Ken; Boulanger, Clara; Brockwell, Sally; Willan, Richard; Piotto, Elena; Louys, Julien

    2017-09-01

    The Wallacea Archipelago provides an extraordinary laboratory for the study of human colonisation and adaptation, yet few detailed archaeological studies have been conducted in the region that span the earliest phase of human settlement. Laili Cave, in northern Timor-Leste, preserves the oldest human occupation in this insular region with a cultural sequence spanning 11,200 to 44,600 cal BP. Small-bodied vertebrates and invertebrates were recovered to the lowest excavated levels, associated with highly concentrated stone artefacts. We report on human behavioural adaptations within the context of Pleistocene environments and changing landscapes using zooarchaeological, stone artefact, bathymetric, and experimental isotopic analyses. Results indicate that Pleistocene humans used the abundant local chert liberally and engaged in mobile broad-spectrum exploitation of invertebrates and fishes from marine, estuarine, and freshwater environments within close proximity of Laili Cave. The faunal assemblage indicates heterogeneous but relatively stable environments during the late Pleistocene. Variability in subsistence strategies over time appears to be a response to changing landscapes and concomitant local resources. This record contrasts with marine specialisations evident from other sites in Timor-Leste and within the broader Wallacean region.

  18. Varespladib (LY315920 Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation

    Directory of Open Access Journals (Sweden)

    Matthew Lewin

    2016-08-01

    Full Text Available Snakebite remains a neglected medical problem of the developing world with up to 125,000 deaths each year despite more than a century of calls to improve snakebite prevention and care. An estimated 75% of fatalities from snakebite occur outside the hospital setting. Because phospholipase A2 (PLA2 activity is an important component of venom toxicity, we sought candidate PLA2 inhibitors by directly testing drugs. Surprisingly, varespladib and its orally bioavailable prodrug, methyl-varespladib showed high-level secretory PLA2 (sPLA2 inhibition at nanomolar and picomolar concentrations against 28 medically important snake venoms from six continents. In vivo proof-of-concept studies with varespladib had striking survival benefit against lethal doses of Micrurus fulvius and Vipera berus venom, and suppressed venom-induced sPLA2 activity in rats challenged with 100% lethal doses of M. fulvius venom. Rapid development and deployment of a broad-spectrum PLA2 inhibitor alone or in combination with other small molecule inhibitors of snake toxins (e.g., metalloproteases could fill the critical therapeutic gap spanning pre-referral and hospital setting. Lower barriers for clinical testing of safety tested, repurposed small molecule therapeutics are a potentially economical and effective path forward to fill the pre-referral gap in the setting of snakebite.

  19. Sunscreens with broad-spectrum absorption decrease the trans TO cis photoisomerization of urocanic acid in the human stratum corneum after multiple UV light exposures

    International Nuclear Information System (INIS)

    Krien, P.M.; Moyal, D.

    1994-01-01

    The trans to cis photoisomerization of urocanic acid (UCA) in skin is considered to play an important role in the mechanism of immunosuppression. We have investigated the effects of skin type and various sunscreens with low sun protection factor (SPF) on the UV-induced cis-UCA formation in human skin after exposure to artificial UV light. The rate of cis-UCA formation depends little on the skin type and is reduced by topical application of sunscreens. The rate of cis-UCA formation decreases with increasing SPF and only broad-spectrum, highly protective sunscreens offer protection against the UV-induced formation of cis-UCA, which accumulates in the stratum corneum after multiple UV exposures. A theoretical approach to estimate the distribution of cis-UCA after irradiation indicates that this compound may diffuse into the deeper layers of the epidermis with D ∼ 10 -17 m 2 /s, and that its elimination from the stratum corneum is mainly due to desquamation. (author)

  20. Allometric basis of enrofloxacin scaling in green iguanas.

    Science.gov (United States)

    Maxwell, L K; Jacobson, E R

    2008-02-01

    When body size varies greatly, drug disposition can best be described as an allometric function of body weight. Therefore, the allometry of standard metabolic rate (SMR; 3/4 power) and body surface area (BSA; 2/3 power) have been advocated as surrogate markers for the prediction of key pharmacokinetic parameters. The goal of the present study was to examine the allometric basis of pharmacokinetic scaling within a species, green iguanas. Enrofloxacin was administered intravenously to 20 green iguanas (322-3824 g), and noncompartmental analysis was used to calculate standard pharmacokinetic parameters, which were log(10) transformed and regressed against log(10) body weight. The slopes of significant regressions were compared with the values of unity, 3/4, and 2/3. The slope of enrofloxacin total body clearance (Cl) was also compared with the slopes relating SMR and renal Cl of (99m)Tc-diethylenetriamine penta-acetic acid ((99m)DTPA) to body weight in iguanas. Enrofloxacin Cl depended allometrically on body weight with the power of 0.32. The slope of enrofloxacin Cl was significantly less than those of SMR, Cl of (99m)DTPA, and the 2/3 value. Therefore, the relationship between enrofloxacin Cl and body weight does not directly depend on the allometry of BSA, SMR, or renal Cl of (99m)DTPA in iguanas.

  1. Effect of chlorpyrifos and enrofloxacin on selected enzymes in rats.

    Science.gov (United States)

    Barski, D; Spodniewska, A

    2018-03-01

    This study examined the effect of chlorpyrifos and/or enrofloxacin on the activity of acetylcholinesterase (AChE) in the blood and brain, and the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum. The experiment was conducted on Wistar strain rats. Chlorpyrifos was administered with a stomach tube at a dose of 0.04 LD50 for 28 days and enrofloxacin at a dose of 5 mg/kg bw for 5 consecutive days. The experiment found that enrofloxacin changed the activity of the enzymes under study only to a small extent. At the dose applied in the experiment, chlorpyrifos decreased the activity of AChE significantly, both in blood and in the brain, and increased the activity of ALT and AST in rat serum. The administration of chlorpyrifos in combination with enrofloxacin changed the activity of the enzymes under study only slightly. A weaker, but longer, inhibition of AChE activity in both blood and the brain was observed in this group compared to the animals exposed only to chlorpyrifos. However, although enrofloxacin, like chlorpyrifos, increases the activity of ALT and AST in serum, their combined administration did not increase the hepatotoxic effect. Copyright© by the Polish Academy of Sciences.

  2. Enrofloxacin: pharmacokinetics and metabolism in domestic animal species.

    Science.gov (United States)

    López-Cadenas, Cristina; Sierra-Vega, Matilde; García-Vieitez, Juan J; Diez-Liébana, M José; Sahagún-Prieto, Ana; Fernández-Martínez, Nélida

    2013-12-01

    Enrofloxacin is a fluorquinolone exclusively developed for use in veterinary medicine (1980). The kinetics of enrofloxacin are characterized, in general terms, by high bioavailability in most species and rapid absorption after IM, SC or oral administration. However, several studies reported that enrofloxacin showed low bioavailability after oral administration in ruminants. This drug has a broad distribution in the organism, excellent tissue penetration and long serum half-life. Also, enrofloxacin is characterized by a low host toxicity, a broad antibacterial spectrum and high bactericidal activity against major pathogenic bacteria (both Gram-positive and Gram-negative), and intracellular organisms found in diseased animals. The kinetics vary according to the route of administration, formulation, animal species, age, body condition, and physiological status, all of which contribute to differences in drug efficacy. The pharmacokinetic properties of drugs are closely related to their pharmacological efficiency, so it is important to know their behavior in each species that is used. This article reviews the pharmacokinetics of enrofloxacin in several domestic animal species.

  3. Effects on combination of antibiotic-resistant bifidobacteria and corresponding antibiotics of survival of irradiated mice

    International Nuclear Information System (INIS)

    Korshunov, V.M.; Pinegin, B.V.; Ivanova, N.P.; Maltsev, V.N.

    1982-01-01

    Elimination of intestinal dysbacteriosis in irradiated animals by combining antibiotics and peparations of bifidobacteria resistant to these antibiotics prolonging the life of these animals was investigated. Broad spectrum antibiotics are used to treat intestinal dysbacteriosis. Bifidobacterial preparations are used to restore the microbial cenosis and their administration is started after antibiotics are discontinued. There are some flaws to deferred administration of bifidobacteria, since the process of colonization of the intestine with commercial bifidobacterial preparations is rather lengthy, and there is slow elevation of bifidobacterium level in the intestinal tract, whereas exogenous recontamination of the intestine by conditionally pathogenic bacteria is possible after antibiotic therapy is discontinued. Use of antibiotics alone could be the cause of intestinal dysbacteriosis

  4. Degradation of the fluoroquinolone enrofloxacin by electrochemical advanced oxidation processes based on hydrogen peroxide electrogeneration

    Energy Technology Data Exchange (ETDEWEB)

    Guinea, Elena; Garrido, Jose Antonio; Rodriguez, Rosa Maria; Cabot, Pere-Lluis; Arias, Conchita; Centellas, Francesc [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain); Brillas, Enric, E-mail: brillas@ub.ed [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain)

    2010-02-15

    Solutions of the veterinary fluoroquinolone antibiotic enrofloxacin in 0.05 M Na{sub 2}SO{sub 4} of pH 3.0 have been comparatively degraded by electrochemical advanced oxidation processes such as anodic oxidation with electrogenerated H{sub 2}O{sub 2} (AO-H{sub 2}O{sub 2}), electro-Fenton (EF), photoelectro-Fenton (PEF) and solar photoelectro-Fenton (SPEF) at constant current density. The study has been performed using an undivided stirred tank reactor of 100 ml and a batch recirculation flow plant of 2.5 l with an undivided filter-press cell coupled to a solar photoreactor, both equipped with a Pt or boron-doped diamond (BDD) anode and a carbon-polytetrafluoroethylene gas diffusion cathode to generate H{sub 2}O{sub 2} from O{sub 2} reduction. In EF, PEF and SPEF, hydroxyl radical (centre dotOH) is formed from Fenton's reaction between added catalytic Fe{sup 2+} and generated H{sub 2}O{sub 2}. Almost total decontamination of enrofloxacin solutions is achieved in the stirred tank reactor by SPEF with BDD. The use of the batch recirculation flow plant showed that this process is the most efficient and can be viable for industrial application, becoming more economic and yielding higher mineralization degree with raising antibiotic content. This is feasible because organics are quickly oxidized with centre dotOH formed from Fenton's reaction and at BDD from water oxidation, combined with the fast photolysis of complexes of Fe(III) with generated carboxylic acids under solar irradiation. The lower intensity of UVA irradiation used in PEF with BDD causes a slower degradation. EF with BDD is less efficient since centre dotOH cannot destroy the most persistent Fe(III)-oxalate and Fe(III)-oxamate complexes. AO-H{sub 2}O{sub 2} with BDD yields the poorest mineralization because pollutants are only removed with centre dotOH generated at BDD. All procedures are less potent using Pt as anode due to the lower production of centre dotOH at its surface. Enrofloxacin

  5. Degradation of the fluoroquinolone enrofloxacin by electrochemical advanced oxidation processes based on hydrogen peroxide electrogeneration

    International Nuclear Information System (INIS)

    Guinea, Elena; Garrido, Jose Antonio; Rodriguez, Rosa Maria; Cabot, Pere-Lluis; Arias, Conchita; Centellas, Francesc; Brillas, Enric

    2010-01-01

    Solutions of the veterinary fluoroquinolone antibiotic enrofloxacin in 0.05 M Na 2 SO 4 of pH 3.0 have been comparatively degraded by electrochemical advanced oxidation processes such as anodic oxidation with electrogenerated H 2 O 2 (AO-H 2 O 2 ), electro-Fenton (EF), photoelectro-Fenton (PEF) and solar photoelectro-Fenton (SPEF) at constant current density. The study has been performed using an undivided stirred tank reactor of 100 ml and a batch recirculation flow plant of 2.5 l with an undivided filter-press cell coupled to a solar photoreactor, both equipped with a Pt or boron-doped diamond (BDD) anode and a carbon-polytetrafluoroethylene gas diffusion cathode to generate H 2 O 2 from O 2 reduction. In EF, PEF and SPEF, hydroxyl radical (·OH) is formed from Fenton's reaction between added catalytic Fe 2+ and generated H 2 O 2 . Almost total decontamination of enrofloxacin solutions is achieved in the stirred tank reactor by SPEF with BDD. The use of the batch recirculation flow plant showed that this process is the most efficient and can be viable for industrial application, becoming more economic and yielding higher mineralization degree with raising antibiotic content. This is feasible because organics are quickly oxidized with ·OH formed from Fenton's reaction and at BDD from water oxidation, combined with the fast photolysis of complexes of Fe(III) with generated carboxylic acids under solar irradiation. The lower intensity of UVA irradiation used in PEF with BDD causes a slower degradation. EF with BDD is less efficient since ·OH cannot destroy the most persistent Fe(III)-oxalate and Fe(III)-oxamate complexes. AO-H 2 O 2 with BDD yields the poorest mineralization because pollutants are only removed with ·OH generated at BDD. All procedures are less potent using Pt as anode due to the lower production of ·OH at its surface. Enrofloxacin decay always follows a pseudo first-order reaction. Its primary aromatic by-products and short intermediates

  6. Intrapulmonary concentration of enrofloxacin in healthy calves

    Science.gov (United States)

    OTOMARU, Konosuke; HIRATA, Masaya; IKEDO, Tomonobu; HORINOUCHI, Chie; NOGUCHI, Michiko; ISHIKAWA, Shingo; NAGATA, Shun-ichi; HOBO, Seiji

    2015-01-01

    To determine the intrapulmonary concentration of enrofloxacin (ERFX) in calves, plasma, bronchoalveolar lavage fluid (BALF) and alveolar cells samples were obtained from clinically healthy calves. Four clinically healthy calves were administered a single dose of ERFX (5 mg/kg) by subcutaneous injection. Samples of plasma were obtained for each subjects at 0 (before administration), 1 and 2 hr after administration of ERFX. Samples of BALF were obtained from each subject at 0, 1 and 2 hr after administration of ERFX. This examination was conducted two times, one week apart. The mean EFRX concentrations in plasma at 1 and 2 hr after administration were l.23 and 1.29 µg/ml, respectively. The mean EFRX concentrations in pulmonary epithelial lining fluid (ELF) at 1 and 2 hr after administration 8.53 µg/ml and 9.42 µg/ml, respectively. The mean ERFX concentrations of alveolar cells in BALF at 1 and 2 hr after administration were 4.04 µg/ml and 5.19 µg/ml, respectively. These results suggest that the ERFX concentrations in ELF and alveolar cells concentrations in BALF at 1 and 2 hr after administration were higher than the plasma concentrations. PMID:26668174

  7. Clonic Seizures in GAERS Rats after Oral Administration of Enrofloxacin

    Science.gov (United States)

    Bauquier, Sebastien H; Jiang, Jonathan L; Lai, Alan; Cook, Mark J

    2016-01-01

    The aim of this study was to evaluate the effect of oral enrofloxacin on the epileptic status of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Five adult female GAERS rats, with implanted extradural electrodes for EEG monitoring, were declared free of clonic seizures after an 8-wk observation period. Enrofloxacin was then added to their drinking water (42.5 mg in 750 mL), and rats were observed for another 3 days. The number of spike-and-wave discharges and mean duration of a single discharge did not differ before and after treatment, but 2 of the 5 rats developed clonic seizures after treatment. Enrofloxacin should be used with caution in GAERS rats because it might induce clonic seizures. PMID:27298247

  8. Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to Enterobacteriaceae (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial.

    Science.gov (United States)

    López-Cortés, Luis Eduardo; Rosso-Fernández, Clara; Núñez-Núñez, María; Lavín-Alconero, Lucía; Bravo-Ferrer, José; Barriga, Ángel; Delgado, Mercedes; Lupión, Carmen; Retamar, Pilar; Rodríguez-Baño, Jesús

    2017-06-09

    Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable. The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic 'real-practice' trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due to Enterobacteriaceae . The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals. Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals. Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation. The European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov: NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from

  9. Simple detection of residual enrofloxacin in meat products using microparticles and biochips.

    Science.gov (United States)

    Ha, Mi-Sun; Chung, Myung-Sub; Bae, Dong-Ho

    2016-05-01

    A simple and sensitive method for detecting enrofloxacin, a major veterinary fluoroquinolone, was developed. Monoclonal antibody specific for enrofloxacin was immobilised on a chip and fluorescent dye-labelled microparticles were covalently bound to the enrofloxacin molecules. Enrofloxacin in solution competes with the microparticle-immobilised enrofloxacin (enroMPs) to bind to the antibody on the chip. The presence of enrofloxacin was verified by detecting the fluorescence of enrofloxacin-bound microparticles. Under optimum conditions, a high dynamic range was achieved at enrofloxacin concentrations ranging from 1 to 1000 μg kg(-1). The limits of detection and quantification for standard solutions were 5 and 20 μg kg(-1) respectively, which are markedly lower than the maximum residue limit. Using simple extraction methods, recoveries from fortified beef, pork and chicken samples were 43.4-62.3%. This novel method also enabled approximate quantification of enrofloxacin concentration: the enroMP signal intensity decreased with increasing enrofloxacin concentration. Because of its sensitivity, specificity, simplicity and rapidity, the method described herein will facilitate the detection and approximate quantification of enrofloxacin residues in foods in a high-throughput manner.

  10. Tissue distribution of enrofloxacin in African clawed frogs (Xenopus laevis) after intramuscular and subcutaneous administration.

    Science.gov (United States)

    Felt, Stephen; Papich, Mark G; Howard, Antwain; Long, Tyler; McKeon, Gabriel; Torreilles, Stéphanie; Green, Sherril

    2013-03-01

    As part of an enrofloxacin pharmacokinetic study, concentrations of enrofloxacin and ciprofloxacin (metabolite) were measured in various tissues (brain, heart, kidney, liver, lung, and spleen) collected from treated (subcutaneous delivery, n = 3; intramuscular delivery, n = 3; untreated controls, n = 2) adult female Xenopus laevis by using HPLC. Enrofloxacin was rapidly absorbed after administration by either route and readily diffused into all sampled tissues. Enrofloxacin and ciprofloxacin were present in the tissue samples collected at 8 h. The highest average tissue concentrations for enrofloxacin were found in kidney, with the lowest concentrations in liver. Ciprofloxacin tissue concentrations paralleled but were always lower than those of enrofloxacin for all time points and tissues except brain and kidney. These results, together with previously published pharmacokinetic data and known minimal inhibitory concentrations of common pathogenic bacteria, provide a strong evidence-based rationale for choosing enrofloxacin to treat infectious diseases in X. laevis.

  11. A novel blast resistance gene, Pi54rh cloned from wild species of rice, Oryza rhizomatis confers broad spectrum resistance to Magnaporthe oryzae.

    Science.gov (United States)

    Das, Alok; Soubam, D; Singh, P K; Thakur, S; Singh, N K; Sharma, T R

    2012-06-01

    The dominant rice blast resistance gene, Pi54 confers resistance to Magnaporthe oryzae in different parts of India. In our effort to identify more effective forms of this gene, we isolated an orthologue of Pi54 named as Pi54rh from the blast-resistant wild species of rice, Oryza rhizomatis, using allele mining approach and validated by complementation. The Pi54rh belongs to CC-NBS-LRR family of disease resistance genes with a unique Zinc finger (C(3)H type) domain. The 1,447 bp Pi54rh transcript comprises of 101 bp 5'-UTR, 1,083 bp coding region and 263 bp 3'-UTR, driven by pathogen inducible promoter. We showed the extracellular localization of Pi54rh protein and the presence of glycosylation, myristoylation and phosphorylation sites which implicates its role in signal transduction process. This is in contrast to other blast resistance genes that are predicted to be intracellular NBS-LRR-type resistance proteins. The Pi54rh was found to express constitutively at basal level in the leaves, but upregulates 3.8-fold at 96 h post-inoculation with the pathogen. Functional validation of cloned Pi54rh gene using complementation test showed high degree of resistance to seven isolates of M. oryzae collected from different geographical locations of India. In this study, for the first time, we demonstrated that a rice blast resistance gene Pi54rh cloned from wild species of rice provides broad spectrum resistance to M. oryzae hence can be used in rice improvement breeding programme.

  12. Linear biocompatible glyco-polyamidoamines as dual action mode virus infection inhibitors with potential as broad-spectrum microbicides for sexually transmitted diseases

    Science.gov (United States)

    Mauro, Nicolò; Ferruti, Paolo; Ranucci, Elisabetta; Manfredi, Amedea; Berzi, Angela; Clerici, Mario; Cagno, Valeria; Lembo, David; Palmioli, Alessandro; Sattin, Sara

    2016-09-01

    The initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose clusters on the HIV-1 gp120 envelope glycoprotein. Mannosylated glycodendrimers act as HIV entry inhibitors thanks to their ability to block this receptor. Previously, an amphoteric, but prevailingly cationic polyamidoamine named AGMA1 proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such as human papilloma virus HPV-16 and herpes simplex virus HSV-2. An amphoteric, but prevailingly anionic PAA named ISA23 proved inactive. It was speculated that the substitution of mannosylated units for a limited percentage of AGMA1 repeating units, while imparting anti-HIV activity, would preserve the fundamentals of its HPV-16 and HSV-2 infection inhibitory activity. In this work, four biocompatible linear PAAs carrying different amounts of mannosyl-triazolyl pendants, Man-ISA7, Man-ISA14, Man-AGMA6.5 and Man-AGMA14.5, were prepared by reaction of 2-(azidoethyl)-α-D-mannopyranoside and differently propargyl-substituted AGMA1 and ISA23. All mannosylated PAAs inhibited HIV infection. Both Man-AGMA6.5 and Man-AGMA14.5 maintained the HPV-16 and HSV-2 activity of the parent polymer, proving broad-spectrum, dual action mode virus infection inhibitors.

  13. Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases.

    Science.gov (United States)

    Chuck, Chi-Pang; Chen, Chao; Ke, Zhihai; Wan, David Chi-Cheong; Chow, Hak-Fun; Wong, Kam-Bo

    2013-01-01

    Coronaviral infection is associated with up to 5% of respiratory tract diseases. The 3C-like protease (3CL(pro)) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection. We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CL(pro) of severe-acute-respiratory-syndrome-coronavirus. The IC(50) values of the inhibitors were in the range of 4.6-49 μM, demonstrating that the nitrile warhead can effectively inactivate the 3CL(pro) autocleavage process. The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was ~10x more potent than the other inhibitors tested. Crystal structures of the enzyme-inhibitor complexes showed that the nitrile warhead inhibits 3CL(pro) by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1-S4 substrate-binding pockets. We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broad-spectrum inhibition against 3CL(pro) from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC(50) values ranging from 1.3 to 3.7 μM, but no detectable inhibition against caspase-3. In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CL(pro), and they inhibit 3CL(pro) from a broad range of coronaviruses. Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  14. Induction of a peptide with activity against a broad spectrum of pathogens in the Aedes aegypti salivary gland, following Infection with Dengue Virus.

    Directory of Open Access Journals (Sweden)

    Natthanej Luplertlop

    2011-01-01

    Full Text Available The ultimate stage of the transmission of Dengue Virus (DENV to man is strongly dependent on crosstalk between the virus and the immune system of its vector Aedes aegypti (Ae. aegypti. Infection of the mosquito's salivary glands by DENV is the final step prior to viral transmission. Therefore, in the present study, we have determined the modulatory effects of DENV infection on the immune response in this organ by carrying out a functional genomic analysis of uninfected salivary glands and salivary glands of female Ae. aegypti mosquitoes infected with DENV. We have shown that DENV infection of salivary glands strongly up-regulates the expression of genes that encode proteins involved in the vector's innate immune response, including the immune deficiency (IMD and Toll signalling pathways, and that it induces the expression of the gene encoding a putative anti-bacterial, cecropin-like, peptide (AAEL000598. Both the chemically synthesized non-cleaved, signal peptide-containing gene product of AAEL000598, and the cleaved, mature form, were found to exert, in addition to antibacterial activity, anti-DENV and anti-Chikungunya viral activity. However, in contrast to the mature form, the immature cecropin peptide was far more effective against Chikungunya virus (CHIKV and, furthermore, had strong anti-parasite activity as shown by its ability to kill Leishmania spp. Results from circular dichroism analysis showed that the immature form more readily adopts a helical conformation which would help it to cause membrane permeabilization, thus permitting its transfer across hydrophobic cell surfaces, which may explain the difference in the anti-pathogenic activity between the two forms. The present study underscores not only the importance of DENV-induced cecropin in the innate immune response of Ae. aegypti, but also emphasizes the broad-spectrum anti-pathogenic activity of the immature, signal peptide-containing form of this peptide.

  15. Molecular characterisation of the broad-spectrum resistance to powdery mildew conferred by the Stpk-V gene from the wild species Haynaldia villosa.

    Science.gov (United States)

    Qian, C; Cui, C; Wang, X; Zhou, C; Hu, P; Li, M; Li, R; Xiao, J; Wang, X; Chen, P; Xing, L; Cao, A

    2017-11-01

    A key member of the Pm21 resistance gene locus, Stpk-V, derived from Haynaldia villosa, was shown to confer broad-spectrum resistance to wheat powdery mildew. The present study was planned to investigate the resistance mechanism mediated by Stpk-V. Transcriptome analysis was performed in Stpk-V transgenic plants and recipient Yangmai158 upon Bgt infection, and detailed histochemical observations were conducted. Chromosome location of Stpk-V orthologous genes in Triticeae species was conducted for evolutionary study and over-expression of Stpk-V both in barley and Arabidopsis was performed for functional study. The transcriptome results indicate, at the early infection stage, the ROS pathway, JA pathway and some PR proteins associated with the SA pathway were activated in both the resistant Stpk-V transgenic plants and susceptible Yangmai158. However, at the later infection stage, the genes up-regulated at the early stage were continuously held only in the transgenic plants, and a large number of new genes were also activated in the transgenic plants but not in Yangmai158. Results indicate that sustained activation of the early response genes combined with later-activated genes mediated by Stpk-V is critical for resistance in Stpk-V transgenic plants. Stpk-V orthologous genes in the representative grass species are all located on homologous group six chromosomes, indicating that Stpk-V is an ancient gene in the grasses. Over-expression of Stpk-V enhanced host resistance to powdery mildew in barley but not in Arabidopsis. Our results enable a better understanding of the resistance mechanism mediated by Stpk-V, and establish a solid foundation for its use in cereal breeding as a gene resource. © 2017 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.

  16. Phosphatase Inhibitors Function as Novel, Broad Spectrum Botulinum Neurotoxin Antagonists in Mouse and Human Embryonic Stem Cell-Derived Motor Neuron-Based Assays.

    Directory of Open Access Journals (Sweden)

    Erkan Kiris

    Full Text Available There is an urgent need to develop novel treatments to counter Botulinum neurotoxin (BoNT poisoning. Currently, the majority of BoNT drug development efforts focus on directly inhibiting the proteolytic components of BoNT, i.e. light chains (LC. Although this is a rational approach, previous research has shown that LCs are extremely difficult drug targets and that inhibiting multi-serotype BoNTs with a single LC inhibitor may not be feasible. An alternative approach would target neuronal pathways involved in intoxication/recovery, rather than the LC itself. Phosphorylation-related mechanisms have been implicated in the intoxication pathway(s of BoNTs. However, the effects of phosphatase inhibitors upon BoNT activity in the physiological target of BoNTs, i.e. motor neurons, have not been investigated. In this study, a small library of phosphatase inhibitors was screened for BoNT antagonism in the context of mouse embryonic stem cell-derived motor neurons (ES-MNs. Four inhibitors were found to function as BoNT/A antagonists. Subsequently, we confirmed that these inhibitors protect against BoNT/A in a dose-dependent manner in human ES-MNs. Additionally, these compounds provide protection when administered in post-intoxication scenario. Importantly, the inhibitors were also effective against BoNT serotypes B and E. To the best of our knowledge, this is the first study showing phosphatase inhibitors as broad-spectrum BoNT antagonists.

  17. Evaluation of Novel Antimicrobial Peptides as Topical Anti-Infectives with Broad Spectrum Activity Against Combat-Related Bacterial and Fungal Wound Infections

    Science.gov (United States)

    2016-10-01

    Inc. Vallejo, CA 94592 REPORT DATE: October 2016 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort...2016 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2015 - 29 Sep 2016 4. TITLE AND SUBTITLE Evaluation of Novel Antimicrobial Peptides as Topical...antibiotics and early debridement has been associated with a large reduction in burn wound infections. Current topical antibiotics include

  18. Antibiotic prescribing in dental practice in Belgium.

    Science.gov (United States)

    Mainjot, A; D'Hoore, W; Vanheusden, A; Van Nieuwenhuysen, J-P

    2009-12-01

    To assess the types and frequency of antibiotic prescriptions by Belgian dentists, the indications for antibiotic prescription, and dentists' knowledge about recommended practice in antibiotic use. In this cross-sectional survey, dental practitioners were asked to record information about all antibiotics prescribed to their patients during a 2-week period. The dental practitioners were also asked to complete a self-administered questionnaire regarding demographic data, prescribing practices, and knowledge about antibiotic use. A random sample of 268 Belgian dentists participated in the survey. During the 2-week period, 24 421 patient encounters were recorded; 1033 patients were prescribed an antibiotic (4.2%). The median number of prescriptions per dentist for the 2 weeks was 3. Broad spectrum antibiotics were most commonly prescribed: 82% of all prescriptions were for amoxycillin, amoxycillin-clavulanic acid and clindamycin. Antibiotics were often prescribed in the absence of fever (92.2%) and without any local treatment (54.2%). The most frequent diagnosis for which antibiotics were prescribed was periapical abscess (51.9%). Antibiotics were prescribed to 63.3% of patients with periapical abscess and 4.3% of patients with pulpitis. Patterns of prescriptions were confirmed by the data from the self-reported practice. Discrepancies between observed and recommended practice support the need for educational initiatives to promote rational use of antibiotics in dentistry in Belgium.

  19. Stability and Activities of Antibiotics Produced during Infection of the Insect Galleria mellonella by Two Isolates of Xenorhabdus nematophilus

    OpenAIRE

    Maxwell, Philip W.; Chen, Genhui; Webster, John M.; Dunphy, Gary B.

    1994-01-01

    Xenorhabdus nematophilus subsp. dutki, an entomopathogenic bacterium, is vectored by steinernematid nematodes into insects, where it produces broad-spectrum antibiotics. The use of the nematode-bacterium complex against soil-dwelling pest insects could introduce antibiotics into the soil via the dead insect fragments during the emergence phase of the nematodes. Studies on the stability and activities of these antibiotics produced in the insect Galleria mellonella may contribute to assessing t...

  20. Stop Antibiotics on guidance of Procalcitonin Study (SAPS) : a randomised prospective multicenter investigator-initiated trial to analyse whether daily measurements of procalcitonin versus a standard-of-care approach can safely shorten antibiotic duration in intensive care unit patients - calculated sample size: 1816 patients

    NARCIS (Netherlands)

    Assink-de Jong, Evelien; de lange, Dylan W.; van Oers, Jos A.; Nijsten, Maarten W.; Twisk, Jos W.; Beishuizen, Albertus

    2013-01-01

    Background: Unnecessary long-term use of broad-spectrum antibiotics is linked to the emergence and selection of resistant bacteria, prolonged hospitalisation and increased costs. Several clinical trials indicate that the biomarker procalcitonin (PCT) can guide antibiotic therapy. Some of these

  1. Stop Antibiotics on guidance of Procalcitonin Study (SAPS): a randomised prospective multicenter investigator-initiated trial to analyse whether daily measurements of procalcitonin versus a standard-of-care approach can safely shorten antibiotic duration in intensive care unit patients - calculated sample size: 1816 patients

    NARCIS (Netherlands)

    Assink-de Jong, E.; De Lange, D.W.; van Oers, J.A.; Nijsten, M.W.; Twisk, J.W.R.; Beishuizen, A.

    2013-01-01

    Background: Unnecessary long-term use of broad-spectrum antibiotics is linked to the emergence and selection of resistant bacteria, prolonged hospitalisation and increased costs. Several clinical trials indicate that the biomarker procalcitonin (PCT) can guide antibiotic therapy. Some of these

  2. Use of antibiotics in childhood and risk of Type 1 diabetes

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian Hallundbæk; Knop, F K; Lauritsen, Tina Vilsbøll

    2017-01-01

    or bacteriostatic types of antibiotics or for the most frequently used individual classes of antibiotics. No differences were observed in subgroups defined by sex or by age at time of diagnosis. However, filling five or more antibiotic prescriptions in the first 2 years of life specifically was associated...... with a higher odds ratio of 1.35 (95% CI 1.10-1.64). This association appeared to be driven by exposure to broad-spectrum antibiotics within the second year of life. CONCLUSION: Antibiotic exposure in childhood is generally not associated with the risk of developing Type 1 diabetes. Future studies should...

  3. In vitro antibiotic susceptibility of Mycoplasma iguanae proposed sp. nov. isolated from vertebral lesions of green iguanas (Iguana iguana).

    Science.gov (United States)

    Westfall, Megan E; Demcovitz, Dina L; Plourdé, Daisy R; Rotstein, David S; Brown, Daniel R

    2006-06-01

    Mycoplasma iguanae proposed species nova was isolated from vertebral abscesses of two feral iguanas (Iguana iguana) from Florida. Three strains were evaluated for sensitivity to a variety of antibiotics. The minimum inhibitory concentrations for M. iguanae, assessed by broth dilution methods, of clindamycin, doxycycline, enrofloxacin, oxytetracycline, and tylosin (all doxycycline, oxytetracycline, and tylosin were bacteriostatic from 0.1 to 0.5 microg/ml, whereas enrofloxacin was bactericidal at 20 ng/ml. An enrofloxacin dosage of 5-10 mg/kg achieves peak plasma concentrations >1 microg/ml, with an elimination half-life of 6-20 hr, in alligators. Although concentrations achieved in the vertebrae by i.m. or i.v. injection are probably lower than those in plasma, these data suggest that enrofloxacin may be useful to treat M. iguanae mycoplasmosis in iguanas.

  4. Effect of cooking on enrofloxacin residues in chicken tissue.

    Science.gov (United States)

    Lolo, M; Pedreira, S; Miranda, J M; Vázquez, B I; Franco, C M; Cepeda, A; Fente, C

    2006-10-01

    The aim of this study was to determine the effect of different cooking processes (microwaving, roasting, boiling, grilling and frying) on naturally incurred enrofloxacin residues in chicken muscle. Enrofloxacin and its metabolite, ciprofloxacin, were analysed using a validated LC-MS method with limits of detection (LOD) and quantification (LOQ), respectively, of 2 and 5 ng g-1 quinolones in muscle samples. The method was shown to be linear over the range 5-500 ng g-1. Mean intra-day relative standard deviation (RSD) at a concentration of 50 ng g-1 (n = 6) was 6%; inter-day RSD was 12%. A recovery study demonstrated that 65-101%, of the drug and metabolite could be recovered from the tissue. The RSD with naturally incurred roasted chicken breast was 9.18% at a concentration of 11 +/- 1.01 ng g-1 (n = 6). In water, enrofloxacin remained stable for 3 h when heated at 100 degrees C. It was concluded that residue data from raw tissue are valid for estimation of consumer exposure to this drug, as well as the ADI calculations because cooking procedures did not affect enrofloxacin residues, which remained stable during heating. However, there was an apparent decrease in quinolone concentration in tissue because some was lost by exudation into the liquid used for cooking. Conversely, for a cooking procedure with water loss, there was an apparent increase in residue concentration.

  5. Synthetic membrane-targeted antibiotics.

    Science.gov (United States)

    Vooturi, S K; Firestine, S M

    2010-01-01

    Antimicrobial resistance continues to evolve and presents serious challenges in the therapy of both nosocomial and community-acquired infections. The rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant enterococci (VRE) suggests that antimicrobial resistance is an inevitable evolutionary response to antimicrobial use. This highlights the tremendous need for antibiotics against new bacterial targets. Agents that target the integrity of bacterial membrane are relatively novel in the clinical armamentarium. Daptomycin, a lipopeptide is a classical example of membrane-bound antibiotic. Nature has also utilized this tactic. Antimicrobial peptides (AMPs), which are found in all kingdoms, function primarily by permeabilizing the bacterial membrane. AMPs have several advantages over existing antibiotics including a broad spectrum of activity, rapid bactericidal activity, no cross-resistance with the existing antibiotics and a low probability for developing resistance. Currently, a small number of peptides have been developed for clinical use but therapeutic applications are limited because of poor bioavailability and high manufacturing cost. However, their broad specificity, potent activity and lower probability for resistance have spurred the search for synthetic mimetics of antimicrobial peptides as membrane-active antibiotics. In this review, we will discuss the different classes of synthetic membrane-bound antibiotics published since 2004.

  6. Synthesis, Characterization, and In Vitro and In Vivo Evaluations of 4-(N-Docosahexaenoyl 2′, 2′-Difluorodeoxycytidine with Potent and Broad-Spectrum Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Youssef W. Naguib

    2016-01-01

    Full Text Available In this study, a new compound, 4-(N-docosahexaenoyl 2′, 2′-difluorodeoxycytidine (DHA-dFdC, was synthesized and characterized. Its antitumor activity was evaluated in cell culture and in mouse models of pancreatic cancer. DHA-dFdC is a poorly soluble, pale yellow waxy solid, with a molecular mass of 573.3 Da and a melting point of about 96°C. The activation energy for the degradation of DHA-dFdC in an aqueous Tween 80–based solution is 12.86 kcal/mol, whereas its stability is significantly higher in the presence of vitamin E. NCI-60 DTP Human Tumor Cell Line Screening revealed that DHA-dFdC has potent and broad-spectrum antitumor activity, especially in leukemia, renal, and central nervous system cancer cell lines. In human and murine pancreatic cancer cell lines, the IC50 value of DHA-dFdC was up to 105-fold lower than that of dFdC. The elimination of DHA-dFdC in mouse plasma appeared to follow a biexponential model, with a terminal phase t1/2 of about 58 minutes. DHA-dFdC significantly extended the survival of genetically engineered mice that spontaneously develop pancreatic ductal adenocarcinoma. In nude mice with subcutaneously implanted human Panc-1 pancreatic tumors, the antitumor activity of DHA-dFdC was significantly stronger than the molar equivalent of dFdC alone, DHA alone, or the physical mixture of them (1:1, molar ratio. DHA-dFdC also significantly inhibited the growth of Panc-1 tumors orthotopically implanted in the pancreas of nude mice, whereas the molar equivalent dose of dFdC alone did not show any significant activity. DHA-dFdC is a promising compound for the potential treatment of cancers in organs such as the pancreas.

  7. Elimination of Pasteurella pneumotropica from a Mouse Barrier Facility by Using a Modified Enrofloxacin Treatment Regimen

    Science.gov (United States)

    Towne, Justin W; Wagner, April M; Griffin, Kurt J; Buntzman, Adam S; Frelinger, Jeffrey A; Besselsen, David G

    2014-01-01

    Multiple NOD.Cg-Prkdcscid Il2rgtm1WjlTg(HLA-A2.1)Enge/Sz (NSG/A2) transgenic mice maintained in a mouse barrier facility were submitted for necropsy to determine the cause of facial alopecia, tachypnea, dyspnea, and sudden death. Pneumonia and soft-tissue abscesses were observed, and Pasteurella pneumotropica biotype Jawetz was consistently isolated from the upper respiratory tract, lung, and abscesses. Epidemiologic investigation within the facility revealed presence of this pathogen in mice generated or rederived by the intramural Genetically Engineered Mouse Model (GEMM) Core but not in mice procured from several approved commercial vendors. Epidemiologic data suggested the infection originated from female or vasectomized male ND4 mice obtained from a commercial vendor and then comingled by the GEMM Core to induce pseudopregnancy in female mice for embryo implantation. Enrofloxacin delivered in drinking water (85 mg/kg body weight daily) for 14 d was sufficient to clear bacterial infection in normal, breeding, and immune-deficient mice without the need to change the antibiotic water source. This modified treatment regimen was administered to 2400 cages of mice to eradicate Pasteurella pneumotropica from the facility. Follow-up PCR testing for P. pneumotropica biotype Jawetz remained uniformly negative at 2, 6, 12, and 52 wk after treatment in multiple strains of mice that were originally infected. Together, these data indicate that enrofloxacin can eradicate P. pneumotropica from infected mice in a less labor-intensive approach that does not require breeding cessation and that is easily adaptable to the standard biweekly cage change schedule for individually ventilated cages. PMID:25255075

  8. Elimination of Pasteurella pneumotropica from a mouse barrier facility by using a modified enrofloxacin treatment regimen.

    Science.gov (United States)

    Towne, Justin W; Wagner, April M; Griffin, Kurt J; Buntzman, Adam S; Frelinger, Jeffrey A; Besselsen, David G

    2014-09-01

    Multiple NOD. Cg-Prkdc(scid)Il2rg(tm1Wjl)Tg(HLA-A2.1)Enge/Sz (NSG/A2) transgenic mice maintained in a mouse barrier facility were submitted for necropsy to determine the cause of facial alopecia, tachypnea, dyspnea, and sudden death. Pneumonia and soft-tissue abscesses were observed, and Pasteurella pneumotropica biotype Jawetz was consistently isolated from the upper respiratory tract, lung, and abscesses. Epidemiologic investigation within the facility revealed presence of this pathogen in mice generated or rederived by the intramural Genetically Engineered Mouse Model (GEMM) Core but not in mice procured from several approved commercial vendors. Epidemiologic data suggested the infection originated from female or vasectomized male ND4 mice obtained from a commercial vendor and then comingled by the GEMM Core to induce pseudopregnancy in female mice for embryo implantation. Enrofloxacin delivered in drinking water (85 mg/kg body weight daily) for 14 d was sufficient to clear bacterial infection in normal, breeding, and immune-deficient mice without the need to change the antibiotic water source. This modified treatment regimen was administered to 2400 cages of mice to eradicate Pasteurella pneumotropica from the facility. Follow-up PCR testing for P. pneumotropica biotype Jawetz remained uniformly negative at 2, 6, 12, and 52 wk after treatment in multiple strains of mice that were originally infected. Together, these data indicate that enrofloxacin can eradicate P. pneumotropica from infected mice in a less labor-intensive approach that does not require breeding cessation and that is easily adaptable to the standard biweekly cage change schedule for individually ventilated cages.

  9. Development of a highly sensitive and specific immunoassay for enrofloxacin based on heterologous coating haptens.

    Science.gov (United States)

    Wang, Zhanhui; Zhang, Huiyan; Ni, Hengjia; Zhang, Suxia; Shen, Jianzhong

    2014-04-11

    In the paper, an enzyme-linked immunosorbent immunoassay (ELISA) for detection of enrofloxacin was described using one new derivative of enrofloxacin as coating hapten, resulting in surprisingly high sensitivity and specificity. Incorporation of aminobutyric acid (AA) in the new derivative of enrofloxacin had decreased the IC50 of the ELISA for enrofloxacin from 1.3 μg L(-1) to as low as 0.07 μg L(-1). The assay showed neglect cross-reactivity for other fluoroquinolones but ofloxacin (8.23%), marbofloxacin (8.97%) and pefloxacin (7.29%). Analysis of enrofloxacin fortified chicken muscle showed average recoveries from 81 to 115%. The high sensitivity and specificity of the assay makes it a suitable screening method for the determination of low levels of enrofloxacin in chicken muscle without clean-up step. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Evaluation of ameliorative potential of supranutritional selenium on enrofloxacin-induced testicular toxicity.

    Science.gov (United States)

    Rungsung, Soya; Khan, Adil Mehraj; Sood, Naresh Kumar; Rampal, Satyavan; Singh Saini, Simrat Pal

    2016-05-25

    The study was designed to assess the ameliorative potential of selenium (Se) on enrofloxacin-induced testicular toxicity in rats. There was a significant decrease in body weight and non-significant decrease in mean testicular weight of enrofloxacin treated rats. In enrofloxacin treated rats, total sperm count and viability decreased where as sperm abnormalities increased. Testicular histopathology revealed dose dependent dysregulation of spermatogenesis and presence of necrotic debris in seminiferous tubules which was marginally improved with Se. Enrofloxacin also produced a dose dependent decrease in testosterone level. The activity of testicular antioxidant enzymes decreased where as lipid peroxidation increased in a dose-dependent manner. Se supplementation partially restored oxidative stress and sperm damage and did not affect the plasma concentrations of enrofloxacin or ciprofloxacain. The results indicate that enrofloxacin produces a dose-dependent testicular toxicity in rats that is moderately ameliorated with supranutritional Se. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Oxidation of ciprofloxacin and enrofloxacin by ferrate(VI): Products identification, and toxicity evaluation

    International Nuclear Information System (INIS)

    Yang, Bin; Kookana, Rai S.; Williams, Mike; Ying, Guang-Guo; Du, Jun; Doan, Hai; Kumar, Anupama

    2016-01-01

    Ferrate(VI) (Fe(VI)) has been known to react with emerging organic contaminants containing electron-rich organic moieties, such as phenols, anilines, olefins, reduced sulfur and deprotonated amines. Oxidation of fluoroquinolone antibiotics, ciprofloxacin (CIP) and enrofloxacin (ENR), by Fe(VI) were investigated for their reaction products and toxicity changes as well as biodegradability of these products. Ten products were identified for both CIP and ENR reactions with Fe(VI) using a high-resolution accurate-mass Orbitrap mass analyzer. Structural changes to the CIP and ENR molecule included dealkylation, formation of alcohols and amides in piperazine ring and oxygen transfer to the double bond in quinolone structure. An enamine formation mechanism was tentatively proposed to facilitate the interpretation of CIP and ENR oxidation pathways. Toxicity evaluation using Microbial Assay for toxicity Risk Assessment (MARA) bioassay indicated that Fe(VI) oxidation products of CIP and ENR contributed negligible antibacterial potency and Fe(VI) oxidation treatment can remove the residual toxicity of CIP and ENR impacted source waters. The Fe(VI) oxidation treatment resulted in formation of relatively more biodegradable products (based on in silico assessment) than their corresponding parent compounds. The results showed that Fe(VI) has a good potential to degrade fluoroquinolone antibiotics and their antimicrobial potency in natural waters.

  12. Oxidation of ciprofloxacin and enrofloxacin by ferrate(VI): Products identification, and toxicity evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Bin, E-mail: Bin.Yang@csiro.au [CSIRO Land and Water, Waite Campus, PMB 2, Glen Osmond, South Australia 5064 (Australia); Kookana, Rai S.; Williams, Mike [CSIRO Land and Water, Waite Campus, PMB 2, Glen Osmond, South Australia 5064 (Australia); Ying, Guang-Guo [State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Du, Jun; Doan, Hai; Kumar, Anupama [CSIRO Land and Water, Waite Campus, PMB 2, Glen Osmond, South Australia 5064 (Australia)

    2016-12-15

    Ferrate(VI) (Fe(VI)) has been known to react with emerging organic contaminants containing electron-rich organic moieties, such as phenols, anilines, olefins, reduced sulfur and deprotonated amines. Oxidation of fluoroquinolone antibiotics, ciprofloxacin (CIP) and enrofloxacin (ENR), by Fe(VI) were investigated for their reaction products and toxicity changes as well as biodegradability of these products. Ten products were identified for both CIP and ENR reactions with Fe(VI) using a high-resolution accurate-mass Orbitrap mass analyzer. Structural changes to the CIP and ENR molecule included dealkylation, formation of alcohols and amides in piperazine ring and oxygen transfer to the double bond in quinolone structure. An enamine formation mechanism was tentatively proposed to facilitate the interpretation of CIP and ENR oxidation pathways. Toxicity evaluation using Microbial Assay for toxicity Risk Assessment (MARA) bioassay indicated that Fe(VI) oxidation products of CIP and ENR contributed negligible antibacterial potency and Fe(VI) oxidation treatment can remove the residual toxicity of CIP and ENR impacted source waters. The Fe(VI) oxidation treatment resulted in formation of relatively more biodegradable products (based on in silico assessment) than their corresponding parent compounds. The results showed that Fe(VI) has a good potential to degrade fluoroquinolone antibiotics and their antimicrobial potency in natural waters.

  13. Adsorption of enrofloxacin in presence of Zn(II) on a calcareous soil.

    Science.gov (United States)

    Graouer-Bacart, Mareen; Sayen, Stéphanie; Guillon, Emmanuel

    2015-12-01

    As a result of their consumption, excretion, disposal and persistence, antibiotics enter the soil environment and may be transported to surface and ground waters. During their transfer through soils, retention processes play a key role in their mobility. Antibiotics often coexist with heavy metals in soils due to agricultural practices and other sources of inputs. In this context, this study deals with the co-adsorption of Zn(II) and enrofloxacin (ENR), a widely-used veterinary antibiotic, on a calcareous soil using batch retention experiments and X-ray Absorption Near Edge Structure (XANES) spectroscopy. To improve our understanding of the interaction of this emerging organic contaminant with metal cations at the water-soil interface, the ternary system containing ENR, Zn(II) and a selected calcareous soil was investigated over a pH range between 7 and 10, at different solid-solution contact times and ENR concentrations. The presence of Zn(II) slightly influenced the retention of the antibiotic, leading to an increase of the adsorbed ENR amounts. The distribution coefficient Kd value increased from 0.66 Lg(-1) for single ENR adsorption to 1.04 Lg(-1) in presence of Zn(II) at a 1/2 ENR/Zn(II) ratio. The combination of adsorption isotherm data, solution speciation diagrams and XANES spectra evidenced a small proportion of Zn(II)-ENR complexes at soil pH leading to the slight increase of ENR adsorption in presence of zinc. These results suggest that it is necessary to consider the interaction between ENR and metal cations when assessing the mobility of ENR in soils. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Antibiotic-Induced Gut Microbiota Disruption Decreases TNF-α Release by Mononuclear Cells in Healthy Adults

    NARCIS (Netherlands)

    Lankelma, Jacqueline M.; Belzer, Clara; Hoogendijk, Arie J.; Vos, de Alex F.; Vos, de Willem M.; Poll, van der Tom; Wiersinga, W.J.

    2016-01-01

    Objectives:Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however,

  15. Pollution characteristics and environmental risk assessment of typical veterinary antibiotics in livestock farms in Southeastern China.

    Science.gov (United States)

    Wang, Na; Guo, Xinyan; Xu, Jing; Kong, Xiangji; Gao, Shixiang; Shan, Zhengjun

    2014-01-01

    Scientific interest in pollution from antibiotics in animal husbandry has increased during recent years. However, there have been few studies on the vertical exposure characteristics of typical veterinary antibiotics in different exposure matrices from different livestock farms. This study explores the distribution and migration of antibiotics from feed to manure, from manure to soil, and from soil to vegetables, by investigating the exposure level of typical antibiotics in feed, manure, soil, vegetables, water, fish, and pork in livestock farms. A screening environmental risk assessment was conducted to identify the hazardous potential of veterinary antibiotics from livestock farms in southeast China. The results show that adding antibiotics to drinking water as well as the excessive use of antibiotic feed additives may become the major source of antibiotics pollution in livestock farms. Physical and chemical properties significantly affect the distribution and migration of various antibiotics from manure to soil and from soil to plant. Simple migration models can predict the accumulation of antibiotics in soil and plants. The environmental risk assessment results show that more attention should be paid to the terrestrial eco-risk of sulfadiazine, sulfamethazine, sulfamethoxazole, tetracycline, oxytetracycline, chlorotetracycline, ciprofloxacin, and enrofloxacin, and to the aquatic eco-risk of chlorotetracycline, ciprofloxacin, and enrofloxacin. This is the first systematic analysis of the vertical pollution characteristics of typical veterinary antibiotics in livestock farms in southeast China. It also identifies the ecological and human health risk of veterinary antibiotics.

  16. Compliance with Recommendations on Outpatient Antibiotic Prescribing for Respiratory Tract Infections

    DEFF Research Database (Denmark)

    Malo, Sara; Bjerrum, Lars; Feja, Cristina

    2015-01-01

    Inappropriate antibiotic use in primary care, such as in Respiratory Tract Infections (RTIs), is an important cause of bacterial resistance. This study aimed at describing the current pattern of outpatient antibiotic use in acute RTIs in Spain and evaluating adherence to national recommendations......%), whereas low rates were found in acute bronchitis (50%) and non-specific upper RTIs (24%) episodes. A high prescription of broad-spectrum agents and antibiotics not recommended as first choice was observed. In accordance with Spanish guidelines, there exists a potential over-prescribing of antibiotics...

  17. Grievances in cases using antibiotics due to orodental problems and assessment of the need for antibiotics.

    Science.gov (United States)

    Kandemir, S; Ergül, N

    2000-04-01

    To assess the complaints of patients who were prescribed antibiotics following orodental problems and the need for antibiotics prescribed for this purpose. Examinations were carried out in the Department of Oral Diagnosis and Radiology, Ege University, Turkey. A total of 203 patients (129 females and 74 males) between 8-70 years of age (mean age 37.7 +/- 13.9). Examination and report. Frequency of unnecessary antibiotic use. Antibiotic therapy was not necessary for 151 (74.4 per cent) cases. Antibiotics were unnecessarily prescribed in 45 cases of acute irreversible pulpitis, 10 chronic apical abscess, 6 acute apical paradontitis, 7 gingivitis, 10 periodontitis, 4 epulis, 2 TMJ (temporomandibular junction) dysfunction, 2 sharp ridge of alveolar bone, 1 burning mouth syndrome and 1 recurrent aphthous stomatitis. In 108 (53.2 per cent) of the cases, the prescribed antibiotics were found to be penicillins, 102 of which were broad-spectrum. It was also determined that only 6 (7.7 per cent) of the 78 cases diagnosed as acute apical abscess were given drainage as local therapy. Principles for treating dental infections suggest that an antibiotic should only be used to supplement and not substitute for conventional surgical methods. Therefore, in cases with acute apical abscess, mechanical treatment (drainage) should be the first step. Inappropriate antibiotic use is quite widespread in dentistry. Dentists should avoid inappropriate use of antibiotics. To prevent inappropriate administration, necessary precautions need to be taken against dispensing antibiotics without prescription.

  18. MRJP1-containing glycoproteins isolated from honey, a novel antibacterial drug candidate with broad spectrum activity against multi-drug resistant clinical isolates

    Directory of Open Access Journals (Sweden)

    Katrina eBrudzynski

    2015-07-01

    Full Text Available The emergence of extended- spectrum β-lactamase (ESBL is the underlying cause of growing antibiotic resistance among Gram-negative bacteria to β-lactam antibiotics. We recently reported the discovery of honey glycoproteins (glps that exhibited a rapid, concentration-dependent antibacterial activity against both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli that resembled action of cell wall-active β-lactam drugs. Glps showed sequence identity with the Major Royal Jelly Protein 1 (MRJP1 precursor that harbors three antimicrobial peptides: Jelleins 1, 2 and 4. Here, we used semi-quantitative radial diffusion assay and broth microdilution assay to evaluate susceptibility of a number of multi-drug resistant (MDR clinical isolates to the MRJP1-contaning honey glycoproteins. The MDR bacterial strains comprised 3 MRSA, 4 Pseudomonas aeruginosa, 2 Klebsiella pneumoniae, 2 VRE and 5 Extended-spectrum beta-lactamase (ESBL identified as 1 Proteus mirabilis, 3 Escherichia coli and 1 Escherichia coli NDM. Their resistance to different classes of antibiotics was confirmed using automated system Vitek 2. MDR isolates differred in their susceptibility to glps with MIC90 values ranging from 4.8μg/ml against B. subtilis to 14.4μg/ml against ESBL K. pneumoniae, Klebsiella spp ESBL and E. coli and up to 33μg/ml against highly resistant strains of P. aeruginosa. Glps isolated from different honeys showed a similar ability to overcome bacterial resistance to β-lactams suggesting that (a their mode of action is distinct from other classes of β-lactams and that (b the common glps structure was the lead structure responsible for the activity. The results of the current study together with our previous evidence of a rapid bactericidal activity of glps demonstrate that glps possess suitable characteristics to be considered a novel antibacterial drug candidate.

  19. Effects of Enrofloxacin Administration on Semen Quality of Barbari bucks

    Directory of Open Access Journals (Sweden)

    Chandrima Sinha

    2012-07-01

    Full Text Available The present study was undertaken to study the effect of enrofloxacin administration on semen quality of Barbari buck. Six normal, healthy adult Barbari bucks (25-30 Kg aged between 2 to 2.5 years were used as semen donors. The bucks were administered enrofloxacin at the dose of 5mg/kg body weight intra-muscularly daily for 7 days. From each buck biweekly eighteen semen ejaculates (1st to 18th were collected and one sample (0th from each buck was collected before administration of enrofloxacin, using a non-oestrous doe as dummy and investigated for semen quality parameters. There was no significant difference (P≥0.05 in seminal volume between different ejaculates. Mass motility decreased significantly (P≤0.01 and was lowest in 4th ejaculate as compared to mass motility prior to drug administration. Highest significant (P≤0.01 decrease in progressive motility was seen in 9th ejaculate as compared to progressive motility before drug administration. Sperm concentration decreased significantly (P≤0.01 and was found to be lowest in 4th ejaculate as compared to sperm concentration before enrofloxacin administration. Percent live spermatozoa decreased significantly (P≤0.01 and was found to be minmum in 12th ejaculate as compared to sperm concentration prior to drug administration. Highest significant increase (P≤ 0.01 in per cent head, mid-piece and tail abnormalities of spermatozoa was observed in 4th, 3rd and 6th ejaculate respectively following parentral administration of enrofloxacion as compared to ejaculate before drug administration. Following drug administration, the semen quality decreased progressively and then became slowly normal after 14th ejaculate.

  20. Stability of three commonly compounded extemporaneous enrofloxacin suspensions for oral administration to exotic animals.

    Science.gov (United States)

    Petritz, Olivia A; Guzman, David Sanchez-Migallon; Wiebe, Valerie J; Papich, Mark G

    2013-07-01

    To evaluate the stability of 3 extemporaneous oral suspensions of enrofloxacin mixed with readily available flavoring vehicles when stored at room temperature (approx 22°C). Evaluation study. 3 commonly compounded oral suspensions of enrofloxacin. On day 0, commercially available enrofloxacin tablets were compounded with a mixture of distilled water and corn syrup (formulation A) or cherry syrup (formulation B) flavoring vehicles to create suspensions with a nominal enrofloxacin concentration of 22.95 mg/mL, and 2.27% enrofloxacin injectable solution was compounded with a liquid sweetener (formulation C) to create a suspension with a nominal enrofloxacin concentration of 11.35 mg/mL. Preparations were stored in amber-colored vials at room temperature for 56 days. For each preparation, the enrofloxacin concentration was evaluated with high-performance liquid chromatography at prespecified intervals during the study. The pH, odor, and consistency for all suspensions were recorded at the start and completion of the study. Relative to the nominal enrofloxacin concentration, the enrofloxacin concentration strength ranged from 95.80% to 100.69% for formulation A, 108.44% to 111.06% for formulation B, and 100.99% to 103.28% for formulation C. A mild pH increase was detected in all 3 suspensions during the study. Results indicated that, when stored in amber-colored vials at room temperature for 56 days, the enrofloxacin concentration strength in all 3 formulations was retained within acceptance criteria of 90% to 110%. Subjectively, cherry syrup flavoring was better at masking the smell and taste of enrofloxacin than were the other mixing vehicles.

  1. Outpatient consumption of antibiotics in the City of Zagreb (2006-2010).

    Science.gov (United States)

    Golub, Anja; Štimac, Danijela

    2014-02-01

    To investigate outpatient consumption of antibiotics during the 2006-2010 period in the City of Zagreb and compare it with other European countries. Data on outpatient consumption of antibiotics were obtained from all pharmacies in the City of Zagreb. Based on the data obtained, the number of defined daily doses per 1000 inhabitants per day (DDDs/TID) were calculated for each ATC subgroup. Drug Utilization 90% (DU90%) method and ratio indicators were used for the assessment of drug prescribing quality. During the period of five years total antibiotics consumption has declined from 37.38 DDDs/TID in 2006 to 33.28 DDDs/ TID in 2010. The most frequently prescribed subgroup was penicillins (J01C). DU90% segment included 10 out of a total of 32 antibiotics in the year 2006 and 10 out of a total of 23 antibiotics in the year 2010. Leading position in the consumption, in 2006 and 2010, was held by broad-spectrum antibiotics, moreover their consumption increased in 2010. Consumption of antibiotics in Zagreb is still very high and is similar to the consumption in European countries with the highest consumption of antibiotics. Reduced consumption of narrow-spectrum antibiotics and unjustified increase in the consumption of broad-spectrum antibiotics suggess that physicians do not follow clinical guidelines.

  2. Pervasive antibiotic misuse in the Cambodian community: antibiotic-seeking behaviour with unrestricted access

    Directory of Open Access Journals (Sweden)

    Chhorvoin Om

    2017-03-01

    Full Text Available Abstract Background Antibiotic misuse is widespread in resource-limited countries such as Cambodia where the burden of infectious diseases is high and access to antibiotics is unrestricted. We explored healthcare seeking behaviour related to obtaining antibiotics and drivers of antibiotic misuse in the Cambodian community. Methods In-depth interviews were held with family members of patients being admitted in hospitals and private pharmacies termed pharmacy attendants in the catchment areas of the hospitals. Nurses who run community primary healthcare centres located within the hospital catchment areas were invited to attend focus group discussions. Nvivo version 10 was used to code and manage thematic data analysis. Results We conducted individual interviews with 35 family members, 7 untrained pharmacy attendants and 3 trained pharmacists and 6 focus group discussions with 30 nurses. Self-medication with a drug-cocktail was widespread and included broad-spectrum antibiotics for mild illness. Unrestricted access to antibiotics was facilitated by various community enablers including pharmacies or drug outlets, nurse suppliers and unofficial village medical providers referred to as “village Pett” whose healthcare training has historically been in the field and not at university. These enablers supplied the community with various types of antibiotics including broad spectrum fluoroquinolones and cephalosporins. When treatment was perceived to be ineffective patients would prescriber-shop various suppliers who would unfailingly provide them with antibiotics. The main driver of the community’s demand for antibiotics was a mistaken belief in the benefits of antibiotics for a common cold, high temperature, pain, malaria and ‘Roleak’ which includes a broad catch-all for perceived inflammatory conditions. For severe illnesses, patients would attend a community healthcare centre, hospital, or when their finances permitted, a private prescriber

  3. The antibacterial activity and toxicity of enrofloxacin are decreased by nanocellulose conjugated with aminobenzyl purin.

    Science.gov (United States)

    Yasini, Seyed Ali; Zadeh, Mohammad Hossein Balal; Shahdadi, Hossein

    2015-11-01

    The first aim of this study was to synthesize nanocellulose conjugated with aminobenzyl purin (NCABP), and the second aim was to evaluate the effect of NCABP on both toxicity and antibacterial activity of enrofloxacin. Here, the adsorption of enrofloxacin by NCABP was first modeled by molecular dynamic (MD) simulation. In the next step, NCABP was synthesized, and was exposed to enrofloxacin, 1000 μg mL(-1), at various conditions. Then, the quantity of adsorption and release was separately measured. Furthermore, both toxicity and antibacterial activity of NCABP, enrofloxacin, and (NCABP+enrofloxacin) were separately evaluated. In this study, MD simulation clearly showed the adsorption after 50 picoseconds. The adsorption tests revealed that the increase of incubation time and NCABP concentration, at range of 50-200 μg mL(-1), led to increase of adsorption. Moreover, the decrease of pH led to increase of adsorption. Interestingly, NCABP could adsorb enrofloxacin, up to 1000 μg mL(-1), in different types of meat. Moreover, the increase of incubation time and temperature did not release enrofloxacin, but the increase of pH increased release. This study showed that both toxicity and antibacterial activity of enrofloxacin were decreased when exposed together with NCABP. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Enrofloxacin at environmentally relevant concentrations enhances uptake and toxicity of cadmium in the earthworm Eisenia fetida in farm soils

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yinsheng, E-mail: yinshengli@sjtu.edu.cn [School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240 (China); Tang, Hao; Hu, Yingxiu; Wang, Xiuhong; Ai, Xiaojie; Tang, Li [School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240 (China); Matthew, Cory [Institute of Agriculture & Environment, Massey University, Private Bag 11-222, Palmerston North 4442 (New Zealand); Cavanagh, Jo [Landcare Research, PO Box 40, Lincoln 7640 (New Zealand); Qiu, Jiangping [School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240 (China)

    2016-05-05

    Highlights: • Enrofloxacin (EF) and cadmium (Cd) were independently adsorbed in soils. • EF accelerated and increased Cd bioaccumulation in earthworms. • At high concentration EF (10 mg kg{sup −1}) was toxic to earthworms. • EF enhanced Cd induced oxidative stress, and increased burrowing and respiration. • EF did not affect the Cd induced increase in metallothionein in earthworms. - Abstract: Individual and combined effects of enrofloxacin (EF) and cadmium (Cd) on the earthworm Eisenia fetida at environmentally relevant concentrations were investigated. EF is a veterinary antibiotic; Cd is an impurity in phosphatic fertiliser. For both, residues may accumulate in farm soils. In laboratory tests, over 98% of spiked EF was adsorbed by farm soils, with a half-life >8 weeks. However, earthworms absorbed less than 20% of spiked EF. Earthworms in soil with EF concentration 10 mg kg{sup −1} soil experienced transient oxidative stress and exhibited reduced burrowing activity and respiration after an 8-week exposure; EF at 0.1 and 1.0 mg kg{sup −1} soil did not elicit toxicity symptoms. When both were added, Cd did not affect EF uptake, but each increment of spiked EF increased Cd bioaccumulation and associated oxidative stress of earthworms, and also caused decreased burrow length and CO{sub 2} production. However, metallothionein induction was not affected. The enhanced toxicity of Cd to earthworms in the presence of EF at low environmental concentrations may have implications for the health and reproductive success of earthworm populations and highlights the importance of understanding effects of antibiotic contamination of farm soils, and of awareness of environmental effects from interaction between multiple contaminants.

  5. Enrofloxacin at environmentally relevant concentrations enhances uptake and toxicity of cadmium in the earthworm Eisenia fetida in farm soils

    International Nuclear Information System (INIS)

    Li, Yinsheng; Tang, Hao; Hu, Yingxiu; Wang, Xiuhong; Ai, Xiaojie; Tang, Li; Matthew, Cory; Cavanagh, Jo; Qiu, Jiangping

    2016-01-01

    Highlights: • Enrofloxacin (EF) and cadmium (Cd) were independently adsorbed in soils. • EF accelerated and increased Cd bioaccumulation in earthworms. • At high concentration EF (10 mg kg"−"1) was toxic to earthworms. • EF enhanced Cd induced oxidative stress, and increased burrowing and respiration. • EF did not affect the Cd induced increase in metallothionein in earthworms. - Abstract: Individual and combined effects of enrofloxacin (EF) and cadmium (Cd) on the earthworm Eisenia fetida at environmentally relevant concentrations were investigated. EF is a veterinary antibiotic; Cd is an impurity in phosphatic fertiliser. For both, residues may accumulate in farm soils. In laboratory tests, over 98% of spiked EF was adsorbed by farm soils, with a half-life >8 weeks. However, earthworms absorbed less than 20% of spiked EF. Earthworms in soil with EF concentration 10 mg kg"−"1 soil experienced transient oxidative stress and exhibited reduced burrowing activity and respiration after an 8-week exposure; EF at 0.1 and 1.0 mg kg"−"1 soil did not elicit toxicity symptoms. When both were added, Cd did not affect EF uptake, but each increment of spiked EF increased Cd bioaccumulation and associated oxidative stress of earthworms, and also caused decreased burrow length and CO_2 production. However, metallothionein induction was not affected. The enhanced toxicity of Cd to earthworms in the presence of EF at low environmental concentrations may have implications for the health and reproductive success of earthworm populations and highlights the importance of understanding effects of antibiotic contamination of farm soils, and of awareness of environmental effects from interaction between multiple contaminants.

  6. Tissue distribution of enrofloxacin after intramammary or simulated systemic administration in isolated perfused sheep udders.

    Science.gov (United States)

    López Cadenas, Cristina; Fernández Martínez, Nélida; Sierra Vega, Matilde; Diez Liébana, Maria J; Gonzalo Orden, Jose M; Sahagún Prieto, Ana M; García Vieitez, Juan J

    2012-11-01

    To determine the tissue distribution of enrofloxacin after intramammary or simulated systemic administration in isolated perfused sheep udders by measuring its concentration at various sample collection sites. 26 udders (obtained following euthanasia) from 26 healthy lactating sheep. For each isolated udder, 1 mammary gland was perfused with warmed, gassed Tyrode solution. Enrofloxacin (1 g of enrofloxacin/5 g of ointment) was administered into the perfused gland via the intramammary route or systemically via the perfusion fluid (equivalent to a dose of 5 mg/kg). Samples of the perfusate were obtained every 30 minutes for 180 minutes; glandular tissue samples were obtained at 2, 4, 6, and 8 cm from the teat base after 180 minutes. The enrofloxacin content of the perfusate and tissue samples was analyzed via high-performance liquid chromatography with UV detection. After intramammary administration, maximun perfusate enrofloxacin concentration was detected at 180 minutes and, at this time, mean tissue enrofloxacin concentration was detected and mean tissue enrofloxacin concentration was 123.80, 54.48, 36.72, and 26.42 μg/g of tissue at 2, 4, 6, and 8 cm from the teat base, respectively. Following systemic administration, perfusate enrofloxacin concentration decreased with time and, at 180 minutes, tissue enrofloxacin concentrations ranged from 40.38 to 35.58 μg/g of tissue. By 180 minutes after administration via the intramammary or systemic route in isolated perfused sheep mammary glands, mean tissue concentration of enrofloxacin was greater than the minimum inhibitory concentration required to inhibit growth of 90% of many common mastitis pathogens in sheep. Use of either route of administration (or in combination) appears suitable for the treatment of acute mastitis in sheep.

  7. Bacterial fatty acid metabolism in modern antibiotic discovery.

    Science.gov (United States)

    Yao, Jiangwei; Rock, Charles O

    2017-11-01

    Bacterial fatty acid synthesis is essential for many pathogens and different from the mammalian counterpart. These features make bacterial fatty acid synthesis a desirable target for antibiotic discovery. The structural divergence of the conserved enzymes and the presence of different isozymes catalyzing the same reactions in the pathway make bacterial fatty acid synthesis a narrow spectrum target rather than the traditional broad spectrum target. Furthermore, bacterial fatty acid synthesis inhibitors are single-targeting, rather than multi-targeting like traditional monotherapeutic, broad-spectrum antibiotics. The single-targeting nature of bacterial fatty acid synthesis inhibitors makes overcoming fast-developing, target-based resistance a necessary consideration for antibiotic development. Target-based resistance can be overcome through multi-targeting inhibitors, a cocktail of single-targeting inhibitors, or by making the single targeting inhibitor sufficiently high affinity through a pathogen selective approach such that target-based mutants are still susceptible to therapeutic concentrations of drug. Many of the pathogens requiring new antibiotic treatment options encode for essential bacterial fatty acid synthesis enzymes. This review will evaluate the most promising targets in bacterial fatty acid metabolism for antibiotic therapeutics development and review the potential and challenges in advancing each of these targets to the clinic and circumventing target-based resistance. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Spectrophotometric Determination of Gemifloxacin Mesylate, Moxifloxacin Hydrochloride, and Enrofloxacin in Pharmaceutical Formulations Using Acid Dyes

    Directory of Open Access Journals (Sweden)

    Ayman A. Gouda

    2014-01-01

    Full Text Available Simple, rapid, and extractive spectrophotometric methods were developed for the determination of some fluoroquinolones antibiotics: gemifloxacin mesylate (GMF, moxifloxacin hydrochloride (MXF, and enrofloxacin (ENF in pure forms and pharmaceutical formulations. These methods are based on the formation of ion-pair complexes between the basic drugs and acid dyes, namely, bromocresol green (BCG, bromocresol purple (BCP, bromophenol blue (BPB, bromothymol blue (BTB, and methyl orange (MO in acidic buffer solutions. The formed complexes were extracted with chloroform and measured at 420, 408, 416, 415, and 422 nm for BCG, BCP, BPB, BTB, and MO, respectively, for GMF; at 410, 415, 416, and 420 nm for BCP, BTB, BPB, and MO, respectively, for MXF; and at 419 and 414 nm for BCG and BTB, respectively, in case of ENF. The analytical parameters and their effects are investigated. Beer’s law was obeyed in the ranges 1.0–30, 1.0–20, and 2.0–24 μg mL−1 for GMF, MXF, and ENF, respectively. The proposed methods have been applied successfully for the analysis of the studied drugs in pure forms and pharmaceutical formulations. Statistical comparison of the results with the reference methods showed excellent agreement and indicated no significant difference in accuracy and precision.

  9. Ecotoxicological effects of enrofloxacin and its removal by monoculture of microalgal species and their consortium.

    Science.gov (United States)

    Xiong, Jiu-Qiang; Kurade, Mayur B; Jeon, Byong-Hun

    2017-07-01

    Enrofloxacin (ENR), a fluoroquinolone antibiotic, has gained big scientific concern due to its ecotoxicity on aquatic microbiota. The ecotoxicity and removal of ENR by five individual microalgae species and their consortium were studied to correlate the behavior and interaction of ENR in natural systems. The individual microalgal species (Scenedesmus obliquus, Chlamydomonas mexicana, Chlorella vulgaris, Ourococcus multisporus, Micractinium resseri) and their consortium could withstand high doses of ENR (≤1 mg L -1 ). Growth inhibition (68-81%) of the individual microalgae species and their consortium was observed in ENR (100 mg L -1 ) compared to control after 11 days of cultivation. The calculated 96 h EC 50 of ENR for individual microalgae species and microalgae consortium was 9.6-15.0 mg ENR L -1 . All the microalgae could recover from the toxicity of high concentrations of ENR during cultivation. The biochemical characteristics (total chlorophyll, carotenoid, and malondialdehyde) were significantly influenced by ENR (1-100 mg L -1 ) stress. The individual microalgae species and microalgae consortium removed 18-26% ENR at day 11. Although the microalgae consortium showed a higher sensitivity (with lower EC 50 ) toward ENR than the individual microalgae species, the removal efficiency of ENR by the constructed microalgae consortium was comparable to that of the most effective microalgal species. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Effect of repeated oral administration of levofloxacin, enrofloxacin, and meloxicam on antioxidant parameters and lipid peroxidation in rabbits.

    Science.gov (United States)

    Khan, Adil Mehraj; Rampal, Satyavan; Sood, Naresh Kumar

    2016-03-09

    The effect of 21 days of repeated oral administration of levofloxacin and enrofloxacin both alone and in combination with meloxicam, on the oxidative balance in blood was evaluated in rabbits. Rabbits were randomly allocated to six groups of four animals each. Control group was gavaged 5% dextrose and 2% benzyl alcohol. Three groups were exclusively gavaged meloxicam (0.2 mg/kg body weight o.d.), levofloxacin hemihydrate (10 mg/kg body weight b.i.d 12 h), and enrofloxacin (20 mg/kg body weight o.d.), respectively. Two other groups were co-gavaged meloxicam with levofloxacin hemihydrate and enrofloxacin, respectively. A reduction (p enrofloxacin. The activities of enzymes, glutathione peroxidase and superoxide dismutase, were induced (p enrofloxacin-meloxicam co-treated group. The activity of catalase was non-significantly different between various groups. Enrofloxacin-treated groups had higher (p enrofloxacin and meloxicam. © The Author(s) 2016.

  11. The prevalence of nosocomial infections caused by Enterobacter cloacae and antibiotic resistant patterns in samples isolated from patients in two hospitals in Tehran

    Directory of Open Access Journals (Sweden)

    Rahbar M

    2012-06-01

    Conclusion: This study clearly showed the high prevalence of resistance to broad-spectrum beta-lactam antibiotics in the isolated E. cloacae among which 5% were multi drug resistant. All the isolated E. cloacae were susceptible to Colistin. These results can be alarming for physicians treating resistant E. cloacae infections, especially extended-spectrum beta-lactamase producing species.

  12. Effects of combination of antibiotic-resistant bifidobacteria and corresponding antibiotics on survival of irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Korshunov, V.M.; Pinegin, B.V.; Ivanova, N.P.; Mal' tsev, V.N.

    1982-05-01

    Broad-spectrum antibiotics are used to treat intestinal dysbacteriosis of diverse etiology, including postradiation dysbacteriosis. Antibiotic therapy is instrumental in decontaminating the intestine. In addition to pathogenic microorganisms, there is disappearance of lactobacilli and bifidobacteria which perform several important and useful functions. For this reason, in addition to antibiotics, bifidobacterial preparations are used to restore the microbial cenosis and administration thereof is started after antibiotics are discontinued. There are some flaws to deferred administration of bifidobacteria, since the process of colonization of the intestine with commercial bifidobacterial preparations is rather lengthy, and there is slow elevation of bididobacterium level in the intestinal tract, whereas exogenous recontamination of the intestine by conditionally pathogenic bacteria is possible after antibiotic therapy is discontinued. On the other hand, use of antibiotics alone could, in turn, be the cause of intestinal dysbacteriosis. Our objective was to eliminate intestinal dysbacteriosis in irradiated animals by means of combining antibiotics and preparations of bifidobacteria resistant to these antibiotics, and thus prolong the life of these animals.

  13. Severity assessment scores to guide empirical use of antibiotics in community acquired pneumonia.

    Science.gov (United States)

    Singanayagam, Aran; Chalmers, James D

    2013-10-01

    Severity assessment scores were first developed to predict the 30 day mortality in community acquired pneumonia; however, several guidelines have extended their use to guide empirical antibiotic prescription decisions. This approach has theoretical advantages because a decrease in broad-spectrum antibiotic treatment in low-risk patients might reduce antibiotic-related side-effects, and to give broad-spectrum therapy to patients at higher risk of death is intuitive. However, evidence in support of this approach is not clear. In particular, the British Thoracic Society guidelines suggest withholding a macrolide from patients with low CURB 65 scores, despite evidence that these patients have a higher frequency of atypical pathogens than do those with a higher severity of pneumonia. Severity scores do not perform well in some groups and might overestimate disease severity in elderly people, leading to inappropriate broad-spectrum treatment to those at high risk of complications such as Clostridium difficile infection. In this Review, we discuss the evidence for antibiotic prescribing guided by severity score and suggest that more evidence of effect and implementation is needed before this approach can be universally adopted. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. [Antibiotics in the critically ill].

    Science.gov (United States)

    Kolak, Radmila R

    2010-01-01

    Antibiotics are one the most common therapies administered in the intensive care unit setting. This review outlines the strategy for optimal use of antimicrobial agents in the critically ill. In severely ill patients, empirical antimicrobial therapy should be used when a suspected infection may impair the outcome. It is necessary to collect microbiological documentation before initiating empirical antimicrobial therapy. In addition to antimicrobial therapy, it is recommended to control a focus of infection and to modify factors that promote microbial growth or impair the host's antimicrobial defence. A judicious choice of antimicrobial therapy should be based on the host characteristics, the site of injection, the local ecology, and the pharmacokinetics/pharmacodynamics of antibiotics. This means treating empirically with broad-spectrum antimicrobials as soon as possible and narrowing the spectrum once the organism is identified (de-escalation), and limiting duration of therapy to the minimum effective period. Despite theoretical advantages, a combined antibiotic therapy is nor more effective than a mono-therapy in curing infections in most clinical trials involving intensive care patients. Nevertheless, textbooks and guidelines recommend a combination for specific pathogens and for infections commonly caused by these pathogens. Avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will improve patient outcomes while minimizing risks for the development of bacterial resistance. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilisation and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use be evaluated at the local level.

  15. Macroscopic and molecular approaches of enrofloxacin retention in soils in presence of Cu(II).

    Science.gov (United States)

    Graouer-Bacart, Mareen; Sayen, Stéphanie; Guillon, Emmanuel

    2013-10-15

    The co-adsorption of copper and the fluoroquinolone antibiotic enrofloxacin (ENR) at the water-soil interface was studied by means of batch adsorption experiments, and extended X-ray absorption fine structure (EXAFS) spectroscopy. The system was investigated over a pH range between 6 and 10, at different contact times, ionic strengths, and ENR concentrations. Adsorption coefficient - Kd - was determined at relevant environmental concentrations and the value obtained in water at a ionic strength imposed by the soil and at soil natural pH was equal to 0.66Lg(-1). ENR adsorption onto the soil showed strong pH dependence illustrating the influence of the electrostatic interactions in the sorption processes. The simultaneous co-adsorption of ENR and Cu(II) on the soil was also investigated. The presence of Cu(II) strongly influenced the retention of the antibiotic, leading to an increase up to 35% of adsorbed ENR amount. The combined quantitative and spectroscopic results showed that Cu(II) and ENR directly interacted at the water-soil interface to form ternary surface complexes. Cu K-edge EXAFS data indicated a molecular structure where the carboxylate and carbonyl groups of ENR coordinate to Cu(II) to form a 6-membered chelate ring and where Cu(II) bridges between ENR and the soil surface sites. Cu(II) bonds bidentately to the surface in an inner-sphere mode. Thus, the spectroscopic data allowed us to propose the formation of ternary surface complexes with the molecular architecture soil-Cu(II)-ENR. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Investigation of enrofloxacin residues in broiler tissues using ELISA and LC-MS/MS.

    Science.gov (United States)

    Panzenhagen, Pedro Henrique N; Aguiar, Waldemir S; Gouvêa, Raquel; de Oliveira, Andréa M G; Barreto, Fabiano; Pereira, Virgínia L A; Aquino, Maria Helena C

    2016-01-01

    This study investigated the efficiency of an enrofloxacin ELISA test kit to detect the presence of enrofloxacin residues in broiler tissues compared with LC-MS/MS. Broiler tissues from 72 samples consisting of 60 breast muscle, six pools of livers (500 g each) and six pools of kidneys (500 g each) were obtained from six different slaughterhouses. Breast muscle from 10 carcasses and pools of livers and kidneys from approximately 200 carcasses of the same flock were collected from each slaughterhouse. ELISA and HPLC were used to identify and quantify the contamination of the samples with enrofloxacin. A total of 72% of the analysed samples contained enrofloxacin residues detected by the ELISA and 22.2% were detected by LC-MS/MS. The mean values of enrofloxacin contamination found in chicken breast by ELISA and HPLC were 8.63 and 12.25 μg kg(-1), respectively. None of the samples exceeded the maximum limit of 100 μg kg(-1) by both methods set by the European Union as well as the Brazilian Agriculture Ministry. All positive samples for enrofloxacin residues detected by LC-MS/MS were also positive by ELISA. These data confirm the efficiency of the ELISA test, and suggest its use as a screening method for enrofloxacin residues in poultry tissues due to its quick results, low price and ease of applicability.

  17. Effects of ampicillin/sulbactam and enrofloxacin on the blood pressure of isoflurane anesthetized dogs.

    Science.gov (United States)

    Moorer, Jeremiah D; Towle-Millard, Heather A; Gross, Marjorie E; Payton, Mark E

    2013-01-01

    A blinded, prospective, randomized crossover study was performed to determine the effects of ampicillin Na/sulbactam Na and enrofloxacin on the blood pressure (BP) of healthy anesthetized dogs. Eight dogs were anesthetized three different times. They randomly received enrofloxacin, ampicillin Na/sulbactam Na, and saline. Systolic, diastolic, and mean arterial BPs (SAP, DAP, and MAP, respectively), heart rate (HR), O2 saturation of hemoglobin, end-tidal CO2 (ETCO2) concentration, inspired isoflurane concentration, end-tidal isoflurane (ETiso) concentration, respiratory rate, electrocardiogram, and body temperature were measured for 20 min prior to administration of treatment, during administration over 30 min, and for 30 min after administration. There was no significant difference in the SAP or ETiso. There was no significant change in the arterial pressure values over time in the enrofloxacin and ampicillin Na/sulbactam Na groups. The control group's MAP increased over time and was increased compared with the enrofloxacin group at times 25, 35, 45, and 55. The statistical difference between the enrofloxacin and the control groups was due to an increase in the MAP in the control group, not a decrease in the enrofloxacin group's BP. Neither enrofloxacin nor ampicillin Na/sulbactam Na caused hypotension in healthy dogs anesthetized with isoflurane and fentanyl.

  18. A New Green Method for the Quantitative Analysis of Enrofloxacin by Fourier-Transform Infrared Spectroscopy.

    Science.gov (United States)

    Rebouças, Camila Tavares; Kogawa, Ana Carolina; Salgado, Hérida Regina Nunes

    2018-05-18

    Background: A green analytical chemistry method was developed for quantification of enrofloxacin in tablets. The drug, a second-generation fluoroquinolone, was first introduced in veterinary medicine for the treatment of various bacterial species. Objective: This study proposed to develop, validate, and apply a reliable, low-cost, fast, and simple IR spectroscopy method for quantitative routine determination of enrofloxacin in tablets. Methods: The method was completely validated according to the International Conference on Harmonisation guidelines, showing accuracy, precision, selectivity, robustness, and linearity. Results: It was linear over the concentration range of 1.0-3.0 mg with correlation coefficients >0.9999 and LOD and LOQ of 0.12 and 0.36 mg, respectively. Conclusions: Now that this IR method has met performance qualifications, it can be adopted and applied for the analysis of enrofloxacin tablets for production process control. The validated method can also be utilized to quantify enrofloxacin in tablets and thus is an environmentally friendly alternative for the routine analysis of enrofloxacin in quality control. Highlights: A new green method for the quantitative analysis of enrofloxacin by Fourier-Transform Infrared spectroscopy was validated. It is a fast, clean and low-cost alternative for the evaluation of enrofloxacin tablets.

  19. Enrofloxacin degradation in broiler chicken manure under field conditions and its residuals effects to the environment.

    Science.gov (United States)

    Slana, M; Žigon, D; Sollner-Dolenc, M

    2017-05-01

    The rate of degradation of enrofloxacin in broiler chicken manure has been characterised. Its degradation was investigated in manure excreted by broiler chickens in an intensively reared chicken facility; further, the degradation also followed after transfer of the excreta into the natural environment occurred. The effect of enrofloxacin and its degradation products on cucumber and tomato was also investigated. Enrofloxacin degradation was shown to take place within the rearing facility and also continuing after the manure was transferred into the environment. The rates of enrofloxacin degradation and the degree of degradation product formation in the manure heap incubated in the environment were condition specific, both variables depending on the manure sampling depth. The degradation half-lives ranged from 12.7 to 38.1 days for enrofloxacin and from 1.2 to 8.2 days for the main metabolite ciprofloxacin. Only the cucumber showed signs of toxicity when incubated with the composted manure immediately after transfer into field occurred (t = 0). No toxic effects to plants were observed when manure from the last incubation day (60th) of the field study and manure from the last incubation day of the laboratory degradation study were applied. The degradation study under field conditions showed that enrofloxacin and its degradation products degrade fast in the environment. Additionally, the toxic effects to plants decrease with the incubation time of manure containing enrofloxacin residuals.

  20. Pharmacokinetics after intravenous, subcutaneous, and oral administration of enrofloxacin to alpacas.

    Science.gov (United States)

    Gandolf, A Rae; Papich, Mark G; Bringardner, Amy B; Atkinson, Mark W

    2005-05-01

    To determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after p.o, s.c., and i.v. administration of enrofloxacin to alpacas. 6 adult female alpacas. A crossover design was used for administration of 3 single-dose treatments of enrofloxacin to alpacas, which was followed by an observational 14-day multiple-dose regimen. Single-dose treatments consisted of i.v. and s.c. administration of injectable enrofloxacin (5 mg/kg) and p.o administration of enrofloxacin tablets (10 mg/kg) dissolved in grain to form a slurry. Plasma enrofloxacin concentrations were measured by use of high-performance liquid chromatography. The multiple-dose regimen consisted of feeding a mixture of crushed and moistened enrofloxacin tablets mixed with grain. Behavior, appetite, and fecal quality were monitored throughout the 14-day treatment regimen and for 71 additional days following treatment. Mean half-life following i.v., s.c., and p.o. administration was 11.2, 8.7, and 16.1 hours, respectively. For s.c. and p.o administration, mean total systemic availability was 90.18% and 29.31%, respectively; mean maximum plasma concentration was 3.79 and 1.81 microg/mL, respectively; and area under the curve (AUC) was 50.05 and 33.97 (microg x h)/mL, respectively. The s.c. or p.o administration of a single dose of enrofloxacin yielded a ratio for AUC to minimum inhibitory concentration > 100 for many grampositive and gram-negative bacterial pathogens common to camelids. Conclusions and Clinical Relevance-The administration of enrofloxacin (5 mg/kg, s.c., or 10 mg/kg, p.o) may be appropriate for antimicrobial treatment of alpacas.

  1. Mutant prevention concentration and PK-PD relationships of enrofloxacin for Pasteurella multocida in buffalo calves.

    Science.gov (United States)

    Balaje, R M; Sidhu, P K; Kaur, G; Rampal, S

    2013-12-01

    This study validated the use of mutant prevention concentration (MPC) and pharmacokinetic and pharmacodynamic (PK-PD) modeling approach for optimization of dose regimen of enrofloxacin to contain the emergence of Pasteurella multocida resistance. The PK and PD characteristics of enrofloxacin were investigated in buffalo calves after intramuscular administration at a dose rate of 12 mg/kg. The concentration of enrofloxacin and ciprofloxacin in serum were determined by high-performance liquid chromatography. The serum peak concentration (Cmax), terminal half-life (t1/2K10), volume of distribution (Vd(area)/F) and mean residence time (MRT) of enrofloxacin were 1.89 ± 0.35 μg/ml, 5.14 ± 0.66 h, 5.59 ± 0.99 l/kg/h and 8.52 ± 1.29 h, respectively. The percent metabolite conversion ratio of ciprofloxacin to enrofloxacin was 79. The binding of enrofloxacin to plasma proteins was 11%. The MIC, MBC and MPC for enrofloxacin against P. multocida were 0.05, 0.06 μg/ml and 1.50 μg/ml.In vitro and ex-vivo bactericidal activity of enrofloxacin was concentration dependent. Modeling of ex-vivo growth inhibition data to the sigmoid Emax equation provided AUC24h/MIC values to produce bacteriostatic (19 h), bactericidal (43 h) and bacterial eradication (64 h). PK-PD data in conjunction with MPC and MIC90 data predicted dosage schedules for enrofloxacin that may achieve optimum efficacy in respect of bacteriological and clinical cure and minimize the risk of emergence of resistance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Potential of Constructed Wetlands for Removal of Antibiotics from Saline Aquaculture Effluents

    Directory of Open Access Journals (Sweden)

    Maria Bôto

    2016-10-01

    Full Text Available This work aimed to evaluate the potential of constructed wetlands (CWs for removal of antibiotics (enrofloxacin and oxytetracycline and antibiotic resistant bacteria from saline aquaculture wastewaters. Removal of other contaminants (nutrients, organic matter and metals and toxicity reduction and the influence of antibiotics with these processes were evaluated. Thus, nine CWs microcosms, divided into three treatments, were assembled and used to treat wastewater (doped or not with the selected antibiotics between October and December of 2015. Each week treated wastewater was removed and new wastewater (doped or not was introduced in CWs. Results showed >99% of each antibiotic was removed in CWs. After three weeks of adaptation, removal percentages >95% were also obtained for total bacteria and for antibiotic resistant bacteria. Nutrients, organic matter and metal removal percentages in CWs treated wastewater were identical in the absence and in the presence of each antibiotic. Toxicity in treated wastewaters was significantly lower than in initial wastewaters, independently of antibiotics presence. Results showed CWs have a high efficiency for removing enrofloxacin or oxytetracycline as well as antibiotic resistant bacteria from saline aquaculture wastewaters. CWs can also remove other contaminants independently of drug presence, making the aquaculture wastewater possible to be reutilized and/or recirculated.

  3. Spectrophotometric Investigations of Macrolide Antibiotics: A Brief Review

    Directory of Open Access Journals (Sweden)

    Mrudul R. Keskar

    2015-01-01

    Full Text Available Macrolides, one of the most commonly used class of antibiotics, are a group of drugs produced by Streptomyces species. They belong to the polyketide class of natural products. Their activity is due to the presence of a large macrolide lactone ring with deoxy sugar moieties. They are protein synthesis inhibitors and broad-spectrum antibiotics, active against both gram-positive and gram-negative bacteria. Different analytical techniques have been reported for the determination of macrolides such as chromatographic methods, flow injection methods, spectrofluorometric methods, spectrophotometric methods, and capillary electrophoresis methods. Among these methods, spectrophotometric methods are sensitive and cost effective for the analysis of various antibiotics in pharmaceutical formulations as well as biological samples. This article reviews different spectrophotometric methods for the determination of macrolide antibiotics.

  4. Discovery and preclinical development of new antibiotics.

    Science.gov (United States)

    Hughes, Diarmaid; Karlén, Anders

    2014-05-01

    Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted.

  5. Antibiotic prescribing policy and Clostridium difficile diarrhoea.

    LENUS (Irish Health Repository)

    O'Connor, K A

    2012-02-03

    BACKGROUND: Broad-spectrum antibiotics, particularly intravenous cephalosporins, are associated with Clostridium difficile diarrhoea. Diarrhoea due to C. difficile is a growing problem in hospitals, especially among elderly patients. AIM: To establish whether changing an antibiotic policy with the aim of reducing the use of injectable cephalosporins leads to a reduction in the incidence of C. difficile diarrhoea in elderly patients. DESIGN: Retrospective analysis. METHODS: A group of patients who were subject to the new antibiotic policy from the period following July 2000, were compared with patients who were admitted prior to July 2000 and were not subject to the new policy. Infections, antibiotic prescriptions and mortality rates were determined from case notes, and C. difficle diarrhoea rates from microbiological data. RESULTS: Intravenous cephalosporin use fell from 210 to 28 defined daily doses (p < 0.001) following the change in antibiotic policy, with a corresponding increase in piperacillin-tazobactam (p < 0.001) and moxifloxacin (p < 0.001) use. The new policy led to a significant reduction in C. difficile diarrhoea cases. The relative risk of developing C. difficile infection with the old policy compared to the new policy was 3.24 (95%CI 1.07-9.84, p = 0.03). DISCUSSION: The antibiotic policy was successfully introduced into an elderly care service. It reduced both intravenous cephalosporin use and C. difficile diarrhoea.

  6. Involvement of the ABC transporter BcAtrB and the laccase BcLCC2 in defence of Botrytis cinerea against the broad-spectrum antibiotic 2,4-diacetylphloroglucinol

    NARCIS (Netherlands)

    Schouten, A.; Maksimova, O.; Cuesta Arenas, Y.; Berg, van den G.; Raaijmakers, J.M.

    2008-01-01

    The genetic and biochemical basis of defence mechanisms in plant pathogenic fungi against antifungal compounds produced by antagonistic microorganisms is largely unknown. The results of this study show that both degradative and non-degradative defence mechanisms enable the plant pathogenic fungus

  7. Distribution of enrofloxacin and its active metabolite, using an in vivo ultrafiltration sampling technique after the injection of enrofloxacin to pigs.

    Science.gov (United States)

    Messenger, K M; Papich, M G; Blikslager, A T

    2012-10-01

    The objective of this study was to determine the pharmacokinetics (PK) of enrofloxacin in pigs and compare to the tissue interstitial fluid (ISF). Six healthy, young pigs were administered 7.5 mg/kg enrofloxacin subcutaneously (SC). Blood and ISF samples were collected from preplaced intravenous catheters and ultrafiltration sampling probes placed in three different tissue sites (intramuscular, subcutaneous, and intrapleural). Enrofloxacin concentrations were measured using high-pressure liquid chromatography with fluorescence detection, PK parameters were analyzed using a one-compartment model, and protein binding was determined using a microcentrifugation system. Concentrations of the active metabolite ciprofloxacin were negligible. The mean ± SD enrofloxacin plasma half-life, volume of distribution, clearance, and peak concentration were 26.6 ± 6.2 h (harmonic mean), 6.4 ± 1.2 L/kg, 0.18 ± 0.08 L/kg/h, and 1.1 ± 0.3 μg/mL, respectively. The half-life of enrofloxacin from the tissues was 23.6 h, and the maximum concentration was 1.26 μg/mL. Tissue penetration, as measured by a ratio of area-under-the-curve (AUC), was 139% (± 69%). Plasma protein binding was 31.1% and 37.13% for high and low concentrations, respectively. This study demonstrated that the concentration of biologically active enrofloxacin in tissues exceeds the concentration predicted by the unbound fraction of enrofloxacin in pig plasma. At a dose of 7.5 mg/kg SC, the high tissue concentrations and long half-life produce an AUC/MIC ratio sufficient for the pathogens that cause respiratory infections in pigs. © 2011 Blackwell Publishing Ltd.

  8. Effect of enrofloxacin on digoxin clearance and steady-state serum concentrations in dogs.

    OpenAIRE

    Novotny, M J; Shaw, D H

    1991-01-01

    The effect of enrofloxacin on the oral clearance and steady-state concentrations of digoxin in serum was evaluated in dogs. Digoxin was administered orally to six healthy adult Beagle dogs following a multiple-dose regimen of 0.0625 mg every 12 h for 23 days. From days 14 to 23 enrofloxacin was administered orally at a dosage of 2.5 mg/kg every 12 h, with subjects receiving enrofloxacin 2 h prior to digoxin. Trough serum concentrations of digoxin were measured using an immunoassay technique. ...

  9. Antibiotics and Antibiotic Resistance

    Science.gov (United States)

    ... all that ails you. Antibiotics, also known as antimicrobial drugs, are drugs that fight infections caused by bacteria. ... Information for Consumers and Health Professionals Information by drug class Antimicrobial Resistance Animal and Veterinary Related Resources Further information ...

  10. Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity

    Energy Technology Data Exchange (ETDEWEB)

    Hargrove, Tatiana Y.; Garvey, Edward P.; Hoekstra, William J.; Yates, Christopher M.; Wawrzak, Zdzislaw; Rachakonda, Girish; Villalta, Fernando; Lepesheva, Galina I.

    2017-05-01

    ABSTRACT

    Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungusAspergillus fumigatus. VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole, ketoconazole, and posaconazole. The X-ray structure of the VT-1598/A. fumigatusCYP51 complex was determined and depicts the distinctive binding mode of the inhibitor in the enzyme active site, suggesting the molecular basis of the improved drug potency and broad-spectrum antifungal activity. These data show the formation of an optimized hydrogen bond between the phenoxymethyl oxygen of VT-1598 and the imidazole ring nitrogen of His374, the CYP51 residue that is highly conserved across fungal pathogens and fungus specific. Comparative structural analysis ofA. fumigatusCYP51/voriconazole andCandida albicansCYP51/VT-1161 complexes supports the role of H bonding in fungal CYP51/inhibitor complexes and emphasizes the importance of an optimal distance between this interaction and the inhibitor-heme iron interaction. Cellular experiments using twoA. fumigatusstrains (strains 32820 and 1022) displayed a direct

  11. Growing Escherichia coli mutants deficient in riboflavin biosynthesis with non-limiting riboflavin results in sensitization to inactivation by broad-spectrum near-ultraviolet light (320-400 nm)

    International Nuclear Information System (INIS)

    Lloyd, R.E.; Rinkenberger, J.L.; Hug, B.A.; Tuveson, R.W.

    1990-01-01

    Two mutants of Escherichia coli unable to synthesize riboflavin were grown with limiting (2 μg ml -1 ) and non-limiting (10 μg ml -1 ) concentrations of riboflavin. These riboflavin auxotrophs when grown to exponential phase with non-limiting riboflavin are more sensitive to broad spectrum near-ultraviolet light (NUV, 320-400 nm) inactivation than when they are grown with limiting riboflavin. Exponential phase cells of the riboflavin auxotrophs grown with limiting riboflavin are sensitized when irradiated in saline supplemented with riboflavin. This suggests that extracellular riboflavin is important as a NUV sensitizer when intracellular levels of riboflavin are reduced. The concentration of riboflavin in crude extracts from exponentially growing cells correlates well with the sensitivity of these mutants to NUV inactivation. The level of riboflavin supplementation has little effect on the NUV sensitivity of the parental strain. (author)

  12. Enrofloxacin and Macrolides Alone or in Combination with Rifampicin as Antimicrobial Treatment in a Bovine Model of Acute Chlamydia psittaci Infection

    Science.gov (United States)

    Prohl, Annette; Lohr, Markus; Ostermann, Carola; Liebler-Tenorio, Elisabeth; Berndt, Angela; Schroedl, Wieland; Rothe, Michael; Schubert, Evelyn; Sachse, Konrad; Reinhold, Petra

    2015-01-01

    Chlamydia psittaci is a zoonotic bacterium with a wide host range that can cause respiratory disease in humans and cattle. In the present study, effects of treatment with macrolides and quinolones applied alone or in combination with rifampicin were tested in a previously established bovine model of respiratory C. psittaci infection. Fifty animals were inoculated intrabronchially at the age of 6–8 weeks. Seven served as untreated controls, the others were assigned to seven treatment groups: (i) rifampicin, (ii) enrofloxacin, (iii) enrofloxacin + rifampicin, (iv) azithromycin, (v) azithromycin + rifampicin, (vi) erythromycin, and (vii) erythromycin + rifampicin. Treatment started 30 hours after inoculation and continued until 14 days after inoculation (dpi), when all animals were necropsied. The infection was successful in all animals and sufficient antibiotic levels were detected in blood plasma and tissue of the treated animals. Reisolation of the pathogen was achieved more often from untreated animals than from other groups. Nevertheless, pathogen detection by PCR was possible to the same extent in all animals and there were no significant differences between treated and untreated animals in terms of local (i.e. cell count and differentiation of BALF-cells) and systemic inflammation (i.e. white blood cells and concentration of acute phase protein LBP), clinical signs, and pathological findings at necropsy. Regardless of the reduced reisolation rate in treated animals, the treatment of experimentally induced respiratory C. psittaci infection with enrofloxacin, azithromycin or erythromycin alone or in combination with rifampicin was without obvious benefit for the host, since no significant differences in clinical and pathological findings or inflammatory parameters were detected and all animals recovered clinically within two weeks. PMID:25768665

  13. Optimization of condition for conjugation of enrofloxacin to enzymes in chemiluminescence enzyme immunoassay

    Science.gov (United States)

    Yu, Songcheng; Yu, Fei; Zhang, Hongquan; Qu, Lingbo; Wu, Yongjun

    2014-06-01

    In this study, in order to find out a proper method for conjugation of enrofloxacin to label enzymes, two methods were compared and carbodiimide condensation was proved to be better. The results showed that the binding ratio of enrofloxacin and alkaline phosphatase (ALP) was 8:1 and that of enrofloxacin and horseradish peroxidase (HRP) was 5:1. This indicated that conjugate synthesized by carbodiimide condensation was fit for chemiluminescence enzyme immunoassay (CLEIA). Furthermore, data revealed that dialysis time was an important parameter for conjugation and 6 days was best. Buffer to dilute conjugate had little effect on CLEIA. The storage condition for conjugates was also studied and it was shown that the conjugate was stable at 4 °C with no additive up to 30 days. These data were valuable for establishing CLEIA to quantify enrofloxacin.

  14. Formulation of enrofloxacin SLNs and its pharmacokinetics in emu ( Dromaius novaehollandiae) birds

    Science.gov (United States)

    Senthil Kumar, P.; Arivuchelvan, A.; Jagadeeswaran, A.; Punniamurthy, N.; Selvaraj, P.; Richard Jagatheesan, P. N.; Mekala, P.

    2015-08-01

    The study was conducted to formulate the enrofloxacin solid lipid nanoparticles (SLNs) with sustained release profile and improved pharmacological activity and evaluate the pharmacokinetic behaviour of enrofloxacin SLNs after oral routes of administration in emus. The SLNs were prepared using tripalmitin as lipid carrier, Tween 80 and Span 80 as surfactants and polyvinyl alcohol (PVA) as a stabilizer by a hot homogenization coupled with ultrasonication method. The prepared enrofloxacin SLNs formulations were characterized for further investigation in emu birds. The pharmacokinetics of native enrofloxacin was studied after i.v. and oral bolus administration at 10 mg/kg in emu birds and compared with the disposition kinetics of enrofloxacin SLNs. Enrofloxacin and its metabolite ciprofloxacin in plasma were estimated using HPLC and the pharmacokinetic parameters were calculated by a non-compartmental analysis. The results demonstrated that the particle size, polydispersity index, zeta potential, encapsulation efficiency and loading capacity of the SLNs were 154.72 ± 6.11 nm, 0.42 ± 0.11, -28.83 ± 0.60 mV, 59.66 ± 3.22 and 6.13 ± 0.32 %, respectively. AFM and TEM images showed spherical to circular particles with well-defined periphery. In vitro drug release exhibited biphasic pattern with an initial burst release of 18 % within 2 h followed by sustained release over 96 h. Pharmacokinetic results showed that the t 1/2 β , AUC0-∞, V darea/ F, MRT and bioavailability were 3.107, 1.894, 1.594, 2.993 and 1.895 times enhanced ( p enrofloxacin administered orally. The ratio of AUC0- t cipro/AUC0- t enro after administration of native enrofloxacin and enrofloxacin SLNs was less than 10 %. The t 1/2 β and MRT of the metabolite were longer than those of the parent substance. The PK/PD results confirmed that the SLNs extended the enrofloxacin concentration upto 48 h against pathogens susceptible to 0.125 μg/mL in emus. The results indicated that SLNs might be a

  15. Antibiotic-induced gut microbiota disruption during human endotoxemia: a randomised controlled study.

    Science.gov (United States)

    Lankelma, Jacqueline M; Cranendonk, Duncan R; Belzer, Clara; de Vos, Alex F; de Vos, Willem M; van der Poll, Tom; Wiersinga, W Joost

    2017-09-01

    The gut microbiota is essential for the development of the intestinal immune system. Animal models have suggested that the gut microbiota also acts as a major modulator of systemic innate immunity during sepsis. Microbiota disruption by broad-spectrum antibiotics could thus have adverse effects on cellular responsiveness towards invading pathogens. As such, the use of antibiotics may attribute to immunosuppression as seen in sepsis. We aimed to test whether disruption of the gut microbiota affects systemic innate immune responses during endotoxemia in healthy subjects. In this proof-of-principle intervention trial, 16 healthy young men received either no treatment or broad-spectrum antibiotics (ciprofloxacin, vancomycin and metronidazole) for 7 days, after which all were administered lipopolysaccharide intravenously to induce a transient sepsis-like syndrome. At various time points, blood and faeces were sampled. Gut microbiota diversity was significantly lowered by the antibiotic treatment in all subjects. Clinical parameters, neutrophil influx, cytokine production, coagulation activation and endothelial activation during endotoxemia were not different between antibiotic-pretreated and control individuals. Antibiotic treatment had no impact on blood leucocyte responsiveness to various Toll-like receptor ligands and clinically relevant causative agents of sepsis ( Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli ) during endotoxemia. These findings suggest that gut microbiota disruption by broad-spectrum antibiotics does not affect systemic innate immune responses in healthy subjects during endotoxemia in humans, disproving our hypothesis. Further research is needed to test this hypothesis in critically ill patients. These data underline the importance of translating findings in mice to humans. ClinicalTrials.gov (NCT02127749; Pre-results). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  16. Pharmacokinetics of enrofloxacin and marbofloxacin in Japanese quails and common pheasants.

    Science.gov (United States)

    Lashev, L D; Dimitrova, D J; Milanova, A; Moutafchieva, R G

    2015-04-01

    The pharmacokinetics of enrofloxacin and marbofloxacin was studied in Japanese quails and common pheasants. Healthy mature birds from both species and both genders were treated intravenously and orally with enrofloxacin (10 mg/kg) and marbofloxacin (5 mg/kg). After intravenous administration enrofloxacin was extensively metabolised to ciprofloxacin. Metabolites of marbofloxacin were not detected. Values of volume of distribution were respectively 4.63 l/kg and 3.67 l/kg for enrofloxacin and 1.56 l/kg and 1.43 l/kg for marbofloxacin. In quails, total body clearance values were higher than those in pheasants and other avian species. After oral application enrofloxacin was rapidly absorbed in quails, more rapidly than marbofloxacin. Pheasants absorbed both antimicrobials at a lower rate. Higher bioavailability was observed for marbofloxacin (118%). Relatively low bioavailability was established in quails for enrofloxacin (26.4%), accompanied by extensive conversion to ciprofloxacin. Generally, quails absorbed and eliminated both fluoroquinolones more rapidly than pheasants; the latter showed pharmacokinetics similar to poultry. Because of favourable pharmacokinetic properties, marbofloxacin should be preferred for oral administration in Japanese quails and pheasants for treatment of infections caused by equally susceptible pathogens.

  17. Impact of aflatoxin B1 on the pharmacokinetic disposition of enrofloxacin in broiler chickens.

    Science.gov (United States)

    Kalpana, Starling; Srinivasa Rao, G; Malik, Jitendra K

    2015-09-01

    The potential impact of subchronic exposure of aflatoxin B1 was investigated on the pharmacokinetic disposition of enrofloxacin in broiler chickens. Broiler chickens given either normal or aflatoxin B1 (750μg/kg diet) supplemented diet for 6 weeks received a single oral dose of enrofloxacin (10mg/kg body wt). Blood samples were drawn from the brachial vein at predetermined time intervals after drug administration. Enrofloxacin plasma concentrations analyzed by RP-HPLC were significantly lower in aflatoxin B1-exposed broiler chickens at 0.167, 0.5 and 1.0h after drug administration. In aflatoxin B1-exposed broiler chickens, the absorption rate constant (ka) of enrofloxacin (0.20±0.05h(-1)) was significantly decreased as compared to the unexposed birds (0.98±0.31h(-1)). The values of [Formula: see text] , tmax and AUC0-∞ of enrofloxacin were nonsignificantly increased by 17%, 26% and 17% in aflatoxin-exposed broiler chickens, respectively. Subchronic aflatoxin B1 exposure markedly decreased the initial absorption of enrofloxacin without significantly influencing other pharmacokinetic parameters in broiler chickens. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Cytotoxic effects and apoptosis induction of enrofloxacin in hepatic cell line of grass carp (Ctenopharyngodon idellus).

    Science.gov (United States)

    Liu, Bo; Cui, Yanting; Brown, Paul B; Ge, Xianping; Xie, Jun; Xu, Pao

    2015-12-01

    We determined the effect of enrofloxacin on the lactate dehydrogenase (LDH) release, reactive oxygen species (ROS), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), malondialdehyde (MDA), mitochondria membrane potential (ΔΨm) and apoptosis in the hepatic cell line of grass carp (Ctenopharyngodon idellus). Cultured cells were treated with different concentrations of enrofloxacin (12.5-200 ug/mL) for 24 h. We found that the cytotoxic effect of enrofloxacin was mediated by apoptosis, and that this apoptosis occurred in a dose-dependent manner. The doses of 50,100 and 200 μg/mL enrofloxacin increased the LDH release and MDA concentration, induced cell apoptosis and reduced the ΔΨm compared to the control. The highest dose of 200 ug/mL enrofloxacin also significantly induced apoptosis accompanied by ΔΨm disruption and ROS generation and significantly reduced T-AOC and increased MDA concentration compared to the control. Our results suggest that the dose of 200 ug/mL enrofloxacin exerts its cytotoxic effect and produced ROS via apoptosis by affecting the mitochondria of the hepatic cells of grass carp. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Medical Treatment of Diverticular Disease: Antibiotics.

    Science.gov (United States)

    Lué, Alberto; Laredo, Viviana; Lanas, Angel

    2016-10-01

    Diverticular disease (DD) of the colon represents the most common disease affecting the large bowel in western countries. Its prevalence is increasing. Recent studies suggest that changes in gut microbiota could contribute to development of symptoms and complication. For this reason antibiotics play a key role in the management of both uncomplicated and complicated DD. Rifaximin has demonstrated to be effective in obtaining symptoms relief at 1 year in patients with uncomplicated DD and to improve symptoms and maintain periods of remission following acute colonic diverticulitis (AD). Despite absence of data that supports the routine use of antibiotic in uncomplicated AD, they are recommended in selected patients. In patients with AD that develop an abscess, conservative treatment with broad-spectrum antibiotics is successful in up to 70% of cases. In patients on conservative treatment where percutaneous drainage fails or peritonitis develops, surgery is considered the standard therapy. In conclusion antibiotics seem to remain the mainstay of treatment in symptomatic uncomplicated DD and AD. Inpatient management and intravenous antibiotics are necessary in complicated AD, while outpatient management is considered the best strategy in the majority of uncomplicated patients.

  20. Short-term effect of antibiotics on human gut microbiota.

    Directory of Open Access Journals (Sweden)

    Suchita Panda

    Full Text Available From birth onwards, the human gut microbiota rapidly increases in diversity and reaches an adult-like stage at three years of age. After this age, the composition may fluctuate in response to external factors such as antibiotics. Previous studies have shown that resilience is not complete months after cessation of the antibiotic intake. However, little is known about the short-term effects of antibiotic intake on the gut microbial community. Here we examined the load and composition of the fecal microbiota immediately after treatment in 21 patients, who received broad-spectrum antibiotics such as fluoroquinolones and β-lactams. A fecal sample was collected from all participants before treatment and one week after for microbial load and community composition analyses by quantitative PCR and pyrosequencing of the 16S rRNA gene, respectively. Fluoroquinolones and β-lactams significantly decreased microbial diversity by 25% and reduced the core phylogenetic microbiota from 29 to 12 taxa. However, at the phylum level, these antibiotics increased the Bacteroidetes/Firmicutes ratio (p = 0.0007, FDR = 0.002. At the species level, our findings unexpectedly revealed that both antibiotic types increased the proportion of several unknown taxa belonging to the Bacteroides genus, a Gram-negative group of bacteria (p = 0.0003, FDR<0.016. Furthermore, the average microbial load was affected by the treatment. Indeed, the β-lactams increased it significantly by two-fold (p = 0.04. The maintenance of or possible increase detected in microbial load and the selection of Gram-negative over Gram-positive bacteria breaks the idea generally held about the effect of broad-spectrum antibiotics on gut microbiota.

  1. Recent advances in the chemistry and biology of carbapenem antibiotics.

    Science.gov (United States)

    Coulton, S; Hunt, E

    1996-01-01

    The discovery of the olivanic acids and thienamycin aroused considerable interest amongst medicinal chemists and microbiologists around the world. The susceptibility of these agents to metabolic degradation has, however, been a major obstacle in their development. For many years the only notable success from such intensive research was the combination of imipenem with cilastatin, an inhibitor of the renal dipeptidase enzyme DHP-1. The enormous success of Primaxin for the treatment of a range of life-threatening bacterial infections provided the impetus for the discovery of totally synthetic, non-natural carbapenem derivatives that combine the broad spectrum of antimicrobial activity with stability to enzymatic degradation. This has indeed been realised in the development of meropenem; it possesses the broad spectrum of activity and resistance to beta-lactamases that are embodied in imipenem as well as displaying increased stability to human dehydropeptidases. Most recent research has focused upon the development of carbapenem antibiotics which combine broad spectrum antimicrobial activity and metabolic stability with oral absorption, for the treatment of community-acquired infections. Indeed, the pro-drug esters of the tricyclic carbapenems represent the first significant advance in this respect. However, the increased use of carbapenem antibiotics would undoubtedly accelerate the emergence of carbapenem-hydrolysing enzymes. The ultimate challenge could therefore be the design and synthesis of carbapenem derivatives that are resistant to these metallo-beta-lactamases. Due to the enormous problems encountered in the development of the carbapenem antibiotics, this area of research has, in the past, been described as a battlefield that did not bode well for the future [181]. Primaxin and meropenem proved however that these problems were not insurmountable, and are therefore a testimony to the persistence and dedication of those scientists in their war against

  2. Broad- versus Narrow-Spectrum Oral Antibiotic Transition and Outcomes in Health Care-associated Pneumonia.

    Science.gov (United States)

    Buckel, Whitney R; Stenehjem, Edward; Sorensen, Jeff; Dean, Nathan; Webb, Brandon

    2017-02-01

    Guidelines recommend a switch from intravenous to oral antibiotics once patients who are hospitalized with pneumonia achieve clinical stability. However, little evidence guides the selection of an oral antibiotic for patients with health care-associated pneumonia, especially where no microbiological diagnosis is made. To compare outcomes between patients who were transitioned to broad- versus narrow-spectrum oral antibiotics after initially receiving broad-spectrum intravenous antibiotic coverage. We performed a secondary analysis of an existing database of adults with community-onset pneumonia admitted to seven Utah hospitals. We identified 220 inpatients with microbiology-negative health care-associated pneumonia from 2010 to 2012. After excluding inpatient deaths and treatment failures, 173 patients remained in which broad-spectrum intravenous antibiotics were transitioned to an oral regimen. We classified oral regimens as broad-spectrum (fluoroquinolone) versus narrow-spectrum (usually a β-lactam). We compared demographic and clinical characteristics between groups. Using a multivariable regression model, we adjusted outcomes by severity (electronically calculated CURB-65), comorbidity (Charlson Index), time to clinical stability, and length of intravenous therapy. Age, severity, comorbidity, length of intravenous therapy, and clinical response were similar between the two groups. Observed 30-day readmission (11.9 vs. 21.4%; P = 0.26) and 30-day all-cause mortality (2.3 vs. 5.3%; P = 0.68) were also similar between the narrow and broad oral antibiotic groups. In multivariable analysis, we found no statistically significant differences for adjusted odds of 30-day readmission (adjusted odds ratio, 0.56; 95% confidence interval, 0.06-5.2; P = 0.61) or 30-day all-cause mortality (adjusted odds ratio, 0.55; 95% confidence interval, 0.19-1.6; P = 0.26) between narrow and broad oral antibiotic groups. On the basis of analysis of a limited number of patients

  3. Broad-spectrum antiviral properties of andrographolide.

    Science.gov (United States)

    Gupta, Swati; Mishra, K P; Ganju, Lilly

    2017-03-01

    Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. This purified compound has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress, Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). All these properties of andrographolide form the foundation for the use of this miraculous compound to restrain virus replication and virus-induced pathogenesis. The present article covers antiviral properties of andrographolide in variety of viral infections, with the hope of developing of a new highly potent antiviral drug with multiple effects.

  4. Clinical Efficacy and Residue Depletion of 10% Enrofloxacin Enteric-Coated Granules in Pigs.

    Science.gov (United States)

    Lei, Zhixin; Liu, Qianying; Yang, Bing; Xiong, Jincheng; Li, Kun; Ahmed, Saeed; Hong, Liping; Chen, Pin; He, Qigai; Cao, Jiyue

    2017-01-01

    A new, more palatable formulation of 10% enrofloxacin enteric-coated granules was investigated to evaluate the pharmacokinetic effect in plasma, the residue elimination in tissues and the clinical efficacy against Actinobacillus pleuropneumonia (APP) and Mycoplasam suis (MS) in pigs. In this study, the enrofloxacin concentrations in plasma and tissues were detected using high-performance liquid chromatography with phosphate buffer (pH = 3) and acetonitrile. The pharmacokinetics and elimination of enrofloxacin enteric-coated granules were performed after oral administration at a single dose of 10 mg/kg body weight (bw) and 5 mg/kg twice per day for 5 consecutive days, respectively. The in vivo antibacterial efficacy and clinical effectiveness of enrofloxacin enteric-coated granules against APP and MS were assayed at 2.5, 5, 10 mg/kg, compared with tiamulin (8 mg/kg) based on establishment of APP and MS infection models. 56 APP strains were selected and tested for in vitro antibacterial activity of enrofloxacin enteric-coated granules. The main parameters of elimination half-life (t 1/2β ), T max , and area under the curve (AUC) were 14.99 ± 4.19, 3.99 ± 0.10, and 38.93 ± 1.52 μg h/ml, respectively, revealing that the enrofloxacin concentration remained high and with a sustainable distribution in plasma. Moreover, the analysis on the evaluation of enrofloxacin and ciprofloxacin in muscle, fat, liver and kidney showed that the recovery were more than 84% recovery in accordance with the veterinary drug residue guidelines of United States pharmacopeia, and the withdrawal periods were 4.28, 3.81, 4.84, and 3.51 days, respectively, suggesting that the withdrawal period was 5 d after oral administration of 5 mg/kg twice per day. The optimal dosage of enrofloxacin enteric-coated granules against APP and MS was 5 mg/kg, with over 90% efficacy, which was significantly different ( p enrofloxacin enteric-coated granules had significant potential for treating APP and MS

  5. Clinical Efficacy and Residue Depletion of 10% Enrofloxacin Enteric-Coated Granules in Pigs

    Directory of Open Access Journals (Sweden)

    Zhixin Lei

    2017-05-01

    Full Text Available A new, more palatable formulation of 10% enrofloxacin enteric-coated granules was investigated to evaluate the pharmacokinetic effect in plasma, the residue elimination in tissues and the clinical efficacy against Actinobacillus pleuropneumonia (APP and Mycoplasam suis (MS in pigs. In this study, the enrofloxacin concentrations in plasma and tissues were detected using high-performance liquid chromatography with phosphate buffer (pH = 3 and acetonitrile. The pharmacokinetics and elimination of enrofloxacin enteric-coated granules were performed after oral administration at a single dose of 10 mg/kg body weight (bw and 5 mg/kg twice per day for 5 consecutive days, respectively. The in vivo antibacterial efficacy and clinical effectiveness of enrofloxacin enteric-coated granules against APP and MS were assayed at 2.5, 5, 10 mg/kg, compared with tiamulin (8 mg/kg based on establishment of APP and MS infection models. 56 APP strains were selected and tested for in vitro antibacterial activity of enrofloxacin enteric-coated granules. The main parameters of elimination half-life (t1/2β, Tmax, and area under the curve (AUC were 14.99 ± 4.19, 3.99 ± 0.10, and 38.93 ± 1.52 μg h/ml, respectively, revealing that the enrofloxacin concentration remained high and with a sustainable distribution in plasma. Moreover, the analysis on the evaluation of enrofloxacin and ciprofloxacin in muscle, fat, liver and kidney showed that the recovery were more than 84% recovery in accordance with the veterinary drug residue guidelines of United States pharmacopeia, and the withdrawal periods were 4.28, 3.81, 4.84, and 3.51 days, respectively, suggesting that the withdrawal period was 5 d after oral administration of 5 mg/kg twice per day. The optimal dosage of enrofloxacin enteric-coated granules against APP and MS was 5 mg/kg, with over 90% efficacy, which was significantly different (p < 0.05 to the 2.5 mg/kg group, but not to the 10 mg/kg group or the positive

  6. Principles of Antibiotic Management of Community-Acquired Pneumonia.

    Science.gov (United States)

    Bender, Michael T; Niederman, Michael S

    2016-12-01

    Community-acquired pneumonia (CAP) encompasses a broad spectrum of disease severity and may require outpatient, inpatient, or intensive care management. Successful treatment hinges on expedient delivery of appropriate antibiotic therapy tailored to both the likely offending pathogens and the severity of disease. This review summarizes key principles in starting treatment and provides recommended empiric therapy regimens for each site of care. In addition, we discuss the antimicrobial and anti-inflammatory role macrolides play in CAP, as well as specific information for managing individual CAP pathogens such as community-acquired methicillin-resistant Staphylococcus aureus and drug-resistant Streptococcus pneumoniae . We also examine several novel antibiotics being developed for CAP and review the evidence guiding duration of therapy and current best practices for the transition of hospitalized patients from intravenous antibiotics to oral therapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  7. Surface-imprinted nanofilaments for europium-amplified luminescent detection of fluoroquinolone antibiotics.

    Science.gov (United States)

    Zdunek, Jolanta; Benito-Peña, Elena; Linares, Ana; Falcimaigne-Cordin, Aude; Orellana, Guillermo; Haupt, Karsten; Moreno-Bondi, María C

    2013-07-29

    The development and characterization of novel, molecularly imprinted polymer nanofilament-based optical sensors for the analysis of enrofloxacin, an antibiotic widely used for human and veterinary applications, is reported. The polymers were prepared by nanomolding in porous alumina by using enrofloxacin as the template. The antibiotic was covalently immobilized on to the pore walls of the alumina by using different spacers, and the prepolymerization mixture was cast in the pores and the polymer synthesized anchored onto a glass support through UV polymerization. Various parameters affecting polymer selectivity were evaluated to achieve optimal recognition, namely, the spacer arm length and the binding solvent. The results of morphological characterization, binding kinetics, and selectivity of the optimized polymer material for ENR and its derivatives are reported. For sensing purposes, the nanofilaments were incubated in solutions of the target molecule in acetonitrile/HEPES buffer (100 mM, pH 7.5, 50:50, v/v) for 20 min followed by incubation in a 10 mM solution of europium(III) ions to generate a europium(III)-enrofloxacin complex on the polymer surface. The detection event was based on the luminescence of the rare-earth ion (λexc=340 nm; λem=612 nm) that results from energy transfer from the antibiotic excited state to the metal-ion emitting excited state. The limit of detection of the enrofloxacin antibiotic was found to be 0.58 μM. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. In vitro antibiotic susceptibility of Dutch Mycoplasma synoviae field isolates originating from joint lesions and the respiratory tract of commercial poultry.

    Science.gov (United States)

    Landman, W J M; Mevius, D J; Veldman, K T; Feberwee, A

    2008-08-01

    The in vitro susceptibility of 17 Dutch Mycoplasma synoviae isolates from commercial poultry to enrofloxacin, difloxacin, doxycycline, tylosin and tilmicosin was examined. Three isolates originated from joint lesions and 14 were from the respiratory tract. The type strain M. synoviae WVU 1853 was included as a control strain. Antibiotic susceptibility was tested quantitatively using the broth microdilution test. Based on initial and final minimum inhibitory concentration values, all tested isolates were susceptible to doxycycline, tylosin and tilmicosin. Two isolates from the respiratory tract were resistant to enrofloxacin and showed intermediate resistance to difloxacin.

  9. Antibiotics threaten wildlife: circulating quinolone residues and disease in Avian scavengers.

    Directory of Open Access Journals (Sweden)

    Jesús A Lemus

    Full Text Available Antibiotic residues that may be present in carcasses of medicated livestock could pass to and greatly reduce scavenger wildlife populations. We surveyed residues of the quinolones enrofloxacin and its metabolite ciprofloxacin and other antibiotics (amoxicillin and oxytetracycline in nestling griffon Gyps fulvus, cinereous Aegypius monachus and Egyptian Neophron percnopterus vultures in central Spain. We found high concentrations of antibiotics in the plasma of many nestling cinereous (57% and Egyptian (40% vultures. Enrofloxacin and ciprofloxacin were also found in liver samples of all dead cinereous vultures. This is the first report of antibiotic residues in wildlife. We also provide evidence of a direct association between antibiotic residues, primarily quinolones, and severe disease due to bacterial and fungal pathogens. Our results indicate that, by damaging the liver and kidney and through the acquisition and proliferation of pathogens associated with the depletion of lymphoid organs, continuous exposure to antibiotics could increase mortality rates, at least in cinereous vultures. If antibiotics ingested with livestock carrion are clearly implicated in the decline of the vultures in central Spain then it should be considered a primary concern for conservation of their populations.

  10. Removal of five fluoroquinolone antibiotics during broiler manure composting.

    Science.gov (United States)

    Yang, Bing; Meng, Lei; Xue, Nandong

    2018-02-01

    Composting is a cost-effective approach for the removal of antibiotics from the environment; however, the consequence of this approach on fluoroquinolone antibiotics is limited. The fate of five representative fluoroquinolone antibiotics, namely ciprofloxacin, enrofloxacin, lomefloxacin, norfloxacin, and sarafloxacin, was investigated in a pilot-scale composting of broiler manure over 42 days. The effect of antibiotic concentrations (at a dose of 15, 30, or 60 mg/kg for each and a control without antibiotic addition) on the composting process was also assessed. The 42-day composting showed 45.3-75.4% of antibiotic removal with species-specific patterns. However, the observed variations in such removal among both antibiotics concentrations and composting times were not significant in most cases, possibly indicating a slight side-effect of the tested antibiotic concentrations on the composting process. To the best of our knowledge, this study is among few studies with a focus on the persistence of fluoroquinolone antibiotics during a pilot-scale composting, which warrants further study in regards to the mechanism underlying the removal of these compounds during composting.

  11. [Antibiotic prescribing in acute respiratory tract infections in general practice].

    Science.gov (United States)

    Malo, S; Bjerrum, L; Feja, C; Lallana, M J; Poncel, A; Rabanaque, M J

    2015-06-01

    Antimicrobial resistance is a worldwide threat to public health. Acute respiratory tract infections are the main reason for antibiotic prescribing in the Spanish paediatric population. The aim of the study was to describe the frequency of antibiotic prescription and their pattern of use in acute respiratory tract infections diagnosed in children in Primary Care in Aragón (Spain). A study was conducted over a 1-year period on children between 0 and 14 years-old, recording all episodes of acute otitis, acute pharyngotonsillitis, non-specific upper respiratory infection, and acute bronchitis. The proportion of episodes within each diagnosis receiving an antibiotic prescription was calculated, and the prescribing pattern was determined. Half (50%) of the children in Aragón were diagnosed with a respiratory tract infection during the study period. Non-specific upper respiratory infection was the most frequent diagnosis. An antibiotic was prescribed in 75% of pharyngotonsillitis episodes, 72% of otitis, 27% of bronchitis, and 16% of non-specific upper respiratory infections. Broad spectrum antibiotics, mainly amoxicillin and amoxicillin-clavulanic, were predominantly prescribed. Antibiotic prescribing in respiratory tract infections in children was generally high, and the choice of antibiotics was probably inappropriate in a high percentage of cases. Therefore an improvement in antibiotic prescribing in children appears to be needed. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  12. Hematological and Biochemical Alterations due to Over Dosage of Enrofloxacin in Cats

    Directory of Open Access Journals (Sweden)

    Sardar Jafari Shoorijeh, Amin Tamadon1, 2, Mahjoob Vahedi3 and Mohammad Amin Behzadi4*

    2012-01-01

    Full Text Available Enrofloxacin, an antimicrobial agent used to treat bacterial diseases is well tolerated by cats at recommended dosage (5 mg/kg. To investigate the tolerance of high-dose of the Hipralona Enro-I® (5% enrofloxacin solution in cats, 28 urban cats (11 males and 17 females between the weight of 1.3 and 2.4 kg were randomly assigned to a control group (n=4 and three treatment groups (n=8. Each treatment groups were injected low-dose enrofloxacin (5 mg/kg, IM, high-dose enrofloxacin (15 mg/kg, IM, and very high-dose enrofloxacin (25 mg/kg, IM once daily for seven consecutive days. Blood samples were collected from jugular vein before injection of enrofloxacin in the hind limb muscles of cats as self-control, and at 3rd, 7th, 14th, and 21st days after first drug injection. Samples were tested for various hematological and serum biochemical parameters. The systemic tolerance during experiment was investigated via monitoring of behavior and general physical examination. Hematological and serum biochemical parameters were not significantly different between groups. In addition, there was no statistically difference between various sampling days for any treatment group in each parameter. Furthermore, there was no change in the behavior and the general health condition of cats in the control and the three experimental groups. As serum biochemical indications of hepatotoxication and nephrotoxication were not observed. It was concluded that muscular injection of enrofloxacin in doses up to 25 mg/kg (5ED50 for seven consecutive days was tolerated by cats.

  13. Molecular characterization of acquired enrofloxacin resistance in Mycoplasma synoviae field isolates.

    Science.gov (United States)

    Lysnyansky, I; Gerchman, I; Mikula, I; Gobbo, F; Catania, S; Levisohn, S

    2013-07-01

    The in vitro activity of enrofloxacin against 73 Mycoplasma synoviae field strains isolated in Israel and Europe was determined by broth microdilution. Decreased susceptibility to enrofloxacin was identified in 59% of strains, with the MICs ranging from 1 to >16 μg/ml. The estimated MIC50 and MIC90 values for enrofloxacin were 2 and 8 μg/ml, respectively. Moreover, this study showed that 92% of recent Israeli field isolates (2009 to 2011) of M. synoviae have MICs of ≥ 2 μg/ml to enrofloxacin. Comparison of the quinolone resistance-determining regions (QRDRs) in M. synoviae isolates revealed a clear correlation between the presence of one of the amino acid substitutions Asp79-Asn, Thr80-Ala/Ile, Ser81-Pro, and Asp84-Asn/Tyr/His of the ParC QRDR and decreased susceptibility to enrofloxacin (MIC, ≥ 1 μg/ml). Amino acid substitutions at positions GyrA 87, GyrB 401/402, and ParE 420/454 were also identified, but there was no clear-cut correlation with susceptibility to enrofloxacin. Comparison of vlhA molecular profiles revealed the presence of 9 different genotypes in the Israeli M. synoviae field isolates and 10 genotypes in the European isolates; only one vlhA genotype (type 4) was identified in both cohorts. Based on results of vlhA molecular typing, several mechanisms for emergence and dissemination of Israeli enrofloxacin-resistant M. synoviae isolates are suggested.

  14. Concentration of hepatic vitamins A and E in rats exposed to chlorpyrifos and/or enrofloxacin.

    Science.gov (United States)

    Spodniewska, A; Barski, D

    2016-01-01

    The aim of the study was to determine the level of antioxidant vitamins A and E in the liver of rats exposed to chlorpyrifos and/or enrofloxacin. Chlorpyrifos (Group I) was administered at a dose of 0.04 LD50 (6 mg/kg b.w.) for 28 days, and enrofloxacin (Group II) at a dose of 5 mg/kg b.w. for 5 consecutive days. The animals of group III were given both of the mentioned above compounds at the same manner as groups I and II, but enrofloxacin was applied to rats for the last 5 days of chlorpyrifos exposure (i.e. on day 24, 25, 26, 27 and 28). Chlorpyrifos and enrofloxacin were administered to rats intragastrically via a gastric tube. The quantitative determination of vitamins was made by the HPLC method. The results of this study indicated a reduction in the hepatic concentrations of vitamins A and E, compared to the control, which sustained for the entire period of the experiment. The four-week administration of chlorpyrifos to rats resulted in a significant decrease of vitamins in the initial period of the experiment, i.e. up to 24 hours after exposure. For vitamin A the maximum drop was observed after 24 hours (19.24%) and for vitamin E after 6 hours (23.19%). Enrofloxacin caused a slight (3-9%) reduction in the level of the analysed vitamins. In the chlorpyrifos-enrofloxacin co-exposure group reduced vitamins A and E levels were also noted, but changes in this group were less pronounced in comparison to the animals intoxicated with chlorpyrifos only. The decrease in the antioxidant vitamin levels, particularly noticeable in the chlorpyrifos- and the chlorpyrifos combined with enrofloxacin-treated groups, may result not only from the increase in the concentration of free radicals, but also from the intensification of the secondary stages of lipid peroxidation.

  15. Occurrence and risk assessment of four typical fluoroquinolone antibiotics in raw and treated sewage and in receiving waters in Hangzhou, China.

    Science.gov (United States)

    Tong, Changlun; Zhuo, Xiajun; Guo, Yun

    2011-07-13

    A sensitive liquid chromatography-fluorescence detection method, combined with one-step solid-phase extraction, was established for detecting the residual levels of the four typical fluoroquinolone antibiotics (ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin) in influent, effluent, and surface waters from Hangzhou, China. For the various environmental water matrices, the overall recoveries were from 76.8 to 122%, and no obvious interferences of matrix effect were observed. The limit of quantitation of this method was estimated to be 17 ng/L for ciprofloxacin and norfloxacin, 20 ng/L for ofloxacin, and 27 ng/L for enrofloxacin. All of the four typical fluoroquinolone antibiotics were found in the wastewaters and surface waters. The residual contents of the four typical fluoroquinolone antibiotics in influent, effluent, and surface water samples are 108-1405, 54-429, and 7.0-51.6 ng/L, respectively. The removal rates of the selected fluoroquinolone antibiotics were 69.5 (ofloxacin), 61.3 (norfloxacin), and 50% (enrofloxacin), indicating that activated sludge treatment is effective except for ciprofloxacin and necessary to remove these fluoroquinolone antibiotics in municipal sewage. The risk to the aquatic environment was estimated by a ratio of measured environmental concentration and predicted no-effect concentration. At the concentrations, these fluoroquinolone antibiotics were found in influent, effluent, and surface waters, and they should not pose a risk for the aquatic environment.

  16. Synergistic antimicrobial therapy using nanoparticles and antibiotics for the treatment of multidrug-resistant bacterial infection

    Science.gov (United States)

    Gupta, Akash; Saleh, Neveen M.; Das, Riddha; Landis, Ryan F.; Bigdeli, Arafeh; Motamedchaboki, Khatereh; Rosa Campos, Alexandre; Pomeroy, Kenneth; Mahmoudi, Morteza; Rotello, Vincent M.

    2017-06-01

    Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. Antibiotic treatment of resistant infections further contributes to the rapidly increasing number of antibiotic-resistant species and strains. Synthetic macromolecules such as nanoparticles (NPs) exhibit broad-spectrum activity against MDR species, however lack of specificity towards bacteria relative to their mammalian hosts limits their widespread therapeutic application. Here, we demonstrate synergistic antimicrobial therapy using hydrophobically functionalized NPs and fluoroquinolone antibiotics for treatment of MDR bacterial strains. An 8-16-fold decrease in antibiotic dosage is achieved in presence of engineered NPs to combat MDR strains. This strategy demonstrates the potential of using NPs to ‘revive’ antibiotics that have been rendered ineffective due to the development of resistance by pathogenic bacteria.

  17. A high-resolution map of the Grp1 locus on chromosome V of potato harbouring broad-spectrum resistance to the cyst nematode species Globodera pallida and Globodera rostochiensis.

    Science.gov (United States)

    Finkers-Tomczak, Anna; Danan, Sarah; van Dijk, Thijs; Beyene, Amelework; Bouwman, Liesbeth; Overmars, Hein; van Eck, Herman; Goverse, Aska; Bakker, Jaap; Bakker, Erin

    2009-06-01

    The Grp1 locus confers broad-spectrum resistance to the potato cyst nematode species Globodera pallida and Globodera rostochiensis and is located in the GP21-GP179 interval on the short arm of chromosome V of potato. A high-resolution map has been developed using the diploid mapping population RHAM026, comprising 1,536 genotypes. The flanking markers GP21 and GP179 have been used to screen the 1,536 genotypes for recombination events. Interval mapping of the resistances to G. pallida Pa2 and G. rostochiensis Ro5 resulted in two nearly identical LOD graphs with the highest LOD score just north of marker TG432. Detailed analysis of the 44 recombinant genotypes showed that G. pallida and G. rostochiensis resistance could not be separated and map to the same location between marker SPUD838 and TG432. It is suggested that the quantitative resistance to both nematode species at the Grp1 locus is mediated by one or more tightly linked R genes that might belong to the NBS-LRR class.

  18. Novel, broad-spectrum anticonvulsants containing a sulfamide group: pharmacological properties of (S)-N-[(6-chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112).

    Science.gov (United States)

    McComsey, David F; Smith-Swintosky, Virginia L; Parker, Michael H; Brenneman, Douglas E; Malatynska, Ewa; White, H Steve; Klein, Brian D; Wilcox, Karen S; Milewski, Michael E; Herb, Mark; Finley, Michael F A; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Reitz, Allen B; Maryanoff, Bruce E

    2013-11-27

    Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such "neurostabilizers" have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4-9, 10a-i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures. Mechanistically, 4 inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels and was effective as a K(+) channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies.

  19. Kaposi sarcoma-associated herpes virus targets the lymphotactin receptor with both a broad spectrum antagonist vCCL2 and a highly selective and potent agonist vCCL3

    DEFF Research Database (Denmark)

    Lüttichau, Hans R; Johnsen, Anders H; Jurlander, Jesper

    2007-01-01

    virus (KSHV) encodes three chemokine-like proteins named vCCL1, vCCL2, and vCCL3. In this study vCCL3 was probed in parallel with vCCL1 and vCCL2 against a panel of the 18 classified human chemokine receptors. In calcium mobilization assays vCCL1 acted as a selective CCR8 agonist, whereas vCCL2......Large DNA viruses such as herpesvirus and poxvirus encode proteins that target and exploit the chemokine system of their host. These proteins have the potential to block or change the orchestrated recruitment of leukocytes to sites of viral infection. The genome of Kaposi sarcoma-associated herpes...... was found to act as a broad spectrum chemokine antagonist of human chemokine receptors, including the lymphotactin receptor. In contrast vCCL3 was found to be a highly selective agonist for the human lymphotactin receptor XCR1. The potency of vCCL3 was found to be 10-fold higher than the endogenous human...

  20. Effect of Enrofloxacin on Histochemistry, Immunohistochemistry and Molecular Changes in Lamb Articular Cartilage.

    Science.gov (United States)

    Khazaeel, Kaveh; Mazaheri, Yazdan; Hashemi Tabar, Mahmood; Najafzadeh, Hossein; Morovvati, Hassan; Ghadrdan, Alireza

    2015-01-01

    Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections. It is metabolized to ciprofloxacin in the body as active metabolite. Fluoroquinolones change in the articular cartilage, especially with high doses and more than two weeks use. So, due to relatively excessive use of enrofloxacin in mammals and similarity of lambs to human subjects with respect to skeletal activity cycles, this study was done to investigate the effects of enrofloxacin on some cellular and molecular changes in growing lamb articular cartilage to evaluate some possible mechanisms involved these changes. Twelve, 2-month-old male lambs divided into three groups: control group received only normal saline; therapeutic group received 5mg/kg enrofloxacin subcutaneously, daily, for 15 days and toxic group received 35 mg/kg enrofloxacin in the same manner as therapeutic group. Twenty four hours after the last dose, the animals were sacrificed, and their stifle joints were dissected. Sampling from distal femoral and proximal tibial extremities was done quickly for further histological and molecular studies. Collagen-п content was studied with avidin-biotin immunohistochemistry method in different groups. Expression of Sox9 and caspase-3 was evaluated by Real-time PCR. Immunohistochemical changes were included decreases of matrix proteoglycans, carbohydrates, and Collagen-п in the toxic group. Some of these changes were observed in the therapeutic group with less intensity in comparison to the toxic group. Enrofloxacin were significantly decreased (P≤0.05). Sox9 expression in therapeutic and toxic groups compared to control group. But caspase -3 expressions in the toxic group significantly increased (P≤0.0001) with a comparison to other groups, while, between control and therapeutic groups, there were no significant differences. So, it can be concluded that enrofloxacin increases apoptosis in chondrocytes and

  1. Actinomycetes: still a source of novel antibiotics.

    Science.gov (United States)

    Genilloud, Olga

    2017-10-18

    Covering: 2006 to 2017Actinomycetes have been, for decades, one of the most important sources for the discovery of new antibiotics with an important number of drugs and analogs successfully introduced in the market and still used today in clinical practice. The intensive antibacterial discovery effort that generated the large number of highly potent broad-spectrum antibiotics, has seen a dramatic decline in the large pharma industry in the last two decades resulting in a lack of new classes of antibiotics with novel mechanisms of action reaching the clinic. Whereas the decline in the number of new chemical scaffolds and the rediscovery problem of old known molecules has become a hurdle for industrial natural products discovery programs, new actinomycetes compounds and leads have continued to be discovered and developed to the preclinical stages. Actinomycetes are still one of the most important sources of chemical diversity and a reservoir to mine for novel structures that is requiring the integration of diverse disciplines. These can range from novel strategies to isolate species previously not cultivated, innovative whole cell screening approaches and on-site analytical detection and dereplication tools for novel compounds, to in silico biosynthetic predictions from whole gene sequences and novel engineered heterologous expression, that have inspired the isolation of new NPs and shown their potential application in the discovery of novel antibiotics. This review will address the discovery of antibiotics from actinomycetes from two different perspectives including: (1) an update of the most important antibiotics that have only reached the clinical development in the recent years despite their early discovery, and (2) an overview of the most recent classes of antibiotics described from 2006 to 2017 in the framework of the different strategies employed to untap novel compounds previously overlooked with traditional approaches.

  2. Effect of pretreatment female lactating rats with albendazole on preventing developmental and neurobehavioral toxicity of enrofloxacin in suckling pups

    Directory of Open Access Journals (Sweden)

    M. K. Shindala

    2012-01-01

    Full Text Available The aim of the present study was to evaluated the effect of treated female lactating rats with enrofloxacin alone and itsinteraction with albendazole on the occurrence of developmental and neurobehavioral toxicity in suckling pups by usingpercentage of survival of pups to weaning as well as neurobehavioral test (surface righting reflex. The exposure of sucklingpups to enrofloxacin alone through the milk caused sever toxic effects manifested by significant decrease in percentage ofsurvival in pups to weaning to (0% as result from death all pups from dams were treated with enrofloxacin at high dose (480mg/kg, i.m. during the first 5 days of lactation. Whereas, treated lactating female rats with albendazole at (300 mg/kg, orally,1 hour before enrofloxacin (480 mg/kg, i.m. during the first 5 days of lactation protected suckling pups from developmentaltoxic effects of enrofloxacin which mainly appeared as a significant increase in percentage of survival of pups to 100% asresult from survival all suckling pups to weaning, accompanied by preventing the neurobehavioral toxicity of enrofloxacin insuckling pups manifested by highly significant decreased response time to surface righting reflex to (2.64 ± 0.57 minuets inthe postnatal day 3 in compared with pups from dams that treated with enrofloxacin alone which reached to (15.82 ± 0.27minuets. In conclusion, our results suggest that pretreatment of female lactating rats with albendazole protecte suckling pupsfrom developme-ntal and neurobehavioral toxicity of enrofloxacin.

  3. Effects of parenteral administration of enrofloxacin on electrocardiographic parameters in hospitalized dogs

    Directory of Open Access Journals (Sweden)

    Carlos Fernando Agudelo Ramírez

    2012-01-01

    Full Text Available The effect of enrofloxacin on the QT interval of the electrocardiogram was studied in 30 hospitalized dogs. The experimental group (n = 15 received enrofloxacin parenterally (subcutaneously at a dose of 5 mg/kg twice daily and amoxicillin-clavulanate intravenously at a dose of 22 mg/kg three times daily. The control group (n = 15 received only amoxicillin-clavulanate. Electrocardiography was carried out for 5 min once daily for 6 days. The QT interval was corrected by four different formulae. No differences were found between the two groups or within each group for the duration of the study. On the last day of the study the average QT interval for the control and experimental groups was 213.2 ms and 202.9 ms, respectively. Enrofloxacin did not cause prolongation of the QT or corrected QT intervals. We can conclude that the parenteral administration of enrofloxacin in non-cardiac dogs does not adversely affect the electrocardiographic indicators (no prolongation of the QT or corrected QT interval and does not induce ventricular arrhythmias. Parenteral use of enrofloxacin is thus safe and effective in non-cardiac dogs.

  4. Pharmacokinetics of enrofloxacin following oral and subcutaneous administration in the common ringtail possum (Pseudocheirus peregrinus).

    Science.gov (United States)

    Scheelings, T F; Devi, J L; Woodward, A P; Whittem, T

    2015-10-01

    [Correction added on 23 March 2015, after first online publication: Terminal half-life values of enrofloxacin is corrected in the fourth sentence of the abstract] Clinically healthy common ringtail possums (n = 5) received single doses of 10 mg/kg enrofloxacin orally and then 2 weeks later subcutaneously. Serial plasma samples were collected over 24 h for each treatment phase, and enrofloxacin concentrations were determined using a validated HPLC assay. Pharmacokinetic parameters were determined by noncompartmental analysis. Following oral administration, plasma concentrations were of therapeutic relevance (Cmax median 5.45 μg/mL, range 2.98-6.9 μg/mL), with terminal-phase half-life (t½ ) shorter than in other species (median 3.09 h, range 1.79-5.30 h). In contrast, subcutaneous administration of enrofloxacin did not achieve effective plasma concentrations, with plasma concentrations too erratic to fit the noncompartmental model except in one animal. On the basis of the AUC:MIC, enrofloxacin administered at 10 mg/kg orally, but not subcutaneously, is likely to be effective against a range of bacterial species that have been reported in common ringtail possums. © 2015 John Wiley & Sons Ltd.

  5. Preparation and evaluation of enrofloxacin microspheres and tissue distribution in rats.

    Science.gov (United States)

    Yang, Fan; Kang, Jijun; Yang, Fang; Zhao, Zhensheng; Kong, Tao; Zeng, Zhenling

    2015-01-01

    New enrofloxacin microspheres were formulated, and their physical properties, lung-targeting ability, and tissue distribution in rats were examined. The microspheres had a regular and round shape. The mean diameter was 10.06 µm, and the diameter of 89.93% of all microspheres ranged from 7.0 µm to 30.0 µm. Tissue distribution of the microspheres was evaluated along with a conventional enrofloxacin preparation after a single intravenous injection (7.5 mg of enrofloxacin/kg bw). The results showed that the elimination half-life (t1/2β) of enrofloxacin from lung was prolonged from 7.94 h for the conventional enrofloxacin to 13.28 h for the microspheres. Area under the lung concentration versus time curve from 0 h to ∞ (AUC00∞) was increased from 11.66 h·µg/g to 508.00 h·µg/g. The peak concentration (Cmax) in lung was increased from 5.95 µg/g to 93.36 µg/g. Three lung-targeting parameters were further assessed and showed that the microspheres had remarkable lung-targeting capabilities.

  6. Plasma concentrations of enrofloxacin in African grey parrots treated with medicated water.

    Science.gov (United States)

    Flammer, K; Aucoin, D P; Whitt, D A; Prus, S A

    1990-01-01

    Plasma concentrations of enrofloxacin were measured four times during a 7-day treatment period in African grey parrots that were fed with enrofloxacin-medicated drinking water. Water medicated at doubling doses of 0.09, 0.19, 0.38, 0.75, 1.5, and 3.0 mg/ml achieved mean concentrations (+/- SEM) of 0.10 (+/- 0.05), 0.12 (+/- 0.05), 0.12 (+/- 0.03), 0.15 (+/- 0.05), 0.30 (+/- 0.11), and 0.20 (+/- 0.06) micrograms/ml, respectively. A portion of the administered enrofloxacin was metabolized to an equipotent metabolite, ciprofloxacin. Mean ciprofloxacin concentrations paralleled enrofloxacin concentrations but were lower, ranging from 0.04 to 0.27 micrograms/ml. Acceptance of medicated water was adequate at lower doses; however, at doses of 1.5 and 3.0 mg/ml, acceptance was unsatisfactory, and mean weight loss in these groups was significantly higher than the control group. Based on the concentrations achieved in these preliminary trials and the susceptibility patterns of gram-negative bacteria isolated from psittacine birds, drinking water medicated with enrofloxacin at 0.19-0.75 mg/ml might be effective for treating highly susceptible gram-negative bacterial infections in African grey parrots.

  7. Modification of Enrofloxacin Treatment Regimens for Poultry Experimentally Infected with Salmonella enterica Serovar Typhimurium DT104 To Minimize Selection of Resistance▿

    Science.gov (United States)

    Randall, Luke P.; Cooles, Sue W.; Coldham, Nick C.; Stapleton, Ken S.; Piddock, Laura J. V.; Woodward, Martin J.

    2006-01-01

    We hypothesized that higher doses of fluoroquinolones for a shorter duration could maintain efficacy (as measured by reduction in bacterial count) while reducing selection in chickens of bacteria with reduced susceptibility. Chicks were infected with Salmonella enterica serovar Typhimurium DT104 and treated 1 week later with enrofloxacin at the recommended dose for 5 days (water dose adjusted to give 10 mg/kg of body weight of birds or equivalence, i.e., water at 50 ppm) or at 2.5 or 5 times the recommended dose for 2 days or 1 day, respectively. The dose was delivered continuously (ppm) or pulsed in the water (mg/kg) or by gavage (mg/kg). In vitro in sera, increasing concentrations of 0.5 to 8 μg/ml enrofloxacin correlated with increased activity. In vivo, the efficacy of the 1-day treatment was significantly less than that of the 2- and 5-day treatments. The 2-day treatments showed efficacy similar to that of the 5-day treatment in all but one repeat treatment group and significantly (P < 0.01) reduced the Salmonella counts. Dosing at 2.5× the recommended dose and pulsed dosing both increased the peak antibiotic concentrations in cecal contents, liver, lung, and sera as determined by high-pressure liquid chromatography. There was limited evidence that shorter treatment regimens (in particular the 1-day regimen) selected for fewer strains with reduced susceptibility. In conclusion, the 2-day treatment would overall require a shorter withholding time than the 5-day treatment and, in view of the increased peak antibiotic concentrations, may give rise to improved efficacy, in particular for treating respiratory and systemic infections. However, it would be necessary to validate the 2-day regimen in a field situation and in particular against respiratory and systemic infections to validate or refute this hypothesis. PMID:17030564

  8. Immune response in pigs treated with therapeutic doses of enrofloxacin at the time of vaccination against Aujeszky's disease.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Rachubik, Jarosław; Lipowski, Andrzej; Pejsak, Zygmunt

    2015-06-01

    The effect of treatment with enrofloxacin was studied on the postvaccinal immune response in pigs. Forty pigs were used (control not vaccinated (C), control vaccinated (CV), vaccinated, received enrofloxacin (ENRO)). From day -1 to day 3 pigs from ENRO group received enrofloxacin at the recommended dose. Pigs from ENRO and CV groups were vaccinated twice against Aujeszky's disease virus (ADV). There was a significant delay in the production of humoral response of enrofloxacin dosed pigs when compared with CV group. Moreover, in ENRO group the significant decrease in IFN-γ production and significantly lower values of stimulation index after ADV restimulation was noted, as compared with CV group. The secretion of IL-6, IL-10 and TNF-α by PBMC after recall stimulation was also affected in ENRO group. The results indicate that enrofloxacin, in addition to its antimicrobial properties, possess significant immunomodulatory effects and may alter the immune response to vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Use, fate and ecological risks of antibiotics applied in tilapia cage farming in Thailand

    Energy Technology Data Exchange (ETDEWEB)

    Rico, Andreu [Department of Aquatic Ecology and Water Quality Management, Wageningen University, Wageningen University and Research Centre, P.O. Box 47, 6700 AA Wageningen (Netherlands); Oliveira, Rhaul [Department of Biology and CESAM, University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); McDonough, Sakchai [Aquaculture and Aquatic Resources Management, Asian Institute of Technology, P.O. Box 4, Klong Luang, Pathumthani 12120 (Thailand); Matser, Arrienne [Alterra, Wageningen University and Research Centre, P.O. Box 47, 6700 AA Wageningen (Netherlands); Khatikarn, Jidapa [Department of Aquatic Ecology and Water Quality Management, Wageningen University, Wageningen University and Research Centre, P.O. Box 47, 6700 AA Wageningen (Netherlands); Department of Fishery Biology, Faculty of Fisheries, Kasetsart University, Chatuchak 10900, Bangkok (Thailand); Satapornvanit, Kriengkrai [Department of Fishery Biology, Faculty of Fisheries, Kasetsart University, Chatuchak 10900, Bangkok (Thailand); Nogueira, António J.A.; Soares, Amadeu M.V.M.; Domingues, Inês [Department of Biology and CESAM, University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Van den Brink, Paul J. [Department of Aquatic Ecology and Water Quality Management, Wageningen University, Wageningen University and Research Centre, P.O. Box 47, 6700 AA Wageningen (Netherlands); Alterra, Wageningen University and Research Centre, P.O. Box 47, 6700 AA Wageningen (Netherlands)

    2014-08-01

    The use, environmental fate and ecological risks of antibiotics applied in tilapia cage farming were investigated in the Tha Chin and Mun rivers in Thailand. Information on antibiotic use was collected through interviewing 29 farmers, and the concentrations of the most commonly used antibiotics, oxytetracycline (OTC) and enrofloxacin (ENR), were monitored in river water and sediment samples. Moreover, we assessed the toxicity of OTC and ENR on tropical freshwater invertebrates and performed a risk assessment for aquatic ecosystems. All interviewed tilapia farmers reported to routinely use antibiotics. Peak water concentrations for OTC and ENR were 49 and 1.6 μg/L, respectively. Antibiotics were most frequently detected in sediments with concentrations up to 6908 μg/kg d.w. for OTC, and 2339 μg/kg d.w. for ENR. The results of this study indicate insignificant short-term risks for primary producers and invertebrates, but suggest that the studied aquaculture farms constitute an important source of antibiotic pollution. - Highlights: • First study assessing the risks of antibiotics applied in freshwater tilapia cages. • Ten antibiotics were reported to be used by tilapia cage farmers in two Thai rivers. • Peak oxytetracycline and enrofloxacin concentrations were in the order of μg/L. • Antibiotic concentrations in river sediments next to cages were up to several mg/kg. • Antibiotics are not posing a short-term risk for pelagic aquatic organisms. - Antibiotics applied in tilapia cage farming in Thailand are released into surrounding aquatic ecosystems and constitute an important source of environmental pollution.

  10. Use, fate and ecological risks of antibiotics applied in tilapia cage farming in Thailand

    International Nuclear Information System (INIS)

    Rico, Andreu; Oliveira, Rhaul; McDonough, Sakchai; Matser, Arrienne; Khatikarn, Jidapa; Satapornvanit, Kriengkrai; Nogueira, António J.A.; Soares, Amadeu M.V.M.; Domingues, Inês; Van den Brink, Paul J.

    2014-01-01

    The use, environmental fate and ecological risks of antibiotics applied in tilapia cage farming were investigated in the Tha Chin and Mun rivers in Thailand. Information on antibiotic use was collected through interviewing 29 farmers, and the concentrations of the most commonly used antibiotics, oxytetracycline (OTC) and enrofloxacin (ENR), were monitored in river water and sediment samples. Moreover, we assessed the toxicity of OTC and ENR on tropical freshwater invertebrates and performed a risk assessment for aquatic ecosystems. All interviewed tilapia farmers reported to routinely use antibiotics. Peak water concentrations for OTC and ENR were 49 and 1.6 μg/L, respectively. Antibiotics were most frequently detected in sediments with concentrations up to 6908 μg/kg d.w. for OTC, and 2339 μg/kg d.w. for ENR. The results of this study indicate insignificant short-term risks for primary producers and invertebrates, but suggest that the studied aquaculture farms constitute an important source of antibiotic pollution. - Highlights: • First study assessing the risks of antibiotics applied in freshwater tilapia cages. • Ten antibiotics were reported to be used by tilapia cage farmers in two Thai rivers. • Peak oxytetracycline and enrofloxacin concentrations were in the order of μg/L. • Antibiotic concentrations in river sediments next to cages were up to several mg/kg. • Antibiotics are not posing a short-term risk for pelagic aquatic organisms. - Antibiotics applied in tilapia cage farming in Thailand are released into surrounding aquatic ecosystems and constitute an important source of environmental pollution

  11. Enrofloxacin uptake and retention on different types of clays

    Science.gov (United States)

    Wan, Miao; Li, Zhaohiu; Hong, Hanlie; Wu, Qingfeng

    2013-11-01

    The adsorption and retention of enrofloxacin (EN) on different types of clays was studied in batch tests under different pH, contact time, and initial concentration conditions. XRD and FTIR analyses were utilized to characterize EN adsorption and to elucidate mechanisms of EN adsorption. The EN adsorption equilibrium followed the Langmuir isotherm and reached capacities of 667, 228 and 20 mmol/kg at pH 4-5 on the montmorillonite (SWy-2), illite (IMt-2), and kaolinite (KGa-1b), respectively. The pseudo-second-order model fitted the EN sorption kinetics well. Although EN had a much lower adsorption capacity on KGa-1b compared to that on the other two clays, the adsorption rate constant was the fastest at 0.73 kg/mmol-h. Cation exchange interaction was attributed to the major mechanism for EN adsorption on SWy-2 and IMt-2, and non-electrostatic interactions attributed to EN adsorption when solution pH was above 7. Intercalation of EN molecules into the interlayer space of SWy-2 was confirmed by the XRD patterns after EN adsorption. In contrast, the basal spacing and intensity remained the same after EN adsorption on IMt-2 and KGa-1b, indicating that the EN adsorption on the non-swelling clays were limited to the external surfaces.

  12. Distribution of enrofloxacin in intestinal tissue and contents of healthy pigs after oral and intramuscular administrations

    DEFF Research Database (Denmark)

    Wiuff, C.; Lykkesfeldt, J.; Aarestrup, Frank Møller

    2002-01-01

    The concentration of enrofloxacin in plasma, intestinal tissue, lymph nodes and intestinal contents was investigated in healthy pigs after oral (p.o.) and intramuscular (i.m.) administration of a single dose of 2.5 mg/kg bw. Tissue and content samples were collected from jejunum, ileum, caecum...... administration, and maximum concentrations in tissue and plasma were determined later than after i.m. administration. No difference between route of administration was observed in the intestinal content. Enrofloxacin concentrations in faeces during a 5-day dosing regimen with i.m. and p.o. administration were....... On the basis of these results it was concluded that in order to ensure an immediate high concentration of enrofloxacin, and thereby avoid an initial selection for resistant mutants, the intramuscular route seems to be preferable to the oral route....

  13. Labeling of antibiotics for infection diagnosis

    International Nuclear Information System (INIS)

    Benitez, A.; Roca, M.; Martin-Comin, J.

    2006-01-01

    The high impact of infection on daily clinical practice has promoted research into better and more accurate diagnostic and therapeutic methods. Localizing inflammation/infection with nuclear medicine techniques began over 40 years ago. Today, 6 7G a-scintigraphy, 9 9mT c-nanocolloid, 1 11I n and 9 9mT c in vitro labeled leukocytes, and monoclonal anti granulocyte antibodies are widely available for this purpose. While these methods are useful for localizing inflammation, they cannot always differentiate septic from aseptic processes. The ideal properties of an agent for diagnosing infection include: high specificity, early diagnosis, rapid blood clearance, ease of preparation, low toxicity, biodistribution appropriate for the disease under study, absence of immunologic response and low cost. A novel approach to infection diagnosis is the use of radiolabelled antibiotics. Antibiotics localize in the infectious focus, where they are frequently taken up and metabolized by microorganisms. The majority of the various antibiotics studied so far are those of the quinolones group (ciprofloxacin, sparfloxacin, enrofloxacin, levofloxacin, norfloxacin and ofloxacin). More recently, the labeling of ceftizoxime, a semisynthetic third generation cephalosporin, has been reported. The relevant features of labeled antibiotics in research and/or clinical infection diagnosis are the focus of this article

  14. Selection of specific aptamer against enrofloxacin and fabrication of graphene oxide based label-free fluorescent assay.

    Science.gov (United States)

    Dolati, Somayeh; Ramezani, Mohammad; Nabavinia, Maryam Sadat; Soheili, Vahid; Abnous, Khalil; Taghdisi, Seyed Mohammad

    2018-05-15

    Specific ssDNA aptamers for the antibiotic enrofloxacin (ENR) were isolated from an enriched nucleotide library by SELEX (Systematic Evolution of Ligands by EXponential enrichment) method with high binding affinity. After seven rounds, five aptamers were selected and identified. Apt58 with highest affinity and sensitivity (K d  = 14.19 nM) was employed to develop a label-free fluorescent biosensing approach based on aptamer, graphene oxide (GO) and native fluorescence of ENR for determination of ENR residue in raw milk samples. Under optimized experimental conditions, the linear range was from 5 nM to 250 nM and LOD was calculated to be 3.7 nM, and the recovery rate was between 94.1% and 108.5%. The integration of aptamer and GO in this bioassay provides a promising way for rapid, sensitive and cost-effective detection of ENR in real samples like raw milk. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Effect of enrofloxacin on zootechnical performance, behaviour and immunohistopathological response in broiler chicken

    Directory of Open Access Journals (Sweden)

    Veerapandian Sureshkumar

    2013-12-01

    Full Text Available Aim: A safety pharmacology trial was conducted to evaluate the impact of enrofloxacin on zootechnical performance, behaviour and immunohistopathological response in Newcastle disease virus vaccinated broiler chicken after pulsed water medication. Materials and Methods: Experimental group birds were administered with enrofloxacin at recommended therapeutic dose 10mg/Kg body weight, through drinking water for five consecutive days from 43rd to 47th day of age. Zootechnical performance parameters, behavioural and humoral immune response in terms of haemagglutination inhibition (HI titre were assessed at different time interval during pre-treatment, treatment, post-treatment period. Bursa of Fabricius and spleen tissues collected at each sampling point viz. 1, 3, 5, 7 and 9 days post treatment were subjected to histopathological examination. Results: A significant reduction in HI titre was noticed in enrofloxacin administered birds. The decreased HI titre was further substantiated by the histopathological changes observed in bursa of Fabricius and spleen which showed a lymphocytic dispersion and depletion with several areas of lymphoblastic degeneration. Conversely, a down regulatory effect on humoral immunity was observed as evidenced by increased HI titre value noticed from 5th day post treatment onwards and a congruent reversible trend in histopathological changes as indicated by repopulation with lymphocytes on 9th day post treatment. However, there was no significant change in body weight, cumulative feed intake, feed efficiency and behaviour in enrofloxacin administered groups. Conclusion: The present study suggests that the immuno suppressive activity of enrofloxacin may alter the immune response to vaccines, if it is coadministered during vaccination of broilers. On the other hand, enrofloxacin, though it decreased the humoral immune response, it did not have any appreciable effect on broiler's performance. [Vet World 2013; 6(6.000: 337-342

  16. Effect of Sucralfate on the Relative Bioavailability of Enrofloxacin and Ciprofloxacin in Healthy Fed Dogs.

    Science.gov (United States)

    KuKanich, K; KuKanich, B; Guess, S; Heinrich, E

    2016-01-01

    Sucralfate impairs absorption of ciprofloxacin and other fluoroquinolones in humans, but no sucralfate-fluoroquinolone interaction has been reported in dogs. Veterinary formularies recommend avoiding concurrent administration of these medications, which might impact compliance, therapeutic success, and resistance selection from fluoroquinolones. To determine whether a drug interaction exists when sucralfate is administered to fed dogs concurrently with ciprofloxacin or enrofloxacin, and whether a 2 hour delay between fluoroquinolone and sucralfate affects fluoroquinolone absorption. Five healthy Greyhounds housed in a research colony. This was a randomized crossover study. Treatments included oral ciprofloxacin (C) or oral enrofloxacin (E) alone, each fluoroquinolone concurrently with an oral suspension of sucralfate (CS, ES), and sucralfate suspension 2 hours after each fluoroquinolone (C2S, E2S). Fluoroquinolone concentrations were evaluated using liquid chromatography with mass spectrometry. Drug exposure of ciprofloxacin was highly variable (AUC 5.52-22.47 h μg/mL) compared to enrofloxacin (AUC 3.86-7.50 h μg/mL). The mean relative bioavailability for ciprofloxacin and concurrent sucralfate was 48% (range 8-143%) compared to ciprofloxacin alone. Relative bioavailability of ciprofloxacin improved to 87% (range 37-333%) when sucralfate was delayed by 2 hours. By contrast, relative bioavailability for enrofloxacin and concurrent sucralfate was 104% (94-115%). A possible clinically relevant drug interaction for the relative bioavailability of ciprofloxacin with sucralfate was found. No significant difference in bioavailability was documented for enrofloxacin with sucralfate. Further research is warranted in fasted dogs and clinical cases requiring enrofloxacin or other approved fluoroquinolones in combination with sucralfate. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc on behalf of the American

  17. AN AUDIT OF PRESCRIPTION FOR ANTIBIOTIC IN A TERTIARY CARE HOSPITAL IN KOLKATA, INDIA

    Directory of Open Access Journals (Sweden)

    Anjan Adhikari

    2012-12-01

    Full Text Available Antibiotics are most commonly prescribed drugs in tertiary care hospitals; more than 30% of the hospitalised patients were treated with antibiotics. Rational use of antibiotics is very important to ensure the optimum treatment outcomes and to limit the emergence of bacterial resistance. Present study is a hospital based cross-sectional study carried out for a period of three months in different clinical departments of a tertiary care hospital to find out the antibiotics prescribing pattern. Out of total 551 evaluated prescriptions, an antibiotic was prescribed in 45.5% cases. The most commonly prescribed antibiotics were Moxifloxacin 19.5%, Metronidazole 10.4% and Amoxicillin+Cloxacillin 10.2%, broad spectrum antibiotics usage was higher & 87.7% of the antibiotics were prescribed by brand names. The appropriate use of antibiotic is a greatest need of the current situation all over the world. The rising antibiotic resistance is a global problem which is directly related with the irrational prescription of antibiotics.

  18. Susceptibility of bacteria isolated from pigs to tiamulin and enrofloxacin metabolites

    DEFF Research Database (Denmark)

    Lykkeberg, Anne Kruse; Halling-Sørensen, Bent; Jensen, Lars Bogø

    2007-01-01

    :Susceptibilities to metabolites of tiamulin (TIA) and enrofloxacin (ENR) were tested using selected bacteria with previously defined minimal inhibitory concentrations,(,MIC). The TIA metabolites tested were: N-deethyl-tiamulin (I)TIA), 2 beta-hydroxy-tiamulin (2 beta-HTIA),and Sammhydroxy......-tiamulin (8 alpha-HTIA), and the ENR metabolites were: ciprofloxacin (CIP) and enrofloxacin N-oxide (ENR-N). Bacteria, all of porcine origin, we're selected as representatives of bacterial infections (Stap4ylococcus hyicus and Actinobacillus pleuropneumoniae), zoonotic bacteria (Campylobacter coli...

  19. Prophylactic antibiotics for penetrating abdominal trauma.

    Science.gov (United States)

    Brand, Martin; Grieve, Andrew

    2013-11-18

    Penetrating abdominal trauma occurs when the peritoneal cavity is breached. Routine laparotomy for penetrating abdominal injuries began in the 1800s, with antibiotics first being used in World War II to combat septic complications associated with these injuries. This practice was marked with a reduction in sepsis-related mortality and morbidity. Whether prophylactic antibiotics are required in the prevention of infective complications following penetrating abdominal trauma is controversial, however, as no randomised placebo controlled trials have been published to date. There has also been debate about the timing of antibiotic prophylaxis. In 1972 Fullen noted a 7% to 11% post-surgical infection rate with pre-operative antibiotics, a 33% to 57% infection rate with intra-operative antibiotic administration and 30% to 70% infection rate with only post-operative antibiotic administration. Current guidelines state there is sufficient class I evidence to support the use of a single pre-operative broad spectrum antibiotic dose, with aerobic and anaerobic cover, and continuation (up to 24 hours) only in the event of a hollow viscus perforation found at exploratory laparotomy. To assess the benefits and harms of prophylactic antibiotics administered for penetrating abdominal injuries for the reduction of the incidence of septic complications, such as septicaemia, intra-abdominal abscesses and wound infections. Searches were not restricted by date, language or publication status. We searched the following electronic databases: the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library 2013, issue 12 of 12), MEDLINE (OvidSP), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S) and PubMed. Searches were last conducted in January 2013. All randomised controlled trials of antibiotic prophylaxis in patients with penetrating abdominal trauma versus no

  20. Effect Of Laser Irradiation On Biosynthesis Of Antibiotics

    International Nuclear Information System (INIS)

    SALAMA, S.M.; MAHMOUD, S.M.; EL-KABBANY, H.M.

    2010-01-01

    An investigation concerning the effect of He:Ne laser irradiation on some isolated actinomycetes was carried out. Seven isolated actinomycetes were considered as most potent producing broad spectrum antibiotics. The strains have been identified on the basis of taxonomic studies as Streptomyces nogalator (H12), Streptomyces griseoluteus (YM23), Amycolatopsis mediterranei (B40), Glycomyces harbinensis (KA16), Streptosporangium corrugatum (B67), Streptoalloteichus hindustamus (B74) and Streptomyces aurantiogriseus (S15). Seven genotypes were chosen after He:Ne laser irradiation as representative for each isolated strain. The active metabolite from most potent genotype of Streptomyces nogalator (H12) was extracted by ethyl acetate then concentrated under vacuo and the crude fraction was purified using thin layer and column chromatography. Ultra violet maximum absorption peak was recorded at 231.5 and 206 nm. The IR and NMR were consulted to confirm the chemical characteristics of the antibiotic. The biological activity and toxicity were also investigated.

  1. Impact of an electronic sepsis initiative on antibiotic use and health care facility-onset Clostridium difficile infection rates.

    Science.gov (United States)

    Hiensch, Robert; Poeran, Jashvant; Saunders-Hao, Patricia; Adams, Victoria; Powell, Charles A; Glasser, Allison; Mazumdar, Madhu; Patel, Gopi

    2017-10-01

    Although integrated, electronic sepsis screening and treatment protocols are thought to improve patient outcomes, less is known about their unintended consequences. We aimed to determine if the introduction of a sepsis initiative coincided with increases in broad-spectrum antibiotic use and health care facility-onset (HCFO) Clostridium difficile infection (CDI) rates. We used interrupted time series data from a large, tertiary, urban academic medical center including all adult inpatients on 4 medicine wards (June 2011-July 2014). The main exposure was implementation of the sepsis screening program; the main outcomes were the use of broad-spectrum antibiotics (including 3 that were part of an order set designed for the sepsis initiative) and HCFO CDI rates. Segmented regression analyses compared outcomes in 3 time segments: before (11 months), during (14 months), and after (12 months) implementation of a sepsis initiative. Antibiotic use and HFCO CDI rates increased during the period of implementation and the period after implementation compared with baseline; these increases were highest in the period after implementation (level change, 50.4 days of therapy per 1,000 patient days for overall antibiotic use and 10.8 HCFO CDIs per 10,000 patient days; P antibiotic use were not those included in the sepsis order set. The implementation of an electronic sepsis screening and treatment protocol coincided with increased broad-spectrum antibiotic use and HCFO CDIs. Because these protocols are increasingly used, further study of their unintended consequences is warranted. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Comparative pharmacokinetics of enrofloxacin, danofloxacin, and marbofloxacin after intravenous and oral administration in Japanese quail (Coturnix coturnix japonica).

    Science.gov (United States)

    Haritova, Aneliya; Dimitrova, Dimitrichka; Dinev, Toncho; Moutafchieva, Rumyana; Lashev, Lubomir

    2013-03-01

    A population approach was used to evaluate the pharmacokinetic parameters of 3 fluoroquinolones administered to Japanese quail (Coturnix coturnix japonica). Healthy adult quail (n = 50) were divided into 3 groups, each administered a separate intravenous and oral dose of the compounded drug: enrofloxacin at 10 mg/kg (n = 18; 9 male, 9 female), danofloxacin at 10 mg/kg (n = 12; 6 male, 6 female), and marbofloxacin at 5 mg/kg (n = 20; 10 male, 10 female). A fourth group was used as a control (n = 5). Enrofloxacin was metabolized extensively to ciprofloxacin, while no metabolites of either danofloxacin or marbofloxacin were detected. The volume of distribution was high, greater than 1 in all cases, and highest for danofloxacin, followed by enrofloxacin, then marbofloxacin. The total body clearance was higher in quail than that reported for other avian species with the exception of ostriches. As in mammals, the lowest clearance rate of the 3 fluoroquinolones was observed for marbofloxacin. Enrofloxacin was absorbed most rapidly, followed by marbofloxacin, then danofloxacin. The highest bioavailability was observed for danofloxacin followed by marbofloxacin, while very low bioavailability with significant conversion to ciprofloxacin was observed for enrofloxacin. Population analysis showed low intersubject variability for danofloxacin and marbofloxacin in contrast to that for enrofloxacin and its main metabolite, ciprofloxacin. Because of their more favorable pharmacokinetic properties after oral administration, either danofloxacin or marbofloxacin appears to be preferable to enrofloxacin for the treatment of susceptible bacterial infection in Japanese quail.

  3. An audit of empiric antibiotic choice in the inpatient management of community-acquired pneumonia

    LENUS (Irish Health Repository)

    Delaney, F

    2017-04-01

    Adherence to antimicrobial guidelines for empiric antibiotic prescribing in community-acquired pneumonia (CAP) has been reported to be worryingly low. We conducted a review of empiric antibiotic prescribing for sixty consecutive adult patients admitted to the Mercy University Hospital with a diagnosis of CAP. When analysed against local antimicrobial guidelines, guideline concordant empiric antibiotics were given in only 48% of cases, lower than the average rate in comparable studies. Concordance was 100% in cases where the CURB-65 pneumonia severity assessment score, on which the guidelines are based, was documented in the medical notes. The use of excessively broad spectrum and inappropriate antibiotics is a notable problem. This study supports the theory that lack of knowledge regarding pneumonia severity assessment tools and unfamiliarity with therapeutic guidelines are key barriers to guideline adherence, which remains a significant problem despite increased focus on antimicrobial stewardship programs in Ireland

  4. Occurrence of veterinary antibiotics and progesterone in broiler manure and agricultural soil in Malaysia.

    Science.gov (United States)

    Ho, Yu Bin; Zakaria, Mohamad Pauzi; Latif, Puziah Abdul; Saari, Nazamid

    2014-08-01

    Repeated applications of animal manure as fertilizer are normal agricultural practices that may release veterinary antibiotics and hormones into the environment from treated animals. Broiler manure samples and their respective manure-amended agricultural soil samples were collected in selected locations in the states of Selangor, Negeri Sembilan and Melaka in Malaysia to identify and quantify veterinary antibiotic and hormone residues in the environment. The samples were analyzed using ultrasonic extraction followed by solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The broiler manure samples were found to be contaminated with at least six target analytes, namely, doxycycline, enrofloxacin, flumequine, norfloxacin, trimethoprim and tylosin. These analytes were detected in broiler manure samples with maximum concentrations reaching up to 78,516 μg kg(-1) dry weight (DW) (doxycycline). For manure-amended agricultural soil samples, doxycycline and enrofloxacin residues were detected in every soil sample. The maximum concentration of antibiotic detected in soil was 1331 μg kg(-1) DW (flumequine). The occurrence of antibiotics and hormones in animal manure at high concentration poses a risk of contaminating agricultural soil via fertilization with animal manure. Some physico-chemical parameters such as pH, total organic carbon (TOC) and metal content played a considerable role in the fate of the target veterinary antibiotics and progesterone in the environment. It was suggested that these parameters can affect the adsorption of pharmaceuticals to solid environmental matrices. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Population pharmacokinetics of enrofloxacin in purple sea stars (Pisaster ochraceus) following an intracoelomic injection or extended immersion.

    Science.gov (United States)

    Rosenberg, Justin F; Haulena, Martin; Phillips, Brianne E; Harms, Craig A; Lewbart, Gregory A; Lahner, Lesanna L; Papich, Mark G

    2016-11-01

    OBJECTIVE To determine population pharmacokinetics of enrofloxacin in purple sea stars (Pisaster ochraceus) administered an intracoelomic injection of enrofloxacin (5 mg/kg) or immersed in an enrofloxacin solution (5 mg/L) for 6 hours. ANIMALS 28 sea stars of undetermined age and sex. PROCEDURES The study had 2 phases. Twelve sea stars received an intracoelomic injection of enrofloxacin (5 mg/kg) or were immersed in an enrofloxacin solution (5 mg/L) for 6 hours during the injection and immersion phases, respectively. Two untreated sea stars were housed with the treated animals following enrofloxacin administration during both phases. Water vascular system fluid samples were collected from 4 sea stars and all controls at predetermined times during and after enrofloxacin administration. The enrofloxacin concentration in those samples was determined by high-performance liquid chromatography. For each phase, noncompartmental analysis of naïve averaged pooled samples was used to obtain initial parameter estimates; then, population pharmacokinetic analysis was performed that accounted for the sparse sampling technique used. RESULTS Injection phase data were best fit with a 2-compartment model; elimination half-life, peak concentration, area under the curve, and volume of distribution were 42.8 hours, 18.9 μg/mL, 353.8 μg•h/mL, and 0.25 L/kg, respectively. Immersion phase data were best fit with a 1-compartment model; elimination half-life, peak concentration, and area under the curve were 56 hours, 36.3 μg•h/mL, and 0.39 μg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the described enrofloxacin administration resulted in water vascular system fluid drug concentrations expected to exceed the minimum inhibitory concentration for many bacterial pathogens.

  6. The effect of a commercial competitive exclusion product on the selection of enrofloxacin resistance in commensal E. coli in broilers.

    Science.gov (United States)

    Chantziaras, Ilias; Smet, Annemieke; Filippitzi, Maria Eleni; Damiaans, Bert; Haesebrouck, Freddy; Boyen, Filip; Dewulf, Jeroen

    2018-06-07

    The effect of a competitive exclusion product (Aviguard ® ) on the selection of fluoroquinolone resistance in poultry was assessed in vivo in the absence or presence of fluoroquinolone treatment. Two experiments using a controlled seeder-sentinel animal model (2seeders:4sentinels per group) with one-day-old chicks were used. For both experiments,as soon as the chicks were hatched, the animals of two groups were administered Aviguard ® and two groups were left untreated. Three days later, all groups were inoculated with an enrofloxacin-susceptible commensal E. coli strain. Five days after hatching, two animals per group were inoculated either with a bacteriologically-fit or a bacteriologically non-fit enrofloxacin-resistant commensal E. coli strain. In experiment 2, all groups were orally treated for three consecutive days (Day 8-10) with enrofloxacin. Throughout the experiments, faecal excretion of all inoculated E. coli strains was determined on days 2-5-8-11-18-23 by selective plating (via spiral plater). Linear mixed models were used to assess the effect of Aviguard ® on the selection of fluoroquinolone resistance. The use of Aviguard® (penrofloxacin-resistant E. coli when no enrofloxacin treatment was administered. However, this beneficial effect disappeared (p=0.37) when the animals were treated with enrofloxacin. Similarly, bacterial fitness of the enrofloxacin-resistant E. coli strain used for inoculation had an effect (penrofloxacin resistance when no treatment was administered, whereas this effect was no longer present when enrofloxacin was administered (p =0.70). Thus, enrofloxacin treatment cancelled the beneficial effects from administrating Aviguard ® in one-day-old broiler chicks and resulted in a enrofloxacin-resistant flora.

  7. Cephamycins, a New Family of β-Lactam Antibiotics I. Production by Actinomycetes, Including Streptomyces lactamdurans sp. n1

    Science.gov (United States)

    Stapley, E. O.; Jackson, M.; Hernandez, S.; Zimmerman, S. B.; Currie, S. A.; Mochales, S.; Mata, J. M.; Woodruff, H. B.; Hendlin, D.

    1972-01-01

    A number of actinomycetes isolated from soil were found to produce one or more members of a new family of antibiotics, the cephamycins, which are structurally related to cephalosporin C. The cephamycins were produced in submerged fermentation in a wide variety of media by one or more of eight different species of Streptomyces, including a newly described species, S. lactamdurans. These antibiotics exhibit antibacterial activity against a broad spectrum of bacteria which includes many that are resistant to the cephalosporins and penicillins. PMID:4790552

  8. In-use stability of enrofloxacin solution for injection in multi-dose containers

    Directory of Open Access Journals (Sweden)

    Šandor Ksenija

    2012-01-01

    Full Text Available The in-use stability study in this paper was designed as far as possible to simulate the practical usage of multi-dose containers products in veterinary practice and to establish the influence of storage conditions on drug's quality. According to literature data, shelf-live of enrofloxacin solutions for injection tested in this study is 28 days after opening. In-use (open container stability testing of enrofloxacin injection solutions was studied during a period of 112 days, and the physical-chemical parameters and microbiological contamination were assessed. A spectrophotometric method was validated for the quantification of enrofloxacin. The validation method yielded good results and included the selectivity, linearity, intra-assay precision (1.26% RSD, inter-assay precision (1.52% RSD, limit of detection (0.18 μg/mL, limit of quantification (0.54 μg/mL and accuracy. The results of spectrophotometric analyses were presented as the mean drug concentration of enrofloxacin vs. time of sampling. The findings of physical, chemical and microbiological parameters were in accordance with the producers' specifications and no extreme changes during prescribed storage occurred. The study was extended from the drug's proposed shelf-life after opening for the next 84 days and in that period no significant changes were recorded.

  9. Enrofloxacin behavior in presence of soil extracted organic matter: An electrochemical approach

    International Nuclear Information System (INIS)

    Antilén, Monica; Valencia, Camila; Peralta, Emilia; Canales, Camila; Espinosa-Bustos, Christian; Escudey, Mauricio

    2017-01-01

    In this work, a novel and simple method aimed at determining and quantifying Enrofloxacin in presence of Natural Organic Matter (NOM) is proposed. The method was based on the electrochemical oxidation of Enrofloxacin by using cyclic voltammetry as technique. It was found that this analyte presents a good electroactivity, in absence and in presence of NOM. However, this electrochemical behavior is highly pH-dependent, since the reaction is more favorable when less acid the media is. At this point, different pH values were studied in order to corroborate this phenomenon. Additionally, kinetic studies were done to determine the control of the reaction, the number of transferred electrons in the entire process and the rate determining step of the reaction by analyzing the Tafel slope. With these antecedents, a mechanism was proposed and the final product of the reaction was corroborated by using LC-MS. Finally, analytical parameters were studied with the aim of proposing this new method as an electrochemical sensor of Enrofloxacin. It was found that the method is highly linear, precise and accurate. Moreover, this method is not only sensitive but also selective to Enrofloxacin in presence of NOM, in comparison to spectrophotometric methods previously reported.

  10. Mycoplasma contamination in cell cultures treated with ciprofloxacin and enrofloxacin: brief report

    Directory of Open Access Journals (Sweden)

    Bita Soltanian

    2015-02-01

    Conclusion: Our results showed that 20 μg/ml of ciprofloxacin was the dilution of choice for mycoplasma elimination followed by 200 μg/ml of ciprofloxacin. Concentrations of 3, 30 and 300 of enrofloxacin, respectively, are appropriate for mycoplasma removal. More detailed works would be needed to verify the authenticity of the proposed simple and affordable way of mycoplasma elimination.

  11. Luminescence screening of enrofloxacin and ciprofloxacin residues in swine liver after dispersive liquid - liquid microextraction cleanup

    Science.gov (United States)

    A rapid luminescence method was developed to screen residues of enrofloxacin (ENRO) and its metabolite, ciprofloxacin (CIPRO), in swine liver. Target analytes were extracted in acetonitrile-2.5% trifluoroacetic acid-NaCl, cleaned up by dispersive liquid-liquid microextraction (DLLME), and finally de...

  12. Effect of enrofloxacin treatment on plasma endotoxin during bovine Escherichia coli mastitis

    NARCIS (Netherlands)

    Dosogne, H.; Meyer, E.; Sturk, A.; van Loon, J.; Massart-Leën, A. M.; Burvenich, C.

    2002-01-01

    OBJECTIVE AND DESIGN: To investigate the effect of enrofloxacin on endotoxin resorption during bovine Escherichia coli mastitis. ANIMALS: 12 healthy early post partum Holstein cows. TREATMENT: Mastitis was induced by intramammary infusion of 10(4) cfu E. coli P4:032. Six cows were treated twice

  13. A Randomized Double-Blind, Placebo Controlled, Four-Arm Parallel Study Investigating the Effect of a Broad-Spectrum Wellness Beverage on Mood State in Healthy, Moderately Stressed Adults.

    Science.gov (United States)

    Evans, Malkanthi; Antony, Joseph; Guthrie, Najla; Landes, Bernie; Aruoma, Okezie I

    2018-01-01

    The objective of this study was to investigate the effect of a broad-spectrum wellness beverage (Zeal Wellness [ZW]) on standardized measures of mood states, including overall feelings of vitality, in healthy, moderately stressed adults. A randomized, double-blind, placebo-controlled clinical trial was conducted among 99 eligible participants prescreened for moderate stress. Participants were randomized to one of four groups and received ZW once daily (1-dose-ZW; 14 g), ZW twice daily (2-dose-ZW; 28 g), placebo once daily (1-dose-placebo), or placebo twice daily (2-dose-placebo) for 4 weeks. A stress/vitality questionnaire assessed stress and the Profile of Moods (POMS) Questionnaire assessed vigor via mental/physical energy and global mood state. Safety was assessed by clinical chemistry, liver, kidney function, and anthropometric measures and adverse event reporting. Participants receiving 2-dose-ZW reported a 6.6% decrease in scores on POMS-Total Mood Disturbance (TMD; p < 0.05) and a 6.8% decrease in the anger-hostility mood state (p < 0.022) compared to the combined placebo group at day 29. The 2-dose-ZW provided a 12.8% greater improvement in POMS-TMD scores when compared to participants receiving 1-dose-ZW after 28 days of supplementation (p = 0.014). Within groups, there was a 22.4% and a 9.6% decrease in POMS-TMD scores in participants with 2-dose-ZW and 1-dose-ZW, respectively. In addition, participants receiving 2-dose-ZW showed significant improvements (p = 0.001) in the POMS t-score iceberg profile, which represented a shift to a more healthy profile. These data show that daily supplementation with 2-dose-ZW significantly decreased POMS-TMD scores and anger-hostility mood state and shifted the POMS iceberg profile to a healthy profile compared to the combined placebo, reflecting the functional benefit of rice-bran-fruit-vegetable extracts based beverage on health.

  14. Antibiotic policies in acute English NHS trusts: implementation of 'Start Smart-Then Focus' and relationship with Clostridium difficile infection rates.

    Science.gov (United States)

    Llewelyn, Martin J; Hand, Kieran; Hopkins, Susan; Walker, A Sarah

    2015-04-01

    The objective of this study was to establish how antibiotic prescribing policies at National Health Service (NHS) hospitals match the England Department of Health 'Start Smart-Then Focus' recommendations and relate to Clostridium difficile infection (CDI) rates. Antibiotic pharmacists were surveyed regarding recommendations for empirical treatment of common syndromes ('Start Smart') and antimicrobial prescription reviews ('Focus') at their hospital trusts. If no response was provided, policy data were sought from trust websites and the MicroGuide app (Horizon Strategic Partners, UK). Empirical treatment recommendations were categorized as broad spectrum (a β-lactam penicillin/β-lactamase inhibitor, cephalosporin, quinolone or carbapenem) or narrow spectrum. CDI rates were gathered from the national mandatory surveillance system. Data were obtained for 105/145 English acute hospital trusts (72%). β-Lactam/β-lactamase inhibitor combinations were recommended extensively. Only for severe community-acquired pneumonia and pyelonephritis were narrow-spectrum agents recommended first line at a substantial number of trusts [42/105 (40%) and 50/105 (48%), respectively]. Policies commonly recommended dual therapy with aminoglycosides and β-lactams for abdominal sepsis [40/93 trusts (43%)] and undifferentiated severe sepsis [54/94 trusts (57%)]. Most policies recommended treating for ≥ 7 days for most indications. Nearly all policies [100/105 trusts (95%)] recommended antimicrobial prescription reviews, but only 46/96 respondents (48%) reported monitoring compliance. Independent predictors of higher CDI rates were recommending a broad-spectrum regimen for community-acquired pneumonia (P=0.06) and, counterintuitively, a recommended treatment duration of Smart' by recommending broad-spectrum antibiotics for empirical therapy, but this may have the unintended potential to increase the use of broad-spectrum antibiotics and risk of CDI unless better mechanisms are in place

  15. Pharmacokinetic-Pharmacodynamic modeling of enrofloxacin against Escherichia coli in broilers

    Directory of Open Access Journals (Sweden)

    Sang eKana

    2016-01-01

    Full Text Available The purpose of the present study was to establish a pharmacokinetic/pharmacodynamic (PK/PD modeling approach for the dosage schedule design and decreasing the emergence of drug-resistant bacteria. The minimal inhibitory concentration (MIC of 929 E. coli isolates from broilers to enrofloxacin and ciprofloxacin were determined following CLSI guidance. The MIC50 was calculated as the populational PD parameter for enrofloxacin against E. coli in broilers. The 101 E. coli strains with MIC closest to the MIC50 (0.05µg/mL were submitted for serotype identification. The 13 E. coli strains with O and K serotype were further utilitzed for determining pathogencity in mice. Of all the strains tested, the E. coli designated strain Anhui 112 was selected for establishing the disease model and PK/PD study. The pharmacokinetics (PKs of enrofloxacin after oral administration at the dose of 10mg/kg body weights (BW in healthy and infected broilers was evaluated with high-performance liquid chromatography (HPLC method. For intestinal contents after oral administration, the peak concentration (Cmax, the time when the maximum concentration reached (Tmax, and the area under the concentration-time curve (AUC were 21.69~31.69μg/mL, 1.13~1.23h, and 228.97~444.86μg.hr/mL, respectively. The MIC and minimal bactericidal concentration (MBC of enrofloxacin against E. coli (Anhui 112 in Mueller-Hinton (MH broth and intestinal contents were determined to be similar, 0.25μg/mL and 0.5μg/mL respectively. In this study, the sum of concentrations of enrofloxacin and its metabolite (ciprofloxacin was used for the PK/PD integration and modeling. The ex vivo growth inhibition data were fitted to the sigmoid Emax (Hill equation to provide values for intestinal contents of 24h area under concentration–time curve/MIC ratios (AUC0~24h/MIC producing, bacteriostasis (624.94h, bactericidal activity (1065.93h and bacterial eradication (1343.81h. PK/PD modeling was established to

  16. Forgotten antibiotics

    DEFF Research Database (Denmark)

    Pulcini, Céline; Bush, Karen; Craig, William A

    2012-01-01

    In view of the alarming spread of antimicrobial resistance in the absence of new antibiotics, this study aimed at assessing the availability of potentially useful older antibiotics. A survey was performed in 38 countries among experts including hospital pharmacists, microbiologists, and infectious...

  17. Systemic and mammary gland disposition of enrofloxacin in healthy sheep following intramammary administration.

    Science.gov (United States)

    López, Cristina; García, Juan José; Sierra, Matilde; Diez, María José; Pérez, Claudia; Sahagún, Ana Maria; Fernández, Nélida

    2015-04-09

    Mastitis is one of the most important diseases affecting dairy sheep. Antimicrobial drugs are often administered directly through teat to treat or prevent this disease, but data on drug distribution within glandular tissue are scarce and it cannot be estimated from concentrations in milk. Thus, the aim of this study was to investigate systemic and mammary gland distribution of enrofloxacin after intramammary administration. The drug was administered to 6 healthy lactating Assaf sheep with an injector containing an enrofloxacin preparation (1 g drug/5 g ointment). Blood samples were collected at 0, 30, 60, 90, 120, 150 and 180 min. Animals were then sedated and sacrificed, and glandular tissue samples were obtained from treated udders at 2, 4, 6 and 8 cm height. Enrofloxacin concentrations were measured in plasma and tissue samples by UV high-performed liquid chromatography. Mean enrofloxacin plasma concentrations were below 0.5 μg/mL. Mean tissue concentrations decreased in mammary gland with vertical distance from the teat, ranging from 356.6 μg/g at 2 cm to 95.60 μg/g at the base of the udder. Glandular tissue concentrations best fitted to a decreasing monoexponential model, and showed a good correlation with an ex vivo model previously developed. Enrofloxacin concentrations were effective in the entire glandular tissue against the main pathogens causing mastitis in sheep. These results suggest that this drug may be suitable to treat mastitis in sheep by intramammary administration.

  18. Pharmacokinetics of enrofloxacin and ciprofloxacin in Atlantic horseshoe crabs (Limulus polyphemus) after single injection.

    Science.gov (United States)

    Kirby, A; Lewbart, G A; Hancock-Ronemus, A; Papich, M G

    2018-04-01

    The pharmacokinetics of enrofloxacin and the metabolite ciprofloxacin were studied in horseshoe crabs after a single injection of 5 mg/kg. Twelve Atlantic horseshoe crabs (Limulus polyphemus) of undetermined age were injected with enrofloxacin into the dorsal cardiac sinus. Hemolymph samples were collected by syringe and needle at regular intervals for 120 hr. Samples were analyzed by high-pressure liquid chromatography and compartmental analysis performed on the results. Following injection, the elimination half-life (T½), peak concentration, area under the curve (AUC), and volume of distribution (VD) for enrofloxacin were 27.9 (29.13) hr, 8.98 (18.09) μg/ml, 367.38 (35.41) hr μg/ml, and 0.575 (20.48) L/kg, respectively (mean value, CV%). For ciprofloxacin, the elimination T½, peak concentration, and AUC were 61.36 (34.55) hr, 2.34 (24.11) μg/ml, and 304.46 (24.69) μg hr/ml. In these animals, the ciprofloxacin concentrations comprised an average of 45.8% of the total fluoroquinolone concentrations, which is substantial compared to other marine invertebrates. The total AUC produced (sum of enrofloxacin and ciprofloxacin) was 682.69 ± 180.61 μg hr/ml. Concentrations that were achieved after a single dose of 5 mg/kg horseshoe crabs were sufficient to treat bacteria susceptible to enrofloxacin and ciprofloxacin. © 2017 John Wiley & Sons Ltd.

  19. Evaluation of enrofloxacin use in koalas (Phascolarctos cinereus) via population pharmacokinetics and Monte Carlo simulation.

    Science.gov (United States)

    Black, L A; Landersdorfer, C B; Bulitta, J B; Griffith, J E; Govendir, M

    2014-06-01

    Clinically normal koalas (n = 6) received a single dose of intravenous enrofloxacin (10 mg/kg). Serial plasma samples were collected over 24 h, and enrofloxacin concentrations were determined via high-performance liquid chromatography. Population pharmacokinetic modeling was performed in S-ADAPT. The probability of target attainment (PTA) was predicted via Monte Carlo simulations (MCS) using relevant target values (30-300) based on the unbound area under the curve over 24 h divided by the minimum inhibitory concentration (MIC) (fAUC0-24 /MIC), and published subcutaneous data were incorporated (Griffith et al., 2010). A two-compartment disposition model with allometrically scaled clearances (exponent: 0.75) and volumes of distribution (exponent: 1.0) adequately described the disposition of enrofloxacin. For 5.4 kg koalas (average weight), point estimates for total clearance (SE%) were 2.58 L/h (15%), central volume of distribution 0.249 L (14%), and peripheral volume 2.77 L (20%). MCS using a target fAUC0-24 /MIC of 40 predicted highest treatable MICs of 0.0625 mg/L for intravenous dosing and 0.0313 mg/L for subcutaneous dosing of 10 mg/kg enrofloxacin every 24 h. Thus, the frequently used dosage of 10 mg/kg enrofloxacin every 24 h subcutaneously may be appropriate against gram-positive bacteria with MICs ≤ 0.03 mg/L (PTA > 90%), but appears inadequate against gram-negative bacteria and Chlamydiae in koalas. © 2013 John Wiley & Sons Ltd.

  20. Variability in Antibiotic Use Across PICUs.

    Science.gov (United States)

    Brogan, Thomas V; Thurm, Cary; Hersh, Adam L; Gerber, Jeffrey S; Smith, Michael J; Shah, Samir S; Courter, Joshua D; Patel, Sameer J; Parker, Sarah K; Kronman, Matthew P; Lee, Brian R; Newland, Jason G

    2018-03-10

    To characterize and compare antibiotic prescribing across PICUs to evaluate the degree of variability. Retrospective analysis from 2010 through 2014 of the Pediatric Health Information System. Forty-one freestanding children's hospital. Children aged 30 days to 18 years admitted to a PICU in children's hospitals contributing data to Pediatric Health Information System. To normalize for potential differences in disease severity and case mix across centers, a subanalysis was performed of children admitted with one of the 20 All Patient Refined-Diagnosis Related Groups and the seven All Patient Refined-Diagnosis Related Groups shared by all PICUs with the highest antibiotic use. The study included 3,101,201 hospital discharges from 41 institutions with 386,914 PICU patients. All antibiotic use declined during the study period. The median-adjusted antibiotic use among PICU patients was 1,043 days of therapy/1,000 patient-days (interquartile range, 977-1,147 days of therapy/1,000 patient-days) compared with 893 among non-ICU children (interquartile range, 805-968 days of therapy/1,000 patient-days). For PICU patients, the median adjusted use of broad-spectrum antibiotics was 176 days of therapy/1,000 patient-days (interquartile range, 152-217 days of therapy/1,000 patient-days) and was 302 days of therapy/1,000 patient-days (interquartile range, 220-351 days of therapy/1,000 patient-days) for antimethicillin-resistant Staphylococcus aureus agents, compared with 153 days of therapy/1,000 patient-days (interquartile range, 130-182 days of therapy/1,000 patient-days) and 244 days of therapy/1,000 patient-days (interquartile range, 203-270 days of therapy/1,000 patient-days) for non-ICU children. After adjusting for potential confounders, significant institutional variability existed in antibiotic use in PICU patients, in the 20 All Patient Refined-Diagnosis Related Groups with the highest antibiotic usage and in the seven All Patient Refined-Diagnosis Related Groups shared

  1. Antibiotics in typical marine aquaculture farms surrounding Hailing Island, South China: Occurrence, bioaccumulation and human dietary exposure

    International Nuclear Information System (INIS)

    Chen, Hui; Liu, Shan; Xu, Xiang-Rong; Liu, Shuang-Shuang; Zhou, Guang-Jie; Sun, Kai-Feng; Zhao, Jian-Liang; Ying, Guang-Guo

    2015-01-01

    Highlights: • Thirty-seven antibiotics were systematically investigated in typical marine aquaculture farms. • Enrofloxacin was widely detected in the feed samples (16.6–31.8 ng/g). • ETM-H 2 O in the adult shrimp samples may pose a potential risk to human safety. • TMP was bioaccumulative in fish muscles. • Antibiotics were weakly bioaccumulated in mollusks. - Abstract: The occurrence, bioaccumulation, and human dietary exposure via seafood consumption of 37 antibiotics in six typical marine aquaculture farms surrounding Hailing Island, South China were investigated in this study. Sulfamethoxazole, salinomycin and trimethoprim were widely detected in the water samples (0.4–36.9 ng/L), while oxytetracycline was the predominant antibiotic in the water samples of shrimp larvae pond. Enrofloxacin was widely detected in the feed samples (16.6–31.8 ng/g) and erythromycin–H 2 O was the most frequently detected antibiotic in the sediment samples (0.8–4.8 ng/g). Erythromycin–H 2 O was the dominant antibiotic in the adult Fenneropenaeus penicillatus with concentrations ranging from 2498 to 15,090 ng/g. In addition, trimethoprim was found to be bioaccumulative in young Lutjanus russelli with a median bioaccumulation factor of 6488 L/kg. Based on daily intake estimation, the erythromycin–H 2 O in adult F. penicillatus presented a potential risk to human safety

  2. Knowledge, attitudes and practices concerning self-medication with antibiotics among university students in western China.

    Science.gov (United States)

    Lv, Bing; Zhou, Zhongliang; Xu, Guiping; Yang, Dingkun; Wu, Lina; Shen, Qian; Jiang, Minghuan; Wang, Xiao; Zhao, Guilan; Yang, Shimin; Fang, Yu

    2014-07-01

    To evaluate the knowledge, attitude and behaviours of university students on the use of antibiotics. A knowledge-attitude-practice questionnaire was developed and distributed to undergraduate students of Xi'an Jiaotong University, comprising 18 schools/colleges in Shaanxi Province, western China. Chi-square test and logistic regression analysis were applied to identify risk factors associated with self-medication with antibiotics. Of the 731 respondents (response rate = 73.1%), 294 (40.2%) had self-medicated with antibiotics in the past 6 months. Most of the antibiotics (59.2%) for self-medication were purchased without prescription in retail pharmacies. The median score of students' knowledge about antibiotics was 4 (IQR: 3-6) of a maximum possible score of 10. Students had moderately accurate beliefs towards antibiotics. More than half of the students (56.5%) were storing antibiotics frequently. During self-medication, 16.7% of students claimed to have experienced adverse reactions, and 30.6% had used antibiotics to prevent common colds. The majority preferred to use broad-spectrum antibiotics, and nearly half preferred intravenous antibiotics. Over 44% of students had changed antibiotic dosage, and 36.5% had switched to another antibiotic during the treatment course. Logistic regression analysis identified college and home town as independent risk factors for self-medication with antibiotics (P students had inadequate knowledge, moderately accurate beliefs and inappropriate practices concerning antibiotics, and a high rate of self-medication. This highlights the need for focused educational intervention and stricter governmental regulation concerning antibiotic use and sale in retail pharmacies. © 2014 John Wiley & Sons Ltd.

  3. Pharmacokinetics of Enrofloxacin and Danofloxacin in Plasma, Inflammatory Exudate, and Bronchial Secretions of Calves following Subcutaneous Administration

    Science.gov (United States)

    McKellar, Quintin; Gibson, Ian; Monteiro, Ana; Bregante, Miguel

    1999-01-01

    Enrofloxacin (2.5 mg/kg of body weight) and danofloxacin (1.25 mg/kg) were administered subcutaneously to ruminating calves (n = 8) fitted with subcutaneous tissue cages. Concentrations of enrofloxacin, its metabolite ciprofloxacin, and danofloxacin in blood (plasma), tissue cage exudate (following intracaveal injection of 0.3 ml of 1% [vol/wt] carrageenan), and bronchial secretions were measured by high-performance liquid chromatography (HPLC) and microbiological assay (enrofloxacin plus ciprofloxacin and danofloxacin). Mean maximum concentrations (Cmax) ± standard deviations of enrofloxacin (0.24 ± 0.08 μg/ml), ciprofloxacin (0.11 ± 0.03 [total, 0.34 ± 0.10] μg/ml), and danofloxacin (0.23 ± 0.05 μg/ml) were detected in the plasma of calves by HPLC. The Cmax were 0.49 ± 0.17 μg/ml (enrofloxacin equivalents) and 0.24 ± 0.03 μg/ml (danofloxacin) when they were measured by microbiological assay. Mean Cmax in exudate (HPLC) were 0.18 ± 0.07 μg/ml (enrofloxacin), 0.10 ± 0.04 μg/ml (ciprofloxacin), 0.27 ± 0.09 μg/ml (enrofloxacin plus ciprofloxacin), and 0.19 ± 0.05 μg/ml (danofloxacin), and concentrations in exudate exceeded those in plasma from 8 h (enrofloxacin and ciprofloxacin) or 6 h (danofloxacin) after drug administration. The Cmax were 0.34 ± 0.09 μg/ml (enrofloxacin equivalents) and 0.22 ± 0.04 μg/ml (danofloxacin) in exudate when they were measured by the microbiological assay. The maximum mean concentration achieved in bronchial secretions (HPLC) were 0.07 ± 0.04 μg/ml (enrofloxacin), 0.04 ± 0.07 μg/ml (ciprofloxacin), 0.10 ± 0.05 μg/ml (enrofloxacin plus ciprofloxacin), and 0.12 ± 0.09 μg/ml (danofloxacin). The maximum mean concentration in bronchial secretions from a limited number of animals from which samples were available for microbiological assay were 0.27 ± 0.11 μg/ml (n = 4 [enrofloxacin equivalents]) and 0.14 ± 0.02 μg/ml (n = 3 [danofloxacin]). With predictive models of efficacy (Cmax/MIC and area under the

  4. Resistance to non-quinolone antimicrobials in commensal Escherichia coli isolates from chickens treated orally with enrofloxacin.

    Science.gov (United States)

    Jurado, Sonia; Medina, Alberto; de la Fuente, Ricardo; Ruiz-Santa-Quiteria, José A; Orden, José A

    2015-11-01

    The aim of the present study was evaluate how oral administration of enrofloxacin affected the frequency of resistance to different antimicrobials in commensal Escherichia coli isolates from healthy chickens. A further objective of this study was to characterize the mechanisms of resistance in these isolates. A trend towards increased resistance to enrofloxacin, doxycycline and amoxicillin of E. coli isolates from chickens after enrofloxacin administration was observed. The increase in the resistance to doxycycline and amoxicillin was probably due to a co-selection of tetracycline and β-lactam resistance genes by the administration of enrofloxacin. The detection of tetM was much higher than expected (50%), which indicates that this gene may play an important role in tetracycline resistance in E. coli from chickens.

  5. Pharmacokinetics and tissue behavior of enrofloxacin and its metabolite ciprofloxacin in turbot Scophthalmus maximus at two water temperatures

    Science.gov (United States)

    Liang, Junping; Li, Jian; Zhao, Fazhen; Liu, Ping; Chang, Zhiqiang

    2012-07-01

    Turbot Scophthalmus maximus, an important aquaculture species in China, currently suffers from epizootic diseases because of high density aquaculture. Enrofloxacin has been used to treat various systemic bacterial fish infections. However, studies concerning the pharmacokinetics of enrofloxacin in turbot are limited. In this study, the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin, were investigated in the turbot following intravenous and oral administration at 10 mg enrofloxacin/kg body weight, at 16°C and 10°C water temperatures. The concentrations of enrofloxacin and ciprofloxacin in the main tissues (plasma, muscle, liver and kidney) were detected by HPLC. The results show that the plasma concentration-time data for enrofloxacin were best described as a two-compartment open model after intravenous and oral administration. Three pharmacokinetic equations were established between the concentrations and temperatures. The kinetic profile of enrofloxacin was temperature dependent. The absorption half-life of enrofloxacin was 1.99 h and 2.17 h after oral administration, whereas the elimination half-life of the drug was 98.63 h and 136.59 h at 16°C and 10°C, respectively. The peak concentration of enrofloxacin in plasma and tissues was higher at 16°C than that at 10°C, and the peak plasma concentration time in the liver was the shortest at both temperatures among those of other tissues. The plasma C max /MIC ratio varied between 11.08 and 5 540.00 at 16°C; and between 7.92 and 3 960.00 at 10°C. The AUC/MIC ratio was 467.82-280 690.00 at 16°C, and 359.48-215 690.00 at 10°C. These ratios indicate that it is possible to obtain therapeutic efficacy. Very low levels of ciprofloxacin were detected. The AUC ratios of ciprofloxacin and enrofloxacin in plasma suggest that plasma ciprofloxacin might play a minor role in enrofloxacin treatment for turbot.

  6. Distribution and degradation of common antibiotics and linkage to antibiotic resistance genes in the environment of Shenzhen, China

    Science.gov (United States)

    Sun, J.; Qiu, W.; Zheng, C.

    2017-12-01

    Antibiotics, as emerging contaminants, have been widely detected in environmental matrices in China and worldwide, such as wastewater treatment plants (WWTPs), hospital effluents, livestock farms, river water and sediment, soil, groundwater, and seawater. Thus, there exist significant concerns about their potential risks to human and ecosystem health. Compared to other countries, research on antibiotics in China is mainly focused on the watershed level, and there is a lack of information on emission inventory and environmental fate of antibiotics in China. In this study, we investigated the distribution of 21 frequently detected antibiotics in the five representative rivers in Shenzhen, China. Our monitoring results showed that the concentration of the 21 antibiotic contaminants in river waters and sediments ranges from 0.004ng/L to 0.378μg/L and from 0.005ng/kg to 2.089ng/kg, respectively. The data also revealed that the level of antibiotics in the five rivers exhibits strong temporal and spatial variations, and the antibiotic content in dry season is significantly higher than that in flood season. The bacterial resistance rates in sediments were found to be related to antibiotic usages, especially for those antibiotics used in the most recent period. Our degradation experiment results showed that the optimal conditions for the removal of enrofloxacin and pefloxacin were as follows: pH at 3 and the concentration of H2O2 and Fe2+ were 20mM and 0.25mM, respectively. This study can provide basic data useful for addressing the water environmental problems in Shenzhen and for dealing with national pollution control of antibiotics as emerging contaminants.

  7. Treating cattle with antibiotics affects greenhouse gas emissions, and microbiota in dung and dung beetles.

    Science.gov (United States)

    Hammer, Tobin J; Fierer, Noah; Hardwick, Bess; Simojoki, Asko; Slade, Eleanor; Taponen, Juhani; Viljanen, Heidi; Roslin, Tomas

    2016-05-25

    Antibiotics are routinely used to improve livestock health and growth. However, this practice may have unintended environmental impacts mediated by interactions among the wide range of micro- and macroorganisms found in agroecosystems. For example, antibiotics may alter microbial emissions of greenhouse gases by affecting livestock gut microbiota. Furthermore, antibiotics may affect the microbiota of non-target animals that rely on dung, such as dung beetles, and the ecosystem services they provide. To examine these interactions, we treated cattle with a commonly used broad-spectrum antibiotic and assessed downstream effects on microbiota in dung and dung beetles, greenhouse gas fluxes from dung, and beetle size, survival and reproduction. We found that antibiotic treatment restructured microbiota in dung beetles, which harboured a microbial community distinct from those in the dung they were consuming. The antibiotic effect on beetle microbiota was not associated with smaller size or lower numbers. Unexpectedly, antibiotic treatment raised methane fluxes from dung, possibly by altering the interactions between methanogenic archaea and bacteria in rumen and dung environments. Our findings that antibiotics restructure dung beetle microbiota and modify greenhouse gas emissions from dung indicate that antibiotic treatment may have unintended, cascading ecological effects that extend beyond the target animal. © 2016 The Author(s).

  8. Treating cattle with antibiotics affects greenhouse gas emissions, and microbiota in dung and dung beetles

    Science.gov (United States)

    Fierer, Noah; Hardwick, Bess; Simojoki, Asko; Slade, Eleanor; Taponen, Juhani; Viljanen, Heidi; Roslin, Tomas

    2016-01-01

    Antibiotics are routinely used to improve livestock health and growth. However, this practice may have unintended environmental impacts mediated by interactions among the wide range of micro- and macroorganisms found in agroecosystems. For example, antibiotics may alter microbial emissions of greenhouse gases by affecting livestock gut microbiota. Furthermore, antibiotics may affect the microbiota of non-target animals that rely on dung, such as dung beetles, and the ecosystem services they provide. To examine these interactions, we treated cattle with a commonly used broad-spectrum antibiotic and assessed downstream effects on microbiota in dung and dung beetles, greenhouse gas fluxes from dung, and beetle size, survival and reproduction. We found that antibiotic treatment restructured microbiota in dung beetles, which harboured a microbial community distinct from those in the dung they were consuming. The antibiotic effect on beetle microbiota was not associated with smaller size or lower numbers. Unexpectedly, antibiotic treatment raised methane fluxes from dung, possibly by altering the interactions between methanogenic archaea and bacteria in rumen and dung environments. Our findings that antibiotics restructure dung beetle microbiota and modify greenhouse gas emissions from dung indicate that antibiotic treatment may have unintended, cascading ecological effects that extend beyond the target animal. PMID:27226475

  9. Knowledge regarding antibiotic drug action and prescription practices among dentist in Jaipur city, Rajasthan

    Directory of Open Access Journals (Sweden)

    Dushyant Pal Singh

    2015-01-01

    Full Text Available Introduction: Dentists prescribe antibiotics routinely to manage oral and dental infections. Unscrupulous antibiotic prescriptions can be associated with unfavorable side effects and the development of resistance. Thus, the aim of this study was to assess the level of knowledge regarding antibiotic prescription use among dentists in Jaipur City, Rajasthan. Materials and Methods: A questionnaire survey was conducted among 300 dentists in Jaipur city. A validated, self-designed, 21-item, closed-ended questionnaire was used to collect data on knowledge regarding antibiotic prescription. Descriptive statistics were calculated. Results: A total of 300 dental practitioners were included in the study. The majority of the respondents seem to prescribe antibiotics that are broad spectrum or the ones that are commonly used. A considerable percentage of the respondents were not aware of the pregnancy drug risk categories by Food and Drug Administration. The most of the respondents said that they prescribe antibiotics on the basis of the diagnosis, whereas more than two-thirds of the respondents said that they never advise culture sensitivity test before prescribing the antibiotics. Conclusion: Our findings suggest the knowledge of dentists regarding antibiotic prescription is inadequate and more focus should be given to the ongoing training regarding the pharmacological aspects, pertinent medical conditions, and prophylactic use of antibiotics in dentistry.

  10. Antibiotic resistance

    Directory of Open Access Journals (Sweden)

    Marianne Frieri

    2017-07-01

    Full Text Available Summary: Antimicrobial resistance in bacterial pathogens is a challenge that is associated with high morbidity and mortality. Multidrug resistance patterns in Gram-positive and -negative bacteria are difficult to treat and may even be untreatable with conventional antibiotics. There is currently a shortage of effective therapies, lack of successful prevention measures, and only a few new antibiotics, which require development of novel treatment options and alternative antimicrobial therapies. Biofilms are involved in multidrug resistance and can present challenges for infection control. Virulence, Staphylococcus aureus, Clostridium difficile infection, vancomycin-resistant enterococci, and control in the Emergency Department are also discussed. Keywords: Antibiotic resistance, Biofilms, Infections, Public health, Emergency Department

  11. Effects of intramuscularly administered enrofloxacin on the susceptibility of commensal intestinal Escherichia coli in pigs (sus scrofa domestica).

    Science.gov (United States)

    Römer, Antje; Scherz, Gesine; Reupke, Saskia; Meißner, Jessica; Wallmann, Jürgen; Kietzmann, Manfred; Kaspar, Heike

    2017-12-04

    In the European Union, various fluoroquinolones are authorised for the treatment of food producing animals. Each administration poses an increased risk of development and spread of antimicrobial resistance. The aim of this study was to investigate the impact of parenteral administration of enrofloxacin on the prevalence of enrofloxacin and ciprofloxacin susceptibilities in the commensal intestinal E. coli population. E. coli isolates from faeces of twelve healthy pigs were included. Six pigs were administered enrofloxacin on day 1 to 3 and after two weeks for further three days. The other pigs formed the control group. MIC values were determined. Virulence and resistance genes were detected by PCR. Phylogenetic grouping was performed by PCR. Enrofloxacin and ciprofloxacin were analysed in sedimentation samples by HPLC. Susceptibility shifts in commensal E. coli isolates were determined in both groups. Non-wildtype E. coli could be cultivated from two animals of the experimental group for the first time one week after the first administration and from one animal of the control group on day 28. The environmental load with enrofloxacin in sedimentation samples showed the highest amount between days one and five. The repeated parenteral administration of enrofloxacin to pigs resulted in rapidly increased MIC values (day 28: MIC up to 4 mg/L, day 35: MIC ≥ 32mg/L). E. coli populations of the control group in the same stable without direct contact to the experimental group were affected. The parenteral administration of enrofloxacin to piglets considerably reduced the number of the susceptible intestinal E. coli population which was replaced by E. coli strains with increased MIC values against enrofloxacin. Subsequently also pigs of the control were affected suggesting a transferability of strains from the experimental group through the environment to the control group especially as we could isolate the same PFGE strains from both pig groups and the environment.

  12. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis.

    Science.gov (United States)

    Esaiassen, Eirin; Fjalstad, Jon Widding; Juvet, Lene Kristine; van den Anker, John N; Klingenberg, Claus

    2017-07-01

    To systematically review and meta-analyse the relationship between antibiotic exposure in neonates and the following early adverse outcomes: necrotizing enterocolitis (NEC), invasive fungal infections (IFIs) and/or death. Data sources were PubMed, Embase, Medline and the Cochrane Database (to December 2016), supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic exposures (yes versus no, long versus short duration, and/or broad- versus narrow-spectrum regimens) and the risk of developing NEC, IFI and/or death in the neonatal period. Two reviewers extracted data and evaluated the risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, meta-analyses were conducted using the random-effect model. We identified 9 RCTs and 38 observational studies. The quality of the majority of studies was poor to moderate. There was a significant association between prolonged antibiotic exposure and an increased risk of NEC in five observational studies (5003 participants) and/or risk of death in five observational studies (13 534 participants). Eleven of 15 studies with data on broad- versus narrow-spectrum regimens reported an increased risk of IFI after broad-spectrum antibiotic exposure, in particular with third-generation cephalosporins and carbapenems. Meta-analysis was limited by few and old RCTs, insufficient sample sizes and diversity of antibiotic exposure and outcomes reported. Prolonged antibiotic exposure in uninfected preterm infants is associated with an increased risk of NEC and/or death, and broad-spectrum antibiotic exposure is associated with an increased risk of IFI. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Comparative evaluation of therapeutic efficacy of sulfadiazine-trimethoprim, oxytetracycline, enrofloxacin and florfenicol on Staphylococcus aureus-induced arthritis in broilers.

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    Mosleh, N; Shomali, T; Namazi, F; Marzban, M; Mohammadi, M; Boroojeni, A Motamedi

    2016-04-01

    Staphylococcus aureus is an important human and veterinary pathogen that causes economic loss in the poultry industry. This study aimed to compare therapeutic efficacy of 4 commonly used antibiotics in poultry on S. aureus-induced arthritis in broilers. Sixty broilers, 8 weeks of age, were assigned at random into 7 groups as follows: (1) negative control (n = 5); (2) vehicle control (n = 5); (3) sulfadiazine-trimethoprim, 250 ml/1000 l drinking water (n = 10); (4) oxytetracycline 20%, 1 mg/l drinking water (n = 10); (5) florfenicol 10%, 1/1000 v/v in drinking water (n = 10); (6) enrofloxacin 10%, 1/1000 v/v in drinking water (n = 10) and (7) positive control (n = 10). Birds in group 2 were injected with 1 ml of sterile TSB medium into the right tibiotarsal joint on d 0 while other birds (except group 1) were challenged with 1 ml of 1.2 × 10(10) CFU/ml suspension of S. aureus bacteria. Antibiotic therapy was started from d 4 post challenge and continued for 5 d. At the end, birds were weighed and clinical severity of arthritis was determined. After blood collection, birds were slaughtered and tibiotarsal and hip joints were evaluated grossly. The content of inflammatory exudates of tibiotarsal joint and the degree of femoral head necrosis were recorded. Mucin clot test and histopathological evaluation were performed on right tibiotarsal joint. Serum interleukin 6 was also assayed. Sulfadiazine-trimethoprim had higher therapeutic efficiency with regard to most of the assayed criteria, whereas none of the antibiotics significantly affected femoral head necrosis and body weight. These data will help clinicians to have better antibiotic choice in field conditions.

  14. Antibiotic Prescribing Patterns in Outpatient Emergency Clinics at Queen Rania Al Abdullah II Children's Hospital, Jordan, 2013.

    Science.gov (United States)

    Al-Niemat, Sahar I; Aljbouri, Tareq M; Goussous, Lana S; Efaishat, Rania A; Salah, Rehab K

    2014-07-01

    To investigate antibiotics prescribing patterns in the outpatient pediatric emergency clinic at Queen Rania Al Abdullah II Children's Hospital at Royal Medical Services in Amman, Jordan. The data was collected from the emergency pharmacy over the period of a -five consecutive months. The methodology recommended by the World Health Organization for investigating drug use in a health facility was followed. The study measures the percentage of encounter with a prescribed antibiotic and the percentage share of each antibiotic category. The distribution of diagnostic categories that accounted for all antibiotics being prescribed and the distribution of each antibiotic being prescribed for upper respiratory tract infections (URTIs) were also measured. Antibiotic prescribing was frequent during pediatric visits to the outpatient pediatric emergency clinic resulting in a high percentage of encounters (85%) when compared to appropriate. Emergency physicians continue to frequently prescribe broad spectrum antibiotics which accounted for approximately (60%) of the total prescribed antibiotics and (83%) of prescribed antibiotics for upper respiratory tract infections and macrolides (primarily azithromycin) were the leading class among them. Our results showed high consumption of antibiotics by emergency department pediatricians which highlight the importance for interventions to promote rational and judicious prescribing. An insight into factors influencing antibiotics prescribing patterns by military prescribers is required.

  15. Antibiotic Prescribing Patterns in Outpatient Emergency Clinics at Queen Rania Al Abdullah II Children's Hospital, Jordan, 2013

    Directory of Open Access Journals (Sweden)

    Sahar I. Al-Niemat

    2014-07-01

    Full Text Available Objective: To investigate antibiotics prescribing patterns in the outpatient pediatric emergency clinic at Queen Rania Al Abdullah II Children’s Hospital at Royal Medical Services in Amman, Jordan. Methods: The data was collected from the emergency pharmacy over the period of a -five consecutive months. The methodology recommended by the World Health Organization for investigating drug use in a health facility was followed. The study measures the percentage of encounter with a prescribed antibiotic and the percentage share of each antibiotic category. The distribution of diagnostic categories that accounted for all antibiotics being prescribed and the distribution of each antibiotic being prescribed for upper respiratory tract infections (URTIs were also measured. Results: Antibiotic prescribing was frequent during pediatric visits to the outpatient pediatric emergency clinic resulting in a high percentage of encounters (85% when compared to appropriate. Emergency physicians continue to frequently prescribe broad spectrum antibiotics which accounted for approximately (60% of the total prescribed antibiotics and (83% of prescribed antibiotics for upper respiratory tract infections and macrolides (primarily azithromycin were the leading class among them. Conclusion: Our results showed high consumption of antibiotics by emergency department pediatricians which highlight the importance for interventions to promote rational and judicious prescribing. An insight into factors influencing antibiotics prescribing patterns by military prescribers is required.

  16. Trends in antibiotic treatment of acute otitis media and treatment failure in children, 2000-2011.

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    Leah J McGrath

    Full Text Available Guidelines to treat acute otitis media (AOM were published in 2004. Initial declines in prescribing were shown, but it's unknown if they were sustained. We examine trends in antibiotic dispensing patterns to treat AOM among a large population of children. We also document trends in antibiotic failure.Children aged 3 months to 12 years with an AOM diagnosis, enrolled in a commercial claims database between January 1, 2000-December 31, 2011 were included. Pharmacy claims within 7 days of diagnosis were searched for antibiotic prescriptions. Antibiotic failure was defined as a dispensing of a different antibiotic class within 2-18 days after the first prescription. We analyzed trends in antibiotic use and failure by class of antibiotic and year.We identified over 4 million children under 13 years with AOM. The proportion of antibiotic dispensing decreased from 66.0% in 2005 to 51.9% in 2007, after which the instances of dispensing rebounded to pre-guideline levels. However, levels began decreasing again in 2010 and the antibiotic use rate in 2011 was 57.6%. Cephalosporin prescriptions increased by 41.5% over eleven years. Antibiotic failure decreased slightly, and macrolides had the lowest proportion of failures, while all other classes had failure rates around 10%.In recent years, antibiotic dispensing to treat AOM remains high. In addition, the use of broad-spectrum antibiotics is increasing despite having a high rate of treatment failure. Overprescribing of antibiotics and use of non-penicillin therapy for AOM treatment could lead to the development of antibiotic-resistant infections.

  17. Antagonistic activity of antibiotic producing Streptomyces sp. against fish and human pathogenic bacteria

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    Nazmul Hossain

    2014-04-01

    Full Text Available In this study, attempts were made to isolate Streptomyces sp. from soil samples of two different regions of Bangladesh and evaluate their antagonistic activity against fish and human pathogenic bacteria. A total of 10 isolates were identified as Streptomyces sp. based on several morphological, physiological and biochemical tests. Cross streak method was used to observe the antagonistic activity of the Streptomyces sp. isolates against different fish pathogens belonging to the genus Aeromonas, Pseudomonas and Edwardsiella and human clinical isolates belonging to the genus Klebsiella, Salmonella and Streptococcus. Seven Streptomyces sp. isolates showed antagonism against both fish and human pathogenic bacteria. Four isolates viz., N24, N26, N28 and N47 showed broad spectrum of antagonistic activity (80-100% against all genera of fish and human pathogenic bacteria. The isolate N49 exhibited highest spectrum of antagonism against all fish pathogens (90-100% but comparatively lower degree of antagonism against human pathogens (50-60%. Rest of the two isolates (N21 and N23 showed variability in their antagonism. Results showed that broad spectrum antibiotic(s could be developed from the isolates N24, N26, N28 and N47against several human and fish pathogens. The isolate N49 could be a potential source of antibiotic, especially for fish pathogenic bacteria.

  18. An antibiotic-responsive mouse model of fulminant ulcerative colitis.

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    Silvia S Kang

    2008-03-01

    Full Text Available BACKGROUND: The constellation of human inflammatory bowel disease (IBD includes ulcerative colitis and Crohn's disease, which both display a wide spectrum in the severity of pathology. One theory is that multiple genetic hits to the host immune system may contribute to the susceptibility and severity of IBD. However, experimental proof of this concept is still lacking. Several genetic mouse models that each recapitulate some aspects of human IBD have utilized a single gene defect to induce colitis. However, none have produced pathology clearly distinguishable as either ulcerative colitis or Crohn's disease, in part because none of them reproduce the most severe forms of disease that are observed in human patients. This lack of severe IBD models has posed a challenge for research into pathogenic mechanisms and development of new treatments. We hypothesized that multiple genetic hits to the regulatory machinery that normally inhibits immune activation in the intestine would generate more severe, reproducible pathology that would mimic either ulcerative colitis or Crohn's disease. METHODS AND FINDINGS: We generated a novel mouse line (dnKO that possessed defects in both TGFbetaRII and IL-10R2 signaling. These mice rapidly and reproducibly developed a disease resembling fulminant human ulcerative colitis that was quite distinct from the much longer and more variable course of pathology observed previously in mice possessing only single defects. Pathogenesis was driven by uncontrolled production of proinflammatory cytokines resulting in large part from T cell activation. The disease process could be significantly ameliorated by administration of antibodies against IFNgamma and TNFalpha and was completely inhibited by a combination of broad-spectrum antibiotics. CONCLUSIONS: Here, we develop to our knowledge the first mouse model of fulminant ulcerative colitis by combining multiple genetic hits in immune regulation and demonstrate that the resulting

  19. Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain

    2015-01-01

    The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Meal tests...... with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean...... and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition. Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose...

  20. Interactions of antibiotics and extracts of Helichrysum pedunculatum against bacteria implicated in wound infections.

    Science.gov (United States)

    Aiyegoro, O A; Afolayan, A J; Okoh, A I

    2010-03-01

    The effect of combinations of the crude acetone and aqueous extracts of Helichrysum pedunculatum leaves and eight antibiotics was determined by means of checkerboard and time-kill methods. In the checkerboard method, synergy of 45.8% was observed, being independent of Gram reaction, with combinations in the aqueous extract yielding largely (18.8%) antagonistic interactions. The time-kill assay detected synergy (45.8%) that was also independent of Gram reaction with a potentiation of more than 3 orders of the bactericidal activity of the test antibiotics. The crude leaf extracts of H. pedunculatum could thus be considered to be potential source of a broad-spectrum antibiotic-resistance-modifying compounds.

  1. Efficacy assessment of an intramammary treatment with a new recrystallized enrofloxacin vs ceftiofur and parenteral enrofloxacin in dairy cows with nonsevere clinical mastitis.

    Science.gov (United States)

    Viveros, M; Lopez-Ordaz, R; Gutiérrez, L; Miranda-Calderón, J E; Sumano, H

    2018-02-01

    A recrystallized form of enrofloxacin as dehydrate-HCl (enro-C) was assessed for bacteriological and clinical cure efficacies in Holstein-Friesian cows affected of nonsevere clinical mastitis. Treatments were enro-C susp (n = 81), treated with a pharmaceutical suspension of enro-C/quarter; group enro-C pd (n = 80) treated as above, but using enro-C powder suspended in water; group CF (n = 65), treated with ceftiofur HCl/quarter; and group enro R (n = 66), treated with standard enrofloxacin solution (5 mg/kg, intramuscular). Cows had a mean milk production of 31 L/day and were 2-3 lactational periods old. Treatments were administered every 24 hr for 3 days. Groups treated with enro-C exhibited statistically significant (p > .05) better clinical cure as compared to groups treated with CF or enro R (95.06%, 96.25%, 67.79%, and 57.55%, for enro-C susp , enro-C pd , CF, and enro R , respectively). In contrast, probability of bacteriological cure was not statistically different among treatments. Yet, the outstanding clinical and bacteriological cure rates obtained for enro-C for nonsevere cases of mastitis is superior to previously reported data for parenteral enrofloxacin and other antibacterial-intramammary treatments. Impact of using enro-C on the rate and pattern of bacterial resistance, somatic cell counts and milk electric conductivity, must be studied. Also, the use of enro-C for complicated cases of mastitis should be studied and milk withdrawal times must be accurately established. © 2017 John Wiley & Sons Ltd.

  2. Antibiotic prescribing in public and private practice: a cross-sectional study in primary care clinics in Malaysia.

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    Ab Rahman, Norazida; Teng, Cheong Lieng; Sivasampu, Sheamini

    2016-05-17

    Antibiotic overuse is driving the emergence of antibiotic resistance worldwide. Good data on prescribing behaviours of healthcare providers are needed to support antimicrobial stewardship initiatives. This study examined the differences in antibiotic prescribing rates of public and private primary care clinics in Malaysia. We used data from the National Medical Care Survey (NMCS), a nationwide cluster sample of Malaysian public and private primary care clinics in 2014. NMCS contained demographic, diagnoses and prescribing from 129 public clinics and 416 private clinics. We identified all encounters who were prescribed antibiotic and analyse the prescribing rate, types of antibiotics, and diagnoses that resulted in antibiotic. Five thousand eight hundred ten encounters were prescribed antibiotics; antibiotic prescribing rate was 21.1 % (public clinics 6.8 %, private clinics 30.8 %). Antibiotic prescribing was higher in private clinics where they contributed almost 87 % of antibiotics prescribed in primary care. Upper respiratory tract infection (URTI) was the most frequent diagnosis in patients receiving antibiotic therapy and accounted for 49.2 % of prescriptions. Of the patients diagnosed with URTI, 46.2 % received antibiotic treatment (public 16.8 %, private 57.7 %). Penicillins, cephalosporins and macrolides were the most commonly prescribed antibiotics and accounted for 30.7, 23.6 and 16.0 % of all antibiotics, respectively. More recently available broad-spectrum antibiotics such as azithromycin and quinolones were more frequently prescribed in private clinics. Antibiotic prescribing rates are high in both public and private primary care settings in Malaysia, especially in the latter. This study provides evidence of excessive and inappropriate antibiotic prescribing for self-limiting conditions. These data highlights the needs for more concerted interventions targeting both prescribers and public. Improvement strategies should focus on reducing

  3. Pressing Issues of Rational Antibiotic Therapy for Inflammatory Diseases of the Lower Respiratory Tract in Pediatric Practice

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    Ye.N. Okhotnikova

    2015-03-01

    Full Text Available Over the past 30 years, high incidence of acute lower respiratory tract infections of bacterial origin, primarily pneumonia and bronchitis, treatment of which under the spread of antibiotic resistance is often a difficult task, cause alarm. Bronchitis — one of the most common respiratory diseases in childhood after acute respiratory viral infections. Application of antibiotics for acute bronchitis in children is not recommended, but they are prescribed for severe intoxication and prolonged hyperthermia (over 3 days, especially in infants, children with poor premorbid background and high risk of pneumonia. Antibiotic therapy is considered as the only science-based treatment of pneumonia. Taking into account the broad spectrum of modern antibiotics, monotherapy is most suitable. If it is necessary to extend their effect, combination of amoxicillin/clavulanate with macrolides, to which all the major respiratory pathogens are sensitive, is preferred.

  4. Diversity and natural functions of antibiotics produced by beneficial and plant pathogenic bacteria.

    Science.gov (United States)

    Raaijmakers, Jos M; Mazzola, Mark

    2012-01-01

    Soil- and plant-associated environments harbor numerous bacteria that produce antibiotic metabolites with specific or broad-spectrum activities against coexisting microorganisms. The function and ecological importance of antibiotics have long been assumed to yield a survival advantage to the producing bacteria in the highly competitive but resource-limited soil environments through direct suppression. Although specific antibiotics may enhance producer persistence when challenged by competitors or predators in soil habitats, at subinhibitory concentrations antibiotics exhibit a diversity of other roles in the life history of the producing bacteria. Many processes modulated by antibiotics may be inherently critical to the producing bacterium, such as the acquisition of substrates or initiation of developmental changes that will ensure survival under stressful conditions. Antibiotics may also have roles in more complex interactions, including in virulence on host plants or in shaping the outcomes of multitrophic interactions. The innate functions of antibiotics to producing bacteria in their native ecosystem are just beginning to emerge, but current knowledge already reveals a breadth of activities well beyond the historical perspective of antibiotics as weaponry in microbial conflicts.

  5. Working Together to Define Antibiotic Appropriateness: Point Prevalence Survey in 47 Intensive Care Units from 12 US Hospitals, Partnership for Quality Care, March 2017

    Science.gov (United States)

    Trivedi, Kavita K; Ostrowsky, Belinda; Abbo, Lilian M; Srinivasan, Arjun; Bartash, Rachel; Cassera, Fred; Fleisher, Jorge; Kubiak, David W; Letourneau, Alyssa R; Nori, Priya; Parodi, Stephen; Aragon, Laura; Dollard, Eliza; Gagliardo, Christina; Ghitan, Monica; Giles, Amber; Mayer, Suri; Quevedo, Jennifer; Rieg, Gunter; Shteyman, Galina; Vargas, Jaclyn; Kelley, Shannon; Silver, Phyllis

    2017-01-01

    Abstract Background A national assessment of antibiotic appropriateness in intensive care units (ICUs) with benchmarking was performed to assist antibiotic stewardship programs (ASPs) identify improvement opportunities. Methods A Centers for Disease Control and Prevention tool was adapted by an expert panel from the Partnership for Quality Care (PQC), a coalition dedicated to high quality care in US hospitals, to validate appropriate antibiotic use measurement via a point prevalence survey on a single day. Data were collected by ASP personnel at each hospital, de-identified and submitted in aggregate to PQC for benchmarking. Hospitals identified reasons for inappropriate antibiotic use by category and antibiotics misused. Results Forty-seven ICUs from 12 PQC hospitals participated: California (2), Florida (2), Massachusetts (3), Minnesota (1), and New York (4). Most hospitals identified as teaching (83%) with 252-1550 bed size (median: 563) and 20–270 licensed ICU beds (median: 70). All hospitals reported a formal ASP. On March 1, 2017, 362 (54%) of 667 patients in participating ICUs were on antibiotics (range: 8-81 patients); 1 patient was not assessed. Of the remaining 361 antibiotic regimens, 112 (31%) were identified as inappropriate from among all 12 hospitals (range: 9-82%) (figure). The table displays inappropriate antibiotic use by ICU type. Reasons for inappropriate use included unnecessarily broad spectrum of activity (29%), duration longer than necessary (21%), and treatment of a non-infectious syndrome (19%). The antibiotic most commonly misused was vancomycin in 7 (58%) hospitals. Conclusion Up to 80% of antibiotic use in some ICUs is inappropriate, underscoring the need for ASP interventions, standardized assessment tools and benchmarking. Strategies should focus on de-escalation of broad-spectrum antibiotics and reducing duration of therapy. Disclosures D. W. Kubiak, Shionogi: Consultant, Consulting fee. Astellas Pharma: Consultant, Consulting

  6. Lactobacillus GG and tributyrin supplementation reduce antibiotic-induced intestinal injury.

    Science.gov (United States)

    Cresci, Gail; Nagy, Laura E; Ganapathy, Vadivel

    2013-11-01

    Antibiotic therapy negatively alters the gut microbiota. Lactobacillus GG (LGG) decreases antibiotic-associated diarrhea (AAD) symptoms, but the mechanisms are unknown. Butyrate has beneficial effects on gut health. Altered intestinal gene expression occurs in the absence of gut microbiota. We hypothesized that antibiotic-induced changes in gut microbiota reduce butyrate production, varying genes involved with gut barrier integrity and water and electrolyte absorption, lending to AAD, and that simultaneous supplementation with LGG and/or tributyrin would prevent these changes. C57BL/6 mice aged 6-8 weeks received a chow diet while divided into 8 treatment groups (± saline, ± LGG, ± tributyrin, or both). Mice received treatments orally for 7 days with ± broad-spectrum antibiotics. Water intake was recorded daily and body weight was measured. Intestine tissue samples were obtained and analyzed for expression of genes and proteins involved with water and electrolyte absorption, butyrate transport, and gut integrity via polymerase chain reaction and immunohistochemistry. Antibiotics decreased messenger RNA (mRNA) expression (butyrate transporter and receptor, Na(+)/H(+) exchanger, Cl(-)/HCO3 (-), and a water channel) and protein expression (butyrate transporter, Na(+)/H(+) exchanger, and tight junction proteins) in the intestinal tract. LGG and/or tributyrin supplementation maintained intestinal mRNA expression to that of the control animals, and tributyrin maintained intestinal protein intensity expression to that of control animals. Broad-spectrum antibiotics decrease expression of anion exchangers, butyrate transporter and receptor, and tight junction proteins in mouse intestine. Simultaneous oral supplementation with LGG and/or tributyrin minimizes these losses. Optimizing intestinal health with LGG and/or tributyrin may offer a preventative therapy for AAD.

  7. Preparation, characterization and pharmacokinetics of enrofloxacin-loaded solid lipid nanoparticles: influences of fatty acids.

    Science.gov (United States)

    Xie, Shuyu; Zhu, Luyan; Dong, Zhao; Wang, Xiaofang; Wang, Yan; Li, Xihe; Zhou, WenZhong

    2011-04-01

    Enrofloxacin-loaded solid lipid nanoparticles (SLN) were prepared using fatty acids (tetradecanoic acid, palmitic acid, stearic acid) as lipid matrix by hot homogenization and ultrasonication method. The effect of fatty acids on the characteristics and pharmacokinetics of the SLN were investigated. The results showed that the encapsulation efficiency and loading capacity of nanoparticles varied with fatty acids in the order of stearic acid>palmitic acid>tetradecanoic acid. Furthermore, stearic acid-SLN had larger particle size, bigger polydispersity index (PDI) and higher zeta potential compared with the other two fatty acid formulated SLN. The SLN showed sustained releases in vitro and the released enrofloxacin had the same antibacterial activity as that of the native enrofloxacin. Although in vitro release exhibited similar patterns, within 24 h the releasing rates of the three formulations were significantly different (tetradecanoic acid-SLN>palmitic acid-SLN>stearic acid-SLN). Pharmacokinetic study after a single dose of intramuscular administration to mice demonstrated that tetradecanoic acid-SLN, palmitic acid-SLN, and stearic acid-SLN increased the bioavailability by 6.79, 3.56 and 2.39 folds, and extended the mean residence time (MRT) of the drug from 10.60 h to 180.36, 46.26 and 19.09 h, respectively. These results suggest that the enrofloxacin-fatty acid SLN are promising formulations for sustained release while fatty acids had significant influences on the characteristics and performances of the SLN. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. The effect of 'allergenic' and 'nonallergenic' antibiotics on dog keratinocyte viability in vitro.

    Science.gov (United States)

    Voie, Katrine L; Lucas, Benjamin E; Schaeffer, David; Kim, Dewey; Campbell, Karen L; Lavergne, Sidonie N

    2013-10-01

    Immune-mediated adverse drug reactions (drug hypersensitivity) are relatively common in veterinary medicine, but their pathogenesis is not well understood. For an unknown reason, delayed drug hypersensitivity often targets the skin. Antibiotics, especially β-lactams and sulfonamides, are commonly associated with these adverse events. The 'danger theory' hypothesizes that 'danger' signals, such as drug-induced cell death, might be part of the pathogenesis of drug hypersensitivity reactions. The goal of this study was to determine whether antibiotics that are commonly associated with cutaneous drug hypersensitivity (allergenic) decrease canine keratinocyte viability in vitro more than antibiotics that rarely cause such reactions (nonallergenic). Immortalized canine keratinocytes (CPEK cells) were exposed to a therapeutic range of drug concentrations of four 'allergenic' antibiotics (two β-lactams, i.e. amoxicillin and cefalexin, and two sulfonamides, i.e. sulfamethoxazole and sulfadimethoxine) or two 'nonallergenic' antibiotics (enrofloxacin and amikacin) over 48 h (2, 4, 8, 24 and 48 h). The reactive nitroso metabolite of sulfamethoxazole was also tested. Cefalexin (2 mmol/L) significantly decreased cell viability after 48 h (28 ± 7%; P = 0.035). The nitroso metabolite of sulfamethoxazole (100 μmol/L) decreased cell viability after 2 h (21 ± 7%; P = 0.049), but cell numbers were increased after 8 h (22 ± 6%; P = 0.018). In addition, enrofloxacin (500 μmol/L) also significantly decreased cell viability by 37% (±6%; P = 0.0035) at 24 h and by 70% (±8%; P good predictor of the 'allergenic' potential of an antibiotic. Further work is required to investigate other drug-induced 'danger' signals in dog keratinocytes exposed to 'allergenic' antibiotics in vitro. © 2013 ESVD and ACVD.

  9. Effect of enrofloxacin and chlorpyrifos on the levels of vitamins A and E in Wistar rats.

    Science.gov (United States)

    Spodniewska, Anna; Barski, Dariusz; Giżejewska, Aleksandra

    2015-09-01

    This study investigates the effects of enrofloxacin and chlorpyrifos, and their combination on vitamin A and E concentrations in the liver of rats. Results of this study indicated a reduction in the contents of vitamins A and E in the liver, which persisted for the entire period of the experiment. Vitamins A and E concentrations were slightly decreased (2-7%) in enrofloxacin-treated rats. In the group of rats intoxicated with chlorpyrifos, a significant decrease in the level of vitamin A was observed up to the 24th hour, and for vitamin E up to the 3rd day from the discontinuation of intoxication with the compounds under study. In the enrofloxacin-chlorpyrifos co-exposure group reduced vitamins A and E level was also noted. The greatest fall in vitamin A level was observed after 3h, while the contents of vitamin E decreased progressively up to the 3rd day. Changes in this group were less pronounced in comparison to the animals intoxicated with chlorpyrifos only. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. In vitro activity of chloramphenicol, florfenicol and enrofloxacin against Chlamydia pecorum isolated from koalas (Phascolarctos cinereus).

    Science.gov (United States)

    Black, L A; Higgins, D P; Govendir, M

    2015-11-01

    To determine the in vitro susceptibilities of koala isolates of Chlamydia pecorum to enrofloxacin and chloramphenicol, which are frequently used to treat koalas with chlamydiosis, and florfenicol, a derivative of chloramphenicol. The in vitro susceptibilities were determined by culturing three stored isolates and seven clinical swabs of C. pecorum. Susceptibility testing was undertaken using cycloheximide-treated buffalo green monkey kidney cells in 96 well microtitre plates. The minimum inhibitory concentrations (MICs) for all isolates were 0.25-0.50 µg/mL (enrofloxacin), 1-2 µg/mL (chloramphenicol), and 1-2 µg/mL (florfenicol). Minimum bactericidal concentration (MBC) values for five isolates were also determined and were within one two-fold dilution of MICs. The MICs and MBCs of these antimicrobials were within ranges previously reported for other chlamydial species. When combined with previously published pharmacokinetic data, the in vitro susceptibility results support chloramphenicol as a more appropriate treatment option than enrofloxacin for koalas with chlamydiosis. The susceptibility results also indicate florfenicol may be an appropriate treatment option for koalas with chlamydiosis, warranting further investigation. © 2015 Australian Veterinary Association.

  11. Pharmacokinetics of enrofloxacin after oral, intramuscular and bath administration in crucian carp (Carassius auratus gibelio).

    Science.gov (United States)

    Shan, Q; Fan, J; Wang, J; Zhu, X; Yin, Y; Zheng, G

    2018-02-01

    The pharmacokinetics of enrofloxacin (ENR) was studied in crucian carp (Carassius auratus gibelio) after single administration by intramuscular (IM) injection and oral gavage (PO) at a dose of 10 mg/kg body weight and by 5 mg/L bath for 5 hr at 25°C. The plasma concentrations of ENR and ciprofloxacin (CIP) were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR or CIP concentrations using WinNonlin 6.1 software. After IM, PO and bath administration, the maximum plasma concentration (C max ) of 2.29, 3.24 and 0.36 μg/ml was obtained at 4.08, 0.68 and 0 hr, respectively; the elimination half-life (T 1/2β ) was 80.95, 62.17 and 61.15 hr, respectively; the area under the concentration-time curve (AUC) values were 223.46, 162.72 and 14.91 μg hr/ml, respectively. CIP, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration except bath. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the crucian carp using IM, PO and bath immersion administration. © 2017 John Wiley & Sons Ltd.

  12. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Munck, Christian

    morbidity and mortality as well as an increase in the cost of treatment. Understanding how bacteria respond to antibiotic exposure gives the foundations for a rational approach to counteract antimicrobial resistance. In the work presented in this thesis, I explore the two fundamental sources...... of antimicrobial resistance: (1) adaptive mutations and (2) horizontal acquisition of resistance genes from antibiotic gene reservoirs. By studying the geno- and phenotypic changes of E. coli in response to single and drug-pair exposures, I uncover the evolutionary trajectories leading to adaptive resistance. I...... to rationally design drug combinations that limit the evolution of antibiotic resistance due to counteracting evolutionary trajectories. My results highlight that an in-depth knowledge about the genetic responses to the individual antimicrobial compounds enables the prediction of responses to drug combinations...

  13. Veterinarians’ Perception, Knowledge and Practices of Antibiotic Stewardship in Enugu State Southeast, Nigeria

    Directory of Open Access Journals (Sweden)

    Madubuike Umunna ANYANWU

    2017-09-01

    Full Text Available A cross-sectional survey utilizing structured questionnaires was used to study the veterinarians’ perception, knowledge and practices of antibiotic stewardship (ABS in Enugu State, Southeastern Nigeria. Data obtained were analyzed using chi-square on SPSS (Version 15.0 at a significance level of P < 0.05 to determine possible associations between variables and perceptions/knowledge about ABS. Out of 280 respondents, 41 (17.1% had heard about ABS. Minority of the respondents perceived/knew that using antibiotics only when necessary (6.4%, 18, administering antibiotics at the appropriate dose (6.4%, 18 and administering antibiotics for appropriate duration in every case (4.3%, 12 were among the principles of ABS. The study also showed that age, gender, qualification, years of practice and locations did not exert any influence (P > 0.05 on the awareness of respondents about ABS. More than one-third of the respondents wrongly perceived that increasing the use of broad-spectrum antibiotics (35.4%, 99 is one of the goals of ABS, whereas the minority of the respondents rightly perceived/knew that minimizing toxicity and other adverse effects (16.8%, 47 and reducing antibiotic resistance (ABR (43.2%, 121 are also goals of ABS. Only 21.4% (60 had overall knowledge of ABS. Prescribing antibiotics without seeing/examining the patient, prescribing antibiotics for any case suspected to be infectious, prescribing broad-spectrum antibiotics despite availability of narrow-spectrum antibiotics, prescribing different classes/types of antibiotics concurrently to ensure therapeutic efficacy, prescribing overdose of antibiotics to ensure efficacy and non-consultation of the veterinary formulary/other resources when in doubt during prescription, are some of inappropriate/untoward ABS practices/behaviors/attitudes amongst the respondents. No significant association (P > 0.05 was found between practices of ABS and age, gender, qualification, years of practice and

  14. Structures and properties of naturally occurring polyether antibiotics.

    Science.gov (United States)

    Rutkowski, Jacek; Brzezinski, Bogumil

    2013-01-01

    Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties.

  15. Estimation of selected residual antibiotics in muscle, kidney, liver, and egg of layer chicken

    International Nuclear Information System (INIS)

    Amjad, H.; Iqbal, J.; Naeem, M.

    2006-01-01

    The present studies were conducted for the estimation of quinolone residues in our local poultry products. The poultry products included muscle, kidney, liver and egg (yolk and white). The quinolones included in this study were, oxolonic acid, flumequine, enrofloxacin, and ciprofloxacin. An assessment of the variation of each analyte (quinolones antibiotic residues) in these products was made. A comparison was made among the analyte (quinolones) concentrations in different tissues/organs and their internationally permissible safer maximum residue limits (MRLS'). Infra Red spectra were used to detect the presence and identification of different quinolones. HPLC with ODS Column and U.V. detector was used for the quantification. (author)

  16. POPULATION PHARMACOKINETICS OF ENROFLOXACIN AND ITS METABOLITE CIPROFLOXACIN IN THE GREEN SEA URCHIN (STRONGYLOCENTROTUS DROEBACHIENSIS) FOLLOWING INTRACOELOMIC AND IMMERSION ADMINISTRATION.

    Science.gov (United States)

    Phillips, Brianne E; Harms, Craig A; Lewbart, Gregory A; Lahner, Lesanna L; Haulena, Martin; Rosenberg, Justin F; Papich, Mark G

    2016-03-01

    Sea urchin mass mortality events have been attributed to both infectious and noninfectious etiologies. Bacteria, including Vibrio spp. and Pseudoalteromonas spp., have been isolated during specific mortality events. Aquarium collection sea urchins are also subject to bacterial infections and could benefit from antimicrobial treatment, but pharmacokinetic studies have been lacking for this invertebrate group until recently. This study evaluated the pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin in the green sea urchin (Strongylocentrotus droebachiensis) after intracoelomic injection and medicated bath immersion administration. The utility of a population pharmacokinetic method using nonlinear mixed effects modeling (NLME) was also evaluated. Thirty sea urchins were assigned to either the injection or immersion group. Twelve study animals and three untreated controls were utilized for each administration method: enrofloxacin 10 mg/kg intracoelomic injection or a 6-hr enrofloxacin 10 mg/L immersion. Each animal was sampled four times from 0 to 120 hr. Water samples were collected during immersion treatment and posttreatment time points in both groups. Hemolymph and water sample drug concentrations were analyzed using high-performance liquid chromatography, and pharmacokinetic parameters were determined using an NLME population pharmacokinetic method. Enrofloxacin concentrations were fit to a two-compartment model with first-order input for the intracoelomic injection group. The enrofloxacin elimination half-life (t½), peak hemolymph concentration (CMAX), and area under the curve (AUC) were 38.82 hr, 90.92 μg/ml, and 1,199 hr·μg/ml, respectively. Enrofloxacin was modeled to a one-compartment model with first-order input for the immersion treatment. The enrofloxacin t½, CMAX, and AUC were 33.46 hr, 0.48 μg/ml, and 32.88 hr·μg/ml, respectively. Ciprofloxacin was detected in trace concentrations in all hemolymph samples, indicating

  17. Antibiotic resistance monitoring in Vibrio spp. isolated from rearing environment and intestines of abalone Haliotis diversicolor.

    Science.gov (United States)

    Wang, R X; Wang, J Y; Sun, Y C; B L Yang; A L Wang

    2015-12-30

    546 Vibrio isolates from rearing seawater (292 strains) and intestines of abalone (254 strains) were tested to ten antibiotics using Kirby-Bauer diffusion method. Resistant rates of abalone-derived Vibrio isolates to chloramphenicol (C), enrofloxacin (ENX) and norfloxacin (NOR) were 40%) to kanamycin (KNA), furazolidone (F), tetracycline (TE), gentamicin (GM) and rifampin (RA). 332 isolates from seawater (n=258) and abalone (n=74) were resistant to more than three antibiotics. Peaked resistant rates of seawater-derived isolates to multiple antibiotics were overlapped in May and August. Statistical analysis showed that pH had an important effect on resistant rates of abalone-derived Vibrio isolates to RA, NOR, and ENX. Salinity and dissolved oxygen were negatively correlated with resistant rates of seawater-derived Vibrio isolates to KNA, RA, and PG. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Combating Antibiotic Resistance

    Science.gov (United States)

    ... Bacteria Phasing Out Certain Antibiotic Use in Farm Animals FDA: Cutting-Edge Technology Sheds Light on Antibiotic Resistance For More Information Antibiotics and Antibiotic Resistance Antimicrobial Resistance Information for Consumers and Health Professionals CDC: ...

  19. Pharmacokinetic-Pharmacodynamic Modeling of Enrofloxacin Against Escherichia coli in Broilers.

    Science.gov (United States)

    Sang, KaNa; Hao, HaiHong; Huang, LingLi; Wang, Xu; Yuan, ZongHui

    2015-01-01

    The purpose of the present study was to establish a pharmacokinetic/pharmacodynamic (PK/PD) modeling approach for the dosage schedule design and decreasing the emergence of drug-resistant bacteria. The minimal inhibitory concentration (MIC) of 929 Escherichia coli isolates from broilers to enrofloxacin and ciprofloxacin was determined following CLSI guidance. The MIC50 was calculated as the populational PD parameter for enrofloxacin against E. coli in broilers. The 101 E. coli strains with MIC closest to the MIC50 (0.05 μg/mL) were submitted for serotype identification. The 13 E. coli strains with O and K serotype were further utilized for determining pathogencity in mice. Of all the strains tested, the E. coli designated strain Anhui 112 was selected for establishing the disease model and PK/PD study. The PKs of enrofloxacin after oral administration at the dose of 10 mg/kg body weights (BW) in healthy and infected broilers was evaluated with high-performance liquid chromatography (HPLC) method. For intestinal contents after oral administration, the peak concentration (C max), the time when the maximum concentration reached (T max), and the area under the concentration-time curve (AUC) were 21.69-31.69 μg/mL, 1.13-1.23 h, and 228.97-444.86 μg h/mL, respectively. The MIC and minimal bactericidal concentration (MBC) of enrofloxacin against E. coli (Anhui 112) in Mueller-Hinton (MH) broth and intestinal contents were determined to be similar, 0.25 and 0.5 μg/mL respectively. In this study, the sum of concentrations of enrofloxacin and its metabolite (ciprofloxacin) was used for the PK/PD integration and modeling. The ex vivo growth inhibition data were fitted to the sigmoid E max (Hill) equation to provide values for intestinal contents of 24 h area under concentration-time curve/MIC ratios (AUC0-24 h/MIC) producing, bacteriostasis (624.94 h), bactericidal activity (1065.93 h) and bacterial eradication (1343.81 h). PK/PD modeling was

  20. Enrofloxacin and Probiotic Lactobacilli Influence PepT1 and LEAP-2 mRNA Expression in Poultry.

    Science.gov (United States)

    Pavlova, Ivelina; Milanova, Aneliya; Danova, Svetla; Fink-Gremmels, Johanna

    2016-12-01

    Expression of peptide transporter 1 (PepT1) and liver-expressed antimicrobial peptide 2 (LEAP-2) in chickens can be influenced by food deprivation, pathological conditions and drug administration. Effect of three putative probiotic Lactobacillus strains and enrofloxacin on the expression of PepT1 and LEAP-2 mRNA was investigated in Ross 308 chickens. One-day-old chicks (n = 24) were allocated to following groups: control (without treatment); group treated with probiotics via feed; group treated with a combination of probiotics and enrofloxacin; and a group given enrofloxacin only. The drug was administered at a dose of 10 mg kg -1 , via drinking water for 5 days. Samples from liver, duodenum and jejunum were collected 126 h after the start of the treatment. Expression levels of PepT1 and LEAP-2 were determined by real-time polymerase chain reaction and were statistically evaluated by Mann-Whitney test. Enrofloxacin administered alone or in combination with probiotics provoked a statistically significant up-regulation of PepT1 mRNA levels in the measured organ sites. These changes can be attributed to a tendency of improvement in utilization of dietary peptide and in body weight gain. LEAP-2 mRNA expression levels did not change significantly in enrofloxacin-treated chickens in comparison with control group.

  1. Rapid colorimetric sensing of tetracycline antibiotics with in situ growth of gold nanoparticles

    International Nuclear Information System (INIS)

    Shen, Li; Chen, Jing; Li, Na; He, Pingli; Li, Zhen

    2014-01-01

    Highlights: • Tetracyclines directly reduce aurate into gold nanoparticles. • Gold nanoparticles showed characteristic plamson absorbance at 526 nm. • Quantitative detection of tetracyclines with the colorimetric assay. • Tetracyclines spiked urine samples can be detected with the assay. - Abstract: A colorimetric assay utilizing the formation of gold nanoparticles was developed to detect tetracycline antibiotics in fluidic samples. Tetracycline antibiotics showed the capability of directly reducing aurate salts into atomic gold which form gold nanoparticles spontaneously under proper conditions. The resulted gold nanoparticles showed characteristic plasmon absorbance at 526 nm, which can be visualized by naked eyes or with a spectrophotometer. UV–vis absorbance of the resulted gold nanoparticles is correlated directly with the concentrations of tetracycline antibiotics in the solution, allowing for quantitative colorimetric detection of tetracycline antibiotics. Reaction conditions, such as pH, temperature, reaction time, and ionic strength were optimized. Sensitivity of the colorimetric assay can be enhanced by the addition of gold nanoparticle seeds, a LOD as low as 20 ng mL −1 can be achieved with the help of seed particles. The colorimetric assay showed minimum interference from ethanol, methanol, urea, glucose, and other antibiotics such as sulfonamides, amino glycosides etc. Validity of the method was also evaluated on urine samples spiked with tetracycline antibiotics. The method provides a broad spectrum detection method for rapid and sensitive detection of reductive substances such as tetracycline antibiotics in liquid and biological samples

  2. Rapid colorimetric sensing of tetracycline antibiotics with in situ growth of gold nanoparticles.

    Science.gov (United States)

    Shen, Li; Chen, Jing; Li, Na; He, Pingli; Li, Zhen

    2014-08-11

    A colorimetric assay utilizing the formation of gold nanoparticles was developed to detect tetracycline antibiotics in fluidic samples. Tetracycline antibiotics showed the capability of directly reducing aurate salts into atomic gold which form gold nanoparticles spontaneously under proper conditions. The resulted gold nanoparticles showed characteristic plasmon absorbance at 526 nm, which can be visualized by naked eyes or with a spectrophotometer. UV-vis absorbance of the resulted gold nanoparticles is correlated directly with the concentrations of tetracycline antibiotics in the solution, allowing for quantitative colorimetric detection of tetracycline antibiotics. Reaction conditions, such as pH, temperature, reaction time, and ionic strength were optimized. Sensitivity of the colorimetric assay can be enhanced by the addition of gold nanoparticle seeds, a LOD as low as 20 ng mL(-1) can be achieved with the help of seed particles. The colorimetric assay showed minimum interference from ethanol, methanol, urea, glucose, and other antibiotics such as sulfonamides, amino glycosides etc. Validity of the method was also evaluated on urine samples spiked with tetracycline antibiotics. The method provides a broad spectrum detection method for rapid and sensitive detection of reductive substances such as tetracycline antibiotics in liquid and biological samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Rapid colorimetric sensing of tetracycline antibiotics with in situ growth of gold nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Li [Logistics School, Beijing Wuzi University, Beijing 101149 (China); Chen, Jing; Li, Na [Logistics School, Beijing Wuzi University, Beijing 101149 (China); He, Pingli [State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100094 (China); Li, Zhen [State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing 100193 (China)

    2014-08-11

    Highlights: • Tetracyclines directly reduce aurate into gold nanoparticles. • Gold nanoparticles showed characteristic plamson absorbance at 526 nm. • Quantitative detection of tetracyclines with the colorimetric assay. • Tetracyclines spiked urine samples can be detected with the assay. - Abstract: A colorimetric assay utilizing the formation of gold nanoparticles was developed to detect tetracycline antibiotics in fluidic samples. Tetracycline antibiotics showed the capability of directly reducing aurate salts into atomic gold which form gold nanoparticles spontaneously under proper conditions. The resulted gold nanoparticles showed characteristic plasmon absorbance at 526 nm, which can be visualized by naked eyes or with a spectrophotometer. UV–vis absorbance of the resulted gold nanoparticles is correlated directly with the concentrations of tetracycline antibiotics in the solution, allowing for quantitative colorimetric detection of tetracycline antibiotics. Reaction conditions, such as pH, temperature, reaction time, and ionic strength were optimized. Sensitivity of the colorimetric assay can be enhanced by the addition of gold nanoparticle seeds, a LOD as low as 20 ng mL{sup −1} can be achieved with the help of seed particles. The colorimetric assay showed minimum interference from ethanol, methanol, urea, glucose, and other antibiotics such as sulfonamides, amino glycosides etc. Validity of the method was also evaluated on urine samples spiked with tetracycline antibiotics. The method provides a broad spectrum detection method for rapid and sensitive detection of reductive substances such as tetracycline antibiotics in liquid and biological samples.

  4. Antibiotics vs. Appendectomy for Acute Uncomplicated Appendicitis in Adults: Review of the Evidence and Future Directions.

    Science.gov (United States)

    Huston, Jared M; Kao, Lillian S; Chang, Phillip K; Sanders, James M; Buckman, Sara; Adams, Charles A; Cocanour, Christine S; Parli, Sarah E; Grabowski, Julia; Diaz, Jose; Tessier, Jeffrey M; Duane, Therese M

    2017-07-01

    Acute appendicitis is the most common abdominal surgical emergency in the United States, with a lifetime risk of 7%-8%. The treatment paradigm for complicated appendicitis has evolved over the past decade, and many cases now are managed by broad-spectrum antibiotics. We determined the role of non-operative and operative management in adult patients with uncomplicated appendicitis. Several meta-analyses have attempted to clarify the debate. Arguably the most influential is the Appendicitis Acuta (APPAC) Trial. According to the non-inferiority analysis and a pre-specified non-inferiority margin of -24%, the APPAC did not demonstrate non-inferiority of antibiotics vs. appendectomy. Significantly, however, the operations were nearly always open, whereas the majority of appendectomies in the United States are done laparoscopically; and laparoscopic and open appendectomies are not equivalent operations. Treatment with antibiotics is efficacious more than 70% of the time. However, a switch to an antimicrobial-only approach may result in a greater probability of antimicrobial-associated collateral damage, both to the host patient and to antibiotic susceptibility patterns. A surgery-only approach would result in a reduction in antibiotic exposure, a consideration in these days of focus on antimicrobial stewardship. Future studies should focus on isolating the characteristics of appendicitis most susceptible to antibiotics, using laparoscopic operations as controls and identifying long-term side effects such as antibiotic resistance or Clostridium difficile colitis.

  5. Prescribing Antibiotics

    DEFF Research Database (Denmark)

    Pedersen, Inge Kryger; Jepsen, Kim Sune

    2018-01-01

    The medical professions will lose an indispensable tool in clinical practice if even simple infections cannot be cured because antibiotics have lost effectiveness. This article presents results from an exploratory enquiry into “good doctoring” in the case of antibiotic prescribing at a time when...... the knowledge base in the healthcare field is shifting. Drawing on in-depth interviews about diagnosing and prescribing, the article demonstrates how the problem of antimicrobial resistance is understood and engaged with by Danish general practitioners. When general practitioners speak of managing “non......-medical issues,” they refer to routines, clinical expertise, experiences with their patients, and decision-making based more on contextual circumstances than molecular conditions—and on the fact that such conditions can be hard to assess. This article’s contribution to knowledge about how new and global health...

  6. Determination of enrofloxacin by room-temperature phosphorimetry after solid phase extraction on an acrylic polymer sorbent

    Science.gov (United States)

    de Souza, Cabrini F.; Martins, Renata K. S.; da Silva, Andrea R.; da Cunha, Alessandra L. M. C.; Aucélio, Ricardo Q.

    A phosphorimetric method was developed to enable the determination of enrofloxacin using photochemical derivatization which was used to both improve detection limits and to minimize the uncertainty of measurements. Phosphorescence was induced on cellulose containing TlNO3. Absolute limit of detection at the ng range and linear analytical response over three orders of magnitude were achieved. A metrological study was made to obtain the combined uncertainty value and to identify that the precision was mainly affected by the changing of substrates when measuring the signal from each replicate. Pharmaceutical formulations containing enrofloxacin were successfully analyzed by the method and the results were similar to the ones achieved using a HPLC method. A solid phase extraction on an acrylic polymer was optimized to separate enrofloxacin from interferents such as diclofenac and other components from biological matrices, which allowed the successful use of the method in urine analysis.

  7. Application of Enrofloxacin and Orbifloxacin Disks Approved in Japan for Susceptibility Testing of Representative Veterinary Respiratory Pathogens

    Science.gov (United States)

    HARADA, Kazuki; USUI, Masaru; ASAI, Tetsuo

    2014-01-01

    ABSTRACT In this study, susceptibilities of Pasteurella multocida, Mannheimia haemolytica and Actinobacillus pleuropneumoniae to enrofloxacin and orbifloxacin were tested using an agar diffusion method with the commercial disks and a broth microdilution method. Good correlation between the 2 methods for enrofloxacin and orbifloxacin was observed for P. multocida (r = −0.743 and −0.818, respectively), M. haemolytica (r = −0.739 and −0.800, respectively) and A. pleuropneumoniae (r = −0.785 and −0.809, respectively). Based on the Clinical and Laboratory Standards Institute interpretive criteria for enrofloxacin, high-level categorical agreement between the 2 methods was found for P. multocida (97.9%), M. haemolytica (93.8%) and A. pleuropneumoniae (92.0%). Our findings indicate that the tested commercial disks can be applied for susceptibility testing of veterinary respiratory pathogens. PMID:25008965

  8. Synthesis and characterization of polyacrylic acid- grafted-carboxylic graphene/titanium nanotube composite for the effective removal of enrofloxacin from aqueous solutions: Adsorption and photocatalytic degradation studies.

    Science.gov (United States)

    Anirudhan, Thayyath S; Shainy, F; Christa, J

    2017-02-15

    Polyacrylic acid-grafted-carboxylic graphene/titanium nanotube (PAA-g-CGR/TNT) composite was synthesized. It was effectively used as adsorbent as well as photocatalyst. The composite was characterized by FTIR, XRD, SEM, TEM, Surface Area Analyzer, XPS and DRS. The photocatalytic activity of PAA-g-CGR/TNT composite was evaluated on the basis of the degradation of pollutants by using sunlight. The band gap of the prepared photocatalyst was found to be 2.6eV. The removal of the antibiotic enrofloxacin (ENR) was achieved by two step mechanism based on adsorption and photodegradation. The maximum adsorption was observed at pH 5.0. The best fitted kinetic model was found to be pseudo-second-order. The maximum adsorption was observed at 30°C. The maximum adsorption capacity was found to be 13.40mg/g. The kinetics of photodegradation of ENR onto PAA-g-CGR/TNT composite follow first-order kinetics and optimum pH was found to be 5.0. The regeneration and reuse of the adsorbent-cum-photocatalyst were also examined upto five cycles. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Enhanced intracellular delivery and antibacterial efficacy of enrofloxacin-loaded docosanoic acid solid lipid nanoparticles against intracellular Salmonella.

    Science.gov (United States)

    Xie, Shuyu; Yang, Fei; Tao, Yanfei; Chen, Dongmei; Qu, Wei; Huang, Lingli; Liu, Zhenli; Pan, Yuanhu; Yuan, Zonghui

    2017-01-23

    Enrofloxacin-loaded docosanoic acid solid lipid nanoparticles (SLNs) with different physicochemical properties were developed to enhance activity against intracellular Salmonella. Their cellular uptake, intracellular elimination and antibacterial activity were studied in RAW 264.7 cells. During the experimental period, SLN-encapsulated enrofloxacin accumulated in the cells approximately 27.06-37.71 times more efficiently than free drugs at the same extracellular concentration. After incubation for 0.5 h, the intracellular enrofloxacin was enhanced from 0.336 to 1.147 μg/mg of protein as the sizes of nanoparticles were increased from 150 to 605 nm, and from 0.960 to 1.147 μg/mg of protein when the charge was improved from -8.1 to -24.9 mv. The cellular uptake was more significantly influenced by the size than it was by the charge, and was not affected by whether the charge was positive or negative. The elimination of optimal SLN-encapsulated enrofloxacin from the cells was significantly slower than that of free enrofloxacin after removing extracellular drug. The inhibition effect against intracellular Salmonella CVCC541 of 0.24 and 0.06 μg/mL encapsulated enrofloxacin was stronger than 0.6 μg/mL free drug after all of the incubation periods and at 48 h, respectively. Docosanoic acid SLNs are thus considered as a promising carrier for intracellular bacterial treatment.

  10. Profile of antibiotic consumption, sensitivity and resistance in an urban area of Andhra Pradesh, India.

    Science.gov (United States)

    Peripi, Sunita Bhargavi; Thadepalli, Venu Gopala Rao; Khagga, Mukkanti; Tripuraribhatla, Prasanna Krishna; Bharadwaj, Dinesh Kumar

    2012-04-01

    Antibiotics are an important category of drugs in which indiscriminate use can affect the susceptibility patterns among infectious organisms, resulting in antibiotic resistance. Data on antibiotic usage and susceptibility patterns were collected from public and private health centres in Vijayawada, Andhra Pradesh, India, through the use of questionnaires. The data collected were then coded, tabulated, computed and evaluated using statistical analysis. The consumption profile of the different categories of drugs used in public and private hospitals was as follows: nutrition and metabolism products 19.0%; gastrointestinal disorder-related drugs 18.5%; antibiotics 16.8%; anti-pyretics and anti-analgesics 20.6%. These drugs were found to be in high demand. Among the antibiotics, aminoglycosides (amikacin), quinolones (ofloxacin, ciprofloxacin), tetracyclines (doxycycline), penicillin (ampicillin) and sulphonamides (co-trimoxazole) were the most commonly prescribed drugs for antibiotic therapy. 46% of the culture laboratory reports were positive with the following organism profile: Escherichia coli (36%), Klebsiella pneumoniae (16%), Staphylococcus aureus (29%), Enterococcus faecalis (9%) and Pseudomonas aeruginosa (10%). In terms of the sensitivity profile of antibacterials, amikacin (66.9%) was the only antibiotic showing sensitivity patterns, while the majority of antibiotics, such as cotrimoxazole, nalidixic acid, amoxicillin, gentamycin and norfloxacin, had acquired a resistance rate of 55.1%-80.6%. The results of this study suggest that indiscriminate prescription and consumption of new broad-spectrum antibiotics against sensitive organisms results in the development of antimicrobial resistance. Therefore, there is an urgent need to curb the excessive use of antibiotics in local hospitals in order to control the trend of increasing antimicrobial resistance to antibiotics.

  11. Occurrence of trace elements and antibiotics in manure-based fertilizers from the Zhejiang Province of China

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Mingrong [Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, MOA Key Laboratory for Pesticide Residue Detection, Hangzhou 310021 (China); Wu, Huizhen [College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014 (China); Wang, Jianmei; Zhang, Hu [Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, MOA Key Laboratory for Pesticide Residue Detection, Hangzhou 310021 (China); Zhang, Zulin [The James Hutton Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom); Zhang, Yongzhi [Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, MOA Key Laboratory for Pesticide Residue Detection, Hangzhou 310021 (China); Lin, Hui [Environmental Resources and Soil Fertilizer Institute, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021 (China); Ma, Junwei, E-mail: majw@mail.zaas.ac.cn [Environmental Resources and Soil Fertilizer Institute, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021 (China)

    2016-07-15

    The occurrence of seven trace elements and forty three antibiotics was investigated in manure-based fertilizers from the Zhejiang province of China. These trace elements included copper, zinc, arsenic, chromium, mercury, lead and cadmium. The targeted antibiotics included four groups: sulfonamides, tetracyclines, fluoroquinolones and chloramphenicols. The median amounts of copper, zinc, arsenic, chromium, mercury, lead and cadmium in the analyzed samples were 160, 465, 7.9, 21.2, 0.3, 8.1 and 0.6 mg·kg{sup −1}, respectively. Seventeen antibiotics were detected. Enrofloxacin was the most frequently detected compound, with a detection rate of 39.3% and concentrations ranging from 6.7 μg·kg{sup −1} to 4091 μg·kg{sup −1}. Based on the referred loading rates in agricultural soil, 10% of the collected manure-based fertilizer samples might pose a high potential ecological risk due to the presence of antibiotics. - Graphical abstract: Occurrence of seven trace elements and forty three antibiotics was investigated in manure-based fertilizers in Zhejiang province of China. The trace elements included copper, zinc, arsenic, chromium, mercury, lead and cadmium; the targeted antibiotics included four groups: sulfonamides, tetracyclines, fluoroquinolones and chloramphenicols. The medium values of copper, zinc, arsenic, chromium, mercury, lead and cadmium in the analyzed samples were 160, 465, 7.9, 21.2, 0.3, 8.1 and 0.6 mg·kg{sup −1}, respectively. Seventeen antibiotics were detected. Enrofloxacin was the most frequently detected compound with the detection rate of 39.3% and the concentrations ranged from 6.7 μg·kg{sup −1} to 4091 μg·kg{sup −1}. Based on the referred loading rates, 10% of the collected manure-based fertilizers might pose a high potential ecological risk after their application onto agriculture soil due to the presence of antibiotics. - Highlight: • Antibiotics and trace elements were investigated in manure-based fertilizers. • 64% of

  12. Occurrence of trace elements and antibiotics in manure-based fertilizers from the Zhejiang Province of China

    International Nuclear Information System (INIS)

    Qian, Mingrong; Wu, Huizhen; Wang, Jianmei; Zhang, Hu; Zhang, Zulin; Zhang, Yongzhi; Lin, Hui; Ma, Junwei

    2016-01-01

    The occurrence of seven trace elements and forty three antibiotics was investigated in manure-based fertilizers from the Zhejiang province of China. These trace elements included copper, zinc, arsenic, chromium, mercury, lead and cadmium. The targeted antibiotics included four groups: sulfonamides, tetracyclines, fluoroquinolones and chloramphenicols. The median amounts of copper, zinc, arsenic, chromium, mercury, lead and cadmium in the analyzed samples were 160, 465, 7.9, 21.2, 0.3, 8.1 and 0.6 mg·kg"−"1, respectively. Seventeen antibiotics were detected. Enrofloxacin was the most frequently detected compound, with a detection rate of 39.3% and concentrations ranging from 6.7 μg·kg"−"1 to 4091 μg·kg"−"1. Based on the referred loading rates in agricultural soil, 10% of the collected manure-based fertilizer samples might pose a high potential ecological risk due to the presence of antibiotics. - Graphical abstract: Occurrence of seven trace elements and forty three antibiotics was investigated in manure-based fertilizers in Zhejiang province of China. The trace elements included copper, zinc, arsenic, chromium, mercury, lead and cadmium; the targeted antibiotics included four groups: sulfonamides, tetracyclines, fluoroquinolones and chloramphenicols. The medium values of copper, zinc, arsenic, chromium, mercury, lead and cadmium in the analyzed samples were 160, 465, 7.9, 21.2, 0.3, 8.1 and 0.6 mg·kg"−"1, respectively. Seventeen antibiotics were detected. Enrofloxacin was the most frequently detected compound with the detection rate of 39.3% and the concentrations ranged from 6.7 μg·kg"−"1 to 4091 μg·kg"−"1. Based on the referred loading rates, 10% of the collected manure-based fertilizers might pose a high potential ecological risk after their application onto agriculture soil due to the presence of antibiotics. - Highlight: • Antibiotics and trace elements were investigated in manure-based fertilizers. • 64% of manure-based fertilizers

  13. Determination of four fluoroquinolone antibiotics in tap water in Guangzhou and Macao

    International Nuclear Information System (INIS)

    Yiruhan; Wang Qiaojun; Mo Cehui; Li Yanwen; Gao Peng; Tai Yiping; Zhang Yan; Ruan Zhili; Xu Jiawei

    2010-01-01

    Four fluoroquinolone antibiotics (norfloxacin, ciprofloxacin, lomefloxacin, and enrofloxacin) in tap water in Guangzhou and Macao were analyzed using high performance liquid chromatography fluorescence detection. The results showed that all target antibiotics were detected in high rate both in Guangzhou (77.5%) and Macao (100%), ranging from 1.0 to 679.7 ng/L (SD ≤ 37.6) in Guangzhou, and from 2.0 to 37.0 ng/L (SD ≤ 2.5) in Macao. The fluoroquinolone antibiotics pollution in tap water widely distributes in Guangzhou and Macao. In addition, the effect of rainfall on concentration of fluoroquinolone antibiotics in south China was also investigated. Our result indicates that the antibiotic concentration in tap water in Guangzhou tends to obviously reduce at the beginning of rainy season, even decreases below the limit of quantification immediately. Thus, it was clarified that the heavy rain in south China has the function of reducing the fluoroquinolone antibiotics concentrations in tap water. - The antibiotics were detected in the tap water in Guangzhou and Macao using our developed method for fluoresence detection with high performance liquid chromatography

  14. Determination of four fluoroquinolone antibiotics in tap water in Guangzhou and Macao

    Energy Technology Data Exchange (ETDEWEB)

    Yiruhan; Wang Qiaojun [Department of Environmental Engineering, Jinan University, Huangpudadaoxi 601, Guangzhou 510632 (China); Mo Cehui, E-mail: tchmo@jnu.edu.c [Department of Environmental Engineering, Jinan University, Huangpudadaoxi 601, Guangzhou 510632 (China); Li Yanwen; Gao Peng; Tai Yiping; Zhang Yan; Ruan Zhili; Xu Jiawei [Department of Environmental Engineering, Jinan University, Huangpudadaoxi 601, Guangzhou 510632 (China)

    2010-07-15

    Four fluoroquinolone antibiotics (norfloxacin, ciprofloxacin, lomefloxacin, and enrofloxacin) in tap water in Guangzhou and Macao were analyzed using high performance liquid chromatography fluorescence detection. The results showed that all target antibiotics were detected in high rate both in Guangzhou (77.5%) and Macao (100%), ranging from 1.0 to 679.7 ng/L (SD {<=} 37.6) in Guangzhou, and from 2.0 to 37.0 ng/L (SD {<=} 2.5) in Macao. The fluoroquinolone antibiotics pollution in tap water widely distributes in Guangzhou and Macao. In addition, the effect of rainfall on concentration of fluoroquinolone antibiotics in south China was also investigated. Our result indicates that the antibiotic concentration in tap water in Guangzhou tends to obviously reduce at the beginning of rainy season, even decreases below the limit of quantification immediately. Thus, it was clarified that the heavy rain in south China has the function of reducing the fluoroquinolone antibiotics concentrations in tap water. - The antibiotics were detected in the tap water in Guangzhou and Macao using our developed method for fluoresence detection with high performance liquid chromatography

  15. Occurrence and distribution of antibiotics in urban soil in Beijing and Shanghai, China.

    Science.gov (United States)

    Gao, Lihong; Shi, Yali; Li, Wenhui; Liu, Jiemin; Cai, Yaqi

    2015-08-01

    The recycling of reclaimed wastewater for irrigation and road cleaning is an important strategy to minimize water scarcity in megacities. However, little is known regarding the potential accumulation of antibiotics contained in reclaimed wastewater in urban soil. We investigated the occurrence and distribution of eight quinolones (QNs), nine sulfonamides (SAs), and five macrolides (MLs) antibiotics in urban surface soil in Beijing and Shanghai, China. QNs, especially norfloxacin (NOR), ofloxacin (OFL), and ciprofloxacin (CIP) were the predominant antibiotics in urban surface soil, and NOR revealed the highest average concentration of 94.6 μg kg(-1). The antibiotic concentrations in urban soil in our study were higher than those detected in agricultural soils after long-term wastewater irrigation and manure fertilization. The concentrations of antibiotics in Shanghai urban soil showed a significant negative correlation with soil pH and a positive correlation with total organic carbon (TOC), reflecting the effect of speciation and soil organic matter content on sorption and retention. In addition, antibiotic concentrations in the urban soil were positively correlated with heavy metal contents, likely due to their coexistence in reclaimed wastewater and the promoting effect of metals on the sorption of antibiotics. In several soil samples, NOR, OFL, CIP, enrofloxacin (ENR), and fleroxacin (FLE) showed higher concentrations than the trigger value of 100 μg kg(-1) in soil, indicating a potential risk for the environment.

  16. In vitro antibiotic susceptibility of Dutch Mycoplasma synoviae field isolates originating from joint lesions and the respiratory tract of commercial poultry

    OpenAIRE

    2008-01-01

    Abstract The in vitro susceptibility of 17 Dutch Mycoplasma synoviae field isolates, 3 originating from joint pathology and 14 from the respiratory tract of commercial poultry, for enrofloxacin, difloxacin, doxycycline, tylosin and tilmicosin was examined. The M. synoviae ATCC 25204 was included as a control strain. The antibiotic susceptibility was tested quantitatively using the broth microdilution test. Based on initial and final MIC values, all tested isolates were susceptible ...

  17. Residues of veterinary antibiotics in manures from feedlot livestock in eight provinces of China.

    Science.gov (United States)

    Zhao, Ling; Dong, Yuan Hua; Wang, Hui

    2010-02-01

    The residue levels of selected fluoroquinolones, sulfonamides and tetracyclines in 143 animal dung samples collected in 2007 from large-scale livestock and poultry feedlots in 8 provinces were determined by using ultrasonic extraction and liquid chromatography. Recoveries from spiked pig dung samples (spike level=1mg/kg) ranged from 73.9 to 102.0% for fluoroquinolones, from 81.6 to 92.3% for sulfonamides, and from 57.2 to 72.6% for tetracyclines. Relative standard deviations of the recoveries were less than 10% within the same day. Method quantification limits were measured from 0.031 to 0.150 mg/kg for fluoroquinolones, from 0.023 to 0.082 mg/kg for sulfonamides, and 0.091 to 0.182 mg/kg for tetracyclines in spiked pig manure samples. Analysis of 61 pig, 54 chicken and 28 cow dung samples collected in China revealed that in pig and cow dung, up to 33.98 and 29.59 mg/kg ciprofloxacin, 33.26 and 46.70 mg/kg enrofloxacin, 59.06 and 59.59 mg/kg oxytetracycline, and 21.06 and 27.59 mg/kg chlortetracycline could be detected, respectively. A maximum concentration of 99.43 mg/kg fleroxacin, 225.45 mg/kg norfloxacin, 45.59 mg/kg ciprofloxacin and 1420.76 mg/kg enrofloxacin could be detected in chicken dung. No appreciable sulfonamide antibiotic concentrations (less than 10mg/kg) were found in any animal dung, and only sulfadimidine was observed, at a maximum concentration of 6.04 mg/kg, in chicken dung. Both enrofloxacin and chlortetracycline were detected with a very high occurrence in three animal manure samples. The residue levels for most antibiotics showed significant statistical differences among the sampling districts and the animal species. Copyright 2009 Elsevier B.V. All rights reserved.

  18. Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain

    2015-01-01

    The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Meal tests...... tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postpra