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Sample records for reduce linezolid susceptibility

  1. Risk factors and outcomes associated with vancomycin-resistant Enterococcus infections with reduced susceptibilities to linezolid.

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    Santayana, Elena M; Grim, Shellee A; Janda, William M; Layden, Jennifer E; Lee, Todd A; Clark, Nina M

    2012-09-01

    A retrospective matched case-control study of hospitalized patients with vancomycin-resistant Enterococcus (VRE) infection with reduced susceptibility to linezolid was performed in order to identify risk factors for this infection and describe patient outcomes. Forty-eight linezolid nonsusceptible VRE cases were identified between January 1, 2000, and September 30, 2008, and compared to 96 controls with linezolid-susceptible VRE, matched based on culture date and anatomic site of infection. Demographic, clinical and microbiological data were collected. On univariable analysis, risk factors for reduced linezolid susceptibility included allogeneic hematopoietic stem cell transplant and/or solid organ transplant (odds ratio [OR]: 2.63; 95% confidence interval [CI]: 1.13-6.15; P = 0.025), receipt of immunosuppressive medications (OR: 2.39; 95% CI: 1.08-5.29; P = 0.032) including corticosteroids (OR: 2.40; 95% CI: 1.03-5.58; P = 0.042) and noncorticosteroid immunosuppressives (OR: 2.31; 95% CI: 1.00-5.30; P = 0.049), and receipt of linezolid within 1 year prior to infection (OR: 34.50, 95% CI: 4.60-259.02; P < 0.001). On multivariable analysis, only receipt of linezolid within 1 year remained an independent risk factor for reduced linezolid susceptibility (OR: 31.84; 95% CI: 4.20-241.39; P < 0.001), although most patients with VRE with reduced linezolid susceptibility had not received linezolid in the year prior. Reduced linezolid susceptibility did not impact patient outcomes including clinical or microbiological cure, hospital length of stay, or all-cause mortality.

  2. Activity of ceftobiprole against methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to daptomycin, linezolid or vancomycin, and strains with defined SCCmec types.

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    Farrell, David J; Flamm, Robert K; Sader, Helio S; Jones, Ronald N

    2014-04-01

    Ceftobiprole is a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative pathogens including Pseudomonas aeruginosa. The aim of this study was to evaluate the activity of ceftobiprole against MRSA isolates with decreased susceptibility to daptomycin, linezolid or vancomycin as well as isolates from staphylococcal chromosome cassette mec (SCCmec) types I, II, III and IV. Overall, ceftobiprole demonstrated high potency against the 216 isolates tested, with MIC50 and MIC90 values (minimum inhibitory concentrations required to inhibit 50% and 90% of the isolates, respectively) of 1mg/L and 2mg/L (97.2% susceptible). The MIC90 for ceftobiprole was 2mg/L against the linezolid-non-susceptible, daptomycin-non-susceptible and vancomycin-intermediate (VISA and hVISA) subsets and was 1mg/L against the vancomycin-resistant (VRSA) strains. The MIC50/90 values for ceftobiprole were 2/4, 1/2, 2/2 and 1/1mg/L against SCCmec types I, II, III and IV, respectively. SCCmec type I strains had the highest MICs, with six strains exhibiting a ceftobiprole MIC of 4mg/L and 15 strains at 2mg/L. Ceftobiprole demonstrated potent activity against MRSA, including subsets of isolates with reduced susceptibility to daptomycin, linezolid and vancomycin. The activity of ceftobiprole against these resistant phenotypes indicates that it may have clinical utility in the treatment of infections caused by multidrug-resistant S. aureus and across strains from prevalent SCCmec types.

  3. Linezolid susceptibility in Helicobacter pylori, including strains with multidrug resistance.

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    Boyanova, Lyudmila; Evstatiev, Ivailo; Gergova, Galina; Yaneva, Penka; Mitov, Ivan

    2015-12-01

    Only a few studies have evaluated Helicobacter pylori susceptibility to linezolid. The aim of the present study was to assess linezolid susceptibility in H. pylori, including strains with double/multidrug resistance. The susceptibility of 53 H. pylori strains was evaluated by Etest and a breakpoint susceptibility testing method. Helicobacter pylori resistance rates were as follows: amoxicillin, 1.9%; metronidazole, 37.7%; clarithromycin, 17.0%; tetracycline, 1.9%; levofloxacin, 24.5%; and linezolid (>4 mg/L), 39.6%. The linezolid MIC50 value was 31.2-fold higher than that of clarithromycin and 10.5-fold higher than that of levofloxacin; however, 4 of 11 strains with double/multidrug resistance were linezolid-susceptible. The MIC range of the oxazolidinone agent was larger (0.125-64 mg/L) compared with those in the previous two reports. The linezolid resistance rate was 2.2-fold higher in metronidazole-resistant strains and in strains resistant to at least one antibiotic compared with the remaining strains. Briefly, linezolid was less active against H. pylori compared with clarithromycin and levofloxacin, and linezolid resistance was linked to resistance to metronidazole as well as to resistance to at least one antibiotic. However, linezolid activity against some strains with double/multidrug resistance may render the agent appropriate to treat some associated H. pylori infections following in vitro susceptibility testing of the strains. Clinical trials are required to confirm this suggestion.

  4. Two novel point mutations in clinical Staphylococcus aureus reduce linezolid susceptibility and switch on the stringent response to promote persistent infection.

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    Wei Gao

    Full Text Available Staphylococcus aureus frequently invades the human bloodstream, leading to life threatening bacteremia and often secondary foci of infection. Failure of antibiotic therapy to eradicate infection is frequently described; in some cases associated with altered S. aureus antimicrobial resistance or the small colony variant (SCV phenotype. Newer antimicrobials, such as linezolid, remain the last available therapy for some patients with multi-resistant S. aureus infections. Using comparative and functional genomics we investigated the molecular determinants of resistance and SCV formation in sequential S. aureus isolates from a patient who had a persistent and recurrent S. aureus infection, after failed therapy with multiple antimicrobials, including linezolid. Two point mutations in key staphylococcal genes dramatically affected clinical behaviour of the bacterium, altering virulence and antimicrobial resistance. Most strikingly, a single nucleotide substitution in relA (SACOL1689 reduced RelA hydrolase activity and caused accumulation of the intracellular signalling molecule guanosine 3', 5'-bis(diphosphate (ppGpp and permanent activation of the stringent response, which has not previously been reported in S. aureus. Using the clinical isolate and a defined mutant with an identical relA mutation, we demonstrate for the first time the impact of an active stringent response in S. aureus, which was associated with reduced growth, and attenuated virulence in the Galleria mellonella model. In addition, a mutation in rlmN (SACOL1230, encoding a ribosomal methyltransferase that methylates 23S rRNA at position A2503, caused a reduction in linezolid susceptibility. These results reinforce the exquisite adaptability of S. aureus and show how subtle molecular changes cause major alterations in bacterial behaviour, as well as highlighting potential weaknesses of current antibiotic treatment regimens.

  5. Experimental study of the efficacy of linezolid alone and in combinations against experimental meningitis due to Staphylococcus aureus strains with decreased susceptibility to beta-lactams and glycopeptides.

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    Cabellos, Carmen; Garrigós, Carmen; Taberner, Ferran; Force, Enriqueta; Pachón-Ibañez, M Eugenia

    2014-09-01

    To evaluate in vitro and in vivo efficacies of linezolid, vancomycin, and the combination of linezolid and rifampicin against two Staphylococcus aureus strains with reduced susceptibility to beta-lactams and one of them also to glycopeptides. In vitro killing curves and a rabbit model: Meningitis was induced by intracisternal inoculation of 10(8) CFU/ml of each strain. Five hours later (0 h), rabbits were randomly assigned to control or to therapeutic groups. CSF bacterial counts, lactate and protein concentrations, and pharmacokinetic parameters were determined. In vivo: linezolid and its combination with rifampicin reduced bacterial concentrations at 24 h, median cfu/mL 4.85 vs 3.87 (p < 0.05) for linezolid and 5.02 vs 4.21 (p < 0.05) for linezolid + rifampicin, against the glycopeptide intermediate S. aureus (GISA) strain and improved inflammatory parameters. Despite the need for more experimental data, our results suggest that linezolid and its combinations could be considered as a potential alternative in difficult-to-treat CNS infections and especially in those due to GISA strains and deserve more studies. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. Vancomycin-resistant Enterococcus spp.: validation of susceptibility testing and in vitro activity of vancomycin, linezolid, tigecycline and daptomycin

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    Rathe, Mathias; Kristensen, Lise; Ellermann-Eriksen, Svend;

    2010-01-01

    Vancomycin-resistant enterococci (VRE) have emerged to become a significant nosocomial pathogen. However, detection may be challenging and treatment possibilities are limited. Reports of resistance to linezolide, daptomycin and tigecycline underline the need for reliable susceptibility testing wi...

  7. Effectiveness of Linezolid, 127I-Linezolid and 131I-Linezolid Against Methicillin-Susceptible Staphylococcus Aureus by Time Kill Curve Methods

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    Hasan Demiroğlu

    2015-02-01

    Full Text Available Objective: Linezolid (LNZ is one of the most effective treatments against Gram positive bacteria. However LNZ resistant intermediate strains have recently emerged in worldwide. The aim of the study was to compare the minimum inhibitory concentration (MIC, minimum bactericidal concentration (MBC and minimum biofilm inhibitory concentration (MBIC of LNZ, 127I-LNZ and 131I-LNZ against methicillin susceptible Staphylococcus aureus ATCC 35556 (MSSA biofilms. Methods: LNZ radiolabeled with 131I and cold labeling study with 127I was performed. Radiolabeling and inactive labeling quality-control studies of LNZ were carried out by using TLC (Thin Layer Radiochromatography and HPLC (High Pressure Liquid Chromatography. LNZ, 127I-LNZ and 131I-LNZ against biofilm-forming MSSA was investigated, using a twofold serial broth microtiter method, biofilm challenge, and bacterial count recovery. Results: The binding yield was obtained to be about 86±2% for radiolabeled LNZ. Minimal inhibitory concentration (MIC and minimal bactericidal concentration for LNZ, 127I-LNZ and 131I-LNZ ranged from 1 to 2 µg/mL respectively. In time-kill studies LNZ, 127I-LNZ and 131I-LNZ were bactericidal against staphylococci, producing ≥3 Log10 decrease in viable counts (cfu/mL within 6 h at 2xMIC. Following the biofilm formation on polystyrene U-bottom microtiter plates to investigate the minimal biofilm inhibitory concentration (MBIC of LNZ, 127I-LNZ and 131I-LNZ was defined as the minimal concentration of antibiotic required to inhibite the biofilm. None of the LNZ, 127I-LNZ and 131I-LNZ killed 100% of biofilm associated cells. Mean cell survival in biofilms treated with 64 µg/mL LNZ, 127I-LNZ and 131I-LNZ (64 µg/mL was 48%, 49%, and 33%, respectively. Conclusion: Our results show that radiolabeled Linezolid demonstrated that 24 h of exposure to 64 µg/mL, promise in treating biofilm producing Staphylococcus aureus.

  8. Susceptibility profile of methicillin-resistant Staphylococcus aureus to linezolid in clinical isolates

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    Shariq, Ali; Tanvir, Syed Bilal; Zaman, Atif; Khan, Salman; Anis, Armeena; Khan, Misha Aftab; Ahmed, Sumaira

    2017-01-01

    Objective: To determine the resistance and sensitivity pattern of methicillin-resistant Staphylococcus aureus (MRSA) isolates to linezolid (LZD) along with its prevalence in a tertiary care hospital of Karachi, Pakistan. Materials and Methods: A cross-sectional study was carried out. This study lasted for about 1 year. Prevalence and sensitivity of LZD, vancomycin, and oxacillin was tested against isolates of MRSA. Results: Out of total 369 specimens 165 were found to be MRSA making the prevalence in our study 44.7%. All of the isolates which were tested positive for MRSA were susceptible to LZD and no resistance was noted when compared with previous studies performed in Europe and USA. Conclusion: Stringent implementation of infection control measures along with screening for resistance in patients on prolonged LZD therapy or who previously went under LZD therapy should be performed, coupled with judicious usage of the aforementioned antibiotic should be undertaken, as sufficient data is not available at this point for the clinical spectrum of LZD resistant S. aureus, antimicrobial resistance.

  9. Linezolid Toxicity and Mitochondrial Susceptibility: A Novel Neurological Complication in a Lebanese Patient

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    Abou Hassan, Ossama K.; Karnib, Mohamad; El-Khoury, Riyad; Nemer, Georges; Ahdab-Barmada, Mamdouha; BouKhalil, Pierre

    2016-01-01

    The recent rise in the use of linezolid to treat a variety of resistant pathogens has uncovered many side effects. Some patients develop lactic acidosis, myelosuppression, optic or peripheral neuropathies, and myopathies. We evaluated an elderly patient who presented to the Emergency Room with linezolid toxicity and a novel neurologic complication characterized by bilateral globi pallidi necrosis. Mitochondrial ribosome inhibition was described to be the predisposing factor. The patient belongs to the mitochondrial J1 haplotype known to be associated with side effects of the drug. We recommend based on the molecular profile of the illness pretreatment considerations and complication management. PMID:27703432

  10. Linezolid Resistance in Staphylococci

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    Stefania Stefani

    2010-06-01

    Full Text Available Linezolid, the first oxazolidinone to be used clinically, is effective in the treatment of infections caused by various Gram-positive pathogens, including multidrug resistant enterococci and methicillin-resistant Staphylococus aureus. It has been used successfully for the treatment of patients with endocarditis and bacteraemia, osteomyelitis, joint infections and tuberculosis and it is often used for treatment of complicated infections when other therapies have failed. Linezolid resistance in Gram-positive cocci has been encountered clinically as well as in vitro, but it is still a rare phenomenon. The resistance to this antibiotic has been, until now, entirely associated with distinct nucleotide substitutions in domain V of the 23S rRNA genes. The number of mutated rRNA genes depends on the dose and duration of linezolid exposure and has been shown to influence the level of linezolid resistance. Mutations in associated ribosomal proteins also affect linezolid activity. A new phenicol and clindamycin resistance phenotype has recently been found to be caused by an RNA methyltransferase designated Cfr. This gene confers resistance to lincosamides, oxazolidinones, streptogramin A, phenicols and pleuromutilins, decrease the susceptibility of S. aureus to tylosin, to josamycin and spiramycin and thus differs from erm rRNA methylase genes. Research into new oxazolidinones with improved characteristics is ongoing. Data reported in patent applications demonstrated that some oxazolidinone derivatives, also with improved characteristics with respect to linezolid, are presently under study: at least three of them are in an advanced phase of development.

  11. A Faropenem, Linezolid, and Moxifloxacin Regimen for Both Drug-Susceptible and Multidrug-Resistant Tuberculosis in Children: FLAME Path on the Milky Way.

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    Deshpande, Devyani; Srivastava, Shashikant; Nuermberger, Eric; Pasipanodya, Jotam G; Swaminathan, Soumya; Gumbo, Tawanda

    2016-11-01

     The regimen of linezolid and moxifloxacin was found to be efficacious in the hollow fiber system model of pediatric intracellular tuberculosis. However, its kill rate was slower than the standard 3-drug regimen of isoniazid, rifampin, and pyrazinamide. We wanted to examine the effect of adding a third oral agent, faropenem, to this dual combination.  We performed a series of studies in the hollow fiber system model of intracellular Mycobacterium tuberculosis, by mimicking pediatric pharmacokinetics of each antibiotic. First, we varied the percentage of time that faropenem persisted above minimum inhibitory concentration (TMIC) on the moxifloxacin-linezolid regimen. After choosing the best faropenem exposure, we performed experiments in which we varied the moxifloxacin and linezolid doses in the triple regimen. Finally, we performed longer-duration therapy validation experiments. Bacterial burden was quantified using both colony-forming units per milliliter (CFU/mL) and time to positivity (TTP). Kill slopes were modeled using exponential regression.  TTP was a more sensitive measure of bacterial burden than CFU/mL. A faropenem TMIC > 62% was associated with steepest microbial kill slope. Regimens of standard linezolid and moxifloxacin plus faropenem TMIC > 60%, as well as higher-dose moxifloxacin, achieved slopes equivalent to those of the standard regimen based by both TTP and CFU/mL over 28 days of treatment.  We have developed an oral faropenem-linezolid-moxifloxacin (FLAME) regimen that is free of first-line drugs. The regimen could be effective against both multidrug-resistant and drug-susceptible tuberculosis in children. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  12. A Faropenem, Linezolid, and Moxifloxacin Regimen for Both Drug-Susceptible and Multidrug-Resistant Tuberculosis in Children: FLAME Path on the Milky Way

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    Deshpande, Devyani; Srivastava, Shashikant; Nuermberger, Eric; Pasipanodya, Jotam G.; Swaminathan, Soumya; Gumbo, Tawanda

    2016-01-01

    Background. The regimen of linezolid and moxifloxacin was found to be efficacious in the hollow fiber system model of pediatric intracellular tuberculosis. However, its kill rate was slower than the standard 3-drug regimen of isoniazid, rifampin, and pyrazinamide. We wanted to examine the effect of adding a third oral agent, faropenem, to this dual combination. Methods. We performed a series of studies in the hollow fiber system model of intracellular Mycobacterium tuberculosis, by mimicking pediatric pharmacokinetics of each antibiotic. First, we varied the percentage of time that faropenem persisted above minimum inhibitory concentration (TMIC) on the moxifloxacin-linezolid regimen. After choosing the best faropenem exposure, we performed experiments in which we varied the moxifloxacin and linezolid doses in the triple regimen. Finally, we performed longer-duration therapy validation experiments. Bacterial burden was quantified using both colony-forming units per milliliter (CFU/mL) and time to positivity (TTP). Kill slopes were modeled using exponential regression. Results. TTP was a more sensitive measure of bacterial burden than CFU/mL. A faropenem TMIC > 62% was associated with steepest microbial kill slope. Regimens of standard linezolid and moxifloxacin plus faropenem TMIC > 60%, as well as higher-dose moxifloxacin, achieved slopes equivalent to those of the standard regimen based by both TTP and CFU/mL over 28 days of treatment. Conclusions. We have developed an oral faropenem-linezolid-moxifloxacin (FLAME) regimen that is free of first-line drugs. The regimen could be effective against both multidrug-resistant and drug-susceptible tuberculosis in children. PMID:27742640

  13. Linezolid resistance in Enterococcus faecium isolated in Ontario, Canada.

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    Patel, Samir N; Memari, Nader; Shahinas, Dea; Toye, Baldwin; Jamieson, Frances B; Farrell, David J

    2013-12-01

    Recent studies have described linezolid-resistant MRSA and vancomycin-resistant enterococci (VRE) occurring worldwide, including an outbreak of linezolid-resistant MRSA. The objective of this study was to determine if linezolid-resistant enterococci are present in clinical isolates in Ontario, Canada. From January 2010 to June 2012, all enterococcal isolates submitted to the Public Health Ontario Laboratory (PHOL) for confirmation of VRE and susceptibility testing were included in this study. Of 2829 enterococcal isolates tested, 12 Enterococcus faecium were found to be resistant to linezolid. All linezolid-resistant isolates were also resistant to ampicillin, ciprofloxacin, and vancomycin. In addition, 33% of isolates were non-susceptible to daptomycin, whereas 41% were resistant to quinupristin/dalfopristin. Molecular characterization of these isolates showed that 8/12 isolates (66.7%) contained the mutation G2576T in 23S rRNA, which has been associated with linezolid resistance. Amplification and sequencing of L3- and L4-coding genes did not reveal mutations associated with linezolid resistance. One isolate contained the cfr gene, which is associated with linezolid resistance, and has been found in staphylococcal species and E. faecalis. These data show that occurrence of linezolid resistance is still rare among enterococcal isolates referred to PHOL though detection of cfr in E. faecium is concerning as it has the potential to disseminate among other enterococci.

  14. Antimicrobial activity of linezolid combined with minocycline against vancomycin-resistant Enterococci

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    WU Jing; JIANG Tian-tong; SU Jian-rong; LI Li

    2013-01-01

    Background Vancomycin-resistant Enterococci (VRE) cause serious infections that are difficult to treat.We carried out this study to determine the mutant prevention concentration (MPC) of linezolid when combined with minocycline against VRE strains,to determine the mechanism of drug resistance in vitro,and to provide a theoretical basis for the rational use of drugs against VRE.Methods The minimum inhibitory concentrations (MICs) of linezolid and minocycline against 30 Enterococci (E.) isolates (including 20 VRE strains) were determined by the broth microdilution method.Drug interactions were assessed by the checkerboard microdilution tests and confirmed by time-kill studies.Two vancomycin-susceptible strains N27 and N40 (linezolid MIC,2 g/ml; minocycline MIC,4 μg/ml) and control strains E.faecalis ATCC 29212 and ATCC 51299 were also tested.The MPCs of linezolid and minocycline (alone and combined) were determined using the agar dilution method.Strains showing stable resistance were analyzed by polymerase chain reaction (PCR) amplification of domain V of the 23S rRNA gene.Results Checkerboard titration studies revealed synergistic effects of combination therapy in 26.7% of 30 E.isolates.Antagonism was not observed.The G2576U mutation was detected in stable linezolid-resistant strains of ATCC 29212,N40,and N27 before and after resistance screening,and MIC values increased with the number of G2576U mutations.The MPC of linezolid against E.decreased dramatically when combined with minocycline,and vice versa.Conclusion Linezolid or minocycline alone produce resistant strains; however,their joint use may reduce the MPC of each agent against VRE,thereby decreasing resistant mutants and bacterial infections.

  15. Therapeutic drug management of linezolid: a missed opportunity for clinicians?

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    Cattaneo, Dario; Gervasoni, Cristina; Cozzi, Valeria; Castoldi, Simone; Baldelli, Sara; Clementi, Emilio

    2016-12-01

    Some studies have shown that adjustments to the linezolid dose guided by therapeutic drug monitoring (TDM) can reduce interindividual variability in drug exposure and improve linezolid tolerability. In this study, 6 years of linezolid TDM, a diagnostic service for our hospital and others in the Milan (Italy) area, is described. Samples were collected immediately before the morning dose intake (trough concentrations) in steady-state conditions. Linezolid concentrations were quantified by a validated high-performance liquid chromatography (HPLC) method. Four hundred linezolid trough concentrations from 220 patients were collected. A 20-fold variability in linezolid levels was observed. Positive and significant correlations between linezolid trough concentrations and patient age (r = 0.325, P 80 years and with impaired renal function, are at a higher risk of overexposure to linezolid. Despite the observed progressive increase in linezolid concentrations over time, most physicians did not change the drug dose according to the TDM results, even in the presence of frank overexposure to linezolid.

  16. Linezolid resistant Staphylococcus aureus

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    Pavani Gandham

    2014-08-01

    Full Text Available Linezolid is the only antibiotic available as an oral formulation for resistant staphylococcal infections. It is effective in skin and soft tissue infections, nosocomial pneumonias including VAP, infective endocarditis and MRSA meningitis. It is also effective in the eradication of both nasal and throat colonization of MRSA. Its high bioavailability and post antibiotic effect, ease of switching to oral therapy during its use and the fact that it can be used in patients of all ages, also in patients with liver disease and poor kidney function and its increased effectiveness over glycopeptides makes this drug a precious drug in the treatment of resistant staphylococcal infections. Linezolid resistance in staphylococcus is defined as a linezolid MIC of and #8805;8 mg/L. Reported Linezolid resistance in India and elsewhere is 2-20%. There is clonal dissemination of Linezolid Resistant Staphylococcus aureus (LRSA within or across health care settings which demands continuous surveillance to determine the emergent risk of resistance strains and to establish guidelines for appropriate use. Clinical laboratories should confirm any LRSA preferably by a second method, prior to using linezolid for serious infections. Effective surveillance, more judicious use of this antibiotic, avoiding linezolid usage for empiric therapy in hospital acquired staphylococcus infections, optimization of the pharmacological parameters of the antibiotics in specific clinical situation, decreasing bacterial load by timely surgical debridement or drainage of collections, use of combination therapies would prevent the emergence of resistance to linezolid in staphylococcus aureus. [Int J Res Med Sci 2014; 2(4.000: 1253-1256

  17. Resistance to Linezolid

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    Vester, Birte; Ntokou, Eleni

    2017-01-01

    Linezolid is an antimicrobial agent that binds to the bacterial ribosome and thereby inhibits protein synthesis. Soon after its release as a clinical drug, it became clear that bacteria could become resistant to linezolid. The resistance mechanisms are mainly causing alteration of the drug target...... site, but probably efflux might also play a role. The resistance is still rare in surveillance studies, but outbreaks of resistant clones from hospitals have been observed. So far the main mechanisms of resistance are occurrence of mutations in ribosomal genes or obtaining plasmids with a gene coding...... for a methyltransferase providing resistance. The most obvious way to avoid resistance may be development of derivatives of linezolid overcoming the known resistance mechanisms....

  18. Profilo terapeutico e farmacoeconomico di linezolid

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    Mario Eandi

    2004-06-01

    Full Text Available The incidence of nosocomial infections from Gram-positive pathogens has been increasing in the last two decades, alongside the development of antibiotic resistance in many bacteria. Glycopeptidic drugs are the most widely used options for these patients, but some bacterial strains with low sensibility to vancomycin and teicoplanin are starting to emerge, warranting careful monitoring and control of nosocomial and also community- acquired infections. This paper outlines a clinical, therapeutic and economic profile of linezolid, the first drug of the only new antibiotic class developed in the last thirty years. In clinical trials, linezolid has demonstrated very promising efficacy and safety in the treatment of antibiotic-resistant infections, in particular those caused by methicillin-resistant staphylococci (MRSA, obtaining greater or equal clinical and microbiological success rates than the standard options. Linezolid, as most newer drugs, has higher acquisition costs than the alternatives, but also bears interesting features that may modify the formation of infection treatment costs. In particluar, linezolid is very well absorbed after oral administration, allowing the planning of sequential iv/os strategies that have the potential to reduce health care costs and to improve the quality of life of the patients by shortening the length of hospitalization. Economic evaluations have demonstrated that this advantage is not merely theoretical, but that it can be achieved in real practice. In particular, linezolid has been shown to be more cost-effective than teicoplanin and vancomycin in the treatment of hospitalized, MRSA-related nosocomial pneumonia and severe infections.

  19. Detection of linezolid resistance due to the optrA gene in Enterococcus faecalis from poultry meat from the American continent (Colombia)

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    Cavaco, Lina; Bernal, J F; Zankari, Ea;

    2017-01-01

    Three Enterococcus isolates obtained from retail chicken collected in 2010-11 as part of the Colombian Integrated Program for Antimicrobial Resistance Surveillance (COIPARS) showed reduced susceptibility towards linezolid (MIC 8 mg/L). This study aimed at characterizing the isolates resistant to ...

  20. Linezolid induced black hairy tongue

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    Govindan Balaji

    2014-01-01

    Full Text Available Black hairy tongue (BHT also called as lingua villosa nigra, is a self limiting benign condition characterized by hypertrophy and elongation of filiform papillae of tongue with brown or black discoloration. Smoking, poor oral hygiene, xerostomia, using peroxide containing mouth washes, substance abuse and drugs (steroids, methyldopa, olanzapine, etc are the predisposing factors. However its occurrence in relation to linezolid ingestion among south Indians has not been reported in PubMed database. Here we report a case, where significant association of linezolid intake with BHT was found in a 10-year-old boy, who was treated with tablet linezolid for post surgical infection of left side radial neck fracture. This case is reported for the rarity of occurrence with linezolid therapy. According to Naranjo adverse drug reaction (ADR causality scale, the association of BHT due to linezolid in our case was probable.

  1. Applicability of a Single Time Point Strategy for the Prediction of Area Under the Concentration Curve of Linezolid in Patients

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    Srinivas, Nuggehally R; Syed, Muzeeb

    2016-01-01

    Background and Objectives: Linezolid, a oxazolidinone, was the first in class to be approved for the treatment of bacterial infections arising from both susceptible and resistant strains of Gram-positive bacteria. Since overt exposure of linezolid may precipitate serious toxicity issues, therapeu......Background and Objectives: Linezolid, a oxazolidinone, was the first in class to be approved for the treatment of bacterial infections arising from both susceptible and resistant strains of Gram-positive bacteria. Since overt exposure of linezolid may precipitate serious toxicity issues...

  2. Linezolid-induced optic neuropathy

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    Divya Karuppannasamy

    2014-01-01

    Full Text Available Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic optic neuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment.

  3. Prophylactic stretching does not reduce cramp susceptibility.

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    Miller, Kevin C; Harsen, James D; Long, Blaine C

    2017-08-10

    Some clinicians advocate stretching to prevent muscle cramps. It is unknown whether static or proprioceptive neuromuscular facilitation (PNF) stretching increases cramp threshold frequency (TFc ), a quantitative measure of cramp susceptibility. Fifteen individuals completed this randomized, counterbalanced, cross-over study. We measured passive hallux range of motion (ROM) and then performed 3 minutes of either static stretching, PNF stretching (hold-relax-with agonist contraction), or no stretching. ROM was reassessed and TFc was measured. PNF stretching increased hallux extension (pre-PNF 81 ± 11°, post-PNF 90 ± 10°; P 0.05). Static stretching increased hallux extension (pre-static 80 ± 11°, post-static 88 ± 9°; P 0.05). No ROM changes occurred with no stretching (P > 0.05). TFc was unaffected by stretching (no stretching 18 ± 7 Hz, PNF 16 ± 4 Hz, static 16 ± 5 Hz; P = 0.37). Static and PNF stretching increased hallux extension, but neither increased TFc . Acute stretching may not prevent muscle cramping. Muscle Nerve, 2017. © 2017 Wiley Periodicals, Inc.

  4. Forewarning reduces fraud susceptibility in vulnerable consumers

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    Scheibe, Susanne; Notthoff, Nanna; Menkin, Josephine; Ross, Lee; Shadel, Doug; Deevy, Martha; Carstensen, Laura L.

    2014-01-01

    Telemarketing fraud is pervasive and older consumers are disproportionally targeted. Given laboratory research showing that forewarning can effectively counter influence appeals, we conducted a field experiment to test whether forewarning could protect people who had been victimized in the past. A research assistant with prior experience as a telemarketer pitched a mock scam two or four weeks after participants were warned about the same scam or an entirely different scam. Both warnings reduc...

  5. Endocarditis caused by methicillin-susceptible Staphylococcus aureus with reduced susceptibility to vancomycin: a case report

    Directory of Open Access Journals (Sweden)

    Famiglietti Angela

    2011-07-01

    Full Text Available Abstract Introduction Staphylococcus aureus is the most common cause of acute infective endocarditis. Recent reports have described heteroresistance to vancomycin associated with methicillin-resistant Staphylococcus aureus. We present the first case report in Argentina of the failure of treatment with vancomycin in endocarditis caused by methicillin-susceptible Staphylococcus aureus containing subpopulations with reduced susceptibility to vancomycin. Case presentation We report the case of a 66-year-old Hispanic man with infective endocarditis complicated by septic emboli in the lumbosacral spine and the left iliopsoas muscle. This disease was caused by methicillin-susceptible Staphylococcus aureus containing subpopulations with reduced susceptibility to vancomycin. He was initially treated with cephalothin and gentamicin but developed a rash caused by beta-lactams and interstitial nephritis. For that reason, the treatment was subsequently switched to vancomycin but he failed to respond. The infection resolved after administration of vancomycin in combination with gentamicin and rifampin. Conclusion Our case report provides important evidence for the existence of subpopulations of methicillin-susceptible Staphylococcus aureus that have reduced susceptibility to vancomycin which would account for treatment failure. Our case raises an alert about the existence of these strains and highlights the need to determine the vancomycin minimum inhibitory concentration of Staphylococcus aureus to screen for the presence of strains that have reduced vancomycin susceptibility at different infection sites.

  6. Forewarning reduces fraud susceptibility in vulnerable consumers

    Science.gov (United States)

    Scheibe, Susanne; Notthoff, Nanna; Menkin, Josephine; Ross, Lee; Shadel, Doug; Deevy, Martha; Carstensen, Laura L.

    2014-01-01

    Telemarketing fraud is pervasive and older consumers are disproportionally targeted. Given laboratory research showing that forewarning can effectively counter influence appeals, we conducted a field experiment to test whether forewarning could protect people who had been victimized in the past. A research assistant with prior experience as a telemarketer pitched a mock scam two or four weeks after participants were warned about the same scam or an entirely different scam. Both warnings reduced unequivocal acceptance of the mock scam although outright refusals (as opposed to expressions of skepticism) were more frequent with the same scam warning than the different scam warning. The same scam warning, but not the different scam warning, lost effectiveness over time. Findings demonstrate that social psychological research can inform effective protection strategies against telemarketing fraud. PMID:25328263

  7. Forewarning reduces fraud susceptibility in vulnerable consumers.

    Science.gov (United States)

    Scheibe, Susanne; Notthoff, Nanna; Menkin, Josephine; Ross, Lee; Shadel, Doug; Deevy, Martha; Carstensen, Laura L

    2014-01-01

    Telemarketing fraud is pervasive and older consumers are disproportionally targeted. Given laboratory research showing that forewarning can effectively counter influence appeals, we conducted a field experiment to test whether forewarning could protect people who had been victimized in the past. A research assistant with prior experience as a telemarketer pitched a mock scam two or four weeks after participants were warned about the same scam or an entirely different scam. Both warnings reduced unequivocal acceptance of the mock scam although outright refusals (as opposed to expressions of skepticism) were more frequent with the same scam warning than the different scam warning. The same scam warning, but not the different scam warning, lost effectiveness over time. Findings demonstrate that social psychological research can inform effective protection strategies against telemarketing fraud.

  8. Pancytopenia due to linezolid treatment.

    Science.gov (United States)

    Parlak, Emine; Tan, Hüseyin

    2015-09-01

    Antibiotic-resistant infections constitute a significant portion of severe childhood infections. A gradually increasing resistance and treatment difficulty are observed in infections caused by enterococci, staphylococci and pneumococci. Linezolid is one of the new antibiotics which has recently been introduced for clinical use with gram positive efficiency. In this article, a pediatric patient with vancomycin-resistant enterococcus infection who developed reversible bone marrow supression related with use of linesolid was presented. A shunt was inserted in a ten-month old female patient who had been operated at the age of one month because of meningomyelocele and who had developed hydrocephalus. Linezolid and meropenem treatment was started when vancomycin-resistant Enterococcus faecium and extended-spectrum beta-lactamase positive Escherichia coli grew in cerebrospinal fluid culture. In the second week of treatment, cerebrospinal fluid findings improved. However, bone marrow supression was observed. Linezolid treatment was discontinued. In the follow-up, the blood cell counts returned to normal levels.

  9. Global analysis of the impact of linezolid onto virulence factor production in S. aureus USA300.

    Science.gov (United States)

    Bonn, Florian; Pané-Farré, Jan; Schlüter, Rabea; Schaffer, Marc; Fuchs, Stephan; Bernhardt, Jörg; Riedel, Katharina; Otto, Andreas; Völker, Uwe; van Dijl, Jan Maarten; Hecker, Michael; Mäder, Ulrike; Becher, Dörte

    2016-05-01

    The translation inhibitor linezolid is an antibiotic of last resort against Gram-positive pathogens including methicillin resistant strains of the nosocomial pathogen Staphylococcus aureus. Linezolid is reported to inhibit production of extracellular virulence factors, but the molecular cause is unknown. To elucidate the physiological response of S. aureus to linezolid in general and the inhibition of virulence factor synthesis in particular a holistic study was performed. Linezolid was added to exponentially growing S. aureus cells and the linezolid stress response was analyzed with transcriptomics and quantitative proteomics methods. In addition, scanning and transmission electron microscopy experiments as well as fluorescence microscopy analyses of the cellular DNA and membrane were performed. As previously observed in studies on other translation inhibitors, S. aureus adapts its protein biosynthesis machinery to the reduced translation efficiency. For example the synthesis of ribosomal proteins was induced. Also unexpected results like a decline in the amount of extracellular and membrane proteins were obtained. In addition, cell shape and size changed after linezolid stress and cell division was diminished. Finally, the chromosome was condensed after linezolid stress and lost contact to the membrane. These morphological changes cannot be explained by established theories. A new hypothesis is discussed, which suggests that the reduced amount of membrane and extracellular proteins and observed defects in cell division are due to the disintegration of transertion complexes by linezolid.

  10. Linezolid-induced haematological toxicity

    OpenAIRE

    Ortega-Eslava, A. (A.); Aquerreta, I. (Irene); Leache, L. (Leire); Moraza, L. (Libe)

    2015-01-01

    Objetivo: determinar la incidencia de toxicidad hematológica por linezolid. Estudiar la influencia del aclaramiento renal en su aparición y la efectividad de la piridoxina en su prevención. Método: estudio observacional retrospectivo de todos los pacientes tratados con linezolid en un hospital universitario en seis meses. Se consideró toxicidad hematológica a la disminución del 25% de la hemoglobina, del 25% de las plaquetas y/o del 50% de neutrófilos al final respecto al...

  11. Probable Linezolid-Induced Pancytopenia

    Directory of Open Access Journals (Sweden)

    Nita Lakhani

    2005-01-01

    Full Text Available A 75-year-old male outpatient with cardiac disease, diabetes, chronic renal insufficiency and iron deficiency anemia was prescribed linezolid 600 mg twice daily for a methicillin-resistant Staphylococcus aureus diabetic foot osteomyelitis. After one week, his blood counts were consistent with baseline values. The patient failed to return for subsequent blood work. On day 26, he was admitted to hospital with acute renal failure secondary to dehydration, and was found to be pancytopenic (erythrocytes 2.5x1012/L, leukocytes 2.9x109/L, platelets 59x109/L, hemoglobin 71 g/L. The patient was transfused, and linezolid was discontinued. His blood counts improved over the week and remained at baseline two months later. The patient's decline in blood counts from baseline levels met previously established criteria for clinical significance. Application of the Naranjo scale indicated a probable relationship between pancytopenia and linezolid. Clinicians should be aware of this rare effect with linezolid, and prospectively identify patients at risk and emphasize weekly hematological monitoring.

  12. Successful treatment of pulmonary Nocardia farcinica infection with linezolid: case report and literature review

    Directory of Open Access Journals (Sweden)

    Tian Shen

    Full Text Available Nocardia infection is rare but potentially fatal. Therapy of Nocardia infection remains difficult. Linezolid, a novel oxazolidinone antibiotic, has proven to be effective, but clinical data are limited. Here we describe a case of a 45-year-old man with pulmonary N. farcinica infection following a liver transplantation. The initial therapy was trimethoprim-sulfamethoxazole, which showed no effect. According to susceptibility test, linezolid was administered with clearly improving the patient's condition. The treatment was stopped for anemia as drug related adverse event, and the therapy lasted for as long as 5 months. At the end of treatment clinical cure was confirmed and anemia reversed after discontinuation of linezolid. We also analyzed the clinical data of previously published reports by literature review, focusing on the efficacy and safety of linezolid treatment for Nocardia infection.

  13. Impact of Molecular Epidemiology and Reduced Susceptibility to Glycopeptides and Daptomycin on Outcomes of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia.

    Directory of Open Access Journals (Sweden)

    Hao-Yuan Lee

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA bacteremia was associated with high mortality, but the risk factors associated with mortality remain controversial.A retrospective cohort study was designed. All patients with MRSA bacteremia admitted were screened and collected for their clinical presentations and laboratory characteristics. Minimum inhibitory concentration (MIC and staphylococcal cassette chromosome mec (SCCmec type of bacterial isolates were determined. Risk factors for mortality were analyzed.Most MRSA isolates from the 189 enrolled patients showed reduced susceptibility to antibiotics, including MIC of vancomycin ≥ 1.5 mg/L (79.9%, teicoplanin ≥ 2 mg/L (86.2%, daptomycin ≥ 0.38 mg/L (73.0% and linezolid ≥ 1.5 mg/L (64.0%. MRSA with vancomycin MIC ≥ 1.5 mg/L and inappropriate initial therapy were the two most important risk factors for mortality (both P < 0.05; odds ratio = 7.88 and 6.78. Hospital-associated MRSA (HA-MRSA, carrying SCCmec type I, II, or III, was associated with reduced susceptibility to vancomycin, teicoplanin or daptomycin and also with higher attributable mortality (all P < 0.05. Creeping vancomycin MIC was linked to higher MIC of teicoplanin and daptomycin (both P < 0.001, but not linezolid (P = 0.759.Giving empirical broad-spectrum antibiotics for at least 5 days to treat catheter-related infections, pneumonia, soft tissue infection and other infections was the most important risk factor for acquiring subsequent HA-MRSA infection. Choice of effective anti-MRSA agents for treating MRSA bacteremia should be based on MIC of vancomycin, teicoplanin and daptomycin. Initiation of an effective anti-MRSA agent without elevated MIC in 2 days is crucial for reducing mortality.

  14. [Sideroblastic anemia after prolonged linezolid therapy].

    Science.gov (United States)

    Kakimoto, Tsunayuki; Nakazato, Tomonori; Miura, Reiko; Kurai, Hanako; Yamashita, Daisuke; Sagara, Yuko; Ishida, Akaru

    2008-11-01

    Linezolid is an effective and well-tolerated antibiotic for the treatment of infections caused by Gram-positive pathogens. Some reports have shown that linezolid treatment for more than 2 weeks has been associated with reversible bone marrow suppression, especially thrombocytopenia and anemia. We encountered a case of sideroblastic anemia following prolonged linezolid therapy in a laryngeal cancer patient. He received linezolid therapy for multiple abscesses due to MRSA. Before treatment, the Hb level was 12.5 g/dl and then slowly decreased to 5.9 g/dl for 2 months during treatment. Ringed sideroblasts were detected in the bone marrow. Linezolid was discontinued and the Hb level was slowly increased. This case was considered to reflect a rare complication of linezolid therapy.

  15. Antimicrobial activity of linezolid against Gram-positive cocci isolated in Brazil

    Directory of Open Access Journals (Sweden)

    Sader Helio S.

    2001-01-01

    Full Text Available The new oxazolidinone linezolid and other antimicrobial agents used to treat Gram-positive infections were tested against 1,585 Gram-positive cocci; 1,260 staphylococci and enterococci isolates from patients hospitalized in Brazilian hospitals, and 325 S. pneumoniae isolates for patients with community acquired infections. Susceptibility testing was performed using broth microdilution according to NCCLS procedures. Linezolid was the most active compound and the only drug that inhibited 100% of the isolates at the susceptible breakpoint (< 4 mg/mL. Resistance to vancomycin was very rare (99.9% susceptibility, and both quinupristin/dalfopristin and gatifloxacin were active against approximately 90% of the strains evaluated. All other compounds inhibited less than 65% of the isolates. The excellent in vitro Gram-positive activity by linezolid, in this study, indicate that this compound may represent an important therapeutic option for the treatment of infections caused by these pathogens in Brazil.

  16. Antimicrobial activity of linezolid against Gram-positive cocci isolated in Brazil

    Directory of Open Access Journals (Sweden)

    Helio S. Sader

    Full Text Available The new oxazolidinone linezolid and other antimicrobial agents used to treat Gram-positive infections were tested against 1,585 Gram-positive cocci; 1,260 staphylococci and enterococci isolates from patients hospitalized in Brazilian hospitals, and 325 S. pneumoniae isolates for patients with community acquired infections. Susceptibility testing was performed using broth microdilution according to NCCLS procedures. Linezolid was the most active compound and the only drug that inhibited 100% of the isolates at the susceptible breakpoint (< 4 mg/mL. Resistance to vancomycin was very rare (99.9% susceptibility, and both quinupristin/dalfopristin and gatifloxacin were active against approximately 90% of the strains evaluated. All other compounds inhibited less than 65% of the isolates. The excellent in vitro Gram-positive activity by linezolid, in this study, indicate that this compound may represent an important therapeutic option for the treatment of infections caused by these pathogens in Brazil.

  17. Cluster of linezolid-resistant Enterococcus faecium ST117 in Norwegian hospitals.

    Science.gov (United States)

    Hegstad, Kristin; Longva, Jørn-Åge; Hide, Reidar; Aasnæs, Bettina; Lunde, Tracy M; Simonsen, Gunnar Skov

    2014-10-01

    A linezolid-resistant, vancomycin-susceptible Enterococcus faecium strain was isolated from 3 patients who had not received linezolid. The first patient was hospitalized in the same hospitals and wards as the 2 following patients. The E. faecium isolates were resistant to linezolid (minimum inhibitory concentration 8-32 mg/l), ampicillin, and high levels of gentamicin. Resistance to linezolid was associated with a G2576T mutation in 23S rDNA. The cfr linezolid resistance gene was not detected. The 3 isolates showed identical DNA fingerprints by pulsed-field gel electrophoresis, belonged to ST117, and harboured virulence genes esp, hyl, acm, efaAfm, srgA, ecbA, scm, pilA, pilB, and pstD typically associated with high-risk E. faecium genotypes. The linezolid-resistant E. faecium high-risk clone caused bacteraemia in the first 2 cancer patients and survived in the hospital environment for more than a year before appearing in the urethral catheter of the third patient.

  18. Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.

    Science.gov (United States)

    Ashizawa, Nobuyuki; Tsuji, Yasuhiro; Kawago, Koyomi; Higashi, Yoshitsugu; Tashiro, Masato; Nogami, Makiko; Gejo, Ryuichi; Narukawa, Munetoshi; Kimura, Tomoatsu; Yamamoto, Yoshihiro

    2016-05-01

    Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration.

  19. In vitro activity of ceftobiprole, linezolid, tigecycline, and 23 other antimicrobial agents against Staphylococcus aureus isolates in China.

    Science.gov (United States)

    Wang, Hui; Liu, Yudong; Sun, Hongli; Xu, Yingchun; Xie, Xiuli; Chen, Minjun

    2008-10-01

    We investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in China and determined the susceptibility of S. aureus to 26 antimicrobial agents, including ceftobiprole, linezolid, and tigecycline. A total of 798 isolates were collected and tested by agar dilution. The mean prevalence of MRSA was 50.4%, the highest in Shanghai (80.3%), followed by those in Beijing (55.5%) and Shenyang (50.0%). Only 4.2% to 12.6% of MRSA were susceptible to erythromycin, fluoroquinolones, gentamicin, and tetracycline. All isolates were susceptible to teicoplanin, vancomycin, linezolid, tigecycline, and ceftobiprole.

  20. Linezolid

    Science.gov (United States)

    ... It works by stopping the growth of bacteria. Antibiotics will not work for colds, flu, and other ... raisins; bananas; sour cream; pickled herring; liver (especially chicken liver); dried meats and sausage (including hard salami ...

  1. Staphylococcus aureus with reduced susceptibility to vancomycin in healthcare settings.

    Science.gov (United States)

    Spagnolo, A M; Orlando, P; Panatto, D; Amicizia, D; Perdelli, F; Cristina, M L

    2014-12-01

    Glycopeptide resistance in Staphylococcus aureus is a source of great concern because, especially in hospitals, this class of antibiotics, particularly vancomycin, is one of the main resources for combating infections caused by methicillin-resistant Staphylococcus aureus strains (MRSA). Reduced susceptibility to vancomycin (VISA) was first described in 1996 in Japan; since then, a phenotype with heterogeneous resistance to vancomycin (h-VISA) has emerged. H-VISA isolates are characterised by the presence of a resistant subpopulation, typically at a rate of 1 in 10(5) organisms, which constitutes the intermediate stage betweenfully vancomycin-susceptible S. aureus (VSSA) and VISA isolates. As VISA phenotypes are almost uniformly cross-resistant to teicoplanin, they are also called Glycopeptides-intermediate Staphylococcus aureus strains (GISA) and, in the case of heterogeneous resistance to glycopeptides, h-GISA. The overall prevalence of h-VISA is low, accounting for approximately 1.3% of all MRSA isolates tested. Mortality due to h-GISA infections is very high (about 70%), especially among patients hospitalised in high-risk departments, such as intensive care units (ICU). Given the great clinical relevance of strains that are heteroresistant to glycopeptides and the possible negative impact on treatment choices, it is important to draw up and implement infection control practices, including surveillance, the appropriate use of isolation precautions, staff training, hand hygiene, environmental cleansing and good antibiotic stewardship.

  2. [In vitro activity of linezolid, moxifloxacin, levofloxacin, clindamycin and rifampin, alone and in combination, against Staphylococcus aureus and Staphylococcus epidermidis].

    Science.gov (United States)

    Soriano, A; Jurado, A; Marco, F; Almela, M; Ortega, M; Mensa, J

    2005-06-01

    Information about the in vitro effect of combinations of anti-staphylococcal agents on staphylococci is scarce. The aim of the study was to evaluate the in vitro activity of linezolid, moxifloxacin, levofloxacin, clindamycin and rifampin, alone or in combination, against Staphylococcus spp. Two Staphylococcus aureus and two Staphylococcus epidermidis strains isolated from blood cultures were studied using the killing curve method. The combinations analyzed were linezolid+moxifloxacin, linezolid+levofloxacin, linezolid+clindamycin, linezolid+rifampin, moxifloxacin+rifampin, moxifloxacin+clindamycin, levofloxacin+rifampin and levofloxacin+clindamycin. The following concentrations (mg/l) were used: 8 and 16 for linezolid, 2 for moxifloxacin, 3 for levofloxacin, 2 for clindamycin and 2 and 5 for rifampin. The activity was considered synergistic when a reduction in growth of at least 2 log(10) was produced with the combination in comparison to the most active antibiotic alone; antagonistic when a growth of at least 2 log(10) was produced with the combination in comparison to the most active antibiotic alone; and indifferent if the variation was less than 1 log(10). Linezolid and clindamycin were bacteriostatic, while moxifloxacin and levofloxacin were bactericidal. Rifampin was bacteriostatic against S. aureus and bactericidal against S. epidermidis. Linezolid and clindamycin reduced the bactericidal activity of levofloxacin and moxifloxacin, however an antagonistic effect was only observed against S. aureus. Other combinations of linezolid, rifampin, clindamycin, levofloxacin or moxifloxacin were indifferent. Linezolid and clindamycin antagonize the bactericidal activity of fluorquinolones against staphylococci. There was no difference between any other combinations against either S. aureus or S. epidermidis.

  3. Linezolid-induced haematological toxicity.

    Science.gov (United States)

    Moraza, Libe; Leache, Leire; Aquerreta, Irene; Ortega, Ana

    2015-11-01

    Objetivo: determinar la incidencia de toxicidad hematológica por linezolid. Estudiar la influencia del aclaramiento renal en su aparición y la efectividad de la piridoxina en su prevención. Método: estudio observacional retrospectivo de todos los pacientes tratados con linezolid en un hospital universitario en seis meses. Se consideró toxicidad hematológica a la disminución del 25% de la hemoglobina, del 25% de las plaquetas y/o del 50% de neutrófilos al final respecto al inicio del tratamiento. Se comparó en los pacientes con y sin fallo renal (aclaramiento de creatinina inferior a 50 mL/min), con más o menos de 30 mL/min, y con o sin piridoxina, la incidencia de toxicidad hematológica mediante Chi-Cuadrado y la disminución en el porcentaje de variables analíticas hematológicas mediante U Mann-Whitney. Resultados: se evaluaron 38 pacientes. Dieciséis (42%) presentaron toxicidad hematológica (2 por disminución de hemoglobina, 9 de plaquetas y 8 de neutrófilos). En 2 pacientes (5%) se suspendió el tratamiento por plaquetopenia. La incidencia de toxicidad fue similar en pacientes con y sin insuficiencia renal, 42% vs. 42%, p = 0,970, con más o menos de 30 mL/min, 67% vs. 40%, p = 0,369, con piridoxina o sin ella, 47,8% vs. 33%, p = 0,376. Los pacientes con fallo renal presentaron una reducción significativamente mayor de plaquetas, p = 0,0185. Conclusiones: un 42% de los pacientes presentó toxicidad hematológica, más frecuentemente disminución de plaquetas y neutrófilos. Esta no fue significativamente mayor en los pacientes con fallo renal, ni en aquellos sin piridoxina. Se halló mayor reducción de plaquetas en los pacientes con insuficiencia renal.

  4. Linezolid bladder irrigation as adjunctive treatment for a vancomycin-resistant Enterococcus faecium catheter-associated urinary tract infection.

    Science.gov (United States)

    Hill, David M; Wood, G Christopher; Hickerson, William L

    2015-02-01

    To describe the first reported successful use of adjunctive linezolid bladder irrigation. An 89-year-old woman with 10% TBSA burns developed septic shock and anuric acute kidney insufficiency. She acquired a urinary tract infection caused by vancomycin-resistant Enterococcus faecium (VREfm). Based on clinical status, a linezolid bladder irrigation was initiated in addition to high-dose intravenous linezolid and demonstrated microbiological cure with 7 days of treatment. Linezolid is primarily hepatically cleared and has no labeled indication for urinary tract infections. Anuria adds an additional complication of potentially reduced urinary drug concentrations. Bladder irrigation offers the benefit of achieving high local drug concentrations, but there are no data regarding such a route for linezolid. This case report is the first demonstrating the use, stability, safety, and efficacy of linezolid as a continuous bladder irrigation. Linezolid use as a bladder irrigation may be a feasible route of administration in anuric, critically ill patients with VREfm and few antimicrobial options. Further studies are warranted. © The Author(s) 2014.

  5. Fermented liquid feed reduces susceptibility of broilers for Salmonella enteriditis

    NARCIS (Netherlands)

    Heres, L.; Engel, B.; Knapen, van F.; Jong, de M.C.M.; Wagenaar, J.A.; Urlings, B.A.P.

    2003-01-01

    The presence of Salmonella in chickens is a problem because poultry meat is recognized as a source of human salmonellosis. Fermented feed has characteristics like a high number of lactobacilli and high concentration of lactic acid, which could make chickens less susceptible for infection with Salmon

  6. Fermented liquid feed reduces susceptibility of broilers for Salmonella enteriditis

    NARCIS (Netherlands)

    Heres, L.; Engel, B.; Knapen, van F.; Jong, de M.C.M.; Wagenaar, J.A.; Urlings, B.A.P.

    2003-01-01

    The presence of Salmonella in chickens is a problem because poultry meat is recognized as a source of human salmonellosis. Fermented feed has characteristics like a high number of lactobacilli and high concentration of lactic acid, which could make chickens less susceptible for infection with

  7. Emergence of a Candida krusei Isolate with Reduced Susceptibility to Caspofungin during Therapy

    OpenAIRE

    Hakki, Morgan; Staab, Janet F.; Marr, Kieren A.

    2006-01-01

    Clinical failure associated with reduced susceptibility to caspofungin has been described in Candida albicans and C. parapsilosis. We report a case of Candida krusei infection that progressed despite caspofungin therapy. Reduced microbial susceptibility to all three echinocandins (caspofungin, anidulafungin, and micafungin) was noted but was not associated with mutations in FKS1.

  8. Fermented liquid feed reduces susceptibility of broilers for Salmonella enteritidis.

    Science.gov (United States)

    Heres, L; Engel, B; van Knapen, F; de Jong, M C M; Wagenaar, J A; Urlings, H A P

    2003-04-01

    The presence of Salmonella in chickens is a problem because poultry meat is recognized as a source of human salmonellosis. Fermented feed has characteristics like a high number of lactobacilli and high concentration of lactic acid, which could make chickens less susceptible for infection with Salmonella. Fermented feed might therefore prevent the colonization of chickens with Salmonella. Two studies were performed to quantify the effect of fermented liquid feed on the susceptibility of broilers for Salmonella. The fermented feed was prepared by fermenting a dry broiler feed supplemented with 1.4 parts of water. Lactobacillus plantarum was used for fermentation. The fermented liquid feed (FLF) contained 10(9) to 10(10) cfu lactobacilli per gram, and the pH was 4. Individually housed control chickens and FLF-fed chickens were inoculated with 10(2) to 10(7) cfu Salmonella enteritidis (SE). Colonization was estimated by cloacal swabs and quantitative caecal culture. The proportion of SE-shedding chickens was decreased in FLF-fed chickens. FLF-fed chickens required a longer time after inoculation or a higher inoculation dose to get the same proportion of infected chickens in comparison with dry feed-fed chickens. The level of cecal colonization with Salmonella in the ceca was not different at the end of the experimental period. The results indicate that FLF can hamper the introduction of Salmonella in broiler flocks because the chickens are less susceptible for infection. Fermented liquid feed might therefore be a new hurdle in the strategy to control Salmonella in chicken flocks.

  9. Reduced intrinsic heart rate is associated with reduced arrhythmic susceptibility in guinea-pig heart.

    Science.gov (United States)

    Osadchii, Oleg E

    2014-12-01

    In the clinical setting, patients with slower resting heart rate are less prone to cardiovascular death compared with those with elevated heart rate. However, electrophysiological adaptations associated with reduced cardiac rhythm have not been thoroughly explored. In this study, relationships between intrinsic heart rate and arrhythmic susceptibility were examined by assessments of action potential duration (APD) rate adaptation and inducibility of repolarization alternans in sinoatrial node (SAN)-driven and atrioventricular (AV)-blocked guinea-pig hearts perfused with Langendorff apparatus. Electrocardiograms, epicardial monophasic action potentials, and effective refractory periods (ERP) were assessed in normokalemic and hypokalemic conditions. Slower basal heart rate in AV-blocked hearts was associated with prolonged ventricular repolarization during spontaneous beating, and with attenuated APD shortening at increased cardiac activation rates during dynamic pacing, when compared with SAN-driven hearts. During hypokalemic perfusion, the inducibility of repolarization alternans and tachyarrhythmia by rapid pacing was found to be lower in AV-blocked hearts. This difference was ascribed to prolonged ERP in the setting of reduced basal heart rate, which prevented ventricular capture at critically short pacing intervals required to induce arrhythmia. Reduced basal heart rate is associated with electrophysiological changes that prevent electrical instability upon an abrupt cardiac acceleration.

  10. Linezolid-resistant staphylococcal bacteraemia: A multicentre case-case-control study in Italy.

    Science.gov (United States)

    Russo, Alessandro; Campanile, Floriana; Falcone, Marco; Tascini, Carlo; Bassetti, Matteo; Goldoni, Paola; Trancassini, Maria; Della Siega, Paola; Menichetti, Francesco; Stefani, Stefania; Venditti, Mario

    2015-03-01

    The aim of this multicentre study was to analyse the characteristics of patients with bloodstream infections due to staphylococcal strains resistant to linezolid. This was a retrospective case-case-control study of patients hospitalised in three large teaching hospitals in Italy. A linezolid-resistant (LIN-R) Staphylococcus spp. group and a linezolid-susceptible (LIN-S) Staphylococcus spp. group were compared with control patients to determine the clinical features and factors associated with isolation of LIN-R strains. All LIN-R Staphylococcus spp. strains underwent molecular typing. Compared with the LIN-S group, central venous catheters were the main source of infection in the LIN-R group. The LIN-R and LIN-S groups showed a similar incidence of severe sepsis or septic shock, and both showed a higher incidence of these compared with the control group. Overall, patients in the LIN-R group had a higher 30-day mortality rate. Multivariate analysis found previous linezolid therapy, linezolid therapy >14 days, antibiotic therapy in the previous 30 days, antibiotic therapy >14 days, previous use of at least two antibiotics and hospitalisation in the previous 90 days as independent risk factors associated with isolation of a LIN-R strain. The G2576T mutation in domain V of 23S rRNA was the principal mechanism of resistance; only one strain of Staphylococcus epidermidis carried the cfr methylase gene (A2503), together with L4 insertion (71GGR72) and L3 substitution (H146Q). LIN-R strains are associated with severe impairment of clinical conditions and unfavourable patient outcomes. Reinforcement of infection control measures may have an important role in preventing these infections.

  11. Multicenter assessment of the linezolid spectrum and activity using the disk diffusion and Etest methods: report of the Zyvox® Antimicrobial Potency Study in Latin America (LA-ZAPS

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    Ballow Charles H.

    2002-01-01

    Full Text Available Linezolid was the first clinically applied member of the new antimicrobial class called the "oxazolidinones". These agents have a powerful spectrum of activity focussed against Gram-positive organisms including strains with documented resistances to other antimicrobial classes. We conducted a multicenter surveillance (Zyvox Antimicrobial Potency Study; ZAPS trial of qualifying Gram-positive isolates from 24 medical centers in eight countries in Latin America. The activity and spectrum of linezolid was compared to numerous agents including glycopeptides, quinupristin/dalfopristin, b-lactams and fluoroquinolones when testing 2,640 strains by the standardized disk diffusion method or Etest (AB BIODISK, Solna, Sweden. The linezolid spectrum was complete against staphylococci (median zone diameter, 29 - 32 mm, as was the spectrum of vancomycin and quinupristin/dalfopristin. Among the enterococci, no linezolid resistance was detected, and the susceptibility rate was 93.1 - 96.4%. Only the vancomycin-susceptible Enterococcus faecium strains remained susceptible (92.8% to quinupristin/dalfopristin. Marked differences in the glycopeptide resistance patterns (van A versus van B were noted for the 22 isolates of VRE, thus requiring local susceptibility testing to direct therapy. Streptococcus pneumoniae and other species were very susceptible (100.0% to linezolid, MIC90 at 0.75 mug/ml. Penicillin non-susceptible rate was 27.7% and erythromycin resistance was at 17.4%. Other streptococci were also completely susceptible to linezolid (MIC90, 1 mug/ml. These results provide the initial benchmark of potency and spectrum for linezolid in Latin American medical centers. Future comparisons should recognize that the oxazolidinones possess essentially a complete spectrum coverage of the monitored staphylococci, enterococci and streptococcal isolates in 2000-2001. This positions linezolid as the widest spectrum empiric choice against multi-resistant Gram

  12. Multicenter assessment of the linezolid spectrum and activity using the disk diffusion and Etest methods: report of the Zyvox® Antimicrobial Potency Study in Latin America (LA-ZAPS

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    Charles H. Ballow

    Full Text Available Linezolid was the first clinically applied member of the new antimicrobial class called the "oxazolidinones". These agents have a powerful spectrum of activity focussed against Gram-positive organisms including strains with documented resistances to other antimicrobial classes. We conducted a multicenter surveillance (Zyvox Antimicrobial Potency Study; ZAPS trial of qualifying Gram-positive isolates from 24 medical centers in eight countries in Latin America. The activity and spectrum of linezolid was compared to numerous agents including glycopeptides, quinupristin/dalfopristin, b-lactams and fluoroquinolones when testing 2,640 strains by the standardized disk diffusion method or Etest (AB BIODISK, Solna, Sweden. The linezolid spectrum was complete against staphylococci (median zone diameter, 29 - 32 mm, as was the spectrum of vancomycin and quinupristin/dalfopristin. Among the enterococci, no linezolid resistance was detected, and the susceptibility rate was 93.1 - 96.4%. Only the vancomycin-susceptible Enterococcus faecium strains remained susceptible (92.8% to quinupristin/dalfopristin. Marked differences in the glycopeptide resistance patterns (van A versus van B were noted for the 22 isolates of VRE, thus requiring local susceptibility testing to direct therapy. Streptococcus pneumoniae and other species were very susceptible (100.0% to linezolid, MIC90 at 0.75 mug/ml. Penicillin non-susceptible rate was 27.7% and erythromycin resistance was at 17.4%. Other streptococci were also completely susceptible to linezolid (MIC90, 1 mug/ml. These results provide the initial benchmark of potency and spectrum for linezolid in Latin American medical centers. Future comparisons should recognize that the oxazolidinones possess essentially a complete spectrum coverage of the monitored staphylococci, enterococci and streptococcal isolates in 2000-2001. This positions linezolid as the widest spectrum empiric choice against multi-resistant Gram

  13. Reduced lentivirus susceptibility in sheep with TMEM154 mutations.

    Science.gov (United States)

    Heaton, Michael P; Clawson, Michael L; Chitko-Mckown, Carol G; Leymaster, Kreg A; Smith, Timothy P L; Harhay, Gregory P; White, Stephen N; Herrmann-Hoesing, Lynn M; Mousel, Michelle R; Lewis, Gregory S; Kalbfleisch, Theodore S; Keen, James E; Laegreid, William W

    2012-01-01

    Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154) that exceeded genome-wide significance (unadjusted p-value 3×10(-9)). Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E) at position 35 were associated with infection while a third haplotype with lysine (K) at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-valuesheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-valuesheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection.

  14. Linezolid-induced black hairy tongue: a case report

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    Khasawneh Faisal Abdullah

    2013-02-01

    Full Text Available Abstract Introduction Linezolid-induced black hairy tongue has been rarely reported. The purpose of this paper is to report a case of linezolid-induced black hairy tongue and review the literature. Case presentation A 56-year-old Caucasian man was admitted with community-acquired pneumonia that failed to respond to levofloxacin 750mg daily. He was started on linezolid and meropenem and was subsequently discharged home on oral linezolid 600mg every 12 hours and intravenous ertapenem 1g daily. On a follow-up clinic visit, day 14 of linezolid therapy, he complained of dysgeusia and his tongue examination was consistent with black hairy tongue. After he finished his antibiotic course, his complaints resolved with regular tongue brushing. Conclusion Black hairy tongue is characterized by abnormal hypertrophy and elongation of filiform papillae. Five reported cases of linezolid-induced black hairy tongue were identified in a MEDLINE search (from January 2000 to June 2012. The Naranjo Probability Scale revealed a probable adverse drug reaction of linezolid-induced black hairy tongue. Potential contributing factors included other antibiotics, drug–drug interaction and poor oral hygiene. Health care professionals should be aware of the possibility of linezolid-induced black hairy tongue. Thorough history for other possible contributing factors should be obtained. Patients on linezolid should be counseled to perform good oral hygiene.

  15. Dietary tyramine restriction for hospitalized patients on linezolid: an update.

    Science.gov (United States)

    Rumore, Martha M; Roth, Marc; Orfanos, Areti

    2010-06-01

    Linezolid is a weak, reversible monoamine oxidase inhibitor. The current practice at most hospitals is to place patients receiving linezolid on a tyramine-restricted diet. This process typically involves both the hospital's pharmacy department and the food and nutrition department. A literature search assessing the interaction between linezolid and tyramine was conducted, and the amount of tyramine in a typical unrestricted diet for a hospitalized patient was reviewed. Although patients receiving linezolid should avoid consuming large amounts of foods containing high concentrations of tyramine, such foods in large amounts are not components of meals for inpatients. Therefore, dietary tyramine restriction in hospitalized patients is not generally required.

  16. Reduced lentivirus susceptibility in sheep with TMEM154 mutations.

    Directory of Open Access Journals (Sweden)

    Michael P Heaton

    2012-01-01

    Full Text Available Visna/Maedi, or ovine progressive pneumonia (OPP as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154 that exceeded genome-wide significance (unadjusted p-value 3×10(-9. Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E at position 35 were associated with infection while a third haplotype with lysine (K at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-value<0.0001, 95% CI 5-1,100. In a combined analysis of nine cohorts with 2,705 sheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-value<0.0001, 95% CI 2.36-3.43. Although rare, some sheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection.

  17. Mutant prevention concentrations of pradofloxacin for susceptible and mutant strains of Escherichia coli with reduced fluoroquinolone susceptibility.

    Science.gov (United States)

    Marcusson, Linda L; Komp Lindgren, Patricia; Olofsson, Sara K; Hughes, Diarmaid; Cars, Otto

    2014-10-01

    Pharmacodynamic and mutant prevention properties of the fluoroquinolone pradofloxacin (PRA) were measured against a set of 17 Escherichia coli strains carrying no, one or two known mutations conferring reduced fluoroquinolone susceptibility. The strains included susceptible wild-types, isogenic constructed mutants, isogenic selected mutants and clinical isolates. The effectiveness of PRA was determined with regard to preventing the selection of resistant mutants, using static and changing concentrations of drug. Ciprofloxacin was used as a reference drug. Minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) of PRA for the susceptible wild-type strains were in the range 0.012-0.016mg/L and 0.2-0.3mg/L, respectively, giving a mean±standard deviation mutant prevention index (MPI=MPC/MIC) of 17.7±1.1. The mean MPI PRA of the 14 mutant strains was 19.2±12, and the mean MPI across all 17 strains was 18.9±10.8. In an in vitro kinetic model in which PRA was diluted with a half-life of 7h to mimic in vivo conditions, an initial concentration of PRA of 1.6-2.4mg/L (8-10× MPC), giving a PRA AUC/MPC ratio of 73-92, and a T>MPC of 21-23h was sufficient to prevent the selection of resistant mutants from the three susceptible wild-type strains. Dosing to reduce selection for antibiotic resistance in veterinary therapy has a role in reducing the reservoir of resistant mutants. We conclude that a level of dosing that prevents the selection of resistant mutants during therapy should be achievable in vivo. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  18. Nalidixic acid resistance predicting reduced ciprofloxacin susceptibility of Salmonella enterica serovar Typhi

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    Shyamapada Mandal

    2012-10-01

    Full Text Available Objective: To evaluate the applicability of nalidixic acid (Nx resistance in determining reduced susceptibility to ciprofloxacin (Cp among Salmonella enterica serovar Typhi (S. Typhi clinical isolates. Methods: The correlation between Cp MIC (minimum inhibitory concentration values and that Nx, and between Cp MICs and zone diameter of inhibition (ZDI around 30-毺 g Nx disc for 421 S. Typhi isolates were determined by scattergram analysis. The specificity and sensitivity, in determining Cp reduced-susceptibility, of Nx resistance by disk testing and MIC determination were calculated. Results: For the test S. Typhi isolates the simultaneous presence of Nx-resistance and decreased Cp susceptibility has been recorded. The Nx sensitive S. Typhi isolates were sensitive to Cp; the disc diffusion and MIC breakpoints cannot determine Cp resistance. The sensitivity of Nx disc was 100 %, and the specificity was 89.20 % in determining Cp reduced-susceptibility of S. Typhi isolates; when MICs of Nx were compared with MICs of Cp, the sensitivity and specificity of the approach were 100 % and 95.95 %, respectively. Conclusion: Association between Nx-resistance and reduced susceptibility to Cp was noticed (P 曑 0.001 among the S. Typhi isolates, and thus Nx-resistance might be an indication of decreased susceptibility to Cp.

  19. Linezolid-induced thrombocytopenia in two patients with renal dysfunction

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    Engin Melek

    2016-12-01

    Full Text Available Linezolid is an oxazolidinone antibiotic, active against gram positive bacteria that are resistant to other antibiotics including glycopeptides. Thrombocytopenia is an adverse effect of linezolid. Although various risk factors have been suggested, the mechanisms behind this side effect are largely unknown. Here, we report two adolescents with the diagnosis of chronic kidney disease who developed thrombocytopenia following treatment with linezolid. Our purpose in highlighting these cases is to increase the clinical awareness concerning this side effect of linezolid. While it is well known that thrombocytopenia may develop during linezolid treatment, it is relatively unknown that patients with renal dysfunction have an increased risk for the development of thrombocytopenia compared to patients without renal dysfunction. [Cukurova Med J 2016; 41(4.000: 808-810

  20. An Intrinsic Pattern of Reduced Susceptibility to Fluoroquinolones in Pediatric Isolates of Streptococcus pyogenes

    Science.gov (United States)

    Yan, S. Steve; Schreckenberger, Paul C.; Zheng, Xiaotian; Nelson, Nancy A.; Harrington, Susan M.; Tjhio, Joyce; Fedorko, Daniel P.

    2008-01-01

    A total of 116 clinical isolates collected in 2003 from a tertiary pediatric hospital and a primary pediatric department in Chicago, Illinois were screened for reduced susceptibility to selected fluoroquinolones by disc diffusion. Correlation between reduced susceptibility and point mutations in the quinolone resistance-determining region of parC and gyrA genes were evaluated, and point mutations were compared with other reports of isolates derived from adult or mixed patient populations. 9% of isolates had reduced susceptibility to one or more of these fluoroquinolones by Etest: ciprofloxacin, levofloxacin, moxifloxacin. A single point mutation (Ser-79) in parC seemed responsible for the reduced susceptibility. Resistant S. pyogenes isolates were compared using M/emm type, RepPCR, and pulsed-field gel electrophoresis (PFGE). RepPCR provided no more separation of strains than M/emm typing and PFGE results with SgrA1 were more discriminatory than with SmaI. The majority of these isolates were M/emm type 6. PFGE analysis using SgrA1 demonstrated 2 different resistant strains among the M/emm type 6 isolates. The findings suggest that a population of S. pyogenes with an intrinsic reduced susceptibility to fluoroquinolones exists in pediatric clinical isolates. Monitoring of amino acid changes in both parC and gyrA will assist in the prediction of emergence of high level fluoroquinolone resistance. PMID:18554840

  1. Efficacy of Linezolid and Fosfomycin in Catheter-Related Biofilm Infection Caused by Methicillin-Resistant Staphylococcus aureus

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    Dong Chai

    2016-01-01

    Full Text Available As long-standing clinical problems, catheter-related infections and other chronic biofilm infections are more difficult to treat due to the high antibiotic resistance of biofilm. Therefore, new treatments are needed for more effective bacteria clearance. In this study, we evaluated the antibacterial activities of several common antibiotics alone and their combinations against biofilm-embedded methicillin-resistant staphylococcus aureus (MRSA infections, both in vitro and in vivo. In brief, fosfomycin, levofloxacin, and rifampin alone or in combination with linezolid were tested in vitro against planktonic and biofilm-embedded MRSA infection in three MRSA stains. The synergistic effects between linezolid and the other three antibiotics were assessed by fractional inhibitory concentration index (FICI and time-kill curves, where the combination of linezolid plus fosfomycin showed the best synergistic effect in all strains. For further evaluation in vivo, we applied the combination of linezolid and fosfomycin in a catheter-related biofilm rat model and found that viable bacteria counts in biofilm were significantly reduced after treatment (P<0.05. In summary, we have shown here that the combination of linezolid and fosfomycin treatment had improved therapeutic effects on biofilm-embedded MRSA infection both in vitro and in vivo, which provided important basis for new clinical therapy development.

  2. In vitro antimicrobial activity of linezolid tested against vancomycin-resistant enterococci isolated in Brazilian hospitals

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    Reis Adriana O.

    2001-01-01

    Full Text Available The emergence of vancomycin-resistant enterococci (VRE has been described recently in Brazil. This is in contrast to the USA and Europe, where the VRE appeared in the late 1980s. The progressive increase in VRE isolation poses important problems in the antimicrobial therapy of nosocomial infections. Treatment options and effective antimicrobial agents for VRE are often limited and the possibility of transfer of vancomycin genes to other Gram-positive microorganisms continues. In the search for antimicrobial agents for multiresistant Gram-positive cocci, compounds such as linezolid and quinupristin/dalfopristin have been evaluated. The present study was conducted to evaluate the in vitro activity of the oxazolidinone linezolid and 10 other antimicrobial agents, including quinupristin-dalfopristin, against multiresistant enterococci isolated in Brazilian hospitals. Thirty-three vancomycin resistant isolates (17 Enterococcus faecium and 16 E. faecalis, were analyzed. Strains were isolated from patients at São Paulo Hospital, Oswaldo Cruz Hospital, Hospital do Servidor Público Estadual, Santa Marcelina Hospital, Santa Casa de Misericórdia de São Paulo, and Hospital de Clínicas do Paraná. The samples were tested by a broth microdilution method following the National Committee for Clinical Laboratory Standards (NCCLS recommendations. All isolates were molecular typed using pulsed-field gel electrophoresis (PFGE. Linezolid was the most active compound against these multiresistant enterococci, showing 100% inhibition at the susceptible breakpoints. Quinupristin/dalfopristin and teicoplanin showed poor activity against both species. The molecular typing results suggest that there has been interhospital spread of vancomycin resistant E. faecium and E. faecalis among Brazilian hospitals. The results of this study indicate that linezolid is an appropriate therapeutic option for the treatment of vancomycin-resistant enterococci infections in Brazil.

  3. In vitro antimicrobial activity of linezolid tested against vancomycin-resistant enterococci isolated in Brazilian hospitals

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    Adriana O. Reis

    Full Text Available The emergence of vancomycin-resistant enterococci (VRE has been described recently in Brazil. This is in contrast to the USA and Europe, where the VRE appeared in the late 1980s. The progressive increase in VRE isolation poses important problems in the antimicrobial therapy of nosocomial infections. Treatment options and effective antimicrobial agents for VRE are often limited and the possibility of transfer of vancomycin genes to other Gram-positive microorganisms continues. In the search for antimicrobial agents for multiresistant Gram-positive cocci, compounds such as linezolid and quinupristin/dalfopristin have been evaluated. The present study was conducted to evaluate the in vitro activity of the oxazolidinone linezolid and 10 other antimicrobial agents, including quinupristin-dalfopristin, against multiresistant enterococci isolated in Brazilian hospitals. Thirty-three vancomycin resistant isolates (17 Enterococcus faecium and 16 E. faecalis, were analyzed. Strains were isolated from patients at São Paulo Hospital, Oswaldo Cruz Hospital, Hospital do Servidor Público Estadual, Santa Marcelina Hospital, Santa Casa de Misericórdia de São Paulo, and Hospital de Clínicas do Paraná. The samples were tested by a broth microdilution method following the National Committee for Clinical Laboratory Standards (NCCLS recommendations. All isolates were molecular typed using pulsed-field gel electrophoresis (PFGE. Linezolid was the most active compound against these multiresistant enterococci, showing 100% inhibition at the susceptible breakpoints. Quinupristin/dalfopristin and teicoplanin showed poor activity against both species. The molecular typing results suggest that there has been interhospital spread of vancomycin resistant E. faecium and E. faecalis among Brazilian hospitals. The results of this study indicate that linezolid is an appropriate therapeutic option for the treatment of vancomycin-resistant enterococci infections in Brazil.

  4. Activities of the oxazolidinones linezolid and eperezolid in experimental intra-abdominal abscess due to Enterococcus faecalis or vancomycin-resistant Enterococcus faecium.

    Science.gov (United States)

    Schülin, T; Thauvin-Eliopoulos, C; Moellering, R C; Eliopoulos, G M

    1999-12-01

    The in vivo effectiveness of oxazolidinones eperezolid (U-100592) and linezolid (U-100766) against one strain each of Enterococcus faecalis and vancomycin-resistant Enterococcus faecium was examined in a rat model of intra-abdominal abscess. MICs of both drugs were 2 microg/ml for each strain. At doses of 25 mg/kg of body weight twice daily intravenously or orally, linezolid produced small but statistically significant reductions in abscess bacterial density for E. faecalis. The reduction in viable cells observed would not likely be clinically relevant. Eperezolid was ineffective at this dose. At a dosage of 100 mg/kg/day, linezolid treatment led to an approximately 100-fold reduction in viable cells per gram of abscess. Against E. faecium infections, intravenous eperezolid and oral linezolid were effective, reducing densities approximately 2 log(10) CFU/g. Both oxazolidinones demonstrated activity against enterococci in this model. However, results were modest with the dosing regimens employed.

  5. Reduced susceptibility to praziquantel among naturally occurring Kenyan isolates of Schistosoma mansoni.

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    Sandra D Melman

    2009-08-01

    Full Text Available The near exclusive use of praziquantel (PZQ for treatment of human schistosomiasis has raised concerns about the possible emergence of drug-resistant schistosomes.We measured susceptibility to PZQ of isolates of Schistosoma mansoni obtained from patients from Kisumu, Kenya continuously exposed to infection as a consequence of their occupations as car washers or sand harvesters. We used a an in vitro assay with miracidia, b an in vivo assay targeting adult worms in mice and c an in vitro assay targeting adult schistosomes perfused from mice. In the miracidia assay, in which miracidia from human patients were exposed to PZQ in vitro, reduced susceptibility was associated with previous treatment of the patient with PZQ. One isolate ("KCW" that was less susceptible to PZQ and had been derived from a patient who had never fully cured despite multiple treatments was studied further. In an in vivo assay of adult worms, the KCW isolate was significantly less susceptible to PZQ than two other isolates from natural infections in Kenya and two lab-reared strains of S. mansoni. The in vitro adult assay, based on measuring length changes of adults following exposure to and recovery from PZQ, confirmed that the KCW isolate was less susceptible to PZQ than the other isolates tested. A sub-isolate of KCW maintained separately and tested after three years was susceptible to PZQ, indicative that the trait of reduced sensitivity could be lost if selection was not maintained.Isolates of S. mansoni from some patients in Kisumu have lower susceptibility to PZQ, including one from a patient who was never fully cured after repeated rounds of treatment administered over several years. As use of PZQ continues, continued selection for worms with diminished susceptibility is possible, and the probability of emergence of resistance will increase as large reservoirs of untreated worms diminish. The potential for rapid emergence of resistance should be an important

  6. Ribosomal protein L3 mutations are associated with cfr-mediated linezolid resistance in clinical isolates of Staphylococcus cohnii.

    Science.gov (United States)

    Xu, Hongtao; Tian, Rui; Li, Yanming; Chen, Dongke; Liu, Yalin; Hu, Yunjian; Xiao, Fei

    2015-06-01

    From June, 2012 to November, 2013 five linezolid-resistant Staphylococcus cohnii isolates were identified in our hospital in Beijing, China. The investigation of the resistance mechanisms confirmed that the cfr-carrying plasmids were the main cause of linezolid resistance in those clinical isolates. Moreover, all the five isolates had ribosomal protein L3 mutations, which had different coordinate effect on cfr-mediated linezolid resistance directly through the substitution of serine 158 by phenylalanine or tyrosine in L3 protein. In this study, two types of plasmids (p432, p438) (Accession No. KM114207) were found, which share high sequence identity with previously reported cfr-carrying pRM01 and pMHZ plasmids originated from northern and southern China, showing wide regional dissemination in China. The stability of linezolid resistance was studied by passaging single colonies serially on antibiotic-free blood medium, which showed that the susceptible derivatives emerged until the passages 39-42 with the elimination of cfr-carrying plasmid. Thus the high stability of this plasmid may pose a risk for the transmission among patients or even cause an outbreak in clinical settings.

  7. Mechanism of Reduced Susceptibility to Fosfomycin in Escherichia coli Clinical Isolates

    Science.gov (United States)

    Ohkoshi, Yasuo; Sato, Toyotaka; Suzuki, Yuuki; Yamamoto, Soh; Shiraishi, Tsukasa; Ogasawara, Noriko

    2017-01-01

    In recent years, multidrug resistance of Escherichia coli has become a serious problem. However, resistance to fosfomycin (FOM) has been low. We screened E. coli clinical isolates with reduced susceptibility to FOM and characterized molecular mechanisms of resistance and reduced susceptibility of these strains. Ten strains showing reduced FOM susceptibility (MIC ≥ 8 μg/mL) in 211 clinical isolates were found and examined. Acquisition of genes encoding FOM-modifying enzyme genes (fos genes) and mutations in murA that underlie high resistance to FOM were not observed. We examined ability of FOM incorporation via glucose-6-phosphate (G6P) transporter and sn-glycerol-3-phosphate transporter. In ten strains, nine showed lack of growth on M9 minimum salt agar supplemented with G6P. Eight of the ten strains showed fluctuated induction by G6P of uhpT that encodes G6P transporter expression. Nucleotide sequences of the uhpT, uhpA, glpT, ptsI, and cyaA shared several deletions and amino acid mutations in the nine strains with lack of growth on G6P-supplemented M9 agar. In conclusion, reduction of uhpT function is largely responsible for the reduced sensitivity to FOM in clinical isolates that have not acquired FOM-modifying genes or mutations in murA. However, there are a few strains whose mechanisms of reduced susceptibility to FOM are still unclear. PMID:28197413

  8. Mechanism of Reduced Susceptibility to Fosfomycin in Escherichia coli Clinical Isolates

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    Yasuo Ohkoshi

    2017-01-01

    Full Text Available In recent years, multidrug resistance of Escherichia coli has become a serious problem. However, resistance to fosfomycin (FOM has been low. We screened E. coli clinical isolates with reduced susceptibility to FOM and characterized molecular mechanisms of resistance and reduced susceptibility of these strains. Ten strains showing reduced FOM susceptibility (MIC ≥ 8 μg/mL in 211 clinical isolates were found and examined. Acquisition of genes encoding FOM-modifying enzyme genes (fos genes and mutations in murA that underlie high resistance to FOM were not observed. We examined ability of FOM incorporation via glucose-6-phosphate (G6P transporter and sn-glycerol-3-phosphate transporter. In ten strains, nine showed lack of growth on M9 minimum salt agar supplemented with G6P. Eight of the ten strains showed fluctuated induction by G6P of uhpT that encodes G6P transporter expression. Nucleotide sequences of the uhpT, uhpA, glpT, ptsI, and cyaA shared several deletions and amino acid mutations in the nine strains with lack of growth on G6P-supplemented M9 agar. In conclusion, reduction of uhpT function is largely responsible for the reduced sensitivity to FOM in clinical isolates that have not acquired FOM-modifying genes or mutations in murA. However, there are a few strains whose mechanisms of reduced susceptibility to FOM are still unclear.

  9. Mechanism of Reduced Susceptibility to Fosfomycin in Escherichia coli Clinical Isolates.

    Science.gov (United States)

    Ohkoshi, Yasuo; Sato, Toyotaka; Suzuki, Yuuki; Yamamoto, Soh; Shiraishi, Tsukasa; Ogasawara, Noriko; Yokota, Shin-Ichi

    2017-01-01

    In recent years, multidrug resistance of Escherichia coli has become a serious problem. However, resistance to fosfomycin (FOM) has been low. We screened E. coli clinical isolates with reduced susceptibility to FOM and characterized molecular mechanisms of resistance and reduced susceptibility of these strains. Ten strains showing reduced FOM susceptibility (MIC ≥ 8 μg/mL) in 211 clinical isolates were found and examined. Acquisition of genes encoding FOM-modifying enzyme genes (fos genes) and mutations in murA that underlie high resistance to FOM were not observed. We examined ability of FOM incorporation via glucose-6-phosphate (G6P) transporter and sn-glycerol-3-phosphate transporter. In ten strains, nine showed lack of growth on M9 minimum salt agar supplemented with G6P. Eight of the ten strains showed fluctuated induction by G6P of uhpT that encodes G6P transporter expression. Nucleotide sequences of the uhpT, uhpA, glpT, ptsI, and cyaA shared several deletions and amino acid mutations in the nine strains with lack of growth on G6P-supplemented M9 agar. In conclusion, reduction of uhpT function is largely responsible for the reduced sensitivity to FOM in clinical isolates that have not acquired FOM-modifying genes or mutations in murA. However, there are a few strains whose mechanisms of reduced susceptibility to FOM are still unclear.

  10. Linezolid desensitization for a patient with multiple medication hypersensitivity reactions.

    Science.gov (United States)

    Bagwell, Autumn D; Stollings, Joanna L; White, Katie D; Fadugba, Olajumoke O; Choi, Jane J

    2013-01-01

    To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions. A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol. Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols. Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.

  11. Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility.

    Science.gov (United States)

    Chandra, Ramesh; Francis, T Chase; Nam, Hyungwoo; Riggs, Lace M; Engeln, Michel; Rudzinskas, Sarah; Konkalmatt, Prasad; Russo, Scott J; Turecki, Gustavo; Iniguez, Sergio D; Lobo, Mary Kay

    2017-07-05

    Previous research demonstrates that Slc6a15, a neutral amino acid transporter, is associated with depression susceptibility. However, no study examined Slc6a15 in the ventral striatum [nucleus accumbens (NAc)] in depression. Given our previous characterization of Slc6a15 as a striatal dopamine receptor 2 (D2)-neuron-enriched gene, we examined the role of Slc6a15 in NAc D2-neurons in mediating susceptibility to stress in male mice. First, we showed that Slc6a15 mRNA was reduced in NAc of mice susceptible to chronic social defeat stress (CSDS), a paradigm that produces behavioral and molecular adaptations that resemble clinical depression. Consistent with our preclinical data, we observed Slc6a15 mRNA reduction in NAc of individuals with major depressive disorder (MDD). The Slc6a15 reduction in NAc occurred selectively in D2-neurons. Next, we used Cre-inducible viruses combined with D2-Cre mice to reduce or overexpress Slc6a15 in NAc D2-neurons. Slc6a15 reduction in D2-neurons caused enhanced susceptibility to a subthreshold social defeat stress (SSDS) as observed by reduced social interaction, while a reduction in social interaction following CSDS was not observed when Slc6a15 expression in D2-neurons was restored. Finally, since both D2-medium spiny neurons (MSNs) and D2-expressing choline acetyltransferase (ChAT) interneurons express Slc6a15, we examined Slc6a15 protein in these interneurons after CSDS. Slc6a15 protein was unaltered in ChAT interneurons. Consistent with this, reducing Slc5a15 selectively in NAc D2-MSNs, using A2A-Cre mice that express Cre selectively in D2-MSNs, caused enhanced susceptibility to SSDS. Collectively, our data demonstrate that reduced Slc6a15 in NAc occurs in MDD individuals and that Slc6a15 reduction in NAc D2-neurons underlies stress susceptibility.SIGNIFICANCE STATEMENT Our study demonstrates a role for reduced Slc6a15, a neutral amino acid transporter, in nucleus accumbens (NAc) in depression and stress susceptibility. The

  12. A severe infective endocarditis successfully treated with linezolid

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    Graziano Antonio Minafra

    2010-03-01

    Full Text Available Despite significant improvements in surgical and medical therapy, prosthetic valve endocarditis (PVE is a diagnostic and therapeutic challenge and is often associated with a severe prognosis. We report a case of a 59-year-old woman, with  PVE and bacterial endocarditis (Streptococcus bovis successfully treated with linezolid. Linezolid is a bacteriostatic oxazolidinone antibiotic that has been proven to be effective for the treatment of patients with pneumonia, skin and soft tissue infections, and infections due to Gram-positive cocci. Linezolid is not yet recognised as a standard therapy for infective endocarditis, but its use becomes a necessity when infection is due to multidrug-resistant microorganisms.

  13. Endurance Exercise Training Reduces Cardiac Sodium/Calcium Exchanger Expression in Animals Susceptible to Ventricular Fibrillation

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    Monica eKukielka

    2011-02-01

    Full Text Available Aim: Increased sodium/calcium exchanger activity (NCX1, an important regulator of cardiomyocyte cystolic calcium may provoke arrhythmias. Exercise training can decrease NCX1 expression in animals with heart failure improving cytosolic calcium regulation, and could thereby reduce the risk for ventricular fibrillation (VF. Methods: To test this hypothesis, a 2-min coronary occlusion was made during the last min. of exercise in dogs with healed myocardial infarctions; 23 had VF (S, susceptible and 13 did not (R, resistant. The animals were randomly assigned to either 10-wk exercise training (progressively increasing treadmill running (S n = 9; R n = 8 or 10-wk sedentary (S n = 14; R n = 5 groups. At the end of the 10-wk period, the exercise + ischemia test provoked VF in sedentary but not trained susceptible dogs. On a subsequent day, cardiac tissue was harvested and NCX1 protein expression was determined by Western blot. Results: In the sedentary group, NCX1 expression was significantly (ANOVA, P<0.05 higher in susceptible compared to resistant dogs. In contrast, NCX1 levels were similar in the exercise trained resistant and susceptible animals. Conclusion: These data suggest that exercise training can restore a more normal NCX1 level in dogs susceptible to ventricular fibrillation, improving cystolic calcium regulation and could thereby reduce the risk for sudden death following myocardial infarction.

  14. Sarcandra glabra Extract Reduces the Susceptibility and Severity of Influenza in Restraint-Stressed Mice

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    Hui-Juan Cao

    2012-01-01

    Full Text Available Sarcandra glabra, as a type of “antipyretic-detoxicate drugs”, has always been widely used in traditional Chinese medicine (TCM. The Sarcandra glabra extract (SGE is applied frequently as anti-inflammatory and anti-infectious drug in folk medicine. However, relative experiment data supporting this effective clinical consequence was limited. In order to mimic the physiological conditions of the susceptible population, we employed restraint stress mouse model to investigate the effect of SGE against influenza. Mice were infected with influenza virus three days after restraint, while SGE was orally administrated for 10 consecutive days. Body weight, morbidity, and mortality were recorded daily. Histopathologic changes, susceptibility genes expressions and inflammatory markers in lungs were determined. Our results showed that restraint stress significantly increased susceptibility and severity of influenza virus. However, oral administration of SGE could reduce morbidity, mortality and significantly prolonged survival time. The results further showed that SGE had a crucial effect on improving susceptibility markers levels to recover the balance of host defense system and inhibiting inflammatory cytokines levels through down-regulation of NF-κB protein expression to ameliorate the lung injury. These data showed that SGE reduced the susceptibility and severity of influenza.

  15. Mechanisms of Reduced Susceptibility to Ciprofloxacin in Escherichia coli Isolates from Canadian Hospitals

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    Patricia J Baudry-Simner

    2012-01-01

    Full Text Available OBJECTIVE: To determine whether plasmid-mediated quinolone resistance (PMQR determinants play a role in the increasing resistance to fluoroquinolones among Escherichia coli isolates in Canadian hospitals, and to determine the mechanisms of reduced susceptibility to ciprofloxacin in a recent collection of 190 clinical E coli isolates.

  16. Comparison of human and soil Candida tropicalis isolates with reduced susceptibility to fluconazole.

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    Yun-Liang Yang

    Full Text Available Infections caused by treatment-resistant non-albicans Candida species, such as C. tropicalis, has increased, which is an emerging challenge in the management of fungal infections. Genetically related diploid sequence type (DST strains of C. tropicalis exhibiting reduced susceptibility to fluconazole circulated widely in Taiwan. To identify the potential source of these wildly distributed DST strains, we investigated the possibility of the presence in soil of such C. tropicalis strains by pulsed field gel electrophoresis (PFGE and DST typing methods. A total of 56 C. tropicalis isolates were recovered from 26 out of 477 soil samples. Among the 18 isolates with reduced susceptibility to fluconazole, 9 belonged to DST149 and 3 belonged to DST140. Both DSTs have been recovered from our previous studies on clinical isolates from the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY program. Furthermore, these isolates were more resistant to agricultural azoles. We have found genetically related C. tropicalis exhibiting reduced susceptibility to fluconazole from the human hosts and environmental samples. Therefore, to prevent patients from acquiring C. tropicalis with reduced susceptibility to azoles, prudent use of azoles in both clinical and agricultural settings is advocated.

  17. Vancomycin, teicoplanin, daptomycin, and linezolid MIC creep in methicillin-resistant Staphylococcus aureus is associated with clonality

    Science.gov (United States)

    Hsieh, Yu-Chia; Lin, Yu-Chun; Huang, Yhu-Chering

    2016-01-01

    Abstract The purpose of this study is to evaluate the susceptibility trend of vancomycin, teicoplanin, daptomycin, and linezolid against methicillin-resistant Staphylococcus aureus (MRSA) blood isolates of different clones over an 11-year period. From 2000 to 2010, all bloodstream MRSA isolates from Chang Gung Memorial Hospital in Taiwan were prospectively collected. Three periods, namely 2000 to 2001, 2004 to 2005, and 2010, were included and 124 MRSA isolates were selected from each period. Minimum inhibitory concentrations (MICs) were determined by E-test. All the isolates were molecularly characterized. MRSA molecular epidemiology evolved from 1 predominant pulsotype (type A) to 5 major pulsotypes of 3 clonal complexes (CC). Vancomycin, teicoplanin, and daptomycin MICs creep were observed, particularly for pulsotype A-CC 239-staphylococcal cassette chromosome mec (SCCmec) III though its prevalence dramatically decreased since 2004 to 2005. Throughout the study period, the overall vancomycin modal MIC was stable at 1.5 mg/L, but teicoplanin and linezolid modal MIC increased to 2 and 2 mg/L, respectively. Isolates with teicoplanin and linezolid ≧ 2 ug/mL belonged to multiple clones. Pulsotype F-ST5-SCCmec II with a high rate of teicoplanin MIC ≧ 2 ug/mL continued clonal spread. Teicoplanin MIC had a high correlation with linezolid MIC. Molecular epidemiology MRSA bloodstream isolates in northern Taiwan evolved from 2000 throughout 2010, which was subsequently associated with the changing distribution of antibiotic MICs. While vancomycin MIC level remained unchanged, teicoplanin, daptomycin, and linezolid MIC levels increased. The impact of these changes on clinical treatment response deserves further investigations. PMID:27741120

  18. Linezolid resistant Staphylococcus haemolyticus:First case report from India

    Institute of Scientific and Technical Information of China (English)

    Varsha Gupta; Shivani Garg; Ruby Jain; Sudhir Garg; Jagdish Chander

    2012-01-01

    Linezolid is being increasingly used in the treatment of infections with gram-positive organisms especially methicillin resistant Staphylococcal isolates. Though resistance to this antimicrobial is emerging but it is extremely rare. Here we document first case of linezolid resistant Staphylococcus haemolyticus (S.haemolyticus) from India. This organism was isolated from pus oozing from a postsurgical site in 61 year old male hailing from an adjoining state of Haryana.

  19. Linezolid som behandling af infektiøs endokarditis

    DEFF Research Database (Denmark)

    Lauridsen, Trine Kiilerich; Arpi, Magnus; Bruun, Niels Eske

    2010-01-01

    In Denmark enterococci causes 15 to 20% of all endocarditis (IE) cases. The development of multi-resistant bacterial strains has increased the need for new antibiotics. Linezolid is an alternative to conventional treatment of infections with gram positive cocci. In this case report linezolid was ...... was used to treat IE in a patient, who was allergic to penicillin and where conventional treatment caused development of acute renal failure. No side effects were observed and the patient responded well to the treatment....

  20. Increasing pathomorphism of pulmonary tuberculosis: an observational study of slow clinical, microbiological and imaging response of lung tuberculosis to specific treatment. Which role for linezolid?

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    Roberto Manfredi

    Full Text Available During recent years, a progressive emerging of tuberculosis occurred, related to the overall increased age of general population, primary and secondary (iatrogenic immunodeficiencies, the availability of invasive procedures, surgical interventions and intensive care supports, bone marrow and solid organ transplantation, and especially the recent immigration flows of people often coming from areas endemic for tuberculosis, and living with evident social-economical disadvantages, and with a reduced access to health care facilities. Since January 2006, at our reference centre we followed 81 consecutive cases of pulmonary tuberculosis, with 65 of them which remained evaluable for the absence of extrapulmonary complications, and a continuative and effective clinical and therapeutic follow-up. The majority of episodes of evaluable pulmonary tuberculosis (49 cases out of 65: 75,4% occurred in patients who immigrated from developing countries. In two patients multiresistant (MDR Mycobacterium tuberculosis strains were found, while two more subjects (both immigrated from Eastern Europe suffered from a disease due to extremely resistant (XDR M. tuberculosis strains. Although enforcing all possible measures to increase patients' adherence to treatment (empowerment, delivery of oral drugs under direct control, use of i.v. formulation whenever possible, over 72% of evaluable patients had a very slow clinical, microbiological, and imaging ameliorement (1-6 months, with persistance of sputum and/or bronchoalveolar lavage (BAL fluid positive for M.tuberculosis microscopy and/or culture for over 1-4 months (mean 9.2±3.2 weeks, during an apparently adequate treatment. When excluding patients suffering from XDR and MDR tuberculosis, in four subjects we observed that off-label linezolid adjunct together with at least three drugs with residual activity against tuberculosis, led to a significantly more rapid clinical-radiological improvement and negative

  1. Molecular characterization of clinical Streptococcus pneumoniae isolates with reduced susceptibility to fluoroquinolones emerging in Italy.

    Science.gov (United States)

    Montanari, Maria Pia; Tili, Emily; Cochetti, Ileana; Mingoia, Marina; Manzin, Aldo; Varaldo, Pietro Emanuele

    2004-01-01

    Fifteen Streptococcus pneumoniae clinical isolates with reduced fluoroquinolone susceptibility (defined as a ciprofloxacin MIC of > or = 4 microg/ml), all collected in Italy in 2000-2003, were typed and subjected to extensive molecular characterization to define the contribution of drug target alterations and efflux mechanisms to their resistance. Serotyping and pulsed-field gel electrophoresis analysis indicated substantial genetic unrelatedness among the 15 isolates, suggesting that the new resistance traits arise in multiple indigenous strains rather than through clonal dissemination. Sequencing of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE demonstrated that point mutations producing single amino acid changes were more frequent in topoisomerase IV (parC mutations in 14 isolates and parE mutations in 13) than in DNA gyrase subunits (gyrA mutations in 7 isolates and no gyrB mutations observed). No isolate displayed a quinolone efflux system susceptible to carbonyl cyanide m-chlorophenylhydrazone; conversely, four-fold or greater MIC reductions in the presence of reserpine were observed in all 15 isolates with ethidium bromide, in 13 with ulifloxacin, in 9 with ciprofloxacin, in 5 with norfloxacin, and in none with five other fluoroquinolones. The effect of efflux pump activity on the level and profile of fluoroquinolone resistance in our strains was minor compared with that of target site modifications. DNA mutations and/or efflux systems other than those established so far might contribute to the fluoroquinolone resistance expressed by our strains. Susceptibility profiles to nonquinolone class antibiotics and resistance-associated phenotypic and genotypic characteristics were also determined and correlated with fluoroquinolone resistance. A unique penicillin-binding protein profile was observed in all five penicillin-resistant isolates, whereas the same PBP profile as S. pneumoniae R6 was exhibited by all six penicillin-susceptible

  2. Identification of hepatitis C virus genotype 2a replicon variants with reduced susceptibility to ribavirin.

    Science.gov (United States)

    Hmwe, Su Su; Aizaki, Hideki; Date, Tomoko; Murakami, Kyoko; Ishii, Koji; Miyamura, Tatsuo; Koike, Kazuhiko; Wakita, Takaji; Suzuki, Tetsuro

    2010-03-01

    Ribavirin (RBV), a nucleoside analogue, is used in the treatment of hepatitis C virus (HCV) infection in combination with interferons. However, potential mechanisms of RBV resistance during HCV replication remain poorly understood. Serial passage of cells harboring HCV genotype 2a replicon in the presence of RBV resulted in the reduced susceptibility of the replicon to RBV. Transfection of fresh cells with RNA from RBV-resistant replicon cells demonstrated that the RBV resistance observed is largely replicon-derived. Four major amino acid substitutions: T1134S in NS3, P1969S in NS4B, V2405A in NS5A, and Y2471H in NS5B region, were identified. Site-directed mutagenesis of these mutations into the replicon indicated that Y2471H plays a role in the reduced susceptibility to RBV and leads to decrease in replication fitness. The results, in addition to analysis of sequence database, suggest that HCV variants with reduced susceptibility to RBV identified are preferential to genotype 2a.

  3. Linezolid minimum inhibitory concentration (MIC) creep in methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates at a single Japanese center.

    Science.gov (United States)

    Miyazaki, Motoyasu; Nagata, Nobuhiko; Miyazaki, Hiroyuki; Matsuo, Koichi; Takata, Tohru; Tanihara, Shinichi; Kamimura, Hidetoshi

    2014-01-01

    The aim of this study was to evaluate whether linezolid minimum inhibitory concentration (MIC) creep occurred in Staphylococcus aureus clinical isolates, including methicillin-resistant S. aureus (MRSA), over a recent 5-year period at a single Japanese center. A total of 453 MRSA and 195 methicillin-susceptible S. aureus (MSSA) isolates recovered from inpatients from April 1, 2008 to March 31, 2013 were analyzed. The MIC of linezolid was determined by automated Vitek-2 system. The modal MIC, MIC range, MIC50 and MIC90 (MICs required to inhibit the growth of 50% and 90% of organisms, respectively), geometric mean MIC and percentages of susceptible and resistant isolates were evaluated for each fiscal year. None of the S. aureus isolates were resistant to linezolid. Isolates with an MIC of >1 µg/mL were more common in the MSSA samples than in the MRSA samples (91.3% versus 38.2%, pMRSA isolates (p=0.006, r(2)=0.945 according to a linear regression analysis) over the 5-year period; however, no increase was observed in the MSSA isolates. The frequency of MRSA isolates with an MIC of 1 µg/mL decreased (from 76.3% in 2008 to 35.4% in 2012) and the isolates with MICs of >1 µg/mL increased over time (from 23.7% in 2008 to 64.6% in 2012). This report demonstrates the occurrence of linezolid MIC creep, as determined using the geometric mean MIC, in MRSA clinical isolates at a single Japanese center.

  4. High-level aminoglycoside resistance and reduced susceptibility to vancomycin in nosocomial enterococci

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    Luna Adhikari

    2010-01-01

    Full Text Available Objectives: The objectives of the present study were to identify the species of enterococci isolated from nosocomial infections and to determine the antibiotic susceptibility pattern with reference to high-level aminoglycosides and vancomycin. Materials and Methods: Enterococci were isolated from various clinical samples collected from patients after 72 hours of hospitalization. Various species of Enterococcus were identified by standard methods. High-level aminoglycoside resistance and vancomycin susceptibility in enterococci were detected by disk-diffusion and agar-screen methods. Results: One hundred eighty enterococcal strains were isolated from various clinical samples. Various species of Enterococcus - Enterococcus fecalis 130 (72.22%, Enterococcus casseliflavus 24 (13.33%, Enterococcus fecium 17 (9.44%, Enterococcus durans 7 (3.89% and Enterococcus dispar 2 (1.11% - were isolated. The highest resistance to aminoglycoside was observed among E. fecium, followed by E. durans, E. fecalis and E. casseliflavus, both by disk-diffusion and agar-screen methods. The high-level aminoglycoside resistance (HLAR was significantly (P<0.05 higher in E. fecium by agar-screen method. All enterococci showed minimum inhibitory concentration (MIC of ≤8 ΅g/mL to vancomycin. Sixteen (12.31% E. fecalis and 3 (12.5% E. fecium strains were intermediately resistant to vancomycin (MIC= 8 ΅g/mL, whereas other strains were susceptible to vancomycin. Conclusion: The occurrence of high-level aminoglycoside resistance in enterococcal isolates in our setup was high. Even though none of the enterococcal strains showed resistance to vancomycin, yet reduced susceptibility to vancomycin was noticed in our study. This would require routine testing of enterococcal isolates for HLAR and vancomycin susceptibility. Agar-screen method was found to be superior to disk-diffusion method in detecting resistant strains to aminoglycosides and vancomycin.

  5. Activity of daptomycin or linezolid in combination with rifampin or gentamicin against biofilm-forming Enterococcus faecalis or E. faecium in an in vitro pharmacodynamic model using simulated endocardial vegetations and an in vivo survival assay using Galleria mellonella larvae.

    Science.gov (United States)

    Luther, Megan K; Arvanitis, Marios; Mylonakis, Eleftherios; LaPlante, Kerry L

    2014-08-01

    Enterococci are the third most frequent cause of infective endocarditis. A high-inoculum stationary-phase in vitro pharmacodynamic model with simulated endocardial vegetations was used to simulate the human pharmacokinetics of daptomycin at 6 or 10 mg/kg of body weight/day or linezolid at 600 mg every 12 h (q12h), alone or in combination with gentamicin at 1.3 mg/kg q12h or rifampin at 300 mg q8h or 900 mg q24h. Biofilm-forming, vancomycin-susceptible Enterococcus faecalis and vancomycin-resistant Enterococcus faecium (vancomycin-resistant enterococcus [VRE]) strains were tested. At 24, 48, and 72 h, all daptomycin-containing regimens demonstrated significantly more activity (decline in CFU/g) than any linezolid-containing regimen against biofilm-forming E. faecalis. The addition of gentamicin to daptomycin (at 6 or 10 mg/kg) in the first 24 h significantly improved bactericidal activity. In contrast, the addition of rifampin delayed the bactericidal activity of daptomycin against E. faecalis, and the addition of rifampin antagonized the activities of all regimens against VRE at 24 h. Also, against VRE, the addition of gentamicin to linezolid at 72 h improved activity and was bactericidal. Rifampin significantly antagonized the activity of linezolid against VRE at 72 h. In in vivo Galleria mellonella survival assays, linezolid and daptomycin improved survival. Daptomycin at 10 mg/kg improved survival significantly over that with linezolid against E. faecalis. The addition of gentamicin improved the efficacy of daptomycin against E. faecalis and those of linezolid and daptomycin against VRE. We conclude that in enterococcal infection models, daptomycin has more activity than linezolid alone. Against biofilm-forming E. faecalis, the addition of gentamicin in the first 24 h causes the most rapid decline in CFU/g. Of interest, the addition of rifampin decreased the activity of daptomycin against both E. faecalis and VRE.

  6. Linezolid-resistant mucoid Staphylococcus haemolyticus from a tertiary-care centre in Delhi.

    Science.gov (United States)

    Matlani, M; Shende, T; Bhandari, V; Dawar, R; Sardana, R; Gaind, R

    2016-05-01

    We report an unusual morphological mucoid variant of Staphylococcus haemolyticus associated with linezolid resistance from a patient with sepsis. Linezolid resistance and mucoid character together made this pathogen difficult to treat. To our knowledge this is the first such report.

  7. Estradiol reduces susceptibility of CD4+ T cells and macrophages to HIV-infection.

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    Marta Rodriguez-Garcia

    Full Text Available The magnitude of the HIV epidemic in women requires urgent efforts to find effective preventive methods. Even though sex hormones have been described to influence HIV infection in epidemiological studies and regulate different immune responses that may affect HIV infection, the direct role that female sex hormones play in altering the susceptibility of target cells to HIV-infection is largely unknown. Here we evaluated the direct effect of 17-β-estradiol (E2 and ethinyl estradiol (EE in HIV-infection of CD4(+ T-cells and macrophages. Purified CD4(+ T-cells and monocyte-derived macrophages were generated in vitro from peripheral blood and infected with R5 and X4 viruses. Treatment of CD4(+ T-cells and macrophages with E2 prior to viral challenge reduced their susceptibility to HIV infection in a dose-dependent manner. Addition of E2 2 h after viral challenge however did not result in reduced infection. In contrast, EE reduced infection in macrophages to a lesser extent than E2 and had no effect on CD4(+ T-cell infection. Reduction of HIV-infection induced by E2 in CD4(+ T-cells was not due to CCR5 down-regulation, but was an entry-mediated mechanism since infection with VSV-G pseudotyped HIV was not modified by E2. In macrophages, despite the lack of an effect of E2 on CCR5 expression, E2-treatment reduced viral entry 2 h after challenge and increased MIP-1β secretion. These results demonstrate the direct effect of E2 on susceptibility of HIV-target cells to infection and indicate that inhibition of target cell infection involves cell-entry related mechanisms.

  8. Molecular Characterization of Reduced Susceptibility to Biocides in Clinical Isolates of Acinetobacter baumannii

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    Fei Lin

    2017-09-01

    Full Text Available Active efflux is regarded as a common mechanism for antibiotic and biocide resistance. However, the role of many drug efflux pumps in biocide resistance in Acinetobacter baumannii remains unknown. Using biocide-resistant A. baumannii clinical isolates, we investigated the incidence of 11 known/putative antimicrobial resistance efflux pump genes (adeB, adeG, adeJ, adeT1, adeT2, amvA, abeD, abeM, qacE, qacEΔ1, and aceI and triclosan target gene fabI through PCR and DNA sequencing. Reverse transcriptase quantitative PCR was conducted to assess the correlation between the efflux pump gene expression and the reduced susceptibility to triclosan or chlorhexidine. The A. baumannii isolates displayed high levels of reduced susceptibility to triclosan, chlorhexidine, benzalkonium, hydrogen peroxide, and ethanol. Most tested isolates were resistant to multiple antibiotics. Efflux resistance genes were widely distributed and generally expressed in A. baumannii. Although no clear relation was established between efflux pump gene expression and antibiotic resistance or reduced biocide susceptibility, triclosan non-susceptible isolates displayed relatively increased expression of adeB and adeJ whereas chlorhexidine non-susceptible isolates had increased abeM and fabI gene expression. Increased expression of adeJ and abeM was also demonstrated in multiple antibiotic resistant isolates. Exposure of isolates to subinhibitory concentrations of triclosan or chlorhexidine induced gene expression of adeB, adeG, adeJ and fabI, and adeB, respectively. A point mutation in FabI, Gly95Ser, was observed in only one triclosan-resistant isolate. Multiple sequence types with the major clone complex, CC92, were identified in high level triclosan-resistant isolates. Overall, this study showed the high prevalence of antibiotic and biocide resistance as well as the complexity of intertwined resistance mechanisms in clinical isolates of A. baumannii, which highlights the

  9. Extreme ocean acidification reduces the susceptibility of eastern oyster shells to a polydorid parasite.

    Science.gov (United States)

    Clements, J C; Bourque, D; McLaughlin, J; Stephenson, M; Comeau, L A

    2017-04-21

    Ocean acidification poses a threat to marine organisms. While the physiological and behavioural effects of ocean acidification have received much attention, the effects of acidification on the susceptibility of farmed shellfish to parasitic infections are poorly understood. Here we describe the effects of moderate (pH 7.5) and extreme (pH 7.0) ocean acidification on the susceptibility of Crassostrea virginica shells to infection by a parasitic polydorid, Polydora websteri. Under laboratory conditions, shells were exposed to three pH treatments (7.0, 7.5 and 8.0) for 3- and 5-week periods. Treated shells were subsequently transferred to an oyster aquaculture site (which had recently reported an outbreak of P. websteri) for 50 days to test for effects of pH and exposure time on P. websteri recruitment to oyster shells. Results indicated that pH and exposure time did not affect the length, width or weight of the shells. Interestingly, P. websteri counts were significantly lower under extreme (pH 7.0; ~50% reduction), but not moderate (pH 7.5; ~20% reduction) acidification levels; exposure time had no effect. This study suggests that extreme levels - but not current and projected near-future levels - of acidification (∆pH ~1 unit) can reduce the susceptibility of eastern oyster shells to P. websteri infections. © 2017 John Wiley & Sons Ltd.

  10. Apoplastic Nucleoside Accumulation in Arabidopsis Leads to Reduced Photosynthetic Performance and Increased Susceptibility Against Botrytis cinerea.

    Science.gov (United States)

    Daumann, Manuel; Fischer, Marietta; Niopek-Witz, Sandra; Girke, Christopher; Möhlmann, Torsten

    2015-01-01

    Interactions between plant and pathogen often occur in the extracellular space and especially nucleotides like ATP and NAD have been identified as key players in this scenario. Arabidopsis mutants accumulating nucleosides in the extracellular space were generated and studied with respect to susceptibility against Botrytis cinerea infection and general plant fitness determined as photosynthetic performance. The mutants used are deficient in the main nucleoside uptake system ENT3 and the extracellular nucleoside hydrolase NSH3. When grown on soil but not in hydroponic culture, these plants markedly accumulate adenosine and uridine in leaves. This nucleoside accumulation was accompanied by reduced photosystem II efficiency and altered expression of photosynthesis related genes. Moreover, a higher susceptibility toward Botrytis cinerea infection and a reduced induction of pathogen related genes PR1 and WRKY33 was observed. All these effects did not occur in hydroponically grown plants substantiating a contribution of extracellular nucleosides to these effects. Whether reduced general plant fitness, altered pathogen response capability or more direct interactions with the pathogen are responsible for these observations is discussed.

  11. Apoplastic nucleoside accumulation in Arabidopsis leads to reduced photosynthetic performance and increased susceptibility against Botrytis cinerea

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    Manuel eDaumann

    2015-12-01

    Full Text Available ABSTRACT Interactions between plant and pathogen often occur in the extracellular space and especially nucleotides like ATP and NAD have been identified as key players in this scenario. Arabidopsis mutants accumulating nucleosides in the extracellular space were generated and studied with respect to susceptibility against Botrytis cinerea infection and general plant fitness determined as photosynthetic performance. The mutants used are deficient in the main nucleoside uptake system ENT3 and the extracellular nucleoside hydrolase NSH3. When grown on soil but not in hydroponic culture, these plants markedly accumulate adenosine and uridine in leaves. This nucleoside accumulation was accpmpanied by reduced photosystem II efficiency and altered expression of photosynthesis related genes. Moreover, a higher susceptibility towards Botrytis cinerea infection and a reduced induction of pathogen related genes PR1 and WRKY33 was observed. All these effects did not occur in hydroponically grown plants substantiating a contribution of extracellular nucleosides to these effects. Whether reduced general plant fitness, altered pathogen response capability or more direct interactions with the pathogen are responsible for these observations is discussed.

  12. Linezolid as rescue treatment for left-sided infective endocarditis

    DEFF Research Database (Denmark)

    Lauridsen, Trine Kiilerich; Bruun, Louise E; Rasmussen, R V

    2012-01-01

    The increasing number of resistant bacterial strains in infective endocarditis (IE) emphasizes the need for a constant development of antimicrobials. Linezolid is an oxazolidinone with an effect on Gram-positive cocci. Only a few casuistic reports describe its utilization in the treatment of IE...... linezolid were antibiotic intolerance (n = 13), nephrotoxicity (n = 5), pharmaceutical interactions (n = 1), inadequate clinical response (n = 14), or inadequate microbial response (n = 5). No significant differences in the cure rate (74 % vs. 71 %, p > 0.05), in-hospital mortality (13 % vs. 14 %, p > 0.......05), or post-discharge mortality at 12 months follow-up (26 % vs. 26 %, p > 0.05) were observed. In the current study, we found that linezolid, in general, was well tolerated and associated with the same outcome as in patients with Gram-positive IE treated with other antibiotics....

  13. Nosocomial methicillin-resistant staphylococcus aureus (MRSA pneumonia: linezolid or vancomycin? - comparison of pharmacology and clinical efficacy

    Directory of Open Access Journals (Sweden)

    Pletz Mathias W

    2010-11-01

    Full Text Available Abstract The incidence of nosocomial pneumonia involving methicillin-resistant Staphylococcus aureus strains (MRSA is on the rise worldwide. For years, vancomycin has been used as the drug of choice in the treatment of MRSA infections and was recommended as such by clinical guidelines. There is growing evidence that vancomycin, despite low resistance rates is a suboptimal therapeutic option in critically ill patients, particularly in patients with pneumonia. Disadvantages of vancomycin are i slow bactericide action, ii poor penetration into pulmonary tissue, iii the globally slowly increasing vancomycin MICs ("creep" that result in increased clinical failure despite being susceptible according to defined break points and iv nephrotoxicity. In contrast to other novel antibiotics with MRSA activity, Linezolid is currently approved for the treatment of nosocomial pneumonia in the USA and Europe. Several studies have compared vancomycin with linezolid for nosocomial pneumonia with conflicting results. This review compares both substances regarding pharmacodynamics, resistance, safety and clinical efficacy and discusses preliminary data of the ZEPHyR study. This study compared linezolid versus vancomycin in patients with proven MRSA pneumonia and was the largest trial ever conducted in this population.

  14. Mutations associated with reduced surotomycin susceptibility in Clostridium difficile and Enterococcus species.

    Science.gov (United States)

    Adams, Hannah M; Li, Xiang; Mascio, Carmela; Chesnel, Laurent; Palmer, Kelli L

    2015-07-01

    Clostridium difficile infection (CDI) is an urgent public health concern causing considerable clinical and economic burdens. CDI can be treated with antibiotics, but recurrence of the disease following successful treatment of the initial episode often occurs. Surotomycin is a rapidly bactericidal cyclic lipopeptide antibiotic that is in clinical trials for CDI treatment and that has demonstrated superiority over vancomycin in preventing CDI relapse. Surotomycin is a structural analogue of the membrane-active antibiotic daptomycin. Previously, we utilized in vitro serial passage experiments to derive C. difficile strains with reduced surotomycin susceptibilities. The parent strains used included ATCC 700057 and clinical isolates from the restriction endonuclease analysis (REA) groups BI and K. Serial passage experiments were also performed with vancomycin-resistant and vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis. The goal of this study is to identify mutations associated with reduced surotomycin susceptibility in C. difficile and enterococci. Illumina sequence data generated for the parent strains and serial passage isolates were compared. We identified nonsynonymous mutations in genes coding for cardiolipin synthase in C. difficile ATCC 700057, enoyl-(acyl carrier protein) reductase II (FabK) and cell division protein FtsH2 in C. difficile REA type BI, and a PadR family transcriptional regulator in C. difficile REA type K. Among the 4 enterococcal strain pairs, 20 mutations were identified, and those mutations overlap those associated with daptomycin resistance. These data give insight into the mechanism of action of surotomycin against C. difficile, possible mechanisms for resistance emergence during clinical use, and the potential impacts of surotomycin therapy on intestinal enterococci.

  15. Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures.

    Science.gov (United States)

    Awad, Patricia N; Sanon, Nathalie T; Chattopadhyaya, Bidisha; Carriço, Josianne Nunes; Ouardouz, Mohamed; Gagné, Jonathan; Duss, Sandra; Wolf, Daniele; Desgent, Sébastien; Cancedda, Laura; Carmant, Lionel; Di Cristo, Graziella

    2016-07-01

    Atypical febrile seizures are considered a risk factor for epilepsy onset and cognitive impairments later in life. Patients with temporal lobe epilepsy and a history of atypical febrile seizures often carry a cortical malformation. This association has led to the hypothesis that the presence of a cortical dysplasia exacerbates febrile seizures in infancy, in turn increasing the risk for neurological sequelae. The mechanisms linking these events are currently poorly understood. Potassium-chloride cotransporter KCC2 affects several aspects of neuronal circuit development and function, by modulating GABAergic transmission and excitatory synapse formation. Recent data suggest that KCC2 downregulation contributes to seizure generation in the epileptic adult brain, but its role in the developing brain is still controversial. In a rodent model of atypical febrile seizures, combining a cortical dysplasia and hyperthermia-induced seizures (LHS rats), we found a premature and sustained increase in KCC2 protein levels, accompanied by a negative shift of the reversal potential of GABA. In parallel, we observed a significant reduction in dendritic spine size and mEPSC amplitude in CA1 pyramidal neurons, accompanied by spatial memory deficits. To investigate whether KCC2 premature overexpression plays a role in seizure susceptibility and synaptic alterations, we reduced KCC2 expression selectively in hippocampal pyramidal neurons by in utero electroporation of shRNA. Remarkably, KCC2 shRNA-electroporated LHS rats show reduced hyperthermia-induced seizure susceptibility, while dendritic spine size deficits were rescued. Our findings demonstrate that KCC2 overexpression in a compromised developing brain increases febrile seizure susceptibility and contribute to dendritic spine alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Economic burden of inpatient and outpatient antibiotic treatment for methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections: a comparison of linezolid, vancomycin, and daptomycin

    Directory of Open Access Journals (Sweden)

    Stephens JM

    2013-09-01

    peripherally inserted central catheter line costs, linezolid became slightly more expensive than vancomycin (by $285, but remained less costly than daptomycin (by $2,316. Conclusion: Outpatient costs of managing MRSA cSSTI may be reduced by 30%–50% with oral linezolid compared with vancomycin or daptomycin. Results from this analysis support potential economic benefit and cost savings of using linezolid versus traditional OPAT when total inpatient and outpatient medical costs are evaluated. Keywords: economic model, OPAT, cost

  17. Analysis of gyrA and parC mutations in enterococci from environmental samples with reduced susceptibility to ciprofloxacin

    DEFF Research Database (Denmark)

    Petersen, A.; Jensen, Lars Bogø

    2004-01-01

    The quinolone resistance determining regions of gyrA and parC in four species of enterococci from environmental samples with reduced susceptibility to ciprofloxacin were sequenced. The nucleotide sequence variations of parC could be related to the different enterococcal species. Mutations...... in Enterococcus faecalis and Enterococcus faecium related to reduced susceptibility were identical to mutations detected in E jaecalis and E. faecium of clinical origin. A minimal inhibitory concentration of 8 mug ml(-1) to ciprofloxacin was not associated with any mutations in the gyrA and parC gene...... of Enterococcus casseliflavus and Enterococcus gallinarum. These two species may be intrinsically less susceptible to ciprofloxacin....

  18. Reduced susceptibility to Fusarium head blight in Brachypodium distachyon through priming with the Fusarium mycotoxin deoxynivalenol.

    Science.gov (United States)

    Blümke, Antje; Sode, Björn; Ellinger, Dorothea; Voigt, Christian A

    2015-06-01

    The fungal cereal pathogen Fusarium graminearum produces deoxynivalenol (DON) during infection. The mycotoxin DON is associated with Fusarium head blight (FHB), a disease that can cause vast grain losses. Whilst investigating the suitability of Brachypodium distachyon as a model for spreading resistance to F. graminearum, we unexpectedly discovered that DON pretreatment of spikelets could reduce susceptibility to FHB in this model grass. We started to analyse the cell wall changes in spikelets after infection with F. graminearum wild-type and defined mutants: the DON-deficient Δtri5 mutant and the DON-producing lipase disruption mutant Δfgl1, both infecting only directly inoculated florets, and the mitogen-activated protein (MAP) kinase disruption mutant Δgpmk1, with strongly decreased virulence but intact DON production. At 14 days post-inoculation, the glucose amounts in the non-cellulosic cell wall fraction were only increased in spikelets infected with the DON-producing strains wild-type, Δfgl1 and Δgpmk1. Hence, we tested for DON-induced cell wall changes in B. distachyon, which were most prominent at DON concentrations ranging from 1 to 100 ppb. To test the involvement of DON in defence priming, we pretreated spikelets with DON at a concentration of 1 ppm prior to F. graminearum wild-type infection, which significantly reduced FHB disease symptoms. The analysis of cell wall composition and plant defence-related gene expression after DON pretreatment and fungal infection suggested that DON-induced priming of the spikelet tissue contributed to the reduced susceptibility to FHB.

  19. Reduced noise susceptibility in littermate offspring from heterozygous animals of the German waltzing guinea pig.

    Science.gov (United States)

    Skjönsberg, Åsa; Mannström, Paula

    2015-07-08

    The German waltzing guinea pig is a spontaneously mutated strain with severe auditory and vestibular impairment caused by a so far unknown genetic mutation. The animals are born deaf and show a circling behavior. The heterozygote animals of this guinea pig strain have functionally normal hearing and balance. However, these animals have, in earlier studies, shown an increased resistance to noise compared with normal wild-type guinea pigs. In the present study, we explored the functional hearing with auditory brainstem response thresholds before and at different time points after noise exposure. Symptom-free littermates from heterozygote couples of the German waltzing guinea pigs were exclusively used for the study, which, after the hearing test, were sent back for breeding to confirm their genotype (i.e. heterozygote or normal). The aim of this paper was to ascertain that the previously shown reduced susceptibility to noise trauma in the heterozygote animals of the German waltzing guinea pig was also evident when littermates were used as control animals. The findings are important for further analysis of the heterozygote animals of this strain and for future investigations of the underlying mechanisms behind the diverse susceptibility to exposures of loud sound.

  20. Ceftibuten-containing agar plate for detecting group B streptococci with reduced penicillin susceptibility (PRGBS).

    Science.gov (United States)

    Kamiya, Chitose; Kimura, Kouji; Doyama, Yo; Miyazaki, Akira; Morimoto, Makiko; Banno, Hirotsugu; Nagano, Noriyuki; Jin, Wanchun; Wachino, Jun-ichi; Yamada, Keiko; Arakawa, Yoshichika

    2015-08-01

    Penicillins remain first-line agents for treatment of group B Streptococcus (Streptococcus agalactiae; GBS) infections; however, several reports have confirmed the existence of GBS with reduced penicillin susceptibility (PRGBS). Because no selective agar plates for detection of PRGBS are available to date, in this investigation, we developed the selective agar plate for detection of PRGBS. We used 19 genetically well-confirmed PRGBS isolates and 38 penicillin-susceptible GBS isolates identified in Japan. For preparation of trial PRGBS-selective agar plates, we added 1 of antimicrobial agents (among oxacillin, ceftizoxime, and ceftibuten) to a well-established GBS-selective agar plate. Among 12 trial PRGBS-selective agar plates, Muller-Hinton agar containing 128 μg/mL ceftibuten with 5% sheep blood, 8 μg/mL gentamicin, and 12 μg/mL nalidixic acid was the most appropriate selective agar for PRGBS, showing 100% sensitivity and 81.6% specificity. In cases of potential nosocomial spread of PRGBS, the selective agar plate could be useful and reliable.

  1. Linezolid and Rasagiline - A culprit for serotonin syndrome

    Directory of Open Access Journals (Sweden)

    Mohamed Hisham

    2016-01-01

    Full Text Available A 65-year-old female patient was admitted to the hospital for cellulitis. She had a history of diabetes mellitus and parkinsonism on levodopa/carbidopa, rasagiline, ropinirole, trihexyphenidyl, amantadine, metformin, and glipizide. We present here a case of rare incidence of serotonin syndrome associated with linezolid and rasagiline.

  2. Linezolid and Rasagiline - A culprit for serotonin syndrome

    OpenAIRE

    Mohamed Hisham; Mundalipalayam N Sivakumar; Nandakumar, V; S Lakshmikanthcharan

    2016-01-01

    A 65-year-old female patient was admitted to the hospital for cellulitis. She had a history of diabetes mellitus and parkinsonism on levodopa/carbidopa, rasagiline, ropinirole, trihexyphenidyl, amantadine, metformin, and glipizide. We present here a case of rare incidence of serotonin syndrome associated with linezolid and rasagiline.

  3. Detection of the classical G2576U mutation in linezolid resistant Staphylococcus aureus along with isolation of linezolid resistant Enterococcus faecium from a patient on short-term linezolid therapy: First report from India

    Directory of Open Access Journals (Sweden)

    S Rai

    2015-01-01

    Full Text Available Purpose: Linezolid is an effective drug against methicillin-resistant Staphylococcus aureus (MRSA and vancomycin-resistant enterococci (VRE. We describe the emergence of linezolid resistance in MRSA and VRE from India. Material and Methods: One MRSA and two VRE strains were isolated from a patient on linezolid therapy of one week duration. All three isolates were resistant to linezolid with minimal inhibitory concentrations (MIC ≥4 mg/L. The 746-bp region flanking the possible G2576U mutation on the corresponding DNA from the 23S rRNA was amplified by polymerase chain reaction (PCR and amplicons were sequenced for all the three isolates. Conjugation experiments using the linezolid resistant MRSA (LRMRSA and linezolid resistant VRE (LRVRE isolates as donors and wild strains of corresponding genera as recipients were performed. Results: The MRSA isolate had the classical G2576U mutation. High quality value scores in the sequencing software validated the mutation. Conjugation studies did not indicate presence of transferable resistance for linezolid. Sequencing did not indicate presence of any mutation in the two LRVRE isolates. Conclusions: This is the first report from India citing resistance in Staphylococcus and Enterococcus against Linezolid.

  4. Reduced Susceptibility to Cefepime in Clinical Isolates of Enterobacteriaceae Producing OXA-1 Beta-Lactamase.

    Science.gov (United States)

    Torres, Eva; López-Cerero, Lorena; Rodríguez-Martínez, José Manuel; Pascual, Álvaro

    2016-03-01

    An increase of Enterobacteriaceae isolates with reduced susceptibility to cefepime (FEP) and amoxicillin/clavulanate (AMC) has been observed in our area. The aim of this study was to characterize this antibiotic resistance phenotype and its molecular epidemiology. A total of 33 Enterobacteriaceae strains were studied. blaOXA-1 genes and their genetic environment were analyzed by polymerase chain reaction (PCR) and sequencing. Plasmids were transferred by conjugation and/or transformation and classified using PCR-based inc/rep typing and IncF subtyping. Escherichia coli isolates were typed by phylogroup, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Outer membrane proteins were studied by sodium dodecylsulfate-polyacrylamide gel electrophoresis and expression of blaOXA-1 genes by reverse transcription-PCR. FEP minimum inhibitory concentration yielded values of 1-16 mg/L. Twenty-nine (87.9%) isolates produced OXA-1, of which 24 (82.7%) were located in class 1 integron, and 9 (27.3%) produced TEM-1. Among the 24 E. coli OXA-1-producers, PFGE revealed two main clusters: one belonged to C-ST88 and the other to B23-ST131. Thirteen plasmids containing blaOXA-1 were transferred, nine belonged to IncF replicon (4 F2:A1:B-, 2 F1:A1:B1, 1 F1:A2:B-, 1 F18:A2:B1, 1 F5:A-:B1) and four were nontypeable. In conclusion, reduced susceptibility to FEP was mostly due to OXA-1 beta-lactamase. In E. coli, this increase is mainly due to the dissemination of two clones, which have captured different IncF plasmids. Among non-E. coli strains, five isolates produced OXA-1 and one isolate produced only TEM-1.

  5. Pharmacokinetics of Linezolid and Ertapenem in experimental parapneumonic pleural effusion

    Directory of Open Access Journals (Sweden)

    Tsatsakis Aristidis

    2010-05-01

    Full Text Available Abstract Objective To determine the extent of linezolid and ertapenem penetration into the empyemic fluid using a rabbit model of empyema. Methods An empyema was created via the intrapleural injection of Escherichia coli bacteria (ATCC 35218 into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracocentesis, 24 hours post inoculation, linezolid (10 mg/kg and ertapenem (60 mg/kg were administered intravenously into 10 and 8 infected empyemic rabbits, respectively. Antibiotic levels were determined in samples of pleural fluid and blood serum, collected serially at 1, 2, 4, 6 and 8 hours, after administration each of the two antibiotics. Results Linezolid as well as ertapenem penetrate well into the empyemic pleural fluid, exhibiting a slower onset and decline compared to the corresponding blood serum levels. Equilibration between blood serum and pleural fluid compartments seems to occur at 1.5 hours for both linezolid and ertapenem, with peak pleural fluid levels (Cmaxpf of 2.02 ± 0.73 «mu»g/ml and Cmaxpf of 3.74 ± 1.39 «mu»g/ml, correspondingly occurring 2 hours post antibiotics administration and decreasing very slowly thereafter. The serum concentrations for both antibiotics were significantly lower from the corresponding pleural fluid ones during the 8 hours collecting data, with the exception of samples collected at the 1st hour (Cmaxserum of 2.1 ± 1.2 «mu»g/ml for linezolid and Cmaxserum of 6.26 ± 2.98 «mu»g/ml for ertapenem. Conclusion Pleural fluid levels of both antibiotics are inhibitory for common specified pathogens causing empyema.

  6. Azithromycin resistance is coevolving with reduced susceptibility to cephalosporins in Neisseria gonorrhoeae in Ontario, Canada.

    Science.gov (United States)

    Allen, Vanessa G; Seah, Christine; Martin, Irene; Melano, Roberto G

    2014-05-01

    Azithromycin (AZM) is routinely recommended as a component of dual therapy for gonorrhea in combination with third-generation cephalosporins (3GC). In this study, we examined the prevalence of AZM-resistant (AZM(r)) Neisseria gonorrhoeae from July 2010 to February 2013, assessed the rate of concurrent cephalosporin resistance under the current treatment recommendations, and analyzed the clonal distribution of AZM(r) isolates in Ontario, Canada. Nineteen AZM(r) clinical isolates (one per patient; MIC, ≥2 μg/ml) were included in the study. Susceptibility profiles of these isolates to 11 antibiotics, molecular typing, characterization of macrolide resistance mechanisms, and penicillin-binding protein 2 (PBP2) patterns were determined for all the isolates. Two groups were defined based on AZM(r) level; group A isolates displayed high-level resistance (MIC, ≥2,048 μg/ml) due to mutations (A2143G) in the four copies of the 23S rRNA rrl gene, and group B isolates had moderate resistance to AZM (MICs, 2 to 8 μg/ml, C2599T mutation in the rrl gene), with a subgroup belonging to sequence type 3158 (ST3158) (n = 8), which also showed reduced susceptibility to 3GC (MICs, 0.12 to 0.25 μg/ml, PBP2 pattern XXXIV). This AZM(r) phenotype was not observed in previous provincial surveillance in 2008 (the ST3158 clone was found, with AZM MICs of 0.25 to 0.5 μg/ml associated with mtrR mutations). We hypothesized that the AZM mutant prevention concentration (MPC) in the ST3158 subpopulation we found in 2008 was higher than the MPC in wild-type isolates (AZM MIC, ≤0.031 μg/ml), increasing the chances of additional selection of AZM(r) mutations. Full AZM resistance is now emerging in this clone together with reduced susceptibility to 3GC, threatening the future efficacy of these antibiotics as therapeutic options for treatment of gonorrhea.

  7. Reduced susceptibility to extended-spectrum β-lactams in V. cholerae isolated in Bangladesh

    Directory of Open Access Journals (Sweden)

    Daniela Ceccarelli

    2016-10-01

    Full Text Available β-lactams are antibiotic molecules able to inhibit cell wall biosynthesis. Among other mechanisms, resistance in Gram-negative bacteria is mostly associated with production of β-lactamase enzymes able to bind and hydrolyze the β-lactam ring. Extended-spectrum β-lactamases extend this ability also to 3rd- and 4th generation cephalosporins as well as to carbapenems and monobactams. V. cholerae is the causative agent of epidemic cholera and a public health burden for developing countries like Bangladesh. Although appropriate oral or intravenous rehydration is the therapy of choice for cholera, severe infections and V. cholerae associated septicemia are treated with antimicrobial drugs including doxycycline, erythromycin, azithromycin, ciprofloxacin and/or third-generation cephalosporins. In the years after introduction of antibiotics in clinical practice, V. cholerae developed resistance to commonly used drugs worldwide mostly through gene acquisition via horizontal gene transfer. Reduced susceptibility of V. cholerae to third-generation cephalosporins has been occasionally documented. However, carbapenemase-producing V. cholerae has been reported at higher rates than resistance to extended spectrum β-lactams, mainly associated with blaNDM-1 emergence and successful plasmid dissemination. Recent findings suggest limited β-lactam resistance is present in V. cholerae O1 isolates collected during ecological and epidemiological surveillance in Bangladesh. However a trend to intermediate-susceptibility insurgence was observed. Horizontal gene transfer of β-lactam resistance from enteric pathogens to environmental microorganisms should not be underrated, given the ability of V. cholerae to acquire new genetic information.

  8. Reduced Susceptibility to Extended-Spectrum β-Lactams in Vibrio cholerae Isolated in Bangladesh.

    Science.gov (United States)

    Ceccarelli, Daniela; Alam, Munirul; Huq, Anwar; Colwell, Rita R

    2016-01-01

    β-lactams are antibiotic molecules able to inhibit cell wall biosynthesis. Among other mechanisms, resistance in Gram-negative bacteria is mostly associated with production of β-lactamase enzymes able to bind and hydrolyze the β-lactam ring. Extended-spectrum β-lactamases extend this ability also to third- and fourth-generation cephalosporins, as well as to carbapenems and monobactams. Vibrio cholerae is the causative agent of epidemic cholera and a public health burden for developing countries like Bangladesh. Although appropriate oral or intravenous rehydration is the therapy of choice for cholera, severe infections and V. cholerae-associated septicemia are treated with antimicrobial drugs, including doxycycline, erythromycin, azithromycin, ciprofloxacin, and/or third-generation cephalosporins. In the years after the introduction of antibiotics in clinical practice, V. cholerae developed resistance to commonly used drugs worldwide mostly through gene acquisition via horizontal gene transfer. Reduced susceptibility of V. cholerae to third-generation cephalosporins has been occasionally documented. However, carbapenemase-producing V. cholerae has been reported at higher rates than resistance to extended-spectrum β-lactams, mainly associated with blaNDM-1 emergence and successful plasmid dissemination. Recent findings suggest limited β-lactam resistance is present in V. cholerae O1 isolates collected during ecological and epidemiological surveillance in Bangladesh. However, a trend to intermediate-susceptibility insurgence was observed. Horizontal gene transfer of β-lactam resistance from enteric pathogens to environmental microorganisms should not be underrated, given the ability of V. cholerae to acquire new genetic information.

  9. Reduced Susceptibility to Extended-Spectrum β-Lactams in Vibrio cholerae Isolated in Bangladesh

    Science.gov (United States)

    Ceccarelli, Daniela; Alam, Munirul; Huq, Anwar; Colwell, Rita R.

    2016-01-01

    β-lactams are antibiotic molecules able to inhibit cell wall biosynthesis. Among other mechanisms, resistance in Gram-negative bacteria is mostly associated with production of β-lactamase enzymes able to bind and hydrolyze the β-lactam ring. Extended-spectrum β-lactamases extend this ability also to third- and fourth-generation cephalosporins, as well as to carbapenems and monobactams. Vibrio cholerae is the causative agent of epidemic cholera and a public health burden for developing countries like Bangladesh. Although appropriate oral or intravenous rehydration is the therapy of choice for cholera, severe infections and V. cholerae-associated septicemia are treated with antimicrobial drugs, including doxycycline, erythromycin, azithromycin, ciprofloxacin, and/or third-generation cephalosporins. In the years after the introduction of antibiotics in clinical practice, V. cholerae developed resistance to commonly used drugs worldwide mostly through gene acquisition via horizontal gene transfer. Reduced susceptibility of V. cholerae to third-generation cephalosporins has been occasionally documented. However, carbapenemase-producing V. cholerae has been reported at higher rates than resistance to extended-spectrum β-lactams, mainly associated with blaNDM-1 emergence and successful plasmid dissemination. Recent findings suggest limited β-lactam resistance is present in V. cholerae O1 isolates collected during ecological and epidemiological surveillance in Bangladesh. However, a trend to intermediate-susceptibility insurgence was observed. Horizontal gene transfer of β-lactam resistance from enteric pathogens to environmental microorganisms should not be underrated, given the ability of V. cholerae to acquire new genetic information.

  10. Elevated chitin content reduces the susceptibility of Candida species to caspofungin.

    Science.gov (United States)

    Walker, Louise A; Gow, Neil A R; Munro, Carol A

    2013-01-01

    The echinocandin antifungal drugs inhibit synthesis of the major fungal cell wall polysaccharide β(1,3)-glucan. Echinocandins have good efficacy against Candida albicans but reduced activity against other Candida species, in particular Candida parapsilosis and Candida guilliermondii. Treatment of Candida albicans with a sub-MIC level of caspofungin has been reported to cause a compensatory increase in chitin content and to select for sporadic echinocandin-resistant FKS1 point mutants that also have elevated cell wall chitin. Here we show that elevated chitin in response to caspofungin is a common response in various Candida species. Activation of chitin synthesis was observed in isolates of C. albicans, Candida tropicalis, C. parapsilosis, and C. guilliermondii and in some isolates of Candida krusei in response to caspofungin treatment. However, Candida glabrata isolates demonstrated no exposure-induced change in chitin content. Furthermore, isolates of C. albicans, C. krusei, C. parapsilosis, and C. guilliermondii which were stimulated to have higher chitin levels via activation of the calcineurin and protein kinase C (PKC) signaling pathways had reduced susceptibility to caspofungin. Isolates containing point mutations in the FKS1 gene generally had higher chitin levels and did not demonstrate a further compensatory increase in chitin content in response to caspofungin treatment. These results highlight the potential of increased chitin synthesis as a potential mechanism of tolerance to caspofungin for the major pathogenic Candida species.

  11. Elevated Chitin Content Reduces the Susceptibility of Candida Species to Caspofungin

    Science.gov (United States)

    Walker, Louise A.; Gow, Neil A. R.

    2013-01-01

    The echinocandin antifungal drugs inhibit synthesis of the major fungal cell wall polysaccharide β(1,3)-glucan. Echinocandins have good efficacy against Candida albicans but reduced activity against other Candida species, in particular Candida parapsilosis and Candida guilliermondii. Treatment of Candida albicans with a sub-MIC level of caspofungin has been reported to cause a compensatory increase in chitin content and to select for sporadic echinocandin-resistant FKS1 point mutants that also have elevated cell wall chitin. Here we show that elevated chitin in response to caspofungin is a common response in various Candida species. Activation of chitin synthesis was observed in isolates of C. albicans, Candida tropicalis, C. parapsilosis, and C. guilliermondii and in some isolates of Candida krusei in response to caspofungin treatment. However, Candida glabrata isolates demonstrated no exposure-induced change in chitin content. Furthermore, isolates of C. albicans, C. krusei, C. parapsilosis, and C. guilliermondii which were stimulated to have higher chitin levels via activation of the calcineurin and protein kinase C (PKC) signaling pathways had reduced susceptibility to caspofungin. Isolates containing point mutations in the FKS1 gene generally had higher chitin levels and did not demonstrate a further compensatory increase in chitin content in response to caspofungin treatment. These results highlight the potential of increased chitin synthesis as a potential mechanism of tolerance to caspofungin for the major pathogenic Candida species. PMID:23089748

  12. Detection of Reduced Susceptibility to Chlorfenapyr- and Bifenthrin-Containing Products in Field Populations of the Bed Bug (Hemiptera: Cimicidae).

    Science.gov (United States)

    Ashbrook, Aaron R; Scharf, Michael E; Bennett, Gary W; Gondhalekar, Ameya D

    2017-06-01

    Insecticide resistance is a major impediment for effective control of Cimex lectularius L. Previous resistance detection studies with bed bugs have focused on certain pyrethroid, neonicotinoid, organochlorine, organophosphate, and carbamate insecticides. Within the pyrethroid class, resistance studies have mostly been limited to deltamethrin, lambda-cyhalothrin, and alpha- and beta-cyfluthrin. The goal of this study was to develop diagnostic concentration bioassays for assessing bed bug susceptibility levels to chlorfenapyr- and bifenthrin-containing products. First, glass vial and filter paper bioassay methods were compared for their utility in susceptibility monitoring. Statistical comparison of toxicity data between bioassays indicated that the vial assay was less confounded by assay susbtrate effects, required less insecticide, and was faster, especially for chlorfenapyr. Next, using vial diagnostic concentrations (LC99) for each insecticide, 10 laboratory-adapted field strains and the Harlan lab-susceptible strain were screened for susceptibility to chlorfenapyr and bifenthrin. The results of this study reveal recent bed bug susceptibility levels to certain chlorfenapyr- and bifenthrin-containing products. Reduced susceptibility was detected in three and five field strains to chlorfenapyr and bifenthrin, respectively. Detection of reduced susceptibility suggests that certain strains may be segregating toward greater chlorfenapyr and bifenthrin resistance. These results merit continuous resistance monitoring efforts to detect chlorfenapyr and bifenthrin susceptibility shifts. Additionally, to reduce insecticide selection pressures and delay resistance development, adoption of integrated bed bug control strategies that combine chemical and nonchemical methods is recommended. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Reduced immune function predicts disease susceptibility in frogs infected with a deadly fungal pathogen

    National Research Council Canada - National Science Library

    Savage, Anna E; Terrell, Kimberly A; Gratwicke, Brian; Mattheus, Nichole M; Augustine, Lauren; Fleischer, Robert C

    2016-01-01

    The relationship between amphibian immune function and disease susceptibility is of primary concern given current worldwide declines linked to the pathogenic fungus Batrachochytrium dendrobatidis (Bd...

  14. Seminational surveillance of fungemia in Denmark: notably high rates of fungemia and numbers of isolates with reduced azole susceptibility

    DEFF Research Database (Denmark)

    Arendrup, Maiken Cavling; Fuursted, Kurt; Gahrn-Hansen, Bente;

    2005-01-01

    laboratory systems documented a continuous increase of candidemia cases since the early 1990s. For the 272 susceptibility-tested isolates, MICs of amphotericin B and caspofungin were within the limits expected for the species or genus. However, decreased azole susceptibility, defined as a fluconazole MIC...... of >8 microg/ml and/or itraconazole MIC of >0.125 microg/ml, was detected for 11 Candida isolates that were neither C. glabrata nor C. krusei. Including intrinsically resistant fungi, we detected decreased susceptibility to fluconazole and/or itraconazole in 87 (32%) current Danish bloodstream fungal...... isolates. We showed a continuous increase of fungemia in Denmark and an annual rate in 2003 to 2004 higher than in most other countries. The proportion of bloodstream fungal isolates with reduced susceptibility to fluconazole and/or itraconazole was also notably high....

  15. Mycobacterium avium complex (MAC) Immune Reconstitution Syndrome (IRIS) With Reduced Susceptibility to Ethambutol in an HIV-Infected Patient.

    Science.gov (United States)

    Adams, Immaculata B; Schafer, Jason J; Roberts, Amity L; Short, William R

    2014-09-01

    To describe a case of Mycobacterium avium complex (MAC) lymphadenitis complicated by immune reconstitution syndrome (IRIS) and reduced susceptibility to ethambutol. A 24-year-old man was diagnosed in October 2012 with advanced HIV infection upon hospitalization for multiple opportunistic infections (OIs). Within 5 months of starting antiretroviral therapy, the patient developed significant cervical lymphadenopathy concerning for MAC/IRIS. Acid-fast bacilli were detected in the primary lymph node biopsy smear, and culture results confirmed the presence of MAC. Susceptibility testing revealed an organism susceptible to azithromycin, with an elevated minimum inhibitory concentration (MIC) to ethambutol (8 µg/mL). Currently, there is no interpretation for an ethambutol MIC of 8 µg/mL for MAC. A review of the primary literature revealed the possibility of decreased ethambutol susceptibility when the MIC is above 1 µg/mL, and therefore, therapy was replaced by rifabutin in combination with azithromycin. Current guidelines recommend a 2-drug regimen for the treatment of MAC, specifically a macrolide plus ethambutol. Guidelines also emphasize MAC susceptibility testing for macrolides only. Susceptibility results from this patient's biopsy prompted an evaluation of the effectiveness of his antimycobacterial regimen. Reduced ethambutol susceptibility in this patient triggered a search of the primary literature that resulted in the decision to replace ethambutol with rifabutin. Additional clinical trials are needed to define susceptibility breakpoints for ethambutol and other antimycobacterial agents used for MAC infection treatment and to direct clinical decisions when elevated MICs to primary agents are identified. © The Author(s) 2014.

  16. Susceptibility of Choristoneura rosaceana (Lepidoptera: Tortricidae) to two new reduced-risk insecticides.

    Science.gov (United States)

    Sial, Ashfaq A; Brunner, Jay F; Doerr, Michael D

    2010-02-01

    The response of field-collected populations of the obliquebanded leafroller, Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae), to chlorantraniliprole, spinetoram, spinosad, and azinphosmethyl was assessed using a diet incorporation bioassay. Populations of obliquebanded leafroller were collected from nine orchards in Chelan, Douglas, Grant, and Okanogan counties of Washington. The neonates of the F1 or F2 generation were used in all assays. The parameters of probit regression lines were estimated and lethal concentration ratios were calculated for all populations compared with a susceptible laboratory population. Significant variation was detected in response to all four insecticides including chlorantraniliprole and spinetoram, which had never been used in the field, lethal concentration ratios were 3.9-39.7 for azinphosmethyl, 0.5-3.6 for spinosad, 1.2-5.3 for chlorantraniliprole, and 0.5-4.1 for spinetoram. Correlation analysis indicated possibility of cross-resistance between spinosad and spinetoram, which are both members of spinosyn class. The occurrence of low but significant levels of resistance against chlorantraniliprole and spinetoram in field-collected populations of C. rosaceana before their first field application indicates that the risk of resistance evolution against these two new reduced-risk insecticides exists. However, it is likely that these low levels of resistance can be managed if the insecticides are used judiciously in conjunction with sound resistance management programs. Implications of these results for developing and implementing resistance management strategies are discussed.

  17. The isolation of Staphylococcus aureus tea tree oil-reduced susceptibility mutants.

    Science.gov (United States)

    Cuaron, Jesus A; Dulal, Santosh; Cooke, Peter H; Torres, Nathanial J; Gustafson, John E

    2014-08-01

    Tea tree oil (TTO)-reduced susceptibility (TTORS) mutants of two Staphylococcus aureus laboratory strains were isolated utilizing TTO gradient plates. Attempts to isolate TTORS mutants employing agar plates containing single TTO concentrations failed. All TTORS mutants demonstrated a small colony variant (SCV) phenotype and produced cells with a smaller diameter, as determined by scanning electron microscopy. The addition of SCV auxotrophic supplements to media did not lead to an increase in TTORS mutant colony size. Revertants were also isolated from the TTORS mutants following growth in drug-free media, and all revertant strains demonstrated phenotypes similar to their respective parent strains. Transmission electron microscopy revealed that an SH1000 TTORS mutant demonstrated a thinner cell wall and novel septal invaginations compared with parent strain SH1000. In addition, comparative genomic sequencing did not reveal any mutations in an SH1000 TTORS mutant previously linked to well-characterized SCV genotypes. This study demonstrates that TTO can select for a unique SCV phenotype.

  18. Analysis of the gyrA gene of clinical Yersinia ruckeri isolates with reduced susceptibility to quinolones.

    Science.gov (United States)

    Gibello, Alicia; Porrero, M Concepción; Blanco, M Mar; Vela, Ana I; Liébana, Pilar; Moreno, Miguel A; Fernández-Garayzábal, José F; Domínguez, Lucas

    2004-01-01

    Antimicrobial susceptibility of seven clinical strains of Yersinia ruckeri representative of those isolated between 1994 and 2002 from a fish farm with endemic enteric redmouth disease was studied. All isolates displayed indistinguishable pulsed-field gel electrophoresis restriction patterns, indicating that they represented a single strain. However, considering both inhibition zone diameters (IZD) and MICs, the isolates recovered in 2001-2002 formed a separate cluster with lower levels of susceptibility to all the quinolones tested, especially nalidixic acid (NA) and oxolinic acid (OA), compared with the isolates recovered between 1994 and 1998. Analysis of the PCR product of the quinolone resistance-determining region of the gyrA gene from clinical isolates of Y. ruckeri with reduced susceptibility to OA and NA revealed a single amino acid substitution, Ser-83 to Arg-83 (Escherichia coli numbering). Identical substitution was observed in induced OA-resistant mutant strains, which displayed IZD and MICs of quinolones similar to those of the clinical isolates of Y. ruckeri with reduced susceptibility to these antimicrobial agents. These data indicate in that for Y. ruckeri, the substitution of Ser by Arg at position 83 of the gyrA gene is associated with reduced susceptibility to quinolones.

  19. Study on the Linezolid Prescription According to the Approval of Indication in a University Hospital

    OpenAIRE

    Pérez-Cebrián, Manuela; Suárez-Varela, María M. Morales; Font-Noguera, Isabel; Monte-Boquet, Emilio; Poveda-Andrés, Jose Luís; Martín-Moreno, Jose María; RUBIO-LÓPEZ, Nuria; Ruiz-Rojo, Elias; Llopis-González, Agustín

    2015-01-01

    Indications for linezolid use are nosocomial or community-acquired pneumonia and skin infections or soft tissue infection caused by gram-positive microorganisms, but new recommendations may emerge. It is important to balance benefits with risks because severe adverse events have been described in patients taking linezolid treatment. Accordingly, we evaluated the suitability of linezolid prescription according to approval of indication by evaluating the presence of drug-related problems (DRP) ...

  20. Developmental plasticity and reduced susceptibility to natural enemies following host plant defoliation in a specialized herbivore.

    Science.gov (United States)

    Hood, Glen R; Ott, James R

    2010-03-01

    Host-specific phytophagous insects that are short lived and reliant on ephemeral plant tissues provide an excellent system in which to investigate the consequences of disruption in the timing of resource availability on consumer populations and their subsequent interactions with higher tropic levels. The specialist herbivore, Belonocnema treatae (Hymenoptera: Cynipidae) induces galls on only newly flushed leaves of live oak, Quercus fusiformis. In central Texas (USA) episodic defoliation of the host creates variation in the timing of resource availability and results in heterogeneous populations of B. treatae that initiate development at different times. We manipulated the timing of leaf flush in live oak via artificial defoliation to test the hypothesis that a 6- to 8-week delay in the availability of resources alters the timing of this gall former's life cycle events, performance and survivorship on its host, and susceptibility to natural enemies. B. treatae exhibits plasticity in development time, as the interval from egg to emergence was significantly reduced when gallers oviposited into the delayed leaf flush. As a consequence, the phenologies of gall maturation and adult emergence remain synchronized in spite of variation in the timing of resource availability. Per capita gall production and gall-former performance are not significantly affected by the timing of resource availability. The timing of resource availability and natural enemies interact, however, to produce strong effects on survivorship: when exposed to natural enemies, B. treatae developing in galls initiated by delayed oviposition exhibited an order-of-magnitude increase in survivorship. Developmental plasticity allows this gall former to circumvent disruptions in resource availability, maintain synchrony of life cycle events, and results in reduced vulnerability to natural enemies following defoliation of the host plant.

  1. Linezolid-induced interstitial nephritis in a kidney-transplant patient.

    Science.gov (United States)

    Esposito, L; Kamar, N; Guilbeau-Frugier, C; Mehrenberger, M; Modesto, A; Rostaing, L

    2007-11-01

    Linezolid is a recent oral antibiotic used in drug-resistant Gram-positive cocci infections. Herein, we report on the first case of linezolid-related acute renal failure in a kidney-transplant patient. A 60-year-old male having autosomic polycystic kidney disease with liver involvement, on cyclosporin A, mycophenolate mofetil and very low dose prednisolone, presented with an Enterococcus faecium abscess of a huge liver cyst, which was treated by percutaneous drainage and linezolid therapy. Eight days after starting linezolid, he presented with acute renal failure, i.e. serum creatinine increased from 136- 221 micromol/l, associated with mild hypereosinophilia, anemia and thrombocytopenia. There was no skin rash, arthralgia, eosinophiluria or proteinuria. The transplant kidney biopsy, performed 15 days after the beginning of linezolid therapy, showed interstitial nephritis and focal tubular atrophy. After linezolid withdrawal and increasing prednisolone daily dose to 20 mg/d, within a few days, serum creatinine had decreased; after 2 and 4 weeks post linezolid withdrawal, his serum creatinine was 166 and 159 micromol/l, respectively. Because of the potential side effects of linezolid, i.e. myelosuppression and possibly nephrotoxicity, we recommend close monitoring of these parameters when linezolid therapy is attempted in kidney transplant patients.

  2. Ceftobiprole is superior to vancomycin, daptomycin, and linezolid for treatment of experimental endocarditis in rabbits caused by methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Tattevin, P; Basuino, L; Bauer, D; Diep, B A; Chambers, H F

    2010-02-01

    Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (Pceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (Pceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.

  3. Structure-activity relationships of diverse oxazolidinones for linezolid-resistant Staphylococcus aureus strains possessing the cfr methyltransferase gene or ribosomal mutations.

    Science.gov (United States)

    Locke, Jeffrey B; Finn, John; Hilgers, Mark; Morales, Gracia; Rahawi, Shahad; G C, Kedar; Picazo, Juan José; Im, Weonbin; Shaw, Karen Joy; Stein, Jeffrey L

    2010-12-01

    Staphylococcal resistance to linezolid (LZD) is mediated through ribosomal mutations (23S rRNA or ribosomal proteins L3 and L4) or through methylation of 23S rRNA by the horizontally transferred Cfr methyltransferase. To investigate the structural basis for oxazolidinone activity against LZD-resistant (LZD(r)) strains, we compared structurally diverse, clinically relevant oxazolidinones, including LZD, radezolid (RX-1741), TR-700 (torezolid), and a set of TR-700 analogs (including novel CD-rings and various A-ring C-5 substituents), against a panel of laboratory-derived and clinical LZD(r) Staphylococcus aureus strains possessing a variety of resistance mechanisms. Potency against all strains was correlated with optimization of C- and D-rings, which interact with more highly conserved regions of the peptidyl transferase center binding site. Activity against cfr strains was retained with either hydroxymethyl or 1,2,3-triazole C-5 groups but was reduced by 2- to 8-fold in compounds with acetamide substituents. LZD, which possesses a C-5 acetamide group and lacks a D-ring substituent, demonstrated the lowest potency against all strains tested, particularly against cfr strains. These data reveal key features contributing to oxazolidinone activity and highlight structural tradeoffs between potency against susceptible strains and potency against strains with various resistance mechanisms.

  4. Structure-Activity Relationships of Diverse Oxazolidinones for Linezolid-Resistant Staphylococcus aureus Strains Possessing the cfr Methyltransferase Gene or Ribosomal Mutations▿

    Science.gov (United States)

    Locke, Jeffrey B.; Finn, John; Hilgers, Mark; Morales, Gracia; Rahawi, Shahad; G. C., Kedar; Picazo, Juan José; Im, Weonbin; Shaw, Karen Joy; Stein, Jeffrey L.

    2010-01-01

    Staphylococcal resistance to linezolid (LZD) is mediated through ribosomal mutations (23S rRNA or ribosomal proteins L3 and L4) or through methylation of 23S rRNA by the horizontally transferred Cfr methyltransferase. To investigate the structural basis for oxazolidinone activity against LZD-resistant (LZDr) strains, we compared structurally diverse, clinically relevant oxazolidinones, including LZD, radezolid (RX-1741), TR-700 (torezolid), and a set of TR-700 analogs (including novel CD-rings and various A-ring C-5 substituents), against a panel of laboratory-derived and clinical LZDr Staphylococcus aureus strains possessing a variety of resistance mechanisms. Potency against all strains was correlated with optimization of C- and D-rings, which interact with more highly conserved regions of the peptidyl transferase center binding site. Activity against cfr strains was retained with either hydroxymethyl or 1,2,3-triazole C-5 groups but was reduced by 2- to 8-fold in compounds with acetamide substituents. LZD, which possesses a C-5 acetamide group and lacks a D-ring substituent, demonstrated the lowest potency against all strains tested, particularly against cfr strains. These data reveal key features contributing to oxazolidinone activity and highlight structural tradeoffs between potency against susceptible strains and potency against strains with various resistance mechanisms. PMID:20837751

  5. The role of cognitive and affective defense mechanisms in reducing children’s susceptibility to advertising effects

    NARCIS (Netherlands)

    Rozendaal, E.; Buijzen, M.; Valkenburg, P.

    2011-01-01

    The main aim of this study was to develop and test a model of children’s advertising defenses. In this model two paths to reduced advertising susceptibility (i.e., advertised brand attitude) were hypothesized: a cognitive and an affective path. The secondary aim was to compare these paths for two th

  6. Integrated SSFP for functional brain mapping at 7 T with reduced susceptibility artifact

    Science.gov (United States)

    Sun, Kaibao; Xue, Rong; Zhang, Peng; Zuo, Zhentao; Chen, Zhongwei; Wang, Bo; Martin, Thomas; Wang, Yi; Chen, Lin; He, Sheng; Wang, Danny J. J.

    2017-03-01

    Balanced steady-state free precession (bSSFP) offers an alternative and potentially important tool to the standard gradient-echo echo-planar imaging (GE-EPI) for functional MRI (fMRI). Both passband and transition band based bSSFP have been proposed for fMRI. The applications of these methods, however, are limited by banding artifacts due to the sensitivity of bSSFP signal to off-resonance effects. In this article, a unique case of the SSFP-FID sequence, termed integrated-SSFP or iSSFP, was proposed to overcome the obstacle by compressing the SSFP profile into the width of a single voxel. The magnitude of the iSSFP signal was kept constant irrespective of frequency shift. Visual stimulation studies were performed to demonstrate the feasibility of fMRI using iSSFP at 7 T with flip angles of 4° and 25°, compared to standard bSSFP and gradient echo (GRE) imaging. The signal changes for the complex iSSFP signal in activated voxels were 2.48 ± 0.53 (%) and 2.96 ± 0.87 (%) for flip angles (FA) of 4° and 25° respectively at the TR of 9.88 ms. Simultaneous multi-slice acquisition (SMS) with the CAIPIRIHNA technique was carried out with iSSFP scanning to detect the anterior temporal lobe activation using a semantic processing task fMRI, compared with standard 2D GE-EPI. This study demonstrates the feasibility of iSSFP for fMRI with reduced susceptibility artifacts, while maintaining robust functional contrast at 7 T.

  7. A promising approach to effectively reduce cramp susceptibility in human muscles: a randomized, controlled clinical trial.

    Directory of Open Access Journals (Sweden)

    Michael Behringer

    Full Text Available To investigate if the cramp threshold frequency (CTF can be altered by electrical muscle stimulation in a shortened position.A total of 15 healthy male sport students were randomly allocated to an intervention (IG, n = 10 and a non-treatment control group (CG, n = 5. Calf muscles of both legs in the IG were stimulated equally twice a week over 6 weeks. The protocol was 3×5 s on, 10 s off, 150 µs impulse width, 30 Hz above the individual CTF, and was at 85% of the maximal tolerated stimulation energy. One leg was stimulated in a shortened position, inducing muscle cramps (CT, while the opposite leg was fixated in a neutral position at the ankle, hindering muscle cramps (nCT. CTF tests were performed prior to the first and 96 h after the 6(th (3 w and 12(th (6 w training session.After 3 w, the CTF had significantly (p<0.001 increased in CT calves from 23.3±5.7 Hz to 33.3±6.9 Hz, while it remained unchanged in nCT (pre: 23.6±5.7 Hz, mid: 22.3±3.5 Hz and in both legs of the CG (pre: 21.8±3.2 Hz, mid: 22.0±2.7 Hz. Only CT saw further insignificant increases in the CTF. The applied stimulation energy (mA² • µs positively correlated with the effect on the CTF (r = 0.92; p<0.001.The present study may be useful for developing new non-pharmacological strategies to reduce cramp susceptibility.German Clinical Trials Register DRKS00005312.

  8. A reduced susceptibility to chemoconvulsant stimulation in adenylyl cyclase 8 knockout mice

    Science.gov (United States)

    Chen, Xia; Dong, Guoying; Zheng, Changhong; Wang, Hongbing; Yun, Wenwei; Zhou, Xianju

    2015-01-01

    Objective Adenylyl cyclases (ACs) catalyze the synthesis of cAMP from ATP, and cAMP signaling affects a large number of neuronal processes. Ca2+-stimualted adenylyl cyclase 8 (AC8) expressed in the CNS plays a role in synaptic plasticity, drug addiction and ethanol sensitivity, and chronic pain. This study was to aim at examining the contributions of AC8 to epileptogenesis. Methods In this study, we observed the seizure behavior induced by kainic acid (20mg/kg or 30mg/kg) or pilocarpine (350mg/kg) in AC8 KO and wild-type mice. Next we injected kainic acid or pilocarpine to induce status epilepticus (SE), and examined neuronal degeneration (by Fluoro-Jade B staining) and mossy fiber sprouting (by Timm staining) 24 hr and 2 weeks after SE termination in the hippocampus, respectively. Finally, 15min after intraperitoneal injection of kainic acid (30mg/kg), we examined phosphor-ERK1/2 in the hippocampus by western blot and immunochemistry staining. Results We first observed that AC8 KO mutants display reduced susceptibility (including seizure latency and episodes) to two chemoconvulsants, kainic acid and pilocarpine. Moreover, we found that degenerative neurons and mossy fiber sprouting induced by chemoconvulsants were significant decreased in the hippocampus. Further, western blot and immunochemistry analysis revealed that the MAPK signaling in the hippocampus was attenuated in kainic acid-injected AC8 KO mice. Conclusion AC8 is involved in epileptogenesis, and may serve as a potential target for the treatment of epilepsy. PMID:26656781

  9. Is reduced susceptibility to disinfectants and antiseptics a risk in healthcare settings? A point/counterpoint review.

    Science.gov (United States)

    Harbarth, S; Tuan Soh, S; Horner, C; Wilcox, M H

    2014-08-01

    Given the breadth and depth of antiseptic use, it is surprising how few large-scale studies have been undertaken into the consequences of their use, particularly in clinical practice. Depending on your point of view, this may either reflect an assurance that reduced susceptibility to antiseptics, and notably whether this confers cross-resistance to systemically administered antimicrobial agents, is not an issue of concern, or relative ignorance about the potential threat. This point/counterpoint review offers a differentiated perspective and possible answers to the question, 'Should we be worried about reduced susceptibility to disinfectants and antiseptics in healthcare settings?'. This topic was the subject of a debate by MHW (point) and SH (counterpoint) during the SHEA Spring Conference 2013: Advancing healthcare epidemiology and the role of the environment, held in Atlanta, GA, USA on 4(th) May 2013. This review is a general representation of the main themes presented during the debate, rather than a systematic review of the literature. There are examples of reduced susceptibility to antiseptics in clinical practice; however, to date, there is no strong evidence that reduced susceptibility to antiseptics is a major clinical problem. Given the growing number of potential indications for use of biocidal active ingredients, the potential for emergence of reduced susceptibility remains a concern. Changes in the clinical use of antiseptics should be matched with surveillance studies to understand whether there are unintended microbiological or clinical consequences, including the selection of bacterial strains that can survive exposure to antiseptics. Copyright © 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  10. The inactivation of RNase G reduces the Stenotrophomonas maltophilia susceptibility to quinolones by triggering the heat shock response.

    Directory of Open Access Journals (Sweden)

    Alejandra eBernardini

    2015-10-01

    Full Text Available Quinolone resistance is usually due to mutations in the genes encoding bacterial topoisomerases. However different reports have shown that neither clinical quinolone resistant isolates nor in vitro obtained S. maltophilia mutants present mutations in such genes. The mechanisms so far described consist on efflux pumps' overexpression. Our objective is to get information on novel mechanisms of S. maltophilia quinolone resistance. For this purpose, a transposon-insertion mutant library was obtained in S. maltophilia D457.. One mutant presenting reduced susceptibility to nalidixic acid was selected. Inverse PCR showed that the inactivated gene encodes RNase G. Complementation of the mutant with wild-type RNase G allele restored the susceptibility to quinolones. Transcriptomic and real-time RT-PCR analyses showed that several genes encoding heat-shock response proteins were expressed at higher levels in the RNase defective mutant than in the wild-type strain. In agreement with this situation, heat-shock reduces the S. maltophilia susceptibility to quinolone. We can then conclude that the inactivation of the RNase G reduces the susceptibility of S. maltophilia to quinolones, most likely by regulating the expression of heat-shock response genes. Heat-shock induces a transient phenotype of quinolone resistance in S. maltophilia.

  11. Bloodstream infections caused by Acinetobacter species with reduced susceptibility to tigecycline: clinical features and risk factors.

    Science.gov (United States)

    Park, Ga Eun; Kang, Cheol-In; Cha, Min Kyeong; Cho, Sun Young; Seok, Hyeri; Lee, Ji Hye; Kim, Ji Yeon; Ha, Young Eun; Chung, Doo Ryeon; Peck, Kyong Ran; Lee, Nam Yong; Song, Jae-Hoon

    2017-09-01

    During recent decades, the rates of multidrug resistance, including resistance to carbapenems, have increased dramatically among Acinetobacter species. Tigecycline has activity against multidrug-resistant Acinetobacter spp, including carbapenem-resistant isolates. However, reports of tigecycline-resistant Acinetobacter spp are emerging from different parts of the world. The purpose of this study was to evaluate potential risk factors associated with tigecycline non-susceptible Acinetobacter bacteremia. The medical records of 152 patients with Acinetobacter bacteremia attending Samsung Medical Center between January 2010 and December 2014 were reviewed. Non-susceptibility to tigecycline was defined as a minimum inhibitory concentration (MIC) of tigecycline ≥4μg/ml. Cases were patients with tigecycline non-susceptible Acinetobacter bacteremia and controls were those with tigecycline-susceptible Acinetobacter bacteremia. Of the 152 patients included in the study, 61 (40.1%) had tigecycline non-susceptible Acinetobacter bacteremia (case group). These patients were compared to 91 patients with tigecycline-susceptible Acinetobacter bacteremia (control group). The case group showed high resistance to other antibiotics (>90%) except colistin (6.6%) and minocycline (9.8%) when compared to the control group, which exhibited relatively low resistance to other antibiotics (<50%). Multivariate analysis showed that recent exposure to corticosteroids (minimum 20mg per day for more than 5 days within 2 weeks) (adjusted odds ratio (OR) 2.887, 95% confidence interval (CI) 1.170-7.126) and carbapenems (within 2 weeks) (adjusted OR 4.437, 95% CI 1.970-9.991) were significantly associated with tigecycline non-susceptible Acinetobacter bacteremia. Although prior exposure to tigecycline was more common in the case group than in the control group (9.8%, 6/61 vs. 2.2%, 2/91; p=0.046), this variable was found not to be a significant factor associated with tigecycline non-susceptibility

  12. Plasmodium falciparum Na+/H+ Exchanger 1 Transporter Is Involved in Reduced Susceptibility to Quinine ▿

    OpenAIRE

    Henry, Maud; Briolant, Sébastien; Zettor, Agnès; Pelleau, Stéphane; Baragatti, Meili; Baret, Eric; Mosnier, Joel; Amalvict, Rémy; Fusai, Thierry; Rogier, Christophe; Pradines, Bruno

    2009-01-01

    Polymorphisms in the Plasmodium falciparum crt (Pfcrt), Pfmdr1, and Pfmrp genes were not significantly associated with quinine (QN) 50% inhibitory concentrations (IC50s) in 23 strains of Plasmodium falciparum. An increased number of DNNND repeats in Pfnhe-1 microsatellite ms4760 was associated with an increased IC50 of QN (P = 0.0007). Strains with only one DNNND repeat were more susceptible to QN (mean IC50 of 154 nM). Strains with two DNNND repeats had intermediate susceptibility to QN (mea...

  13. Simultaneous quantification of linezolid, tinidazole, norfloxacin, moxifloxacin, levofloxacin, and gatifloxacin in human plasma for therapeutic drug monitoring and pharmacokinetic studies in human volunteers.

    Science.gov (United States)

    Helmy, Sally A

    2013-12-01

    Linezolid may be administered in combination with norfloxacin, gatifloxacin, levofloxacin, moxifloxacin, and tinidazole for the treatment of various infections, such as urinary and respiratory tract infections, to improve the efficacy of the treatment or to reduce the duration of therapy. Knowledge of the antibiotic plasma concentrations combined with bacterial susceptibility evaluated in terms of minimum inhibitory concentration would optimize treatment efficacy while limiting the risk of dose-related adverse effects and avoiding suboptimal concentrations. A new high-performance liquid chromatography assay method was developed and validated for determination of the above-mentioned drugs in small samples of human plasma. After protein precipitation with acetonitrile:methanol (1:1, vol/vol), satisfactory separation was achieved on a Hypersil BDS C18 column (250 × 4.6 mm, 5 μm) using a mobile phase comprising 20 mM sodium dihydrogen phosphate-2 hydrate (pH = 3.2) and acetonitrile at a ratio of 75:25, vol/vol; the elution was isocratic at ambient temperature with a flow rate of 1.5 mL/min. The ultraviolet detector was set at 260 nm. The validated method was applied to assay real plasma samples used for pharmacokinetic studies and therapeutic drug monitoring of the selected drugs. The assay method described was found to be rapid, sensitive, reproducible, precise, and accurate. Linearity was demonstrated over the concentration ranges as follows: 0.1-30 μg/mL for linezolid and tinidazole; 0.05-5 μg/mL for norfloxacin; and 0.1-10 μg/mL for moxifloxacin, levofloxacin, and gatifloxacin (mean r = 0.9999, n = 12). The observed within- and between-day assay precisions were within 12.5%, whereas accuracy ranged between 92.0% and 112% for all the analytes. The lower limit of quantification was 0.1 μg/mL for all the analytes except norfloxacin which was 0.05 μg/mL. This assay method was valid within a wide range of plasma concentrations and may be proposed as a suitable

  14. Linezolid-resistant mucoid Staphylococcus haemolyticus from a tertiary-care centre in Delhi

    Directory of Open Access Journals (Sweden)

    M. Matlani

    2016-05-01

    Full Text Available We report an unusual morphological mucoid variant of Staphylococcus haemolyticus associated with linezolid resistance from a patient with sepsis. Linezolid resistance and mucoid character together made this pathogen difficult to treat. To our knowledge this is the first such report.

  15. Reduced Susceptibility to Rifampicin and Resistance to Multiple Antimicrobial Agents among Brucella abortus Isolates from Cattle in Brazil.

    Science.gov (United States)

    Barbosa Pauletti, Rebeca; Reinato Stynen, Ana Paula; Pinto da Silva Mol, Juliana; Seles Dorneles, Elaine Maria; Alves, Telma Maria; de Sousa Moura Souto, Monalisa; Minharro, Silvia; Heinemann, Marcos Bryan; Lage, Andrey Pereira

    2015-01-01

    This study aimed to determine the susceptibility profile of Brazilian Brucella abortus isolates from cattle to eight antimicrobial agents that are recommended for the treatment of human brucellosis and to correlate the susceptibility patterns with origin, biotype and MLVA16-genotype of the strains. Screening of 147 B. abortus strains showed 100% sensitivity to doxycycline and ofloxacin, one (0.68%) strain resistant to ciprofloxacin, two strains (1.36%) resistant to streptomycin, two strains (1.36%) resistant to trimethoprim-sulfamethoxazole and five strains (3.40%) resistant to gentamicin. For rifampicin, three strains (2.04%) were resistant and 54 strains (36.73%) showed reduced sensitivity. Two strains were considered multidrug resistant. In conclusion, the majority of B. abortus strains isolated from cattle in Brazil were sensitive to the antimicrobials commonly used for the treatment of human brucellosis; however, a considerable proportion of strains showed reduced susceptibility to rifampicin and two strains were considered multidrug resistant. Moreover, there was no correlation among the drug susceptibility pattern, origin, biotype and MLVA16-genotypes of these strains.

  16. Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections, with focus on doxycycline.

    Science.gov (United States)

    Hamad, Tarza; Hellmark, Bengt; Nilsdotter-Augustinsson, Åsa; Söderquist, Bo

    2015-12-01

    In recent years, coagulase-negative staphylococci such as Staphylococcus epidermidis have gained importance as nosocomial pathogens, especially in immunocompromised patients and prosthetic joint infections (PJIs). These infections are often long lasting and difficult to treat due to the production of bacterial biofilm and the transformation of the bacteria into a stationary growth phase. Rifampicin is able to penetrate the biofilm, but to reduce the risk of development of rifampicin resistance it should be used in combination with an additional antibiotic. In this study we used Etest to investigate the antimicrobial susceptibility of 134 clinical isolates of S. epidermidis obtained from PJIs to six oral antibiotics: doxycycline, rifampicin, linezolid, fusidic acid, clindamycin, and ciprofloxacin. We also performed synergy testing on doxycycline in combination with each of the remaining antibiotics. Ninety-three (69%) of the 134 isolates were susceptible to doxycycline, 94/134 (70%) to rifampicin, 56/134 (42%) to clindamycin, 25/134 (19%) to ciprofloxacin, 81/134 (60%) to fusidic acid, and 100% to linezolid. Thirty-two (80%) of the 40 isolates not fully susceptible to rifampicin were susceptible to doxycycline. Doxycycline in combination with each of the other investigated antibiotics exerted an additive effect on nearly half of the isolates, with the exception of clindamycin, which displayed an even higher percentage of additive effect (69%). To conclude, as the majority of the S. epidermidis isolates were susceptible to doxycycline, this antimicrobial agent may provide a potential alternative for combination therapy together with rifampicin. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  17. Antimicrobial Drug Resistance of Salmonella enterica Serovar Typhi in Asia and Molecular Mechanism of Reduced Susceptibility to the Fluoroquinolones▿

    OpenAIRE

    Chau, Tran Thuy; Campbell, James Ian; Galindo, Claudia M; Van Minh Hoang, Nguyen; Diep, To Song; Nga, Tran Thu Thi; van Vinh Chau, Nguyen; Tuan, Phung Quoc; Page, Anne Laure; Ochiai, R Leon; Schultsz, Constance; Wain, John; Zulfiqar A. Bhutta; Parry, Christopher M.; Bhattacharya, Sujit K.

    2007-01-01

    This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between ...

  18. In vitro pharmacokinetic/pharmacodynamic activity of NXL103 versus clindamycin and linezolid against clinical Staphylococcus aureus and Streptococcus pyogenes isolates.

    Science.gov (United States)

    Vidaillac, Celine; Parra-Ruiz, Jorge; Winterfield, Patricia; Rybak, Michael J

    2011-10-01

    NXL103 (linopristin/flopristin, 30/70) is a novel oral streptogramin combination with activity against a large variety of multidrug-resistant Gram-positive pathogens. The objective of this study was to evaluate the in vitro activity of NXL103 in comparison with oral comparators (clindamycin and linezolid). Six clinical isolates [four meticillin-resistant Staphylococcus aureus (MRSA) and two Streptococcus pyogenes] were exposed for 48 h in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model at a starting inoculum of ca. 10(6) colony-forming units (CFU)/mL. Antimicrobial simulations included NXL103 500 mg every 12 h, linezolid 600 mg every 12 h and clindamycin 450 mg every 6 h. Bactericidal and static effects were defined as ≥3log(10) and pyogenes and 0.125-0.25 mg/L for MRSA isolates. In the PK/PD model, NXL103 demonstrated significantly better activity than linezolid and clindamycin (Ppyogenes strains and between 7.3-32 h against MRSA isolates. In contrast, linezolid only exhibited a static effect, whereas clindamycin achieved 3log(10) kill at 6h against the unique clindamycin-susceptible S. pyogenes strain evaluated. In conclusion, at therapeutic concentrations NXL103 exhibits promising activity against both MRSA and S. pyogenes strains, including clindamycin-resistant organisms. Further in vitro and in vivo experiments are warranted to explore the therapeutic benefit of NXL103 for the treatment of Gram-positive skin and soft-tissue infections. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  19. Expression of viral EPS-depolymerase reduces fire blight susceptibility in transgenic pear.

    Science.gov (United States)

    Malnoy, Mickaël; Faize, Mohamed; Venisse, Jean-Stéphane; Geider, Klaus; Chevreau, Elisabeth

    2005-02-01

    Erwinia amylovora is the causal agent of fire blight of Maloideae. One of the main pathogenicity factors of this bacterium is the exopolysaccharide (EPS) of its capsule. In this paper, we used genetic transformation tools to constitutively express an EPS-depolymerase transgene in the pear (Pyrus communis L.) cv. Passe Crassane with the aim of decreasing its high susceptibility to fire blight. Expression of the depolymerase gene in 15 independent transgenic clones led, on average, to low depolymerase activity, although relatively high expression was observed at the transcriptional and translational levels. Only two of the transgenic clones (9X and 10M) consistently showed a decrease in fire blight susceptibility in vitro and in the greenhouse. These clones were also among the highest expressers of depolymerase at the RNA and enzyme activity levels. The correlation observed among all transgenic clones between depolymerase expression and fire blight resistance suggested the potential of this strategy.

  20. Comparative in vitro activity of oritavancin and other agents against methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Sweeney, Debora; Shinabarger, Dean L; Arhin, Francis F; Belley, Adam; Moeck, Greg; Pillar, Chris M

    2017-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections constitute a threat to the public health due to their prevalence and associated mortality and morbidity. Several agents have been recently approved to treat MRSA skin infections including lipoglycopeptides (dalbavancin, oritavancin, and telavancin), ceftaroline, and tedizolid. This study compared the MIC, minimum bactericidal concentration (MBC), and time-kill of these agents alongside daptomycin, linezolid, and vancomycin against MRSA (n=15); meropenem, cefazolin, and nafcillin were also included against methicillin-susceptible S. aureus (MSSA [n=12]). MIC and MBC testing was conducted in accordance with Clinical and Laboratory Standards Institute guidelines, and time-kills were evaluated at multiples of the MIC and the free-drug maximum plasma concentration (fCmax) at both standard and high inoculum densities for a subset of MRSA (n=2) and MSSA (n=2). MRSA and MSSA were highly susceptible to all agents, with the lipoglycopeptides having the most potent activity by MIC50/90. All agents excluding tedizolid and linezolid were bactericidal by MBC for MRSA and MSSA, though dalbavancin and telavancin exhibited strain-specific bactericidal activity for MRSA. All agents excluding tedizolid and linezolid were bactericidal by time-kill at their respective fCmax against MRSA and MSSA at standard inoculum density, though oritavancin exhibited the most rapid bactericidal activity. Oritavancin and daptomycin at their respective fCmax maintained similar kill curves at high inoculum density. In contrast, the killing observed with other agents was typically reduced or slowed at high inoculum density. These data demonstrate the rapid bactericidal activity of oritavancin and daptomycin against S. aureus relative to other MRSA agents regardless of bacterial burden.

  1. Evaluation of the stability of linezolid in aqueous solution and commonly used intravenous fluids

    Directory of Open Access Journals (Sweden)

    Taylor R

    2017-07-01

    Full Text Available Rachel Taylor, Bruce Sunderland, Giuseppe Luna, Petra Czarniak School of Pharmacy, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia Purpose: The aim was to evaluate the stability of linezolid in commonly used intravenous fluids and in aqueous solution to determine the kinetics of degradation and shelf-life values at alkaline pH values. Methods: Forced degradation studies were performed on linezolid in solution to develop a validated high-performance liquid chromatography analysis. Sodium chloride 0.9%, sodium lactate, and glucose 5% and glucose 10% solution containing 2.0 mg/mL linezolid were stored at 25.0°C (±0.1°C for 34 days. The effect of temperature on the stability of linezolid in 0.1 M sodium hydroxide solution was investigated to determine the activation energy. The degradation rates of linezolid at selected pH values at 70.0°C and the influence of ionic strength were also examined. Activation energy data were applied to determine the shelf-life values at selected pH values, and a pH rate profile was constructed over the pH range of 8.7–11.4. The stability of intravenous linezolid (Zyvox® solution was evaluated by storing at 70.0°C for 72 hours. Results: Linezolid was found to maintain >95.0% of its initial concentration after storage at 25.0°C for 34 days in sodium lactate, 0.9% in sodium chloride, and 5% and 10% in glucose solutions. Linezolid was degraded at alkaline pH values by first-order kinetics. Activation energy data showed that temperature, but not ionic strength, influenced the degradation rate significantly. An activation energy of 58.22 kJ/mol was determined for linezolid in 0.1 M sodium hydroxide solution. Linezolid was least stable at high pH values and at elevated temperatures. It was determined that linezolid has adequate stability for the preparation of intravenous fluids for clinical administration. Conclusion: Linezolid was found to have a shelf life of 34 days at 25°C when added to

  2. Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia.

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    Urvashi Bhan

    Full Text Available Post influenza pneumonia is a leading cause of mortality and morbidity, with mortality rates approaching 60% when bacterial infections are secondary to multi-drug resistant (MDR pathogens. Staphylococcus aureus, in particular community acquired MRSA (cMRSA, has emerged as a leading cause of post influenza pneumonia.Linezolid (LZD prevents acute lung injury in murine model of post influenza bacterial pneumonia.Mice were infected with HINI strain of influenza and then challenged with cMRSA at day 7, treated with antibiotics (LZD or Vanco or vehicle 6 hours post bacterial challenge and lungs and bronchoalveolar lavage fluid (BAL harvested at 24 hours for bacterial clearance, inflammatory cell influx, cytokine/chemokine analysis and assessment of lung injury.Mice treated with LZD or Vanco had lower bacterial burden in the lung and no systemic dissemination, as compared to the control (no antibiotic group at 24 hours post bacterial challenge. As compared to animals receiving Vanco, LZD group had significantly lower numbers of neutrophils in the BAL (9×10(3 vs. 2.3×10(4, p < 0.01, which was associated with reduced levels of chemotactic chemokines and inflammatory cytokines KC, MIP-2, IFN-γ, TNF-α and IL-1β in the BAL. Interestingly, LZD treatment also protected mice from lung injury, as assessed by albumin concentration in the BAL post treatment with H1N1 and cMRSA when compared to vanco treatment. Moreover, treatment with LZD was associated with significantly lower levels of PVL toxin in lungs.Linezolid has unique immunomodulatory effects on host inflammatory response and lung injury in a murine model of post-viral cMRSA pneumonia.

  3. Adaptation to NaCl Reduces the Susceptibility of Enterococcus faecalis to Melaleuca alternifolia (Tea Tree) Oil.

    Science.gov (United States)

    Lim, Ee Lin; Hammer, Katherine Ann

    2015-10-01

    This study investigated the hypothesis that the salt adaptation response of Enterococcus faecalis alters susceptibility to tea tree oil (TTO). Six E. faecalis isolates were adapted to 6.5 % NaCl, and then exposed to TTO in phosphate-buffered saline (PBS). One isolate was also exposed to TTO in Brain Heart Infusion Broth (BHIB). The viability of salt-adapted and non-adapted control cells was determined at 0, 45 and 90 min and compared. MICs for several antibiotics and TTO were also determined by E test and broth microdilution, respectively. Results showed that susceptibility to TTO in PBS was significantly reduced after salt adaptation for five isolates (83 %) (P < 0.05). Mean differences between salt-adapted and non-adapted cell counts were 2.51 log at 45 min and 2.13 log at 90 min. However, when E. faecalis ATCC 19433 was exposed to TTO in BHIB, no significant differences were seen. In conclusion, salt adaptation resulted in reduced susceptibility to TTO in PBS for the majority of isolates, indicating that cross protection had occurred. This effect was absent in BHIB, suggesting that the uptake of compatible solutes from the growth medium protected non-adapted cells from TTO. Whether this has implications for the clinical effectiveness of TTO remains to be determined.

  4. Frequency of Reduced Vancomycin Susceptibility among Clinical Staphylococcus aureus Isolated in Ahvaz Iran

    Directory of Open Access Journals (Sweden)

    Mojtaba Moosavian

    2015-11-01

    Full Text Available Introduction:   One   of   the   most   important   agents   in   hospital-acquired   infections   is Staphylococcus aureus. Treatment of methicillin-resistant S. aureus (MRSA infections with decreased susceptibility to vancomycin has recently been more difficult. The aim of this study was to evaluate the possible presence of vancomycin intermediate S. aureus (VISA and vancomycin- resistant S. aureus (VRSA and also to determine the frequency of MRSA in clinical specimens.Methods: In this study, 195 S. aureus isolates were collected from the patients were examined. All of the isolates were identified using standard biochemical tests.  Susceptibility of S. aureus isolates against 10 antibiotics was detected by disk diffusion method and was followed by E-test and vancomycin screen agar methods. Minimum inhibitory concentration (MIC of vancomycin was determined according to the CLSI guidelines.  Also, detection of mecA gene was performed by PCR and finally, the results were compared.Results: All of the isolates were susceptible to vancomycin (i.e. MIC range of vancomycin was between 0.25-2 µg/ml. Out of 195 S. aureus isolates, 99 isolates (50.8% were resistant to methicillin, and mecA gene was detected in 96 isolates. These results also showed that the highest and lowest resistance rate of isolates was to penicillin (96.9% and chloramphenicol (0%, respectively.Conclusion: Our findings showed that vancomycin can still be used as a valuable drug for treatment of S. aureus infections in our region. However, periodic evaluation of vancomycin MIC of S. aureus isolates is critical for monitoring MRSA and preventing the spread of VISA or VRSA among patients.

  5. Brown dog tick, Rhipicephalus sanguineus sensu lato, infestation of susceptible dog hosts is reduced by slow release of semiochemicals from a less susceptible host.

    Science.gov (United States)

    de Oliveira Filho, Jaires Gomes; Ferreira, Lorena Lopes; Sarria, André Lucio Franceschini; Pickett, John A; Birkett, Michael A; Mascarin, Gabriel Moura; de León, Adalberto A Pérez; Borges, Lígia Miranda Ferreira

    2017-01-01

    Domestic dog breeds are hosts for the brown dog tick, Rhipicephalus sanguineus sensu lato, but infestation levels vary among breeds. Beagles are less susceptible to tick infestations than English cocker spaniels due to enhanced production of 2-hexanone and benzaldehyde that act as volatile tick repellents. We report the use of prototype slow-release formulations of these compounds to reduce the burden of R. sanguineus s. l. on English cocker spaniel dogs. Twelve dogs were randomly assigned to two groups with six dogs each. The treated group received collars with slow-release formulations of the compounds attached, while the control group received collars with clean formulations attached. Five environmental infestations were performed, with the number of ticks (at all stages) on the dogs being counted twice a day for 45days. The counts on the number of tick stages found per dog were individually fitted to linear mixed effects models with repeated measures and normal distribution for errors. The mean tick infestation in the treated group was significantly lower than in the control group. For larvae and nymphs, a decrease in tick infestation was observed at the fifth count, and for adults, lower average counts were observed in all counts. The compounds did not interfere with the distribution of the ticks on the body of the dogs, as a similar percentage of ticks was found on the anterior half of the dogs (54.5% for the control group and 56.2% for the treated group). The biological and reproductive parameters of the ticks were not affected by the repellents. This study highlights for the first time the potential use of a novel allomone (repellent)-based formulation for reduction of tick infestation on susceptible dogs. Copyright © 2016 Elsevier GmbH. All rights reserved.

  6. Investigation of mechanism and molecular epidemiology of linezolid-resistant Enterococcus faecalis in China.

    Science.gov (United States)

    Wang, Lipeng; He, Yunyan; Xia, Yun; Wang, Huijuan; Liang, Shumei

    2014-08-01

    Enterococcus is a major cause of important nosocomial infections. Linezolid, the first member of an entirely new class of antibiotics (oxazolidinones), is effective against serious infections caused by Enterococcus. However, resistance to linezolid has been discovered throughout the world rapidly. From 2011 to 2013, nine linezolid-resistant E. faecalis isolates were collected and the possible mechanisms of linezolid resistance, including mutations in domain V of 23S rRNA genes and in ribosomal proteins L3 and L4, and the multiresistance gene cfr, were investigated. Furthermore, an epidemiological survey of the nine linezolid-resistant E. faecalis isolates was performed by pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and DiversiLab. The three methods were compared to evaluate their merits and demerits, respectively. We failed to find the resistance mechanisms that have been revealed in recent years by PCR and sequencing analysis in the linezolid-resistant E. faecalis. Epidemiological investigation suggested that a small-scale outbreak of linezolid-resistant E. faecalis emerged in neurosurgery ICU from March to May of 2013. DiversiLab was a reliable typing tool and a suitable alternative to PFGE because it was as discriminatory as PFGE and better than MLST.

  7. Linezolid, a novel oxazolidinone antibiotic: assessment of monoamine oxidase inhibition using pressor response to oral tyramine.

    Science.gov (United States)

    Antal, E J; Hendershot, P E; Batts, D H; Sheu, W P; Hopkins, N K; Donaldson, K M

    2001-05-01

    The primary objective of this study was to compare the effects of oral linezolid with moclobemide and placebo on the pressor response to oral tyramine. Secondary objectives were to determine possible mechanisms of the effect based on changes in the pharmacokinetics of tyramine and to evaluate alternative methods for quantifying the pressor effect. Subjects received linezolid (625 mg bid orally), moclobemide (150 mg tid orally), or placebo for up to 7 days. Using the oral tyramine dose producing a >30 mmHg increase in systolic blood pressure (SBP) (PD>30), a positive pressor response was defined as a PD>30 index (pretreatment/treatment ratio of PD>30) of > or = 2. There were 8/10, 11/11, and 1/10 responders with linezolid, moclobemide, and placebo, respectively. Responses returned to baseline within 2 days of drug discontinuation. The ratio of mean greatest SBP and heart rate at the time of greatest SBP (GSBP/HR) increased linearly with tyramine dose both pretreatment and during treatment with linezolid and moclobemide. During treatment, responses to tyramine when subjects took linezolid or moclobemide were significantly different from placebo. Both drugs significantly decreased tyramine oral clearance compared with placebo. Urinary excretion of catecholamines and metabolites was consistent with MAOI activity of the drugs, but results were variable. The MAOI activity of linezolid is similar to that of moclobemide, a drug used clinically without food restrictions. Restrictions to normal dietary intake of tyramine-containing foods are not warranted when taking linezolid.

  8. Anti-inflammatory effects of linezolid on carrageenan-induced paw edema in rats.

    Science.gov (United States)

    Matsumoto, Kazuaki; Obara, Shigeaki; Kuroda, Yuko; Kizu, Junko

    2015-12-01

    The immunomodulatory activity of linezolid has recently been reported using in vitro experimental models. However, the anti-inflammatory activity of linezolid has not yet been demonstrated using in vivo experimental models. Therefore, the aim of the present study was to demonstrate the anti-inflammatory activity of linezolid and other anti-MRSA agents using the carrageenan-induced rat paw edema model. The pretreatment with 50 mg/kg linezolid significantly suppressed edema rates, compared with control (5% glucose), with edema rates at 0.5 and 3 h after the administration of carrageenan being 17.3 ± 3.5 and 30.8 ± 3.0%, respectively. On the other hand, edema rates were not suppressed by the pretreatments with 50 mg/kg vancomycin, teicoplanin, arbekacin, and daptomycin. Furthermore, we demonstrated that linezolid exhibited anti-inflammatory activity in a concentration-dependent manner. These effects were observed at linezolid concentrations that are achievable in human serum with conventional dosing. In conclusion, the results of the present study suggest that the anti-inflammatory activities of linezolid, in addition to its antimicrobial effects, have a protective effect against destructive inflammatory responses in areas of inflammation. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Bombay phenotype is associated with reduced plasma-VWF levels and an increased susceptibility to ADAMTS13 proteolysis.

    Science.gov (United States)

    O'Donnell, James S; McKinnon, Thomas A J; Crawley, James T B; Lane, David A; Laffan, Michael A

    2005-09-15

    ABO blood group is an important determinant of plasma von Willebrand factor antigen (VWF:Ag) levels, with lower levels in group O. Previous reports have suggested that ABO(H) sugars affect the susceptibility of VWF to ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 repeats-13) cleavage. To further test this hypothesis, we collected plasma from individuals with the rare Bombay blood group. VWF:Ag levels were significantly lower in Bombay patients (median, 0.69 IU/mL) than in groups AB, A, or B (P Bombays compared with either group O or AB. Increasing urea concentration (0.5 to 2 M) increased the cleavage rate for each blood group but eliminated the differences between groups. We conclude that reduction in the number of terminal sugars on N-linked glycan increases susceptibility of globular VWF to ADAMTS13 proteolysis and is associated with reduced plasma VWF:Ag and VWF:CB levels.

  10. Resistance to Linezolid Caused by Modifications at Its Binding Site on the Ribosome

    DEFF Research Database (Denmark)

    Long, Katherine S.; Vester, Birte

    2012-01-01

    Linezolid is an oxazolidinone antibiotic in clinical use for the treatment of serious infections of resistant Gram-positive bacteria. It inhibits protein synthesis by binding to the peptidyl transferase center on the ribosome. Almost all known resistance mechanisms involve small alterations...... of 23S rRNA has for some time been established as a linezolid resistance mechanism. Although ribosomal proteins L3 and L4 are located further away from the bound drug, mutations in specific regions of these proteins are increasingly being associated with linezolid resistance. However, very little...... of a new generation of oxazolidinones that show improved properties against the known resistance mechanisms....

  11. A cfr-positive clinical staphylococcal isolate from India with multiple mechanisms of linezolid-resistance

    Directory of Open Access Journals (Sweden)

    Vineeth Rajan

    2014-01-01

    Full Text Available Background & objectives: Linezolid, a member of the oxazolidinone class of antibiotics, has been an effective therapeutic option to treat severe infections caused by multidrug resistant Gram positive bacteria. Emergence of linezolid resistant clinical strains is a serious issue in the healthcare settings worldwide. We report here the molecular characterization of a linezolid resistant clinical isolate of Staphylococcus haemolyticus from India. Methods: The species of the clinical isolate was identified by 16S rRNA gene sequencing. The minimum inhibitory concentrations (MICs of linezolid, clindamycin, chloramphenicol and oxacillin were determined by E-test method. To elucidate the mechanism of linezolid-resistance, presence of cfr gene (chloramphenicol florfenicol resistance and mutations in 23S rRNA and ribosomal proteins (L3, L4 and L22 were investigated. Staphylococcal Cassette Chromosome mec (SCCmec typing was performed by multiplex PCR. Results: The study documented a rare clinical S. haemolyticus strain with three independent mechanisms of linezolid-resistance. The strain carried cfr gene, the only known transmissible mechanism of linezolid-resistance. The strain also possessed resistance-conferring mutations such as G 2576 T in domain V of 23S rRNA gene and Met 156 Thr in L3 ribosomal protein. The other ribosomal proteins (L4 and L22 did not exhibit mutations accountable for linezolid-resistance. Restriction digestion by NheI revealed that all the alleles of 23S rRNA gene were mutated. The isolate showed elevated MIC values (>256 ΅g ml -[1] of linezolid, clindamycin, chloramphenicol and oxacillin. Methicillin resistance was conferred by type I SCCmec element. The strain also harboured lsa(B gene which encodes an ABC transporter that can efflux clindamycin. Interpretation & conclusions: The present study reports the first clinical strain from India with transmissible and multiple mechanisms of linezolid-resistance. Judicious use of

  12. Additives to reduce susceptibility of thermosets and thermoplastics to erosion from atomic oxygen

    Science.gov (United States)

    Orwoll, Robert A.

    1990-01-01

    Polymeric materials have many attractive features such as light weight, high strength, and broad applicability in the form of films, fibers, and molded objects. In low earth orbit (LEO), these materials, when exposed on the exterior of the spacecraft, have the serious disadvantage of being susceptible to erosion by atomic oxygen (AO). AO is the most common chemical species at LEO altitudes. AO can be an extremely efficient oxidizing agent as was apparent from the extensive erosion of organic films exposed in STS missions. The mechanism for erosion involves the reaction of oxygen atoms at the surface of the substrate to form small molecular species. The susceptibility of polymeric materials varies with their chemical composition. Films with silicon atoms incorporated in the molecular structures have large coefficients of thermal expansion. This limits their utility. In an alternative approach additives were sought that mix physically and form a protective oxide layer when the film is exposed to AO. A large number of organic compounds containing silicon, germanium, or tin atoms were screened. Most were found to have very limited solubility in the polyetherimide (Ultem) films that were being protected from AO. However, one, bis(triphenyl tin) oxide, (BTO), is miscible in Ultem up to about 25 percent. Films of Ultem polyimide containing up to 25 wt percent BTO were prepared by evaporation of solvent from a solution of Ultem and BTO. The effects of AO on these films were simulated in the oxygen atmosphere of a radio frequency glow-discharge chamber. In the second part of this study, atoms were incorporated in epoxy resins. Experiments are in progress to measure the resistance of films of the cured epoxy to AO in the discharge chamber.

  13. Reduced CD4 T cell activation and in vitro susceptibility to HIV-1 infection in exposed uninfected Central Africans

    Directory of Open Access Journals (Sweden)

    Fontanet Arnaud

    2006-06-01

    Full Text Available Abstract Background Environmentally driven immune activation was suggested to contribute to high rates of HIV-1 infection in Africa. We report here a study of immune activation markers and susceptibility to HIV-1 infection in vitro of forty-five highly exposed uninfected partners (EUs of HIV-1 infected individuals in Central African Republic, in comparison with forty-four low-risk blood donors (UCs. Results Analysis of T lymphocyte subsets and activation markers in whole blood showed that the absolute values and the percentage of HLA-DR+CD4 T cells and of CCR5+CD4 T cells were lower in the EUs than in the UCs (p = 0.0001. Mutations in the CCR5 coding region were not found in either group. Susceptibility to in vitro infection of unstimulated peripheral blood mononuclear cells, prior of PHA activation, was decreased in EUs compared to UCs, either using a CXCR4-tropic or a CCR5-tropic HIV-1 strain (p = 0.02 and p = 0.05, respectively. Levels of MIP-1β, but not of MIP-1α or RANTES, in the supernatants of PHA-activated PBMC, were higher in the EUs than in the UCs (p = 0.007. Conclusion We found low levels of CD4 T cell activation and reduced PBMC susceptibility to HIV-1 infection in Central African EUs, indicating that both may contribute to the resistance to HIV-1 infection.

  14. Molecular mechanism of hepatitis C virus replicon variants with reduced susceptibility to a benzofuran inhibitor, HCV-796.

    Science.gov (United States)

    Howe, Anita Y M; Cheng, Huiming; Johann, Stephen; Mullen, Stanley; Chunduru, Srinivas K; Young, Dorothy C; Bard, Joel; Chopra, Rajiv; Krishnamurthy, Girija; Mansour, Tarek; O'Connell, John

    2008-09-01

    HCV-796 selectively inhibits hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. In hepatoma cells containing a genotype 1b HCV replicon, HCV-796 reduced HCV RNA levels by 3 to 4 log(10) HCV copies/mug total RNA (the concentration of the compound that inhibited 50% of the HCV RNA level was 9 nM). Cells bearing replicon variants with reduced susceptibility to HCV-796 were generated in the presence of HCV-796, followed by G418 selection. Sequence analysis of the NS5B gene derived from the replicon variants revealed several amino acid changes within 5 A of the drug-binding pocket. Specifically, mutations were observed at Leu314, Cys316, Ile363, Ser365, and Met414 of NS5B, which directly interact with HCV-796. The impacts of the amino acid substitutions on viral fitness and drug susceptibility were examined in recombinant replicons and NS5B enzymes with the single-amino-acid mutations. The replicon variants were 10- to 1,000-fold less efficient in forming colonies in cells than the wild-type replicon; the S365L variant failed to establish a stable cell line. Other variants (L314F, I363V, and M414V) had four- to ninefold-lower steady-state HCV RNA levels. Reduced binding affinity with HCV-796 was demonstrated in an enzyme harboring the C316Y mutation. The effects of these resistance mutations were structurally rationalized using X-ray crystallography data. While different levels of resistance to HCV-796 were observed in the replicon and enzyme variants, these variants retained their susceptibilities to pegylated interferon, ribavirin, and other HCV-specific inhibitors. The combined virological, biochemical, biophysical, and structural approaches revealed the mechanism of resistance in the variants selected by the potent polymerase inhibitor HCV-796.

  15. Upregulated HSP27 in human breast cancer cells reduces Herceptin susceptibility by increasing Her2 protein stability

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    Kong Sun-Young

    2008-10-01

    Full Text Available Abstract Background Elucidating the molecular mechanisms by which tumors become resistant to Herceptin is critical for the treatment of Her2-overexpressed metastatic breast cancer. Methods To further understand Herceptin resistance mechanisms at the molecular level, we used comparative proteome approaches to analyze two human breast cancer cell lines; Her2-positive SK-BR-3 cells and its Herceptin-resistant SK-BR-3 (SK-BR-3 HR cells. Results Heat-shock protein 27 (HSP27 expression was shown to be upregulated in SK-BR-3 HR cells. Suppression of HSP27 by specific siRNA transfection increased the susceptibility of SK-BR-3 HR cells to Herceptin. In the presence of Herceptin, Her2 was downregulated in both cell lines. However, Her2 expression was reduced by a greater amount in SK-BR-3 parent cells than in SK-BR-3 HR cells. Interestingly, co-immunoprecipitation analysis showed that HSP27 can bind to Her2. In the absence of Herceptin, HSP27 expression is suppressed and Her2 expression is reduced, indicating that downregulation of Her2 by Herceptin can be obstructed by the formation of a Her2-HSP27 complex. Conclusion Our present study demonstrates that upregulated HSP27 in human breast cancer cells can reduce Herceptin susceptibility by increasing Her2 protein stability.

  16. Comparison of the SUPERCARBA, CHROMagar KPC, and Brilliance CRE screening media for detection of Enterobacteriaceae with reduced susceptibility to carbapenems.

    Science.gov (United States)

    Girlich, Delphine; Poirel, Laurent; Nordmann, Patrice

    2013-02-01

    The recently developed SUPERCARBA medium was evaluated together with 2 commercially available selective culture media containing carbapenems: CHROMagar KPC (CHROMagar) and Brilliance CRE (Oxoid, Thermofisher Scientific). A total of 142 enterobacterial isolates were tested, including 131 isolates with reduced susceptibility to carbapenems. The SUPERCARBA medium has the highest sensitivity (96.5%) (detecting virtually all carbapenemase producers including OXA-48-like producers) as compared to Brilliance CRE (76.3%) and CHROMagar KPC (43%). The specificity of the screening media was similar, ranging from 57% to 68%.

  17. Suboptimal clinical response to ciprofloxacin in patients with enteric fever due to Salmonella spp. with reduced fluoroquinolone susceptibility: a case series

    Directory of Open Access Journals (Sweden)

    Jessamine Peter

    2004-09-01

    Full Text Available Abstract Background Salmonella spp. with reduced susceptibility to fluoroquinolones have higher than usual MICs to these agents but are still considered "susceptible" by NCCLS criteria. Delayed treatment response to fluoroquinolones has been noted, especially in cases of enteric fever due to such strains. We reviewed the ciprofloxacin susceptibility and clinical outcome of our recent enteric fever cases. Methods Salmonella enterica Serotype Typhi (S. Typhi and Serotype Paratyphi (S. Paratyphi blood culture isolates (1998–2002 were tested against nalidixic acid by disk diffusion (DD and agar dilution (AD and to ciprofloxacin by AD using NCCLS methods and interpretive criteria. Reduced fluoroquinolone susceptibility was defined as a ciprofloxacin MIC of 0.125–1.0 mg/L. The clinical records of patients treated with ciprofloxacin for isolates with reduced fluoroquinolone susceptibility were reviewed. Results Seven of 21 (33% S. Typhi and S. Paratyphi isolates had reduced susceptibility to fluoroquinolones (MIC range 0.125–0.5 mg/L. All 7 were nalidixic acid resistant by DD (no zone and by AD (MIC 128- >512 mg/L. The other 14 isolates were nalidixic acid susceptible and fully susceptible to ciprofloxacin (MIC range 0.015–0.03 mg/L. Five of the 7 cases were treated initially with oral ciprofloxacin. One patient remained febrile on IV ciprofloxacin until cefotaxime was added, with fever recurrence when cefotaxime was discontinued. Two continued on oral or IV ciprofloxacin alone but had prolonged fevers of 9–10 days duration, one was switched to IV beta-lactam therapy after remaining febrile for 3 days on oral/IV ciprofloxacin and one was treated successfully with oral ciprofloxacin. Four of the 5 required hospitalization. Conclusions Our cases provide further evidence that reduced fluoroquinolone susceptibility of S. Typhi and S. Paratyphi is clinically significant. Laboratories should test extra-intestinal Salmonella spp. for reduced

  18. Optimization of nebulized delivery of linezolid, daptomycin, and vancomycin aerosol

    Directory of Open Access Journals (Sweden)

    Zarogoulidis P

    2014-08-01

    Full Text Available Paul Zarogoulidis,1 Ioannis Kioumis,1 Sofia Lampaki,1 John Organtzis,1 Konstantinos Porpodis,1 Dionysios Spyratos,1 Georgia Pitsiou,1 Dimitris Petridis,2 Athanasia Pataka,1 Haidong Huang,3 Qiang Li,3 Lonny Yarmus,4 Wolfgang Hohenforst-Schmidt,5 Nikolaos Pezirkianidis,6 Konstantinos Zarogoulidis1 1Pulmonary Department-Oncology Unit, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Department of Food Technology, School of Food Technology and Nutrition, Alexander Technological Educational Institute, Thessaloniki, Greece; 3Department of Respiratory Diseases, Shanghai Hospital, II Military University Hospital, Shanghai, People’s Republic of China; 4Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA; 5II Medical Department, “Coburg” Regional Hospital, Coburg, Germany; 6Surgery Department, Private Cabinet, Serres, Greece Background: At this time, several antibiotics have been investigated as possibilities for aerosol administration, but local therapy has been found to be more efficient in several diseases. Materials and methods: The drugs linezolid (Zyvox, vancomycin (Voncon, and daptomycin (Cubicin were tested with three jet nebulizers with seven different residual cups and different loadings. Moreover, three ultrasound nebulizers were again tested with these drugs, with different loadings and mouthpiece attachments. Results: When drugs are combined with particular cup designs, they significantly lower the droplet size to 1.60 and 1.80 µm, which represents the best combination of Zyvox and cup G and Cubicin and cup D, respectively. Cup design D is suggested as the most effective cup for lowering the droplet size (2.30 µm when considering a higher loading level (8 mL. Conclusion: Modification of current drugs from dry powder to solution is possible, and the residual cup design plays the most important role in droplet size production when the

  19. Reduced Susceptibility to Xanthomonas citri in Transgenic Citrus Expressing the FLS2 Receptor From Nicotiana benthamiana.

    Science.gov (United States)

    Hao, Guixia; Pitino, Marco; Duan, Yongping; Stover, Ed

    2016-02-01

    Overexpression of plant pattern-recognition receptors by genetic engineering provides a novel approach to enhance plant immunity and broad-spectrum disease resistance. Citrus canker disease associated with Xanthomonas citri is one of the most important diseases damaging citrus production worldwide. In this study, we cloned the FLS2 gene from Nicotiana benthamiana cDNA and inserted it into the binary vector pBinPlus/ARS to transform Hamlin sweet orange and Carrizo citrange. Transgene presence was confirmed by polymerase chain reaction (PCR) and gene expression of NbFLS2 was compared by reverse transcription quantitative PCR. Reactive oxygen species (ROS) production in response to flg22Xcc was detected in transgenic Hamlin but not in nontransformed controls. Low or no ROS production was detected from nontransformed Hamlin seedlings challenged with flg22Xcc. Transgenic plants highly expressing NbFLS2 were selected and were evaluated for resistance to canker incited by X. citri 3213. Our results showed that the integration and expression of the NbFLS2 gene in citrus can increase canker resistance and defense-associated gene expression when challenged with X. citri. These results suggest that canker-susceptible Citrus genotypes lack strong basal defense induced by X. citri flagellin and the resistance of these genotypes can be enhanced by transgenic expression of the flagellin receptor from a resistant species.

  20. Efficacy and tolerability of prolonged linezolid therapy in the treatment of orthopedic implant infections.

    Science.gov (United States)

    Soriano, A; Gómez, J; Gómez, L; Azanza, J R; Pérez, R; Romero, F; Pons, M; Bella, F; Velasco, M; Mensa, J

    2007-05-01

    The aim of the study presented here was to assess the efficacy and tolerability of linezolid in the treatment of orthopedic implant infections (OII). Eighty-five patients with an OII treated with linezolid were prospectively followed up for a minimum of 12 months from the end of antibiotic therapy. Outcome was evaluated in relation to the duration and type of symptoms (acute or chronic) and the retention or removal of the implant. For acute and chronic infections, the respective success rates were 100 and 92.3% when the implant was removed and 72.2 and 42.8% when it was not. The median length of linezolid treatment in acute and chronic infections was 47 and 60 days, respectively. Thrombocytopenia was observed in four (4.7%) patients and anemia in five (5.8%). The results suggest oral linezolid is an effective and well-tolerated alternative for treating OII.

  1. Linezolid-induced optic neuropathy in XDR pulmonary TB: A case series.

    Science.gov (United States)

    Srivastava, Anand; Kshetrimayum, Silpa; Gupta, Sanjiv Kumar; Kant, Surya

    2017-04-01

    Optic neuropathy has been reported as a side effect of long-term use of linezolid. This is particularly seen in cases of extensively drug resistant tuberculosis (XDR-TB) where treatment with linezolid may continue for about 24-30 months. We, hereby, report two cases of XDR-TB treated patients with a regimen containing linezolid who developed progressive painless loss of vision during the course of treatment. In both the cases, the visual symptoms resolved completely on withdrawing linezolid. Early recognition of this rare side effect and timely withdrawal may salvage the eyesight of such patients. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  2. In Vitro Activities of Tedizolid and Linezolid against Gram-Positive Cocci Associated with Acute Bacterial Skin and Skin Structure Infections and Pneumonia.

    Science.gov (United States)

    Chen, Ko-Hung; Huang, Yu-Tsung; Liao, Chun-Hsing; Sheng, Wang-Hui; Hsueh, Po-Ren

    2015-10-01

    Tedizolid is a novel, expanded-spectrum oxazolidinone with potent activity against a wide range of Gram-positive pathogens. A total of 425 isolates of Gram-positive bacteria were obtained consecutively from patients with acute bacterial skin and skin structure infections (ABSSSIs) or pneumonia. These isolates included methicillin-susceptible Staphylococcus aureus (MSSA) (n = 100), methicillin-resistant Staphylococcus aureus (MRSA) (n = 100), Streptococcus pyogenes (n = 50), Streptococcus agalactiae (n = 50), Streptococcus anginosus group (n = 75), Enterococcus faecalis (n = 50), and vancomycin-resistant enterococci (VRE) (Enterococcus faecium) (n = 50). The MICs of tedizolid and linezolid were determined by the agar dilution method. Tedizolid exhibited better in vitro activities than linezolid against MSSA (MIC90s, 0.5 versus 2 μg/ml), MRSA (MIC90s, 0.5 versus 2 μg/ml), S. pyogenes (MIC90s, 0.5 versus 2 μg/ml), S. agalactiae (MIC90s, 0.5 versus 2 μg/ml), Streptococcus anginosus group (MIC90s, 0.5 versus 2 μg/ml), E. faecalis (MIC90s, 0.5 versus 2 μg/ml), and VRE (MIC90s, 0.5 versus 2 μg/ml). The tedizolid MICs against E. faecalis (n = 3) and VRE (n = 2) intermediate to linezolid (MICs, 4 μg/ml) were 1 μg/ml and 0.5 μg/ml, respectively. The tedizolid MIC90s against S. anginosus, S. constellatus, and S. intermedius were 0.5, 1, and 0.5 μg/ml, respectively, and the rates of susceptibility based on the U.S. FDA MIC interpretive breakpoints to the isolates were 16%, 28%, and 72%, respectively. Tedizolid exhibited 2- to 4-fold better in vitro activities than linezolid against a variety of Gram-positive cocci associated with ABSSSIs and pneumonia. The lower susceptibilities of tedizolid against isolates of S. anginosus and S. constellatus than against those of S. intermedius in Taiwan were noted. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. Crystal Structure of the Oxazolidinone Antibiotic Linezolid Bound to the 50S Ribosomal Subunit

    Energy Technology Data Exchange (ETDEWEB)

    Ippolito,J.; Kanyo, Z.; Wang, D.; Franceschi, F.; Moore, P.; Steitz, T.; Duffy, E.

    2008-01-01

    The oxazolidinone antibacterials target the 50S subunit of prokaryotic ribosomes. To gain insight into their mechanism of action, the crystal structure of the canonical oxazolidinone, linezolid, has been determined bound to the Haloarcula marismortui 50S subunit. Linezolid binds the 50S A-site, near the catalytic center, which suggests that inhibition involves competition with incoming A-site substrates. These results provide a structural basis for the discovery of improved oxazolidinones active against emerging drug-resistant clinical strains.

  4. Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review

    OpenAIRE

    Villa, Gianluca; Di Maggio, Paola; De Gaudio, A Raffaele; Novelli, Andrea; Antoniotti, Riccardo; Fiaccadori, Enrico; Adembri, Chiara

    2016-01-01

    Background Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected in critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy (CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter changes observed in critically ill septic patients with AKI, who are on CRRT. Method Citations published on PubMed up to January 2016 were systematica...

  5. Reduced susceptibility to vancomycin and biofilm formation in methicillin-resistant Staphylococcus epidermidis isolated from blood cultures

    Directory of Open Access Journals (Sweden)

    Luiza Pinheiro

    2014-11-01

    Full Text Available This study aimed to correlate the presence of ica genes, biofilm formation and antimicrobial resistance in 107 strains of Staphylococcus epidermidis isolated from blood cultures. The isolates were analysed to determine their methicillin resistance, staphylococcal cassette chromosome mec (SCCmec type, ica genes and biofilm formation and the vancomycin minimum inhibitory concentration (MIC was measured for isolates and subpopulations growing on vancomycin screen agar. The mecA gene was detected in 81.3% of the S. epidermidis isolated and 48.2% carried SCCmec type III. The complete icaADBC operon was observed in 38.3% of the isolates; of these, 58.5% produced a biofilm. Furthermore, 47.7% of the isolates grew on vancomycin screen agar, with an increase in the MIC in 75.9% of the isolates. Determination of the MIC of subpopulations revealed that 64.7% had an MIC ≥ 4 μg mL-1, including 15.7% with an MIC of 8 μg mL-1 and 2% with an MIC of 16 μg mL-1. The presence of the icaADBC operon, biofilm production and reduced susceptibility to vancomycin were associated with methicillin resistance. This study reveals a high level of methicillin resistance, biofilm formation and reduced susceptibility to vancomycin in subpopulations of S. epidermidis. These findings may explain the selection of multidrug-resistant isolates in hospital settings and the consequent failure of antimicrobial treatment.

  6. Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections.

    Science.gov (United States)

    Thompson, Corinne N; Thieu, Nga Tran Vu; Vinh, Phat Voong; Duc, Anh Nguyen; Wolbers, Marcel; Vinh, Ha; Campbell, James I; Ngoc, Dung Tran Thi; Hoang, Nguyen Van Minh; Thanh, Tuyen Ha; The, Hao Chung; Nguyen, To Nguyen Thi; Lan, Nguyen Phu Huong; Parry, Christopher M; Chau, Nguyen Van Vinh; Thwaites, Guy; Thanh, Duy Pham; Baker, Stephen

    2016-03-01

    We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally. Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time-kill experiments were performed to evaluate the impact of MIC on the in vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species. Shigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in the gyrA gene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of the qnrS gene allowed Shigella to replicate efficiently in vitro in high concentrations of ciprofloxacin. We found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  7. Reduced susceptibility to interference in the consolidation of motor memory before adolescence.

    Directory of Open Access Journals (Sweden)

    Shoshi Dorfberger

    Full Text Available Are children superior to adults in consolidating procedural memory? This notion has been tied to "critical," early life periods of increased brain plasticity. Here, using a motor sequence learning task, we show, in experiment 1, that a the rate of learning during a training session, b the gains accrued, without additional practice, within a 24 hours post-training interval (delayed consolidation gains, and c the long-term retention of these gains, were as effective in 9, 12 and 17-year-olds and comparable to those reported for adults. However, a follow-up experiment showed that the establishment of a memory trace for the trained sequence of movements was significantly more susceptible to interference by a subsequent motor learning experience (practicing a reversed movement sequence in the 17-year-olds compared to the 9 and 12-year-olds. Unlike the 17-year-olds, the younger age-groups showed significant delayed gains even after interference training. Altogether, our results indicate the existence of an effective consolidation phase in motor learning both before and after adolescence, with no childhood advantage in the learning or retention of a motor skill. However, the ability to co-consolidate different, successive motor experiences, demonstrated in both the 9 and 12-year-olds, diminishes after puberty, suggesting that a more selective memory consolidation process takes over from the childhood one. Only the adult consolidation process is gated by a recency effect, and in situations of multiple, clashing, experiences occurring within a short time-interval, adults may less effectively establish in memory experiences superseded by newer ones.

  8. SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS ESTIMATION OF CEFIXIME TRIHYDRATE AND LINEZOLID IN TABLET DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Patel Satish A

    2013-01-01

    Full Text Available The present manuscript describes simple, sensitive, rapid, accurate, precise and economical spectrophotometric method for the simultaneous determination of Cefixime Trihydrate and Linezolid in bulk and tablet dosage form. The method is based on the simultaneous equations for analysis of both the drugs using 0.05 M Potassium phosphate buffer pH 7.2 as solvent. Cefixime Trihydrate has absorbance maxima at 287.20 nm and Linezolid has absorbance maxima at 250.60 nm in 0.05 M Potassium phosphate buffer pH 7.2. The linearity was obtained in the concentration range of 2-22 μg/ml and 2-18 μg/ml for Cefixime Trihydrate and Linezolid, respectively. The concentrations of the drugs were determined by using simultaneous equations at both the wavelengths. The mean recovery was 100.2 ± 0.56 and 101.23 ± 0.63 for Cefixime Trihydrate and Linezolid, respectively. The method was successfully applied to tablet dosage form. The suitability of this method for the quantitative determination of Cefixime Trihydrate and Linezolid was proved by validation. The proposed method was found to be simple and sensitive for the routine quality control application of Cefixime Trihydrate and Linezolid in combination. The results of analysis have been validated statistically and by recovery studies.

  9. Biogenic acidification reduces sea urchin gonad growth and increases susceptibility of aquaculture to ocean acidification.

    Science.gov (United States)

    Mos, Benjamin; Byrne, Maria; Dworjanyn, Symon A

    2016-02-01

    Decreasing oceanic pH (ocean acidification) has emphasised the influence of carbonate chemistry on growth of calcifying marine organisms. However, calcifiers can also change carbonate chemistry of surrounding seawater through respiration and calcification, a potential limitation for aquaculture. This study examined how seawater exchange rate and stocking density of the sea urchin Tripneustes gratilla that were reproductively mature affected carbonate system parameters of their culture water, which in turn influenced growth, gonad production and gonad condition. Growth, relative spine length, gonad production and consumption rates were reduced by up to 67% by increased density (9-43 individuals.m(-2)) and reduced exchange rates (3.0-0.3 exchanges.hr(-1)), but survival and food conversion efficiency were unaffected. Analysis of the influence of seawater parameters indicated that reduced pH and calcite saturation state (ΩCa) were the primary factors limiting gonad production and growth. Uptake of bicarbonate and release of respiratory CO2 by T. gratilla changed the carbonate chemistry of surrounding water. Importantly total alkalinity (AT) was reduced, likely due to calcification by the urchins. Low AT limits the capacity of culture water to buffer against acidification. Direct management to counter biogenic acidification will be required to maintain productivity and reproductive output of marine calcifiers, especially as the ocean carbonate system is altered by climate driven ocean acidification. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Species composition of larvae cultured after anthelmintic treatment indicates reduced moxidectin susceptibility of immature Cylicocyclus species in horses.

    Science.gov (United States)

    Kooyman, F N J; van Doorn, D C K; Geurden, T; Mughini-Gras, L; Ploeger, H W; Wagenaar, J A

    2016-08-30

    For the control of cyathostomins in horses, the macrocyclic lactones (MLs), moxidectin (MOX) and ivermectin (IVM) are the most commonly used anthelmintics. However, reduced activity, observed as shortening of the egg reappearance period (ERP) has been described. Shortening of the ERP may be caused by a decreased susceptibility of immature worms for MLs. Alternatively, immature worms may develop faster into egg producing adults as a result of repeated ML treatments. The species composition of the larval cultures obtained shortly after ML and pyrantel (PYR) treatment can confirm the hypothesis of decreased ML susceptibility, as this is often class-specific, whereas faster development would also occur after treatment with anthelmintics with a different mode of action. From 3 farms with a known history of shortened ERP, 8 horses per farm were selected and divided into 2 groups. The MOX-PYR-MOX group was treated twice with MOX (day 0 and 126) and once with PYR (day 84) and the IVM-PYR-IVM group was treated twice with IVM (day 0 and 98) and once with PYR (day 56). Cultured infective larvae (L3s) were counted and differentiated with the reverse line blot on pooled samples. Per cyathostomin species, the number of larvae per gram was calculated. The efficacy of all ML treatments was 100% and a shortened ERP was found on all 3 farms. The species composition of the larval cultures after ML treatment did not differ significantly from that after PYR treatment in the IVM-PYR-IVM group, but it did differ in the MOX-PYR-MOX group. The larval cultures obtained after MOX treatment consisted mostly of Cylicocyclus nassatus, while after PYR treatment Cylicostephanus longibursatus was the most abundant species. In the cultures from 42days after MOX treatment 6 cyathostomin species from 3 genera were found on the farm with the lowest activity (farm 1), while on the farm with the highest activity (farm 3) only 3 species from one genus were found in the same number of examined L3s. The

  11. Mode of encapsulation of linezolid by β-cyclodextrin and its role in bovine serum albumin binding.

    Science.gov (United States)

    Natesan, Sudha; Sowrirajan, Chandrasekaran; Yousuf, Sameena; Enoch, Israel V M V

    2015-01-22

    We describe, in this article, the associative interaction between Linezolid and β-Cyclodextrin, and the influence of β-Cyclodextrin on Linezolid's binding to Bovine serum albumin. β-Cyclodextrin forms a 1:1 inclusion complex with Linezolid, with a binding constant value of 3.51×10(2)M(-1). The binding is studied using ultraviolet-visible absorption, fluorescence, nuclear magnetic resonance, and rotating-frame overhauser effect spectroscopic techniques. The amide substituent on the oxazolidinone ring of Linezolid is involved in its binding to β-Cyclodextrin. The binding of the Linezolid to bovine serum albumin, in the absence and the presence of β-Cyclodextrin, is studied by analyzing the fluorescence quenching and Förster resonance energy transfer. The Stern-Volmer quenching constant, the binding constant, and energy transfer occurring on the interaction of the Linezolid with BSA are found to be smaller in the presence of β-Cyclodextrin than in water.

  12. Prepubertal exposure to cow's milk reduces susceptibility to carcinogen-induced mammary tumorigenesis in rats

    DEFF Research Database (Denmark)

    Nielsen, Tina Skau; Khan, Galam; Davis, Jennifer

    2011-01-01

    Cow's milk contains high levels of estrogens, progesterone and insulin-like growth factor 1 (IGF-1), all of which are associated with breast cancer. We investigated whether prepubertal milk exposure affects mammary gland development and carcinogenesis in rats. Sprague-Dawley rats were given either...... whole milk or tap water to drink from postnatal day (PND) 14 to PND 35, and thereafter normal tap water. Mammary tumorigenesis was induced by administering 7,12-dimethylbenz[a]anthracene on PND 50. Milk exposure increased circulating E2 levels on PND 25 by 10-fold (p vaginal...... or apoptosis were seen. IGF-1 mRNA levels were reduced on PND 50 in the mammary glands of rats exposed to milk at puberty. Our results suggest that drinking milk before puberty reduces later risk of developing mammary cancer in rats. This might be mediated by a reduction in the number of TEBs and lower...

  13. New regimens for reducing the duration of the treatment of drug-susceptible pulmonary tuberculosis

    OpenAIRE

    Conde, Marcus B.; Lapa e Silva, José R.

    2011-01-01

    Tuberculosis (TB) remains an important health problem worlwide. The structure necessary for delivering TB treatment and implementing the directly observed treatment accounts for more than two-thirds of its final cost. Furthemore, although with efficacy greater than 90%, the effectiveness of present treatment regimens ranges from 55–85%, depending on the setting, mainly due to poor adherence. Duration of treatment with the current first-line anti-TB drugs is a minimum of 6 months. Reducing the...

  14. Tobacco mutants with reduced microtubule dynamics are less susceptible to TMV.

    Science.gov (United States)

    Ouko, Maurice O; Sambade, Adrian; Brandner, Katrin; Niehl, Annette; Peña, Eduardo; Ahad, Abdul; Heinlein, Manfred; Nick, Peter

    2010-06-01

    A panel of seven SR1 tobacco mutants (ATER1 to ATER7) derived via T-DNA activation tagging and screening for resistance to a microtubule assembly inhibitor, ethyl phenyl carbamate, were used to study the role of microtubules during infection and spread of tobacco mosaic virus (TMV). In one of these lines, ATER2, alpha-tubulin is shifted from the tyrosinylated into the detyrosinated form, and the microtubule plus-end marker GFP-EB1 moves significantly slower when expressed in the background of the ATER2 mutant as compared with the SR1 wild type. The efficiency of cell-to-cell movement of TMV encoding GFP-tagged movement protein (MP-GFP) is reduced in ATER2 accompanied by a reduced association of MP-GFP with plasmodesmata. This mutant is also more tolerant to viral infection as compared with the SR1 wild type, implying that reduced microtubule dynamics confer a comparative advantage in face of TMV infection.

  15. Δ(9)-Tetrahydrocannabinol treatment during human monocyte differentiation reduces macrophage susceptibility to HIV-1 infection.

    Science.gov (United States)

    Williams, Julie C; Appelberg, Sofia; Goldberger, Bruce A; Klein, Thomas W; Sleasman, John W; Goodenow, Maureen M

    2014-06-01

    The major psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), also acts to suppress inflammatory responses. Receptors for THC, CB1, CB2, and GPR55, are differentially expressed on multiple cell types including monocytes and macrophages, which are important modulators of inflammation in vivo and target cells for HIV-1 infection. Use of recreational and medicinal marijuana is increasing, but the consequences of marijuana exposure on HIV-1 infection are unclear. Ex vivo studies were designed to investigate effects on HIV-1 infection in macrophages exposed to THC during or following differentiation. THC treatment of primary human monocytes during differentiation reduced HIV-1 infection of subsequent macrophages by replication competent or single cycle CCR5 using viruses. In contrast, treatment of macrophages with THC immediately prior to or continuously following HIV-1 exposure failed to alter infection. Specific receptor agonists indicated that the THC effect during monocyte differentiation was mediated primarily through CB2. THC reduced the number of p24 positive cells with little to no effect on virus production per infected cell, while quantitation of intracellular viral gag pinpointed the THC effect to an early event in the viral life cycle. Cells treated during differentiation with THC displayed reduced expression of CD14, CD16, and CD163 and donor dependent increases in mRNA expression of selected viral restriction factors, suggesting a fundamental alteration in phenotype. Ultimately, the mechanism of THC suppression of HIV-1 infection was traced to a reduction in cell surface HIV receptor (CD4, CCR5 and CXCR4) expression that diminished entry efficiency.

  16. Δ9-tetrahydrocannabinol treatment during human monocyte differentiation reduces macrophage susceptibility to HIV-1 infection

    Science.gov (United States)

    Williams, Julie C.; Appelberg, Sofia; Goldberger, Bruce A.; Klein, Thomas W.; Sleasman, John W.; Goodenow, Maureen M.

    2014-01-01

    The major psychoactive component of marijuana, Δ9-tetrahydrocannabinol (THC), also acts to suppress inflammatory responses. Receptors for THC, CB1, CB2, and GPR55, are differentially expressed on multiple cell types including monocytes and macrophages, which are important modulators of inflammation in vivo and target cells for HIV-1 infection. Use of recreational and medicinal marijuana is increasing, but the consequences of marijuana exposure on HIV-1 infection are unclear. Ex vivo studies were designed to investigate effects on HIV-1 infection in macrophages exposed to THC during or following differentiation. THC treatment of primary human monocytes during differentiation reduced HIV-1 infection of subsequent macrophages by replication competent or single cycle CCR5 using viruses. In contrast, treatment of macrophages with THC immediately prior to or continuously following HIV-1 exposure failed to alter infection. Specific receptor agonists indicated that the THC effect during monocyte differentiation was mediated primarily through CB2. THC reduced the number of p24 positive cells with little to no effect on virus production per infected cell, while quantitation of intracellular viral gag pinpointed the THC effect to an early event in the viral life cycle. Cells treated during differentiation with THC displayed reduced expression of CD14, CD16, and CD163 and donor dependent increases in mRNA expression of selected viral restriction factors, suggesting a fundamental alteration in phenotype. Ultimately, the mechanism of THC suppression of HIV-1 infection was traced to a reduction in cell surface HIV receptor (CD4, CCR5 and CXCR4) expression that diminished entry efficiency. PMID:24562630

  17. Overwintering Is Associated with Reduced Expression of Immune Genes and Higher Susceptibility to Virus Infection in Honey Bees

    Science.gov (United States)

    Steinmann, Nadja; Corona, Miguel; Neumann, Peter; Dainat, Benjamin

    2015-01-01

    The eusocial honey bee, Apis mellifera, has evolved remarkable abilities to survive extreme seasonal differences in temperature and availability of resources by dividing the worker caste into two groups that differ in physiology and lifespan: summer and winter bees. Most of the recent major losses of managed honey bee colonies occur during the winter, suggesting that winter bees may have compromised immune function and higher susceptibility to diseases. We tested this hypothesis by comparing the expression of eight immune genes and naturally occurring infection levels of deformed wing virus (DWV), one of the most widespread viruses in A. mellifera populations, between summer and winter bees. Possible interactions between immune response and physiological activity were tested by measuring the expression of vitellogenin and methyl farnesoate epoxidase, a gene coding for the last enzyme involved in juvenile hormone biosynthesis. Our data show that high DWV loads in winter bees correlate with reduced expression of genes involved in the cellular immune response and physiological activity and high expression of humoral immune genes involved in antibacterial defense compared with summer bees. This expression pattern could reflect evolutionary adaptations to resist bacterial pathogens and economize energy during the winter under a pathogen landscape with reduced risk of pathogenic viral infections. The outbreak of Varroa destructor infestation could have overcome these adaptations by promoting the transmission of viruses. Our results suggest that reduced cellular immune function during the winter may have increased honey bee’s susceptibility to DWV. These results contribute to our understanding of honey bee colony losses in temperate regions. PMID:26121358

  18. Overwintering Is Associated with Reduced Expression of Immune Genes and Higher Susceptibility to Virus Infection in Honey Bees.

    Directory of Open Access Journals (Sweden)

    Nadja Steinmann

    Full Text Available The eusocial honey bee, Apis mellifera, has evolved remarkable abilities to survive extreme seasonal differences in temperature and availability of resources by dividing the worker caste into two groups that differ in physiology and lifespan: summer and winter bees. Most of the recent major losses of managed honey bee colonies occur during the winter, suggesting that winter bees may have compromised immune function and higher susceptibility to diseases. We tested this hypothesis by comparing the expression of eight immune genes and naturally occurring infection levels of deformed wing virus (DWV, one of the most widespread viruses in A. mellifera populations, between summer and winter bees. Possible interactions between immune response and physiological activity were tested by measuring the expression of vitellogenin and methyl farnesoate epoxidase, a gene coding for the last enzyme involved in juvenile hormone biosynthesis. Our data show that high DWV loads in winter bees correlate with reduced expression of genes involved in the cellular immune response and physiological activity and high expression of humoral immune genes involved in antibacterial defense compared with summer bees. This expression pattern could reflect evolutionary adaptations to resist bacterial pathogens and economize energy during the winter under a pathogen landscape with reduced risk of pathogenic viral infections. The outbreak of Varroa destructor infestation could have overcome these adaptations by promoting the transmission of viruses. Our results suggest that reduced cellular immune function during the winter may have increased honey bee's susceptibility to DWV. These results contribute to our understanding of honey bee colony losses in temperate regions.

  19. Susceptibility of synthetic long-chain alkylbenzenes to degradation in reducing marine sediments

    Science.gov (United States)

    Eganhouse, Robert P.; Pontolillo, James

    2008-01-01

    Long-chain alkylbenzenes (LCABs) synthesized for production of alkylbenzene sulfonate surfactants have been used as molecular markers of anthropogenic waste for 25 years. Synthetic LCABs comprise two classes, the tetrapropylene-based alkylbenzenes (TABs) and the linear alkylbenzenes (LABs). LABs supplanted TABs in the mid-1960s because of improved biodegradability of their sulfonated analogs. Use of LCABs for molecular stratigraphy depends on their preservation in sediments over decadal time scales. Most laboratory and field studies suggest that LABs degrade rapidly under aerobic conditions but are resistant to degradation when oxygen is absent. However, recent work indicates that LABs may not be as persistent under reducing conditions as previously thought. To assess the potential for degradation of LCABs in reducing sediments, box cores collected in 1992 and 2003 near a submarine wastewater outfall system were analyzed using gas chromatography/mass spectrometry. The TABs were effectively preserved; differences between whole-core inventories were within analytical error. By contrast, whole-core inventories of the LABs decreased by about 50-60% during the same time interval. Based on direct comparison of chemical inventories in coeval core sections, LAB transformation rates are estimated at 0.07 ±. 0.01 yr-1. These results indicate that caution should be exercised when using synthetic LCABs for reconstruction of depositional records.

  20. Enhanced ordering reduces electric susceptibility of liquids confined to graphene slit pores

    Science.gov (United States)

    Terrones, Jeronimo; Kiley, Patrick J.; Elliott, James A.

    2016-06-01

    The behaviours of a range of polar and non-polar organic liquids (acetone, ethanol, methanol, N-methyl-2-pyrrolidone (NMP), carbon tetrachloride and water) confined to 2D graphene nanochannels with thicknesses in the range of 4.5 Å to 40 Å were studied using classical molecular dynamics and hybrid density functional theory. All liquids were found to organise spontaneously into ordered layers parallel to the confining surfaces, with those containing polar molecules having their electric dipoles aligned parallel to such surfaces. In particular, monolayers of NMP showed remarkable in-plane ordering and low molecular mobility, suggesting the existence of a previously unknown 2D solid-like phase. Calculations for polar liquids showed dramatically reduced static permittivities normal to the confining surfaces; these changes are expected to improve electron tunnelling across the liquid films, modifying the DC electrical properties of immersed assemblies of carbon nanomaterials.

  1. Enhanced ordering reduces electric susceptibility of liquids confined to graphene slit pores

    Science.gov (United States)

    Terrones, Jeronimo; Kiley, Patrick J.; Elliott, James A.

    2016-01-01

    The behaviours of a range of polar and non-polar organic liquids (acetone, ethanol, methanol, N-methyl-2-pyrrolidone (NMP), carbon tetrachloride and water) confined to 2D graphene nanochannels with thicknesses in the range of 4.5 Å to 40 Å were studied using classical molecular dynamics and hybrid density functional theory. All liquids were found to organise spontaneously into ordered layers parallel to the confining surfaces, with those containing polar molecules having their electric dipoles aligned parallel to such surfaces. In particular, monolayers of NMP showed remarkable in-plane ordering and low molecular mobility, suggesting the existence of a previously unknown 2D solid-like phase. Calculations for polar liquids showed dramatically reduced static permittivities normal to the confining surfaces; these changes are expected to improve electron tunnelling across the liquid films, modifying the DC electrical properties of immersed assemblies of carbon nanomaterials. PMID:27265098

  2. Bacillus subtilis spores reduce susceptibility to Citrobacter rodentium-mediated enteropathy in a mouse model.

    Science.gov (United States)

    D'Arienzo, Rossana; Maurano, Francesco; Mazzarella, Giuseppe; Luongo, Diomira; Stefanile, Rosita; Ricca, Ezio; Rossi, Mauro

    2006-11-01

    The present work was aimed at investigating whether Bacillus subtilis spores, widely used in probiotic as well as pharmaceutical preparations for mild gastrointestinal disorders, can suppress enteric infections. To address this issue, we developed a mouse model of infection using the mouse enteropathogen Citrobacter rodentium, a member of a family of human and animal pathogens which includes the clinically significant enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli strains. This group of pathogens causes transmissible colonic hyperplasia by using attaching and effacing (A/E) lesions to colonize the host colon. Because of its similarities to human enteropathogens, C. rodentium is now widely used as an in vivo model for gastrointestinal infections. Swiss NIH mice were orally administered B. subtilis spores one day before infection with C. rodentium. Mice were sacrificed on day 15 after infection, and distal colon, liver and mesenteric lymph nodes were removed for bacteria counts, morphology, immunohistology and IFNgamma mRNA analysis. We observed that spore predosing was effective in significantly decreasing infection and enteropathy in suckling mice infected with a dose of C. rodentium sufficient to cause colon colonization, crypt hyperplasia and high mortality rates. Moreover, in mice predosed with spores, the number of CD4(+) cells and IFNgamma transcript levels remained high. These results thus indicate that our newly established model of C. rodentium infection is a suitable system for analyzing the effects of probiotic bacteria on enteroinfections and that B. subtilis spores are efficient at reducing C. rodentium infection in mice, leaving unaltered the immune response against the pathogen.

  3. Counter-advertising may reduce parent's susceptibility to front-of-package promotions on unhealthy foods.

    Science.gov (United States)

    Dixon, Helen; Scully, Maree; Kelly, Bridget; Donovan, Robert; Chapman, Kathy; Wakefield, Melanie

    2014-01-01

    Assess the effect of counter-advertisements on parents' appraisals of unhealthy foods featuring front-of-package promotions (FOPPs). A 2 × 2 × 5 between-subjects Web-based experiment. Parents were randomly shown an advertisement (counter-advertisement challenging FOPP/control advertisement) and then a pair of food products from the same category: an unhealthy product featuring an FOPP (nutrient content claim/sports celebrity endorsement) and a healthier control product with no FOPP. Australia. A total of 1,269 Australian-based parents of children aged 5-12 years recruited from an online panel. Parents nominated which product they would prefer to buy and which they thought was healthier, then rated the unhealthy product and FOPP on various characteristics. Differences between advertisement conditions were assessed using logistic regression (product choice tasks) and analysis of variance tests (ratings of unhealthy product and FOPP). Compared with parents who saw a control advertisement, parents who saw a counter-advertisement perceived unhealthy products featuring FOPPs as less healthy, expressed weaker intentions for buying such products, and were more likely to read the nutrition facts panel before nominating choices (all P advertising may help reduce the misleading influence of unhealthy food marketing and improve the accuracy of parents' evaluations of how nutritious promoted food products are. Copyright © 2014 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  4. Ethanol and reactive species increase basal sequence heterogeneity of hepatitis C virus and produce variants with reduced susceptibility to antivirals.

    Science.gov (United States)

    Seronello, Scott; Montanez, Jessica; Presleigh, Kristen; Barlow, Miriam; Park, Seung Bum; Choi, Jinah

    2011-01-01

    Hepatitis C virus (HCV) exhibits a high level of genetic variability, and variants with reduced susceptibility to antivirals can occur even before treatment begins. In addition, alcohol decreases efficacy of antiviral therapy and increases sequence heterogeneity of HCV RNA but how ethanol affects HCV sequence is unknown. Ethanol metabolism and HCV infection increase the level of reactive species that can alter cell metabolism, modify signaling, and potentially act as mutagen to the viral RNA. Therefore, we investigated whether ethanol and reactive species affected the basal sequence variability of HCV RNA in hepatocytes. Human hepatoma cells supporting a continuous replication of genotype 1b HCV RNA (Con1, AJ242652) were exposed to ethanol, acetaldehyde, hydrogen peroxide, or L-buthionine-S,R-sulfoximine (BSO) that decreases intracellular glutathione as seen in patients. Then, NS5A region was sequenced and compared with genotype 1b HCV sequences in the database. Ethanol and BSO elevated nucleotide and amino acid substitution rates of HCV RNA by 4-18 folds within 48 hrs which were accompanied by oxidative RNA damage. Iron chelator and glutathione ester decreased both RNA damage and mutation rates. Furthermore, infectious HCV and HCV core gene were sufficient to induce oxidative RNA damage even in the absence of ethanol or BSO. Interestingly, the dn/ds ratio and percentage of sites undergoing positive selection increased with ethanol and BSO, resulting in an increased detection of NS5A variants with reduced susceptibility to interferon alpha, cyclosporine, and ribavirin and others implicated in immune tolerance and modulation of viral replication. Therefore, alcohol is likely to synergize with virus-induced oxidative/nitrosative stress to modulate the basal mutation rate of HCV. Positive selection induced by alcohol and reactive species may contribute to antiviral resistance.

  5. Effect of Linezolid on Hematologic Recovery in Newly Diagnosed Acute Myeloid Leukemia Patients Following Induction Chemotherapy.

    Science.gov (United States)

    Nedved, Adrienne N; DeFrates, Sean R; Hladnik, Lindsay M; Stockerl-Goldstein, Keith E

    2016-10-01

    Assess the effects of linezolid on hematologic outcomes in newly diagnosed patients with acute myeloid leukemia (AML) following induction chemotherapy. Single-center, retrospective, observational, cohort study. Large, tertiary care academic medical center. A total of 225 patients ≥ 18 years admitted between December 2010 and 2013 with newly diagnosed AML were assessed for inclusion. Patients were identified through the use of ICD-9 codes and chemotherapy ordered via the computerized physician order entry system. Sixty-eight patients met inclusion criteria and were grouped into two arms based on antimicrobial treatment: LZD group (linezolid plus gram-negative antimicrobial, n=21) or control group (vancomycin or daptomycin plus gram-negative antimicrobial, n=47). The LZD group received linezolid ≥ 72 hours. The control group received vancomycin or daptomycin ≥ 72 hours. If patients switched extended gram-positive therapy, they were included in the LZD group as long as they had received ≥ 72 hours of linezolid. The primary end point of time to neutrophil recovery was not statistically different (28 days for LZD group vs 26 days for control group; p=0.675). The preplanned subgroup analysis of patients who received ≥ 14 days of linezolid demonstrated statistically similar median times to neutrophil recovery (29 days for LZD group vs 26 days for control group; p=0.487). Total duration of extended gram-positive antimicrobial therapy was significantly longer in the LZD group (27 days vs 16 days; pchemotherapy. This study provides new insight with a primary focus on the effects of hematologic outcomes when using linezolid in a well-defined acute leukemia population. Further study is warranted with larger populations to assess the potential adverse effects linezolid may have in patients with acute leukemia. © 2016 Pharmacotherapy Publications, Inc.

  6. Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

    Science.gov (United States)

    Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

    2013-12-01

    Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

  7. Emergence and dissemination of a linezolid-resistant Staphylococcus capitis clone in Europe.

    Science.gov (United States)

    Butin, M; Martins-Simões, P; Pichon, B; Leyssene, D; Bordes-Couecou, S; Meugnier, H; Rouard, C; Lemaitre, N; Schramm, F; Kearns, A; Spiliopoulou, I; Hyyryläinen, H-L; Dumitrescu, O; Vandenesch, F; Dupieux, C; Laurent, F

    2017-04-01

    We investigated the epidemiological, clinical, microbiological and genetic characteristics of linezolid-resistant (LZR) Staphylococcus capitis isolates from French ICUs, and compared them with LZR S. capitis isolates from other European countries. All LZR isolates were subjected to antimicrobial susceptibility testing (AST) and the presence of cfr and optrA genes as well as mutations in the 23S rRNA and ribosomal proteins were investigated using specific PCR with sequencing. The genetic relationship between isolates was investigated using PFGE and WGS. Epidemiological data concerning LZR S. capitis were collected retrospectively in French microbiology laboratories. Twenty-one LZR isolates were studied: 9 from France, 11 from Greece and 1 from Finland. All were resistant to methicillin and aminoglycosides. In addition, this unusual AST profile was identified in S. capitis isolates from seven French hospitals, and represented up to 12% of the S. capitis isolates in one centre. A G2576T mutation in 23S rRNA was identified in all isolates; cfr and optrA genes were absent. All isolates belonged to the same clone on the basis of their PFGE profiles, whatever their geographical origin. WGS found at most 212 SNPs between core genomes of the LZR isolates. We identified and characterized an LZR S. capitis clone disseminated in three European countries, harbouring the same multiple resistance and a G2576T mutation in the 23S rRNA. The possible unrecognized wider distribution of this clone, belonging to a species classically regarded as a low-virulence skin colonizer, is of major concern not least because of the increasing use of oxazolidinones.

  8. Clinical Application of Vancomycin and Linezolid in Our Hospital%我院万古霉素和利奈唑胺临床应用分析

    Institute of Scientific and Technical Information of China (English)

    蔡芸; 陈超; 郭代红; 白楠; 梁蓓蓓; 王睿

    2011-01-01

    Objective; To evaluate the application status of vancomycin and linezolid in our hospital. Method: The data of the clinical application of vancomycin (including norvancomycin) and linezolid during January 2008 and September 2010 were analyzed statistically. Result; Vancomycin,norvancomycin and linezolid were used in 23 departments of our hospital. The amount of anti-MRSA antibiotics was the largest in orthopedics,followed by neurosurgery and respiratory department. During the year of 2008-2010,the application amount of vancomycin showed a fluctuant growth, linezolid showed a steady growth, while little change was found in the amount of norvancomycin. Conclusion; Application of vancomycin and linezolid is basically rational. Vancomycin is the main choice of anti-MRSA. More exploratory clinical research on linezoild is needed to reduce the medication pressure of vancomycin.%目的:评价抗耐甲氧西林金黄色葡萄球菌(MRSA)药物万古霉素和利奈唑胺在临床的应用情况.方法:对本院2008年1月~2010年9月万古霉素(含去甲万古霉素)和利奈唑胺的相关数据进行统计、分析.结果:万古霉素和利奈唑胺在本院有23个科室应用.骨科是抗MRSA药物用量最多的科室,其次为神经外科和呼吸科.2008~2010年万古霉素用量基本呈波动性增长;利奈唑胺片和注射剂均稳步增长;去甲万古霉素的用量变化不大.结论:本院万古霉素和利奈唑胺的应用基本合理,目前仍以万古霉素为主,可适当加强利奈唑胺的探索性临床研究,从而减轻万古霉素的用药压力.

  9. Safety of long-term use of linezolid: results of an open-label study

    Directory of Open Access Journals (Sweden)

    Vazquez JA

    2016-09-01

    Full Text Available Jose A Vazquez,1 Anthony C Arnold,2 Robert N Swanson,3 Pinaki Biswas,3 Matteo Bassetti4 1Section of Infectious Diseases, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA; 2UCLA Department of Ophthalmology, Jules Stein Eye Institute, Los Angeles, CA, USA; 3Clinical Research, Global Innovative Pharmaceutical, Pfizer Inc., New York, NY, USA; 4Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Udine, Italy Objective: The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6 weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event. Methods: This was a multicenter, open-label, pilot study of patients aged ≥18 years on long-term linezolid therapy. Matched control patients were included for baseline assessment comparison. Patients were assessed at study entry, monthly while on treatment, at the end of treatment, and 30 days following the last dose. Aggregate ocular safety data were reviewed. Response to treatment was reported. Results: The study was terminated owing to slow enrollment. Twenty-four patients received linezolid; nine patients were included as matched controls. Linezolid was prescribed for a median of 80.5 days (range, 50–254 days. In patients with a reported clinical outcome, the majority were considered improved or cured. Common treatment-related adverse events (AEs included anemia, peripheral neuropathy, polyneuropathy, vomiting, and asthenia, and were consistent with the known safety profile. Most AEs resolved or stabilized with discontinuation of treatment. Results of ophthalmologic tests in the one case adjudicated as probable linezolid-associated optic neuropathy revealed abnormal color vision, characteristic changes in the optic disk

  10. Mosaic-like structure of penicillin-binding protein 2 Gene (penA) in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime.

    Science.gov (United States)

    Ameyama, Satoshi; Onodera, Shoichi; Takahata, Masahiro; Minami, Shinzaburo; Maki, Nobuko; Endo, Katsuhisa; Goto, Hirokazu; Suzuki, Hiroo; Oishi, Yukihiko

    2002-12-01

    Neisseria gonorrhoeae strains with reduced susceptibility to cefixime (MICs, 0.25 to 0.5 micro g/ml) were isolated from male urethritis patients in Tokyo, Japan, in 2000 and 2001. The resistance to cephems including cefixime and penicillin was transferred to a susceptible recipient, N. gonorrhoeae ATCC 19424, by transformation of the penicillin-binding protein 2 gene (penA) that had been amplified by PCR from a strain with reduced susceptibility to cefixime (MIC, 0.5 micro g/ml). The sequences of penA in the strains with reduced susceptibilities to cefixime were different from those of other susceptible isolates and did not correspond to the reported N. gonorrhoeae penA gene sequences. Some regions in the transpeptidase-encoding domain in this penA gene were similar to those in the penA genes of Neisseria perflava (N. sicca), Neisseria cinerea, Neisseria flavescens, and Neisseria meningitidis. These results showed that a mosaic-like structure in the penA gene conferred reductions in the levels of susceptibility of N. gonorrhoeae to cephems and penicillin in a manner similar to that found for N. meningitidis and Streptococcus pneumoniae.

  11. Vibrio cholerae O1 with Reduced Susceptibility to Ciprofloxacin and Azithromycin Isolated from a Rural Coastal Area of Bangladesh

    Science.gov (United States)

    Rashed, Shah M.; Hasan, Nur A.; Alam, Munirul; Sadique, Abdus; Sultana, Marzia; Hoq, Md. Mozammel; Sack, R. Bradley; Colwell, Rita R.; Huq, Anwar

    2017-01-01

    Cholera outbreaks occur each year in the remote coastal areas of Bangladesh and epidemiological surveillance and routine monitoring of cholera in these areas is challenging. In this study, a total of 97 Vibrio cholerae O1 isolates from Mathbaria, Bangladesh, collected during 2010 and 2014 were analyzed for phenotypic and genotypic traits, including antimicrobial susceptibility. Of the 97 isolates, 95 possessed CTX-phage mediated genes, ctxA, ace, and zot, and two lacked the cholera toxin gene, ctxA. Also both CTX+ and CTX− V. cholerae O1 isolated in this study carried rtxC, tcpAET, and hlyA. The classical cholera toxin gene, ctxB1, was detected in 87 isolates, while eight had ctxB7. Of 95 CTX+ V. cholerae O1, 90 contained rstRET and 5 had rstRCL. All isolates, except two, contained SXT related integrase intSXT. Resistance to penicillin, streptomycin, nalidixic acid, sulfamethoxazole-trimethoprim, erythromycin, and tetracycline varied between the years of study period. Most importantly, 93% of the V. cholerae O1 were multidrug resistant. Six different resistance profiles were observed, with resistance to streptomycin, nalidixic acid, tetracycline, and sulfamethoxazole-trimethoprim predominant every year. Ciprofloxacin and azithromycin MIC were 0.003–0.75 and 0.19–2.00 μg/ml, respectively, indicating reduced susceptibility to these antibiotics. Sixteen of the V. cholerae O1 isolates showed higher MIC for azithromycin (≥0.5 μg/ml) and were further examined for 10 macrolide resistance genes, erm(A), erm(B), erm(C), ere(A), ere(B), mph(A), mph(B), mph(D), mef(A), and msr(A) with none testing positive for the macrolide resistance genes. PMID:28270803

  12. Clinical update on linezolid in the treatment of Gram-positive bacterial infections

    Directory of Open Access Journals (Sweden)

    Ager S

    2012-06-01

    Full Text Available Sally Ager, Kate GouldDepartment of Microbiology, Newcastle upon Tyne Hospitals Trust, Freeman Hospital, High Heaton, Newcastle upon Tyne, UKAbstract: Gram-positive pathogens are a significant cause of morbidity and mortality in both community and health care settings. Glycopeptides have traditionally been the antibiotics of choice for multiresistant Gram-positive pathogens but there are problems with their use, including the emergence of glycopeptide-resistant strains, tissue penetration, and achieving and monitoring adequate serum levels. Newer antibiotics such as linezolid, a synthetic oxazolidinone, are available for the treatment of resistant Gram-positive bacteria. Linezolid is active against a wide range of Gram-positive bacteria and has been generally available for the treatment of Gram-positive infections since 2000. There are potential problems with linezolid use, including its bacteriostatic action and the relatively high incidence of reported adverse effects, particularly with long-term use. Long-term use may also be complicated by the development of resistance. However, linezolid has been shown to be clinically useful in the treatment of several serious infections where traditionally bacteriocidal agents have been required and many of its adverse effects are reversible on cessation. It has also been shown to be a cost-effective treatment option in several studies, with its high oral bioavailability allowing an early change from intravenous to oral formulations with consequent earlier patient discharge and lower inpatient costs.Keywords: linezolid, oxazolidinone, multi-resistant, gram-positive, MRSA, VRE, cost-benefit

  13. Study on the Linezolid Resistance Mechanism of Gram Positive Cocci%革兰阳性球菌对利奈唑胺耐药机制的研究

    Institute of Scientific and Technical Information of China (English)

    许宏涛; 陈东科; 赖惠英

    2016-01-01

    目的:对利奈唑胺耐药革兰阳性球菌主要耐药分子机制进行初步研究。方法采用 KB法及 E-test法对6株利奈唑胺耐药革兰阳性球菌进行药敏试验,并应用脉冲场凝胶电泳(PFGE),PCR及测序技术对菌株主要分子流行病学及耐药分子机制进行研究。结果5株柯氏葡萄球菌PFGE分为2型,对利奈唑胺 MIC介于16~64 mg/L,菌株均呈现 cfr基因阳性、L3存在双位点突变;1株粪肠球菌对利奈唑胺 MIC为8 mg/L,耐药与23SrRNA存在 G2576T点突变相关。结论利奈唑胺耐药革兰阳性球菌在临床的出现应引起广泛关注,为有效进行抗感染治疗应重视对利奈唑胺耐药菌株的临床监测。%Abstrac:Objective To study the molecular resistance mechanism of linezolid resistant gram positive cocci.Methods KB and E-test methods were used in antibiotic susceptibility tests.PFGE,PCR and sequencing techniques were applied to study the molecular epidemiological characteristics and resistance mechnisms of linezolid to gram positive cocci.Results The MICs of linezolid of the 5 Staphylococcuscohnii isolates were from 16 to 64 mg/L,and they were all cfr gene positive and with L3 mutations,and there were two PFGE types.The linezolid MIC of oneEnterococcusfaecalis was 8 mg/L with G2576T muta-tion in 23SrRNA.Conclusion There were linezolid resistant gram positive cocci appeared in clinical samples,for the effective anti-infection treatment monitoring linezolid resistant gram positive cocci in clinical lab is important.

  14. First outbreak of linezolid-resistant vancomycin-resistant Enterococcus faecium in an Irish hospital, February to September 2014.

    Science.gov (United States)

    O'Driscoll, C; Murphy, V; Doyle, O; Wrenn, C; Flynn, A; O'Flaherty, N; Fenelon, L E; Schaffer, K; FitzGerald, S F

    2015-12-01

    An outbreak of linezolid-resistant vancomycin-resistant Enterococcus faecium (LRVREfm) occurred in the hepatology ward of a tertiary referral hospital in Ireland between February and September 2014. LRVREfm was isolated from 15 patients; pulsed-field gel electrophoresis confirmed spread of a single clone. This is the first report of an outbreak of linezolid-resistant vancomycin-resistant enterococcus in Ireland.

  15. Lactococcus garvieae carries a chromosomally encoded pentapeptide repeat protein that confers reduced susceptibility to quinolones in Escherichia coli producing a cytotoxic effect.

    Science.gov (United States)

    Gibello, Alicia; Díaz de Alba, Paula; Blanco, M Mar; Machuca, Jesus; Cutuli, M Teresa; Rodríguez-Martínez, José Manuel

    2014-09-01

    This study characterises a chromosomal gene of Lactococcus garvieae encoding a pentapeptide repeat protein designated as LgaQnr. This gene has been implicated in reduced susceptibility to quinolones in this bacterium, which is of relevance to both veterinary and human medicine. All of the L. garvieae isolates analysed were positive for the lgaqnr gene. The expression of lgaqnr in Escherichia coli reduced the susceptibility to quinolones, producing an adverse effect. The reduced susceptibility to ciprofloxacin was 16-fold in E. coli ATCC 25922 and 32-fold in E. coli DH10B, compared to the control strains. The minimum inhibitory concentration of nalidixic acid was also increased 4 or 5-fold. The effect of the expression of lgaqnr in E. coli was investigated by electron microscopy and was observed to affect the structure of the cell and the inner membrane of the recombinant cells.

  16. Successful Treatment of Necrotizing Fasciitis and Streptococcal Toxic Shock Syndrome with the Addition of Linezolid

    Directory of Open Access Journals (Sweden)

    Hana Rac

    2017-01-01

    Full Text Available Necrotizing fasciitis is a deep-seated subcutaneous tissue infection that is commonly associated with streptococcal toxic shock syndrome (TSS. Surgical debridement plus penicillin and clindamycin are the current standard of care. We report a case of necrotizing fasciitis and streptococcal TSS where linezolid was added after a failure to improve with standard therapy. Briefly after isolation of Streptococcus pyogenes from tissue cultures, the patient underwent two surgical debridement procedures and was changed to standard of care therapy. While the patient was hemodynamically stable, the patient’s wounds, leukocytosis, and thrombocytopenia all progressively worsened. After initiation of linezolid, the patient slowly improved clinically. The present report is the first to highlight the role of linezolid in streptococcal necrotizing fasciitis and TSS not improving with standard therapy.

  17. Successful Treatment of Necrotizing Fasciitis and Streptococcal Toxic Shock Syndrome with the Addition of Linezolid

    Science.gov (United States)

    Bojikian, Karine D.; Lucar, Jose

    2017-01-01

    Necrotizing fasciitis is a deep-seated subcutaneous tissue infection that is commonly associated with streptococcal toxic shock syndrome (TSS). Surgical debridement plus penicillin and clindamycin are the current standard of care. We report a case of necrotizing fasciitis and streptococcal TSS where linezolid was added after a failure to improve with standard therapy. Briefly after isolation of Streptococcus pyogenes from tissue cultures, the patient underwent two surgical debridement procedures and was changed to standard of care therapy. While the patient was hemodynamically stable, the patient's wounds, leukocytosis, and thrombocytopenia all progressively worsened. After initiation of linezolid, the patient slowly improved clinically. The present report is the first to highlight the role of linezolid in streptococcal necrotizing fasciitis and TSS not improving with standard therapy. PMID:28299216

  18. 利奈唑胺治疗糖肽类药物治疗无效MRSA的感染分析%Analysis of linezolid in treatment of MRSA infection after ineffective glycopeptide antibiotics treatment

    Institute of Scientific and Technical Information of China (English)

    郭利涛; 刘昱; 王雪; 石秦东; 刘红娟; 滕琰

    2012-01-01

    目的 了解利奈唑胺对于治疗糖肽类药物治疗无明显效果的耐甲氧西林金黄色葡萄球菌(MRSA)感染的效果及优点,为临床用药提供参考.方法 对2008年2月—2009年7月入住我院ICU并细菌培养为MRSA,且确定为致病菌,给予足够剂量的万古霉素或替考拉宁治疗大于5d无明显效果,后给予利奈唑胺治疗收到满意效果的患者进行回顾性分析.结果 所有培养为MRSA的药敏结果均回报对万古霉素、替考拉宁及利奈唑胺敏感.12例患者均根据药敏结果首先选用万古霉素或替考拉宁治疗,疗程均在5d以上,患者血象、体温无明显好转,再次细菌培养仍为MRSA.所有患者给予利奈唑胺治疗后,血象、体温明显好转,再次细菌培养未见细菌生长.4例患者治疗时间超过28d,3例出现三系细胞减低,考虑利奈唑胺致骨髓抑制,停药1周后回复正常.结论 利奈唑胺可以做为治疗糖肽类药物初始治疗失败的革兰阳性菌感染的选择用药;疗程超过28d的患者,有出现骨髓抑制等药物相关性副作用的风险,应密切监测血常规.%Objective To investigate the effect and safety of Linezolid in the treatment of Methicillin-resistant Staphylococcus aureus (MRSA) infection which is after ineffective glycopeptide antibiotics treatment. Methods We retrospectively analyzed 12 cases with positive bacterial culture for MRSA in ICU of our hospital from February, 2008 to July, 2009. These patients were all administered with Linezolid after more than five days ineffective vancomycin or teicoplanin treatment. Results All drug susceptibility test show cultured MRSA was senstive to vancomycin, teicoplanin and linezolid.All 12 patients were first treated with vancomycin or teicoplanin according to the drug susceptibility results. After more than five days treatment,showed no significant amelioration in the patients body temperature or hemogram and bacterial culture were still MRSA positive. But

  19. Impact of antibiotic use during hospitalization on the development of gastrointestinal colonization with Escherichia coli with reduced fluoroquinolone susceptibility.

    Science.gov (United States)

    Han, Jennifer H; Bilker, Warren B; Nachamkin, Irving; Tolomeo, Pam; Mao, Xiangqun; Fishman, Neil O; Lautenbach, Ebbing

    2013-10-01

    Infections due to fluoroquinolone-resistant Escherichia coli (FQREC) are associated with significant morbidity and mortality. Fluoroquinolone resistance likely arises at the level of gastrointestinal colonization. The objective of this study was to identify risk factors for the development of FQREC gastrointestinal tract colonization in hospitalized patients, including the impact of antibiotics prescribed during hospitalization. A prospective cohort study was conducted from 2002 to 2004 within a university health system. Hospitalized patients initially colonized with fluoroquinolone-susceptible E. coli were followed up with serial fecal sampling for new FQREC colonization or until hospital discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQREC colonization, with antibiotic exposure modeled as time-varying covariates. Of 395 subjects, 73 (18.5%) became newly colonized with FQREC. Length of stay before sampling (hazard ratio [HR], 1.02 [95% confidence interval (CI), 1.1-1.03]; P = .003) and malignancy (HR, 0.37 [95% CI, 0.21-0.67]; P = .001) were significantly associated with the development of FQREC colonization. In addition, receipt of a first-generation cephalosporin (HR, 1.19 [95% CI, 1.10-1.29]; P antibiotic use in implementing strategies to reduce the development of new FQREC colonization. Future studies are needed to identify risk factors for infection in hospitalized patients newly colonized with FQREC.

  20. In vitro activities of 11 fluoroquinolones against 816 non-typhoidal strains of Salmonella enterica isolated from Finnish patients with special reference to reduced ciprofloxacin susceptibility

    Science.gov (United States)

    Kotilainen, Pirkko; Pitkänen, Susa; Siitonen, Anja; Huovinen, Pentti; Hakanen, Antti J

    2005-01-01

    Background The number of Salmonella strains with reduced susceptibility to fluoroquinolones has increased during recent years in many countries, threatening the value of this antimicrobial group in the treatment of severe salmonella infections. Methods We analyzed the in vitro activities of ciprofloxacin and 10 additional fluoroquinolones against 816 Salmonella strains collected from Finnish patients between 1995 and 2003. Special attention was focused on the efficacy of newer fluoroquinolones against the Salmonella strains with reduced ciprofloxacin susceptibility. Results The isolates represented 119 different serotypes. Of all 816 Salmonella strains, 3 (0.4%) were resistant to ciprofloxacin (MIC ≥ 4 μg/ml), 232 (28.4%) showed reduced susceptibility to ciprofloxacin (MIC ≥ 0.125 – 2 μg/ml), and 581 (71.2%) were ciprofloxacin-susceptible. The MIC50 and MIC90 values of ciprofloxacin for these strains were 0.032 and 0.25 μg/ml, respectively, being lower than those of the other fluoroquinolone compounds presently on market in Finland (ofloxacin, norfloxacin, levofloxacin, and moxifloxacin). For two newer quinolones, clinafloxacin and sitafloxacin, the MIC50 and MIC90 values were lowest, both 0.016 and 0.064 μg/ml, respectively. Moreover, clinafloxacin and sitafloxacin exhibited the lowest MIC50 and MIC90 values, 0.064 and 0.125 μg/ml, against the 235 Salmonella strains with reduced susceptibility and strains fully resistant to ciprofloxacin. Conclusion Among the registered fluoroquinolones in Finland, ciprofloxacin still appears to be the most effective drug for the treatment salmonella infections. Among the newer preparations, both clinafloxacin and sitafloxacin are promising based on in vitro studies, especially for strains showing reduced ciprofloxacin susceptibility. Their efficacy, however, has not been demonstrated in clinical investigations. PMID:16143044

  1. In vitro activities of 11 fluoroquinolones against 816 non-typhoidal strains of Salmonella enterica isolated from Finnish patients with special reference to reduced ciprofloxacin susceptibility

    Directory of Open Access Journals (Sweden)

    Siitonen Anja

    2005-09-01

    Full Text Available Abstract Background The number of Salmonella strains with reduced susceptibility to fluoroquinolones has increased during recent years in many countries, threatening the value of this antimicrobial group in the treatment of severe salmonella infections. Methods We analyzed the in vitro activities of ciprofloxacin and 10 additional fluoroquinolones against 816 Salmonella strains collected from Finnish patients between 1995 and 2003. Special attention was focused on the efficacy of newer fluoroquinolones against the Salmonella strains with reduced ciprofloxacin susceptibility. Results The isolates represented 119 different serotypes. Of all 816 Salmonella strains, 3 (0.4% were resistant to ciprofloxacin (MIC ≥ 4 μg/ml, 232 (28.4% showed reduced susceptibility to ciprofloxacin (MIC ≥ 0.125 – 2 μg/ml, and 581 (71.2% were ciprofloxacin-susceptible. The MIC50 and MIC90 values of ciprofloxacin for these strains were 0.032 and 0.25 μg/ml, respectively, being lower than those of the other fluoroquinolone compounds presently on market in Finland (ofloxacin, norfloxacin, levofloxacin, and moxifloxacin. For two newer quinolones, clinafloxacin and sitafloxacin, the MIC50 and MIC90 values were lowest, both 0.016 and 0.064 μg/ml, respectively. Moreover, clinafloxacin and sitafloxacin exhibited the lowest MIC50 and MIC90 values, 0.064 and 0.125 μg/ml, against the 235 Salmonella strains with reduced susceptibility and strains fully resistant to ciprofloxacin. Conclusion Among the registered fluoroquinolones in Finland, ciprofloxacin still appears to be the most effective drug for the treatment salmonella infections. Among the newer preparations, both clinafloxacin and sitafloxacin are promising based on in vitro studies, especially for strains showing reduced ciprofloxacin susceptibility. Their efficacy, however, has not been demonstrated in clinical investigations.

  2. Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant and Vancomycin-Intermediate Staphylococcus aureus Infections in vivo.

    Science.gov (United States)

    Ni, Shuaishuai; Wei, Hanwen; Li, Baoli; Chen, Feifei; Liu, Yifu; Chen, Wenhua; Xu, Yixiang; Qiu, Xiaoxia; Li, Xiaokang; Lu, Yanli; Liu, Wenwen; Hu, Linhao; Lin, Dazheng; Wang, Manjiong; Zheng, Xinyu; Mao, Fei; Zhu, Jin; Lan, Le-Fu; Li, Jian

    2017-09-07

    Our previous work (Wang, et al. J. Med. Chem. 2016, 59, 4831-4848) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (pre-administration). In this study, ninety-two chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed the excellent pigment inhibitory activities and low hERG inhibition, along with the improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed firstly with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus) and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.

  3. Loss of function in Mlo orthologs reduces susceptibility of pepper and tomato to powdery mildew disease caused by Leveillula taurica.

    Directory of Open Access Journals (Sweden)

    Zheng Zheng

    Full Text Available Powdery mildew disease caused by Leveillula taurica is a serious fungal threat to greenhouse tomato and pepper production. In contrast to most powdery mildew species which are epiphytic, L. taurica is an endophytic fungus colonizing the mesophyll tissues of the leaf. In barley, Arabidopsis, tomato and pea, the correct functioning of specific homologues of the plant Mlo gene family has been found to be required for pathogenesis of epiphytic powdery mildew fungi. The aim of this study was to investigate the involvement of the Mlo genes in susceptibility to the endophytic fungus L. taurica. In tomato (Solanum lycopersicum, a loss-of-function mutation in the SlMlo1 gene results in resistance to powdery mildew disease caused by Oidium neolycopersici. When the tomato Slmlo1 mutant was inoculated with L. taurica in this study, it proved to be less susceptible compared to the control, S. lycopersicum cv. Moneymaker. Further, overexpression of SlMlo1 in the tomato Slmlo1 mutant enhanced susceptibility to L. taurica. In pepper, the CaMlo2 gene was isolated by applying a homology-based cloning approach. Compared to the previously identified CaMlo1 gene, the CaMlo2 gene is more similar to SlMlo1 as shown by phylogenetic analysis, and the expression of CaMlo2 is up-regulated at an earlier time point upon L. taurica infection. However, results of virus-induced gene silencing suggest that both CaMlo1 and CaMlo2 may be involved in the susceptibility of pepper to L. taurica. The fact that overexpression of CaMlo2 restored the susceptibility of the tomato Slmlo1 mutant to O. neolycopersici and increased its susceptibility to L. taurica confirmed the role of CaMlo2 acting as a susceptibility factor to different powdery mildews, though the role of CaMlo1 as a co-factor for susceptibility cannot be excluded.

  4. Antimicrobial Drug Resistance of Salmonella enterica Serovar Typhi in Asia and Molecular Mechanism of Reduced Susceptibility to the Fluoroquinolones▿

    Science.gov (United States)

    Chau, Tran Thuy; Campbell, James Ian; Galindo, Claudia M.; Van Minh Hoang, Nguyen; Diep, To Song; Nga, Tran Thu Thi; Van Vinh Chau, Nguyen; Tuan, Phung Quoc; Page, Anne Laure; Ochiai, R. Leon; Schultsz, Constance; Wain, John; Bhutta, Zulfiqar A.; Parry, Christopher M.; Bhattacharya, Sujit K.; Dutta, Shanta; Agtini, Magdarina; Dong, Baiqing; Honghui, Yang; Anh, Dang Duc; Canh, Do Gia; Naheed, Aliya; Albert, M. John; Phetsouvanh, Rattanaphone; Newton, Paul N.; Basnyat, Buddha; Arjyal, Amit; La, Tran Thi Phi; Rang, Nguyen Ngoc; Phuong, Le Thi; Van Be Bay, Phan; von Seidlein, Lorenz; Dougan, Gordon; Clemens, John D.; Vinh, Ha; Hien, Tran Tinh; Chinh, Nguyen Tran; Acosta, Camilo J.; Farrar, Jeremy; Dolecek, Christiane

    2007-01-01

    This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between 1993 (4%) and 2005 (97%). In a cross-sectional sample of 381 serovar Typhi strains from 8 Asian countries, Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and central Vietnam, collected in 2002 to 2004, various rates of multidrug resistance (16 to 37%) and nalidixic acid resistance (5 to 51%) were found. The eight Asian countries involved in this study are home to approximately 80% of the world's typhoid fever cases. These results document the scale of drug resistance across Asia. The Ser83→Phe substitution in GyrA was the predominant alteration in serovar Typhi strains from Vietnam (117/127 isolates; 92.1%). No mutations in gyrB, parC, or parE were detected in 55 of these strains. In vitro time-kill experiments showed a reduction in the efficacy of ofloxacin against strains harboring a single-amino-acid substitution at codon 83 or 87 of GyrA; this effect was more marked against a strain with a double substitution. The 8-methoxy fluoroquinolone gatifloxacin showed rapid killing of serovar Typhi harboring both the single- and double-amino-acid substitutions. PMID:17908946

  5. Risk factors for a low linezolid trough plasma concentration in acute infections.

    Science.gov (United States)

    Morata, Laura; Cuesta, Marta; Rojas, Jhon F; Rodriguez, Sebastian; Brunet, Merce; Casals, Gregori; Cobos, Nazareth; Hernandez, Cristina; Martínez, José A; Mensa, Josep; Soriano, Alex

    2013-04-01

    Linezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (C(min)) and to determine factors associated with a C(min) 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of C(min) 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P = 0.001) and infection due to S. aureus (OR, 5.906; 95% CI, 1.651 to 21.126; P = 0.006). A linezolid C(min) of 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy.

  6. Rational development and validation of a new microbiological assay for linezolid and its measurement uncertainty.

    Science.gov (United States)

    Saviano, Alessandro Morais; Francisco, Fabiane Lacerda; Lourenço, Felipe Rebello

    2014-09-01

    The aim of this work was to develop and validate a new microbiological assay to determine potency of linezolid in injectable solution. 2(4) factorial and central composite designs were used to optimize the microbiological assay conditions. In addition, we estimated the measurement uncertainty based on residual error of analysis of variance of inhibition zone diameters. Optimized conditions employed 4 mL of antibiotic 1 medium inoculated with 1% of Staphylococcus aureus suspension, and linezolid in concentrations from 25 to 100 µg mL(-1). The method was specific, linear (Y=10.03X+5.00 and Y=9.20X+6.53, r(2)=0.9950 and 0.9987, for standard and sample curves, respectively), accurate (mean recovery=102.7%), precise (repeatability=2.0% and intermediate precision=1.9%) and robust. Microbiological assay׳s overall uncertainty (3.1%) was comparable to those obtained for other microbiological assays (1.7-7.1%) and for determination of linezolid by spectrophotometry (2.1%) and reverse-phase ultra-performance liquid chromatography (RP-UPLC) (2.5%). Therefore, it is an acceptable alternative method for the routine quality control of linezolid in injectable solution.

  7. A Convenient Synthesis of Antibacterial Linezolid from (S)-Glyceraldehyde Acetonide

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A convenient synthesis of oxazolidinone antibacterial linezolid from readily available L-ascorbic acid is described. The key steps include reductive amination of arylamine and (S)-glyceraldehyde acetonide in the presence of NaBH4 and 4A sieve, followed by hydrolysis and regioselective cyclization.

  8. Detection of high levels of resistance to linezolid and vancomycin in Staphylococcus aureus.

    Science.gov (United States)

    Azhar, Aysha; Rasool, Samreen; Haque, Asma; Shan, Sidra; Saeed, Muhammad; Ehsan, Beenish; Haque, Abdul

    2017-09-01

    Both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) are rapidly overcoming the current array of drugs. One hundred and fifty isolates from a hospital were studied for resistance towards linezolid and vancomycin. Fifty-four (36.0 %) isolates were MRSA. Both MRSA and MSSA showed high resistance towards linezolid when using the disc diffusion method, with the figures being 48.1 and 29.2 %, respectively. The figures for the E-test were 46.3 and 27.0 %, respectively. The vancomycin resistance was remarkable in MRSA (14.8 %), but relatively low in MSSA (3.1 %). The E-test results were 13.0 and 4.16 %, respectively. The cfr gene was detected in 78 % of linezolid-resistant isolates and the vanA operon was detected in 74 % of vancomycin-resistant isolates. This level of resistance against linezolid and vancomycin is unprecedented. These results are alarming and highlight the threat of non-treatable S. aureus strains.

  9. Whole genome analysis of linezolid resistance in Streptococcus pneumoniae reveals resistance and compensatory mutations

    Directory of Open Access Journals (Sweden)

    Légaré Danielle

    2011-10-01

    Full Text Available Abstract Background Several mutations were present in the genome of Streptococcus pneumoniae linezolid-resistant strains but the role of several of these mutations had not been experimentally tested. To analyze the role of these mutations, we reconstituted resistance by serial whole genome transformation of a novel resistant isolate into two strains with sensitive background. We sequenced the parent mutant and two independent transformants exhibiting similar minimum inhibitory concentration to linezolid. Results Comparative genomic analyses revealed that transformants acquired G2576T transversions in every gene copy of 23S rRNA and that the number of altered copies correlated with the level of linezolid resistance and cross-resistance to florfenicol and chloramphenicol. One of the transformants also acquired a mutation present in the parent mutant leading to the overexpression of an ABC transporter (spr1021. The acquisition of these mutations conferred a fitness cost however, which was further enhanced by the acquisition of a mutation in a RNA methyltransferase implicated in resistance. Interestingly, the fitness of the transformants could be restored in part by the acquisition of altered copies of the L3 and L16 ribosomal proteins and by mutations leading to the overexpression of the spr1887 ABC transporter that were present in the original linezolid-resistant mutant. Conclusions Our results demonstrate the usefulness of whole genome approaches at detecting major determinants of resistance as well as compensatory mutations that alleviate the fitness cost associated with resistance.

  10. Risk Factors for a Low Linezolid Trough Plasma Concentration in Acute Infections

    Science.gov (United States)

    Morata, Laura; Cuesta, Marta; Rojas, Jhon F.; Rodriguez, Sebastian; Brunet, Merce; Casals, Gregori; Cobos, Nazareth; Hernandez, Cristina; Martínez, José A.; Mensa, Josep

    2013-01-01

    Linezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (Cmin) and to determine factors associated with a Cmin 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of Cmin 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P = 0.001) and infection due to S. aureus (OR, 5.906; 95% CI, 1.651 to 21.126; P = 0.006). A linezolid Cmin of 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy. PMID:23403416

  11. [Antimicrobial susceptibility of Enterococcus faecalis isolated from patients in Córdoba (Spain)].

    Science.gov (United States)

    Causse, M; Franco-Alvarez de Luna, F; García-Mayorgas, A D; Rodríguez, F C; Casal, M

    2006-06-01

    Enterococcus faecalis is a pathogenic microorganism. The aim of this investigation was to study the antibiotic susceptibility of the strains isolated in Cordoba in a 20-month period (January 2004 to August 2005). Susceptibility rates to betalactamics were 98% to ampicillin and 99% to amoxicillin/clavulanic acid; high-dose aminoglycosides (streptomycin 1000 microg and gentamycin 500 microg) obtained 56% and 76%, respectively. We found no strains resistant to glycopeptides (vancomycin and teicoplanin) or to linezolid.

  12. Monte Carlo simulation analysis of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin pharmacodynamics against intensive care unit-isolated methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Salem, Ahmed Hamed; Zhanel, George G; Ibrahim, Safaa A; Noreddin, Ayman M

    2014-06-01

    The aim of the present study was to compare the potential of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin to achieve their requisite pharmacokinetic/pharmacodynamic (PK/PD) targets against methicillin-resistant Staphylococcus aureus isolates collected from intensive care unit (ICU) settings. Monte Carlo simulations were carried out to simulate the PK/PD indices of the investigated antimicrobials. The probability of target attainment (PTA) was estimated at minimum inhibitory concentration values ranging from 0.03 to 32 μg/mL to define the PK/PD susceptibility breakpoints. The cumulative fraction of response (CFR) was computed using minimum inhibitory concentration data from the Canadian National Intensive Care Unit study. Analysis of the simulation results suggested the breakpoints of 4 μg/mL for ceftobiprole (500 mg/2 h t.i.d.), 0.25 μg/mL for dalbavancin (1000 mg), 0.12 μg/mL for daptomycin (4 mg/kg q.d. and 6 mg/kg q.d.) and tigecycline (50 mg b.i.d.), and 2 μg/mL for linezolid (600 mg b.i.d.) and vancomycin (1 g b.i.d. and 1.5 g b.i.d.). The estimated CFR were 100, 100, 70.6, 88.8, 96.5, 82.4, 89.4, and 98.3% for ceftobiprole, dalbavancin, daptomycin (4 mg/kg/day), daptomycin (6 mg/kg/day), linezolid, tigecycline, vancomycin (1 g b.i.d.) and vancomycin (1.5 g b.i.d.), respectively. In conclusion, ceftobiprole and dalbavancin have the highest probability of achieving their requisite PK/PD targets against methicillin-resistant Staphylococcus aureus isolated from ICU settings. The susceptibility predictions suggested a reduction of the vancomycin breakpoint to 1 μg/mL.

  13. Linezolid analysis of research papers in the subject of adverse drug reaction%利奈唑胺不良反应的文献计量分析

    Institute of Scientific and Technical Information of China (English)

    白艳; 王羽凝; 李其; 王天琳; 孙艳; 王瑾; 王睿

    2015-01-01

    ), Spain (6), New Zealand (5).Literature cited frequency highest was 94.This paper in-volves the injection using linezolid cause severe nervous system toxicity and digestive system adverse drug reaction, aroused people′s concern. Conclusion By reducing the course of medication, dose, or strict tes-ting patients′blood picture during the medication, prevent adverse drug reaction occur.

  14. Resistance to first-line anti-TB drugs is associated with reduced nitric oxide susceptibility in Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Idh, Jonna; Mekonnen, Mekidim; Abate, Ebba;

    2012-01-01

    The relative contribution of nitric oxide (NO) to the killing of Mycobacterium tuberculosis in human tuberculosis (TB) is controversial, although this has been firmly established in rodents. Studies have demonstrated that clinical strains of M. tuberculosis differ in susceptibility to NO, but how...

  15. Seminational surveillance of fungemia in Denmark: notably high rates of fungemia and numbers of isolates with reduced azole susceptibility

    DEFF Research Database (Denmark)

    Arendrup, Maiken Cavling; Fuursted, Kurt; Gahrn-Hansen, Bente;

    2005-01-01

    The aim of this study was to present the first set of comprehensive data on fungemia in Denmark including the distribution of species and range of susceptibility to major antifungal compounds based on a seminational surveillance study initiated in 2003. The catchment area of the participating hos...

  16. Reduced in vitro susceptibility to artemisinin derivatives associated with multi-resistance in a traveller returning from South-East Asia

    Directory of Open Access Journals (Sweden)

    Bertaux Lionel

    2011-09-01

    Full Text Available Abstract Decreased in vitro susceptibility to dihydroartemisinin (21.2 nM and artesunate (16.3 nM associated with decreased susceptibility or resistance to quinine (1131 nM, mefloquine (166 nM, lumefantrine (114 nM, pyronaridine (70.5 nM and piperaquine (91.1 nM is reported in a patient returning from South-East Asia after trekking along the Mekong from the south of Laos to the north of Thailand. Decreased in vitro susceptibility to artemisinin derivatives did not appear to be mediated by the number of copies of pfmdr1 or pfATPase6, pfcrt, pfmdr1 or pfmrp polymorphism. The high IC50 to mefloquine of this Asian isolate was not associated with pfmdr1 copy number. Pfnhe-1 microsatellite ms4760 showed a profile 7 (ms4760-7 with three repeats of DNNND and one repeat of DDDNHNDNHNN, which is associated with high quinine reduced susceptibility. The patient recovered in three days without relapse after treatment with the association of quinine and doxycycline. Decreased in vitro susceptibility to quinine and the delayed effect of doxycycline may both have contributed to the delayed parasite clearance time, D4 (0.5% and D7 (0.004%. The in vitro data, with IC50 for dihydroartemisinin and artesunate were up to ten times those of the reference clone W2, which suggests that this isolate may be resistant to artemisinin derivatives, associated with a decreased susceptibility to quinine.

  17. Linezolid concentrations in infected soft tissue and bone following repetitive doses in diabetic patients with bacterial foot infections1

    OpenAIRE

    Traunmüller, Friederike; Schintler, Michael V.; Spendel, Stephan; Popovic, Martin; Mauric, Oliver; Scharnagl, Erwin; Joukhadar, Christian

    2010-01-01

    Abstract The present study aimed at assessing unbound extracellular concentrations of linezolid in inflamed soft tissue and bone of diabetic patients suffering from severe bacterial foot infections. Linezolid was administered intravenously twice daily at a dosage of 600mg. At steady-state conditions, the microdialysis technique was utilised to sample serially interstitial space fluid from inflamed subcutaneous adipose tissue and metatarsal bone from 0?8h post dose in three represen...

  18. Analysis of amino acid sequences of penicillin-binding protein 2 in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime and ceftriaxone.

    Science.gov (United States)

    Osaka, Kazuyoshi; Takakura, Tadakazu; Narukawa, Kayo; Takahata, Masahiro; Endo, Katsuhisa; Kiyota, Hiroshi; Onodera, Shoichi

    2008-06-01

    Neisseria gonorrhoeae strains with reduced susceptibility to cefixime and ceftriaxone, with minimum inhibitory concentrations (MICs) of cefixime of 0.125-0.25 microg/ml and ceftriaxone of 0.031-0.125 microg/ml, were isolated from male urethritis patients in Tokyo, Japan, in 2006. The amino acid sequences of PenA, penicillin-binding protein 2, in these strains were of two types: PenA mosaic and nonmosaic strains. In the PenA mosaic strain, some regions in the transpeptidase-encoding domain in PenA were similar to those of Neisseria perflava/sicca, Neisseria cinerea, Neisseria flavescens, Neisseria polysaccharea, and Neisseria meningitidis. In the PenA nonmosaic strain, there was a mutation of Ala-501 to Val in PenA. In addition, we performed homology modeling of PenA wild-type and mosaic strains and compared them. The results of the modeling studies suggested that reduced susceptibility to cephems such as cefixime and ceftriaxone is due to a conformational alteration of the beta-lactam-binding pocket. These results also indicated that the mosaic structures and the above point mutation in PenA make a major contribution to the reduced susceptibility to cephem antibiotics.

  19. In vivo emergence of Aspergillus terreus with reduced azole susceptibility and a Cyp51a M217I alteration

    DEFF Research Database (Denmark)

    Arendrup, Maiken C; Jensen, Rasmus; Grif, Katharina;

    2012-01-01

    Azole resistance in Aspergillus terreus isolates was explored. Twenty related (MB) and 6 unrelated A. terreus isolates were included. CYP51A sequencing and RAPD genotyping was performed. Five MB isolates were itraconazole susceptible, whereas the minimum inhibitory concentrations (MICs) for 15 MB...... isolates were elevated (1-2 mg/L). Voriconazole and posaconazole MICs were 0.5-4 and 0.06-0.5 mg/L, respectively, for MB isolates but 0.25-0.5 and...

  20. Reduced Tyk2 gene expression in β-cells due to natural mutation determines susceptibility to virus-induced diabetes

    OpenAIRE

    Izumi, Kenichi; Mine, Keiichiro; Inoue, Yoshitaka; Teshima, Miho; Ogawa, Shuichiro; Kai, Yuji; Kurafuji, Toshinobu; Hirakawa, Kanako; Miyakawa, Daiki; Ikeda, Haruka; Inada, Akari; Hara, Manami; Yamada, Hisakata; Akashi, Koichi; Niho, Yoshiyuki

    2015-01-01

    Accumulating evidence suggests that viruses play an important role in the development of diabetes. Although the diabetogenic encephalomyocarditis strain D virus induces diabetes in restricted lines of inbred mice, the susceptibility genes to virus-induced diabetes have not been identified. We report here that novel Tyrosine kinase 2 (Tyk2) gene mutations are present in virus-induced diabetes-sensitive SJL and SWR mice. Mice carrying the mutant Tyk2 gene on the virus-resistant C57BL/6 backgrou...

  1. A simple high-performance liquid chromatography for the determination of linezolid in human plasma and saliva.

    Science.gov (United States)

    Hara, Shuuji; Uchiyama, Masanobu; Yoshinari, Masami; Matsumoto, Taichi; Jimi, Shiro; Togawa, Atsushi; Takata, Tohru; Takamatsu, Yasushi

    2015-09-01

    Linezolid is an antimicrobial agent for the treatment of multiresistant Gram-positive infections. A practical high-performance liquid chromatography method was developed for the determination of linezolid in human plasma and saliva. Linezolid and an internal standard (o-ethoxybenzamide) were extracted from plasma and saliva with ethyl acetate and analyzed on a Capcell Pak C18 MG column with UV detection at 254 nm. The calibration curve was linear through the range 0.5-50 µg/mL using a 200 μL sample volume. The intra- and interday precisions were all saliva. The accuracies ranged from 98.8 to 110% for both matrices. The mean recoveries of linezolid were 80.8% for plasma and 79.0% for saliva. This method was used to determine the plasma and saliva concentrations of linezolid in healthy volunteers who were orally administered a 600 mg dose of linezolid. Our liquid-liquid extraction procedure is easy and requires a small volume of plasma or saliva (200 μL). This small volume can be advantageous in clinical pharmacokinetic studies, especially if children participate.

  2. Lactic Acidosis Induced by Linezolid Mimics Symptoms of an Acute Intracranial Bleed: A Case Report and Literature Review

    Science.gov (United States)

    Zuccarini, Nichole Suzzanne; Yousuf, Tariq; Wozniczka, Daniel; Rauf, Anis Abdul

    2016-01-01

    Lactic acidosis is common and most often associated with disturbed acid-base balance. Rarely, it can be a life-threatening medication side effect. Hence, determining the etiology of lactic acidosis early in patients is paramount in choosing the correct therapeutic intervention. Although lactic acidosis as an adverse drug reaction of linezolid is a well-recognized and documented clinical entity, the occurrence of such mimicking an acute intracranial bleed has not been reported to our knowledge. The following case is presented as an example of such an occurrence. A 67-year-old woman presented to the emergency department for lethargy, nausea and syncope. The head CT did not demonstrate any bleeding or mass effect, but lab results were significant for elevated lactic acid. The patient recently underwent left total hip replacement surgery, which was complicated by a methicillin-resistant Staphylococcus aureus (MRSA) infection. She received 6 weeks of oral linezolid therapy. And upon learning that key part of her history, the linezolid was discontinued. Her lactic acid rapidly normalized and she was discharged home. Several publications demonstrate that linezolid induces lactic acidosis by disrupting crucial mitochondrial functions. It is essential that clinicians are aware that linezolid can cause lactic acidosis. And, the important reminder is that adverse drug reactions can often mimic common diseases. If it is not recognized early, ominous clinical consequences may occur. In conclusion, linezolid should be suspected and included in the differential diagnosis if lactic acidosis exists with an uncommon clinical picture. PMID:27635182

  3. Comparative study of the effects of pyridoxine, rifampin, and renal function on hematological adverse events induced by linezolid.

    Science.gov (United States)

    Soriano, Alex; Ortega, Mar; García, Sebastián; Peñarroja, Georgina; Bové, Albert; Marcos, Miguel; Martínez, Juan C; Martínez, José A; Mensa, Josep

    2007-07-01

    Hematological disturbances that develop during linezolid treatment are a major concern when linezolid is administered for prolonged periods of time. The aim of this study was to evaluate the influences of pyridoxine, rifampin, and renal function on hematological adverse events. From January 2002 to April 2006, 52 patients received a long-term course of linezolid. Blood cell counts were monitored weekly. Thrombocytopenia was defined as a decrease to or =2 g/liter from the baseline value. Twenty-four patients received linezolid alone, and 28 patients received linezolid plus 200 mg of pyridoxine. The Kaplan-Meier survival method, followed by the log-rank test, was used to estimate the cumulative probability of adverse events, and Cox regression analysis was performed to evaluate the independent predictors of toxicity. The baseline characteristics of the patients in both groups were similar. The cumulative probability of thrombocytopenia and anemia in patients who received pyridoxine was not different from that in patients who did not receive it. Hematological adverse events were less frequent in patients taking rifampin and were more frequent in patients with renal failure. However; the Cox regression analysis showed that rifampin was the only independent predictor associated with a lower risk of thrombocytopenia (hazard ratio, 0.37; 95% confidence interval, 0.14 to 0.98; P = 0.045). In conclusion, pyridoxine did not prevent linezolid-related hematological adverse events, and the coadministration of rifampin was associated with a lower risk of thrombocytopenia.

  4. Propofol Increases Host Susceptibility to Microbial Infection by Reducing Subpopulations of Mature Immune Effector Cells at Sites of Infection

    Science.gov (United States)

    Visvabharathy, Lavanya; Xayarath, Bobbi; Weinberg, Guy; Shilling, Rebecca A.; Freitag, Nancy E.

    2015-01-01

    Anesthetics are known to modulate host immune responses, but separating the variables of surgery from anesthesia when analyzing hospital acquired infections is often difficult. Here, the bacterial pathogen Listeria monocytogenes (Lm) was used to assess the impact of the common anesthetic propofol on host susceptibility to infection. Brief sedation of mice with physiologically relevant concentrations of propofol increased bacterial burdens in target organs by more than 10,000-fold relative to infected control animals. The adverse effects of propofol sedation on immune clearance of Lm persisted after recovery from sedation, as animals given the drug remained susceptible to infection for days following anesthesia. In contrast to propofol, sedation with alternative anesthetics such as ketamine/xylazine or pentobarbital did not increase susceptibility to systemic Lm infection. Propofol altered systemic cytokine and chemokine expression during infection, and prevented effective bacterial clearance by inhibiting the recruitment and/or activity of immune effector cells at sites of infection. Propofol exposure induced a marked reduction in marginal zone macrophages in the spleens of Lm infected mice, resulting in bacterial dissemination into deep tissue. Propofol also significantly increased mouse kidney abscess formation following infection with the common nosocomial pathogen Staphylococcus aureus. Taken together, these data indicate that even brief exposure to propofol severely compromises host resistance to microbial infection for days after recovery from sedation. PMID:26381144

  5. Propofol Increases Host Susceptibility to Microbial Infection by Reducing Subpopulations of Mature Immune Effector Cells at Sites of Infection.

    Directory of Open Access Journals (Sweden)

    Lavanya Visvabharathy

    Full Text Available Anesthetics are known to modulate host immune responses, but separating the variables of surgery from anesthesia when analyzing hospital acquired infections is often difficult. Here, the bacterial pathogen Listeria monocytogenes (Lm was used to assess the impact of the common anesthetic propofol on host susceptibility to infection. Brief sedation of mice with physiologically relevant concentrations of propofol increased bacterial burdens in target organs by more than 10,000-fold relative to infected control animals. The adverse effects of propofol sedation on immune clearance of Lm persisted after recovery from sedation, as animals given the drug remained susceptible to infection for days following anesthesia. In contrast to propofol, sedation with alternative anesthetics such as ketamine/xylazine or pentobarbital did not increase susceptibility to systemic Lm infection. Propofol altered systemic cytokine and chemokine expression during infection, and prevented effective bacterial clearance by inhibiting the recruitment and/or activity of immune effector cells at sites of infection. Propofol exposure induced a marked reduction in marginal zone macrophages in the spleens of Lm infected mice, resulting in bacterial dissemination into deep tissue. Propofol also significantly increased mouse kidney abscess formation following infection with the common nosocomial pathogen Staphylococcus aureus. Taken together, these data indicate that even brief exposure to propofol severely compromises host resistance to microbial infection for days after recovery from sedation.

  6. Investigation into the potential of sub-lethal photodynamic antimicrobial chemotherapy (PACT) to reduce susceptibility of meticillin-resistant Staphylococcus aureus (MRSA) to antibiotics

    Science.gov (United States)

    Cassidy, C. M.; Donnelly, R. F.; Tunney, M. M.

    2009-06-01

    In PACT, a combination of a sensitising drug and visible light cause the selective destruction of microbial cells via singlet oxygen production. As singlet oxygen is a non-specific oxidizing agent and is only present during illumination, development of resistance to this treatment is thought to be unlikely. However, in response to oxidative stress, bacteria can up-regulate oxidative stress genes and associated antibiotic resistance genes. The up-regulation of these genes and potential transfer of genetic material may result in a resistant bacterial population. This study determined whether treatment of clinically isolated meticillin resistant Staphylococcus aureus (MRSA) strains with sub-lethal doses of methylene blue (MB) and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP)-PACT resulted in reduced susceptibility to antibiotics and previously lethal PACT. Exposure of strains to sub-lethal doses of photosensitizer in combination with light had no effect on susceptibility to previously lethal photosensitization. Furthermore, exposure to sub-lethal concentrations of both photosensitizers caused no significant changes in the minimum inhibitory concentration (MIC) for each strain tested. Any differences in susceptibility were not significant as they did not cross breakpoints between resistant and susceptible for any organism or antibiotic tested. Therefore, PACT remains an attractive alternative option for treatment of MRSA infections.

  7. Disruptions in neural connectivity associated with reduced susceptibility to a depth inversion illusion in youth at ultra high risk for psychosis

    Directory of Open Access Journals (Sweden)

    Tina Gupta

    2016-01-01

    Full Text Available Patients with psychosis exhibit a reduced susceptibility to depth inversion illusions (DII in which a physically concave surface is perceived as convex (e.g., the hollow mask illusion. Here, we examined the extent to which lessened susceptibility to DII characterized youth at ultra high risk (UHR for psychosis. In this study, 44 UHR participants and 29 healthy controls judged the apparent convexity of face-like human masks, two of which were concave and the other convex. One of the concave masks was painted with realistic texture to enhance the illusion; the other was shown without such texture. Networks involved with top-down and bottom-up processing were evaluated with resting state functional connectivity magnetic resonance imaging (fcMRI. We examined regions associated with the fronto-parietal network and the visual system and their relations with susceptibility to DII. Consistent with prior studies, the UHR group was less susceptible to DII (i.e., they were characterized by more veridical perception of the stimuli than the healthy control group. Veridical responses were related to weaker connectivity within the fronto-parietal network, and this relationship was stronger in the UHR group, suggesting possible abnormalities of top-down modulation of sensory signals. This could serve as a vulnerability marker and a further clue to the pathogenesis of psychosis.

  8. Reduced susceptibility to polyenes associated with a missense mutation in the ERG6 gene in a clinical isolate of Candida glabrata with pseudohyphal growth.

    Science.gov (United States)

    Vandeputte, Patrick; Tronchin, Guy; Bergès, Thierry; Hennequin, Christophe; Chabasse, Dominique; Bouchara, Jean-Philippe

    2007-03-01

    Little information is available about the molecular mechanisms responsible for polyene resistance in pathogenic yeasts. A clinical isolate of Candida glabrata with a poor susceptibility to polyenes, as determined by disk diffusion method and confirmed by determination of MIC, was recovered from a patient treated with amphotericin B. Quantitative analysis of sterols revealed a lack of ergosterol and an accumulation of late sterol intermediates, suggesting a defect in the final steps of the ergosterol pathway. Sequencing of CgERG11, CgERG6, CgERG5, and CgERG4 genes revealed exclusively a unique missense mutation in CgERG6 leading to the substitution of a cysteine by a phenylalanine in the corresponding protein. In addition, real-time reverse transcription-PCR demonstrated an overexpression of genes encoding enzymes involved in late steps of the ergosterol pathway. Moreover, this isolate exhibited a pseudohyphal growth whatever the culture medium used, and ultrastructural changes of the cell wall of blastoconidia were seen consisting in a thinner inner layer. Cell wall alterations were also suggested by the higher susceptibility of growing cells to Calcofluor white. Additionally, complementation of this isolate with a wild-type copy of the CgERG6 gene restored susceptibility to polyenes and a classical morphology. Together, these results demonstrated that mutation in the CgERG6 gene may lead to a reduced susceptibility to polyenes and to a pseudohyphal growth due to the subsequent changes in sterol content of the plasma membrane.

  9. Reduced in vitro doxycycline susceptibility in plasmodium falciparum field isolates from Kenya is associated with PfTetQ KYNNNN sequence polymorphism.

    Science.gov (United States)

    Achieng, Angela O; Ingasia, Luiser A; Juma, Dennis W; Cheruiyot, Agnes C; Okudo, Charles A; Yeda, Redemptah A; Cheruiyot, Jelagat; Akala, Hoseah M; Johnson, Jacob; Andangalu, Ben; Eyase, Fredrick; Jura, Walter G Z O; Kamau, Edwin

    2014-10-01

    Doxycycline is widely used for malaria prophylaxis by international travelers. However, there is limited information on doxycycline efficacy in Kenya, and genetic polymorphisms associated with reduced efficacy are not well defined. In vitro doxycycline susceptibility profiles for 96 Plasmodium falciparum field isolates from Kenya were determined. Genetic polymorphisms were assessed in P. falciparum metabolite drug transporter (Pfmdt) and P. falciparum GTPase tetQ (PftetQ) genes. Copy number variation of the gene and the number of KYNNNN amino acid motif repeats within the protein encoded by PftetQ were determined. Reduced in vitro susceptibility to doxycycline was defined by 50% inhibitory concentrations (IC50s) of ≥35,000 nM. The odds ratio (OR) of having 2 PfTetQ KYNNNN amino acid repeats in isolates with IC50s of >35,000 nM relative to those with IC50s of IC50 of 6,971 nM, whereas those with a Pfmdt copy number of >1 had a median IC50 of 9,912 nM (P = 0.0245). Isolates with 1 copy of PftetQ had a median IC50 of 6,370 nM, whereas isolates with a PftetQ copy number of >1 had a median IC50 of 3,422 nM (P IC50 of 26,165 nM, whereas isolates with 3 PfTetQ KYNNNN repeats had a median IC50 of 3,352 nM (P = 0.0023). PfTetQ sequence polymorphism is associated with a reduced doxycycline susceptibility phenotype in Kenyan isolates and is a potential marker for susceptibility testing.

  10. Nocardia asteroides peritoneal dialysis-related peritonitis: First case in pediatrics, treated with protracted linezolid.

    Science.gov (United States)

    El-Naggari, Mohamed; El Nour, Ibtisam; Al-Nabhani, Dana; Al Muharrmi, Zakaria; Gaafar, Heba; Abdelmogheth, Anas A W

    2016-01-01

    Nocardia asteroides is a rare pathogen in peritoneal dialysis-related peritonitis. We report on a 13-year-old female with Nocardia asteroides peritonitis complicated by an intra-abdominal abscess. Linezolid was administered intravenously for 3 months and followed by oral therapy for an additional 5 months with close monitoring for adverse effects. The patient was discharged after 3 months of hospitalization on hemodialysis. The diagnosis and management of such cases can be problematic due to the slow growth and difficulty of identifying Nocardia species. The optimal duration of treatment for Nocardia peritonitis is not known. Linezolid can be used for prolonged periods in cases of trimethoprim/sulfamethoxazole-resistant cases with close monitoring for adverse effects.

  11. Serotonin syndrome in an orthopaedic patient secondary to linezolid therapy for MRSA infection.

    LENUS (Irish Health Repository)

    McClean, M

    2012-01-31

    A 67-year-old patient was admitted for incision and drainage of a recurrent methicillin-resistant Staphylococcus aureus (MRSA) hip abscess. Linezolid therapy was initiated postoperatively. Within 48 h the patient developed confusion, agitation, hypertension and acute renal failure. Citalopram was stopped and resolution of symptoms occurred within 48 h of discontinuing the offending agent. The symptoms observed in our patient were consistent with the Sternbach criteria for serotonin syndrome.

  12. The knock-down of the expression of MdMLO19 reduces susceptibility to powdery mildew (Podosphaera leucotricha) in apple (Malus domestica).

    Science.gov (United States)

    Pessina, Stefano; Angeli, Dario; Martens, Stefan; Visser, Richard G F; Bai, Yuling; Salamini, Francesco; Velasco, Riccardo; Schouten, Henk J; Malnoy, Mickael

    2016-10-01

    Varieties resistant to powdery mildew (PM; caused by Podosphaera leucotricha) are a major component of sustainable apple production. Resistance can be achieved by knocking-out susceptibility S-genes to be singled out among members of the MLO (Mildew Locus O) gene family. Candidates are MLO S-genes of phylogenetic clade V up-regulated upon PM inoculation, such as MdMLO11 and 19 (clade V) and MdMLO18 (clade VII). We report the knock-down through RNA interference of MdMLO11 and 19, as well as the complementation of resistance with MdMLO18 in the Arabidopsis thaliana triple mlo mutant Atmlo2/6/12. The knock-down of MdMLO19 reduced PM disease severity by 75%, whereas the knock-down of MdMLO11, alone or in combination with MdMLO19, did not result in any reduction or additional reduction of susceptibility compared with MdMLO19 alone. The test in A. thaliana excluded a role for MdMLO18 in PM susceptibility. Cell wall appositions (papillae) were present in both PM-resistant and PM-susceptible plants, but were larger in resistant lines. No obvious negative phenotype was observed in plants with mlo genes knocked down. Apparently, MdMLO19 plays the pivotal role in apple PM susceptibility and its knock-down induces a very significant level of resistance. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  13. A Natural Variant of the T Cell Receptor-Signaling Molecule Vav1 Reduces Both Effector T Cell Functions and Susceptibility to Neuroinflammation

    Science.gov (United States)

    Kassem, Sahar; Bernard, Isabelle; Dejean, Anne S.; Liblau, Roland; Fournié, Gilbert J.; Colacios, Céline

    2016-01-01

    The guanine nucleotide exchange factor Vav1 is essential for transducing T cell antigen receptor signals and therefore plays an important role in T cell development and activation. Our previous genetic studies identified a locus on rat chromosome 9 that controls the susceptibility to neuroinflammation and contains a non-synonymous polymorphism in the major candidate gene Vav1. To formally demonstrate the causal implication of this polymorphism, we generated a knock-in mouse bearing this polymorphism (Vav1R63W). Using this model, we show that Vav1R63W mice display reduced susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by MOG35-55 peptide immunization. This is associated with a lower production of effector cytokines (IFN-γ, IL-17 and GM-CSF) by autoreactive CD4 T cells. Despite increased proportion of Foxp3+ regulatory T cells in Vav1R63W mice, we show that this lowered cytokine production is intrinsic to effector CD4 T cells and that Treg depletion has no impact on EAE development. Finally, we provide a mechanism for the above phenotype by showing that the Vav1R63W variant has normal enzymatic activity but reduced adaptor functions. Together, these data highlight the importance of Vav1 adaptor functions in the production of inflammatory cytokines by effector T cells and in the susceptibility to neuroinflammation. PMID:27438086

  14. Listeria monocytogenes Strains Selected on Ciprofloxacin or the Disinfectant Benzalkonium Chloride Exhibit Reduced Susceptibility to Ciprofloxacin, Gentamicin, Benzalkonium Chloride, and Other Toxic Compounds▿

    Science.gov (United States)

    Rakic-Martinez, Mira; Drevets, Douglas A.; Dutta, Vikrant; Katic, Vera; Kathariou, Sophia

    2011-01-01

    Listeria monocytogenes is a leading agent for severe food-borne illness and death in the United States and other nations. Even though drug resistance has not yet threatened therapeutic interventions for listeriosis, selective pressure associated with exposure to antibiotics and disinfectants may result in reduced susceptibility to these agents. In this study, selection of several L. monocytogenes strains on either ciprofloxacin (2 μg/ml) or the quaternary ammonium disinfectant benzalkonium chloride (BC; 10 μg/ml) led to derivatives with increased MICs not only to these agents but also to several other toxic compounds, including gentamicin, the dye ethidium bromide, and the chemotherapeutic drug tetraphenylphosphonium chloride. The spectrum of compounds to which these derivatives exhibited reduced susceptibility was the same regardless of whether they were selected on ciprofloxacin or on BC. Inclusion of strains harboring the large plasmid pLM80 revealed that MICs to ciprofloxacin and gentamicin did not differ between the parental and plasmid-cured strains. However, ciprofloxacin-selected derivatives of pLM80-harboring strains had higher MICs than those derived from the plasmid-cured strains. Susceptibility to the antimicrobials was partially restored in the presence of the potent efflux inhibitor reserpine. Taken together, these data suggest that mutations in efflux systems are responsible for the multidrug resistance phenotype of strains selected on ciprofloxacin or BC. PMID:22003016

  15. 利奈唑胺对耐多药结核分枝杆菌及非结核分枝杆菌体外敏感性研究%In vitro bactericidal assay of linezolid on multidrug-resistant tuberculosis and nontuberculous mycobacteria

    Institute of Scientific and Technical Information of China (English)

    张晓飞; 张范华; 张艳; 刘伟; 张嵘

    2014-01-01

    Objective To investigate the mycobactericidal efficacy of linezolid on multidrugresistant tuberculosis (MDR-TB) and nontuberculous mycobacteria (NTM) in vitro.Methods Seven hundred and sixty-two Mycobacterium tuberculosis and 20 NTM isolates from Hangzhou were identified by using hsp65 gene sequencing from March to June,2013.Seventy MDR-TB isolates,which were screened by using proportion method,and twenty NTM isolates were tested the MIC to linezolid,and the differences of MICs to linezolid between MDR-TB and NTM werw analyzed in vitro.Results All 70 MDR-TB isolates were inhibited at concentrations of ≤ 1 mg/L by linezolid,MIC50 was 0.5 mg/L and MIC90 1 mg/L.Of all 8 isolates inhibited at concentration of 1 mg/L,there were 6 isolates resistant to isoniazid,rifampin,streptomycin and ethambutol,suggesting this resistance pattern may reduce sensitivity to linezolid.Among the NTM isolates,18 Mycobacterium intracellulare isolates,whose MICs to linezolid at 8-16 mg/L,were non-resistant isolates,while 2 Mycobacterium abscessus isolates displaying MICs > 32 mg/L,were resistant to linezolid.Conclusions Linezolid showed great activity to MDR-TB and there were no linezolid-resistant MDR-TB isolates identified in this study.However,MICs of MDR-TB against linezolid increased with their resistant numbers to first-line agents.This study also showed that different NTM species have varied sensitivity to linezolid.%目的 研究利奈唑胺对耐多药结核分枝杆菌(MDR-TB)和非结核分枝杆菌(NTM)的体外药物敏感性.方法 2013年3至6月使用hsp65基因测序比对的方法鉴定杭州地区762株结核分枝杆菌和20株NTM,通过比例法药敏试验获得70株MDR-TB,测定其与20株NTM对利奈唑胺的MIC,分析利奈唑胺对MDR-TB和NTM体外抑菌浓度的差异.结果 所测70株MDR-TB的利奈唑胺MIC均≤1 mg/L,MIC50为0.5 mg/L,MIC90为1 mg/L.对异烟肼、利福平、链霉素和乙胺丁醇耐药的MDR-TB菌株占MIC为1 mg/L菌株的6/8,提示

  16. Treatment failure in a typhoid patient infected with nalidixic acid resistant S. enterica serovar Typhi with reduced susceptibility to Ciprofloxacin: a case report from Cameroon

    Directory of Open Access Journals (Sweden)

    Asonganyi Etienne DN

    2005-06-01

    Full Text Available Abstract Background Fluoroquinolones or third generation cephalosporins are the drugs of choice for the treatment of typhoid fever. Treatment failure with fluoroquinolones has been reported in Asia and Europe. We report a case of ciprofloxacin treatment failure in typhoid fever in Cameroon. Case presentation A 29-year-old female patient with suspected typhoid fever from Kumba, Cameroon, yielded growth of Salmonella enterica serovar Typhi in blood culture. The isolate was resistant to nalidixic acid but sensitive to ciprofloxacin by disc diffusion test. However, the patient did not respond to treatment with ciprofloxacin, although the isolate was apparently susceptible to ciprofloxacin. Conclusion Treatment failure with ciprofloxacin in our case indicates the presence of nalidixic acid resistant S. enterica serovar Typhi (NARST with reduced susceptibility to ciprofloxacin in Cameroon (Central Africa.

  17. Reduced CX3CL1 Secretion Contributes to the Susceptibility of Oral Leukoplakia-Associated Fibroblasts to Candida albicans

    Science.gov (United States)

    Cheng, Ran; Li, Duo; Shi, Xueke; Gao, Qinghong; Wei, Changlei; Li, Xiaoyu; Li, Yan; Zhou, Hongmei

    2016-01-01

    Candida leukoplakia (OLK) is a kind of oral leukoplakia combined with chronic candidal infection, which plays an important role in the malignant transformation of OLK. However, little is known about the etiology, including susceptibility of leukoplakia to candidal adhesion, invasion and infection. Some antimicrobial peptides secreted by oral epithelial cells or fibroblasts potentially have antifungal activities against Candida albicans (C. albicans). In this study, we established three co-culture models to simulate different C. albicans-fibroblasts interactions during progression of candida leukoplakia. The susceptibility of oral leukoplakia-associated fibroblasts (LKAFs) to C. albicans and its underlying mechanism were determined. Samples of 14 LKAFs and 10 normal fibroblasts (NFs) were collected. The co-culture models showed that LKAFs had promoted the adhesion, invasion, and survival of C. albicans compared with NFs. CX3CL1, a chemokine with antifungal activity, was less abundant in LKAFs than NFs. Overexpression of CX3CL1 via transfection in LKAFs could partly restore the resistance to C. albicans. We also showed that inhibition of ERK could suppress CX3CL1 secretion. While phosphor-ERK was inhibited in LKAFs compared with NFs. Besides, the mRNA expression of a shedding enzyme for CX3CL1, disintegrin and metalloproteinase domain (ADAM) 17 was decreased in LKAFs than NFs. In conclusion, LKAFs produced and secreted less CX3CL1 by inhibiting the ERK signaling pathway, thereby contributing to impaired cell resistance to C. albicans. PMID:27891323

  18. Reduced CX3CL1 secretion contributes to the susceptibility of oral leukoplakia-associated fibroblasts to Candida albicans

    Directory of Open Access Journals (Sweden)

    Ran Cheng

    2016-11-01

    Full Text Available Candida leukoplakia (OLK is a kind of oral leukoplakia combined with chronic candidal infection, which plays an important role in the malignant transformation of OLK. However, little is known about the etiology, including susceptibility of leukoplakia to candidal adhesion, invasion and infection. Some antimicrobial peptides secreted by oral epithelial cells or fibroblasts potentially have antifungal activities against Candida albicans (C. albicans. In this study, we established three co-culture models to simulate different C. albicans-fibroblasts interactions during progression of candida leukoplakia. The susceptibility of oral leukoplakia-associated fibroblasts (LKAFs to C. albicans and its underlying mechanism were determined. Samples of 14 LKAFs and 10 normal fibroblasts (NFs were collected. The co-culture models showed that LKAFs had promoted the adhesion, invasion, and survival of C. albicans compared with NFs. CX3CL1, a chemokine with antifungal activity, was less abundant in LKAFs than NFs. Overexpression of CX3CL1 via transfection in LKAFs could partly restore the resistance to C. albicans. We also showed that inhibition of ERK could suppress CX3CL1 secretion. While phosphor-ERK was inhibited in LKAFs compared with NFs. Besides, the expression of a shedding enzyme for CX3CL1, disintegrin and metalloproteinase domain (ADAM 17 was decreased in LKAFs than NFs. In conclusion, LKAFs produced and secreted less CX3CL1 by inhibiting the ERK signaling pathway, thereby contributing to impaired cell resistance to C. albicans.

  19. A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility.

    Science.gov (United States)

    Garcia-Effron, Guillermo; Katiyar, Santosh K; Park, Steven; Edlind, Thomas D; Perlin, David S

    2008-07-01

    Candida parapsilosis has emerged as a common cause of invasive fungal infection, especially in Latin America and in the neonatal setting. C. parapsilosis is part of a closely related group of organisms that includes the species Candida orthopsilosis and Candida metapsilosis. All three species show elevated MICs for the new echinocandin class drugs caspofungin, micafungin, and anidulafungin relative to other Candida species. Despite potential impacts on therapy, the mechanism behind this reduced echinocandin susceptibility has not been determined. In this report, we investigated the role of a naturally occurring Pro-to-Ala substitution at amino acid position 660 (P660A), immediately distal to the highly conserved hot spot 1 region of Fks1p, in the reduced-echinocandin-susceptibility phenotype. Kinetic inhibition studies demonstrated that glucan synthase from the C. parapsilosis group was 1 to 2 logs less sensitive to echinocandin drugs than the reference enzyme from C. albicans. Furthermore, clinical isolates of C. albicans and C. glabrata which harbor mutations at this equivalent position also showed comparable 2-log decreases in target enzyme sensitivity, which correlated with increased MICs. These mutations also resulted in 2.4- to 18.8-fold-reduced V(max) values relative to those for the wild-type enzyme, consistent with kinetic parameters obtained for C. parapsilosis group enzymes. Finally, the importance of the P660A substitution for intrinsic resistance was confirmed by engineering an equivalent P647A mutation into Fks1p of Saccharomyces cerevisiae. The mutant glucan synthase displayed characteristic 2-log decreases in sensitivity to the echinocandin drugs. Overall, these data firmly indicate that a naturally occurring P660A substitution in Fks1p from the C. parapsilosis group accounts for the reduced susceptibility phenotype.

  20. Clinical experience with linezolid in the treatment of resistant gram-positive infections.

    Science.gov (United States)

    Antony, S J; Diaz-Vasquez, E; Stratton, C

    2001-10-01

    This study presents our clinical experience with linezolid in 19 patients with serious resistant gram-positive infections enrolled as part of the compassionate study. In this prospective, non-randomized, noncomparative study, 19 patients were enrolled as part of the National Compassionate Study Protocol conducted by Pharmacia-Upjohn. At the time of this writing, these patients had not been published in the literature. All of the patients had to have documented evidence of serious gram-positive infections in normally sterile sites and should have been unable to tolerate available antimicrobial therapy or be unresponsive to available drugs. Clinical characteristics, laboratory values, and pharmacokinetic and pharmacodynamic parameters were obtained. Patients were followed both short-term and long-term after completion of therapy. Nineteen patients were enrolled: 13 females and 6 males. The average age was 63 years. The average length of therapy with linezolid was 22 days. Methicillin-resistant Staphylococcus aureus (MRSA) was treated in eight patients, methicillin-resistant Staphylococcus epidermidis (MRSE) in two patients, vancomycin-resistant Enterococcus faecium (VREF) in eight patients, and coagulase-negative Staphylococcus in two patients. Co-infecting organisms include Enterococcus species colonization in six patients, Pseudomonas species in one patient, Serratia marcenens in one patient, and Candida albicans in one patient. Sterile sites that were infected included bone and joint (wounds and septic joints) in six patients, gastrointestinal system (hepatobiliary, liver abscess, Crohn's) in five patients, genitourinary (kidney and urine) in two patients, blood in five patients, respiratory in one patient, and aortic valve in 1 patient. Linezolid was given at 600 mg IV every 12 hours with a mean length of therapy of 22 days. Surgical drainage was used in combination with linezolid in 11 of the patients. Seventy nine percent of these patients achieved clinical and

  1. Concentration-Dependent Synergy and Antagonism of Linezolid and Moxifloxacin in the Treatment of Childhood Tuberculosis: The Dynamic Duo

    Science.gov (United States)

    Deshpande, Devyani; Srivastava, Shashikant; Nuermberger, Eric; Pasipanodya, Jotam G.; Swaminathan, Soumya; Gumbo, Tawanda

    2016-01-01

    Background. No treatment regimens have been specifically designed for children, in whom tuberculosis is predominantly intracellular. Given their activity as monotherapy and their ability to penetrate many diseased anatomic sites that characterize disseminated tuberculosis, linezolid and moxifloxacin could be combined to form a regimen for this need. Methods. We examined microbial kill of intracellular Mycobacterium tuberculosis (Mtb) by the combination of linezolid and moxifloxacin multiple exposures in a 7-by-7 mathematical matrix. We then used the hollow fiber system (HFS) model of intracellular tuberculosis to identify optimal dose schedules and exposures of moxifloxacin and linezolid in combination. We mimicked pediatric half-lives and concentrations achieved by each drug. We sampled the peripheral compartment on days 0, 7, 14, 21, and 28 for Mtb quantification, and compared the slope of microbial kill of Mtb by these regimens to the standard regimen of isoniazid, rifampin, and pyrazinamide, based on exponential decline regression. Results. The full exposure-response surface identified linezolid-moxifloxacin zones of synergy, antagonism, and additivity. A regimen based on each of these zones was then used in the HFS model, with observed half-lives of 4.08 ± 0.66 for linezolid and 3.80 ± 1.34 hours for moxifloxacin. The kill rate constant was 0.060 ± 0.012 per day with the moxifloxacin-linezolid regimen in the additivity zone vs 0.083 ± 0.011 per day with standard therapy, translating to a bacterial burden half-life of 11.52 days vs 8.53 days, respectively. Conclusions. We identified doses and dose schedules of a linezolid and moxifloxacin backbone regimen that could be highly efficacious in disseminated tuberculosis in children. PMID:27742639

  2. Reduced erythrocyte susceptibility and increased host clearance of young parasites slows Plasmodium growth in a murine model of severe malaria

    Science.gov (United States)

    Khoury, David S.; Cromer, Deborah; Best, Shannon E.; James, Kylie R.; Sebina, Ismail; Haque, Ashraful; Davenport, Miles P.

    2015-05-01

    The best correlate of malaria severity in human Plasmodium falciparum (Pf) infection is the total parasite load. Pf-infected humans could control parasite loads by two mechanisms, either decreasing parasite multiplication, or increasing parasite clearance. However, few studies have directly measured these two mechanisms in vivo. Here, we have directly quantified host clearance of parasites during Plasmodium infection in mice. We transferred labelled red blood cells (RBCs) from Plasmodium infected donors into uninfected and infected recipients, and tracked the fate of donor parasites by frequent blood sampling. We then applied age-based mathematical models to characterise parasite clearance in the recipient mice. Our analyses revealed an increased clearance of parasites in infected animals, particularly parasites of a younger developmental stage. However, the major decrease in parasite multiplication in infected mice was not mediated by increased clearance alone, but was accompanied by a significant reduction in the susceptibility of RBCs to parasitisation.

  3. High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells

    DEFF Research Database (Denmark)

    Bottley, G; Watherston, O G; Hiew, Y-L

    2007-01-01

    a role for E7 in tumour immune evasion. We show that knockdown of E7 expression in HPV16- and HPV18-transformed cervical carcinoma cells by RNA interference increased expression of major histocompatibility complex (MHC) class I at the cell surface and reduced susceptibility of these cells to natural...... killer (NK) cells. Tetracycline-regulated induction of HPV16 E7 resulted in reduced expression of cell surface MHC class I molecules and increased NK cell killing. Our results suggest that, for HPV-associated malignancies, reduced MHC class I expression is the result of an active immune evasion strategy......High-risk human papillomavirus (HPV) is a major causative agent of cervical cancer and the E6 and E7 genes encode the major HPV oncoproteins. The E7 protein from high-risk HPV types alters cell cycle progression and represses genes encoding components of the antigen-presentation pathway, suggesting...

  4. RNAi-mediated knockdown of a Spodoptera frugiperda trypsin-like serine-protease gene reduces susceptibility to a Bacillus thuringiensis Cry1Ca1 protoxin.

    Science.gov (United States)

    Rodríguez-Cabrera, Lianet; Trujillo-Bacallao, Damian; Borrás-Hidalgo, Orlando; Wright, Denis J; Ayra-Pardo, Camilo

    2010-11-01

    SfT6 has been identified in a subtracted cDNA library of Spodoptera frugiperda larval midgut transcripts as a serine-protease gene downregulated within 24 h of intoxication with Bacillus thuringiensis Cry1Ca1 protein. In the present study, the specific role of SfT6 during Cry1Ca1 intoxication was investigated by RT-PCR and in vivo RNA interference. Quantitative real-time RT-PCR analysis showed SfT6 mRNA levels in the midgut tissue were significantly reduced after injecting or feeding 4th-instar larvae with specific long-size dsRNA. Gut juice-mediated in vitro protoxin activation and susceptibility for Cry1Ca1 were investigated in Sft6-knockdown larvae and compared with control treated with nonspecific dsRNA. Our results demonstrate SfT6 plays a determinant role in Cry1Ca1 toxicity against S. frugiperda since a decreased expression caused a reduced protoxin activation by larval gut juice and reduced susceptibility of insects to toxin in bioassays. We propose SfT6 downregulation occurring at the early stages of Cry1Ca1 intoxication is part of a complex and multifaceted defensive mechanism triggered in the insect gut to withstand B. thuringiensis pathogenesis.

  5. Multi-drug resistance and reduced susceptibility to ciprofloxacin among Salmonella enterica serovar Typhi isolates from the Middle East and Central Asia

    Directory of Open Access Journals (Sweden)

    B.A. Rahman

    2014-07-01

    Full Text Available Typhoid fever is common in developing countries, with an estimated 120 million infections and 700 000 annual deaths, worldwide. Fluoroquinolones have been the treatment of choice for infection with multidrug-resistant (MDR Salmonella enterica serovar Typhi (S. Typhi. However, alarming reports of fluoroquinolone-resistance and failure of typhoid fever treatment have recently been published. To determine the proportion of S. Typhi isolates with reduced susceptibility to ciprofloxacin (RSC from six countries in the Middle East and Central Asia, 968 S. Typhi isolates collected between 2002 and 2007 from Egypt, Uzbekistan, Pakistan, Qatar, Jordan and Iraq were tested for antibiotic susceptibility to five antibiotics using the disc-diffusion method. MDR was defined as resistance to amicillin, chloramphenicol and trimethoprim-sulfamethoxazole. The E-test was employed to determine the MIC of ciprofloxacin only. Nalidixic acid resistance was evaluated as a marker for RSC. Interpretations were made according to CLSI guidelines. MDR strains were considerably more prevalent in Iraq (83% and Pakistan (52% compared with the other countries studied (13–52%. Nearly all isolates were susceptible (99.7% to ceftriaxone. RSC was detected in a total of 218 isolates (22%, mostly from Iraq (54/59, 92%, Uzbekistan (98/123, 80%, Qatar (23/43, 54% and Pakistan (31/65, 47%. Many of these (21% were also MDR. Use of nalidixic acid resistance as an indicator for RSC was 99% sensitive and 98% specific. This study reinforces the need for routine antimicrobial susceptibility surveillance of enteric fever isolates and close review of current therapeutic policies in the region.

  6. Telmisartan reduces atrial arrhythmia susceptibility through the regulation of RAS-ERK and PI3K-Akt-eNOS pathways in spontaneously hypertensive rats.

    Science.gov (United States)

    Wang, Wei-Wei; Zhang, Fei-Long; Chen, Jian-Hua; Chen, Xue-Hai; Fu, Fa-Yuan; Tang, Mi-Rong; Chen, Liang-Long

    2015-08-01

    Telmisartan is an angiotensin II receptor blocker that displays unique PPAR-γ modulating activity. PPAR-γ agonists have been shown to decrease susceptibility to atrial fibrillation through their antioxidant and antiapoptotic effects. The aim of this study was to determine whether telmisartan would have a greater effect on susceptibility to atrial arrhythmia in a hypertensive rat model than valsartan, which is a traditional angiotensin II receptor blocker. In this study, spontaneously hypertensive rats were treated with 10 mg·(kg body mass)(-1)·d(-1) telmisartan (TEL group), 10 mg·(kg body mass)(-1)·d(-1) valsartan (VAL group), or vehicle (saline; SHR group) for 4 weeks. Age-matched Wistar-Kyoto rats (WKY) were used as normotensive controls. After 4 weeks of treatment, we performed echocardiographic assessment, electrophysiological analysis, histological evaluation, and Western blot analysis. Telmisartan decreased systolic blood pressure to a similar extent as valsartan. Relative to the WKY controls, atrial arrhythmia susceptibility was significantly increased in the SHR group, and was significantly decreased by both telmisartan and valsartan, albeit to a greater extent with telmisartan. Arrhythmogenic atrial remodeling, including enlargement of the left atrium, myocyte hypertrophy, interstitial fibrosis, and myocyte apoptosis, was observed in the SHR group, and was accompanied by activated RAS-ERK signaling and suppressed PI3K-Akt-eNOS signaling. The results suggest that telmisartan reduced susceptibility to atrial arrhythmia to a greater extent than valsartan, ameliorated atrial remodeling, and reversed imbalances in the RAS-ERK and PI3K-Akt-eNOS pathways.

  7. A nonsense mutation in the ERG6 gene leads to reduced susceptibility to polyenes in a clinical isolate of Candida glabrata.

    Science.gov (United States)

    Vandeputte, Patrick; Tronchin, Guy; Larcher, Gérald; Ernoult, Emilie; Bergès, Thierry; Chabasse, Dominique; Bouchara, Jean-Philippe

    2008-10-01

    Unlike the molecular mechanisms that lead to azole drug resistance, the molecular mechanisms that lead to polyene resistance are poorly documented, especially in pathogenic yeasts. We investigated the molecular mechanisms responsible for the reduced susceptibility to polyenes of a clinical isolate of Candida glabrata. Sterol content was analyzed by gas-phase chromatography, and we determined the sequences and levels of expression of several genes involved in ergosterol biosynthesis. We also investigated the effects of the mutation harbored by this isolate on the morphology and ultrastructure of the cell, cell viability, and vitality and susceptibility to cell wall-perturbing agents. The isolate had a lower ergosterol content in its membranes than the wild type, and the lower ergosterol content was found to be associated with a nonsense mutation in the ERG6 gene and induction of the ergosterol biosynthesis pathway. Modifications of the cell wall were also seen, accompanied by increased susceptibility to cell wall-perturbing agents. Finally, this mutation, which resulted in a marked fitness cost, was associated with a higher rate of cell mortality. Wild-type properties were restored by complementation of the isolate with a centromeric plasmid containing a wild-type copy of the ERG6 gene. In conclusion, we have identified the molecular event responsible for decreased susceptibility to polyenes in a clinical isolate of C. glabrata. The nonsense mutation detected in the ERG6 gene of this isolate led to a decrease in ergosterol content. This isolate may constitute a useful tool for analysis of the relevance of protein trafficking in the phenomena of azole resistance and pseudohyphal growth.

  8. Clinical and Microbiological Aspects of Linezolid Resistance Mediated by the cfr Gene Encoding a 23S rRNA Methyltransferase▿

    Science.gov (United States)

    Arias, Cesar A.; Vallejo, Martha; Reyes, Jinnethe; Panesso, Diana; Moreno, Jaime; Castañeda, Elizabeth; Villegas, Maria V.; Murray, Barbara E.; Quinn, John P.

    2008-01-01

    The cfr (chloramphenicol-florfenicol resistance) gene encodes a 23S rRNA methyltransferase that confers resistance to linezolid. Detection of linezolid resistance was evaluated in the first cfr-carrying human hospital isolate of linezolid and methicillin-resistant Staphylococcus aureus (designated MRSA CM-05) by dilution and diffusion methods (including Etest). The presence of cfr was investigated in isolates of staphylococci colonizing the patient's household contacts and clinical isolates recovered from patients in the same unit where MRSA CM-05 was isolated. Additionally, 68 chloramphenicol-resistant Colombian MRSA isolates recovered from hospitals between 2001 and 2004 were screened for the presence of the cfr gene. In addition to erm(B), the erm(A) gene was also detected in CM-05. The isolate belonged to sequence type 5 and carried staphylococcal chromosomal cassette mec type I. We were unable to detect the cfr gene in any of the human staphylococci screened (either clinical or colonizing isolates). Agar and broth dilution methods detected linezolid resistance in CM-05. However, the Etest and disk diffusion methods failed to detect resistance after 24 h of incubation. Oxazolidinone resistance mediated by the cfr gene is rare, and acquisition by a human isolate appears to be a recent event in Colombia. The detection of cfr-mediated linezolid resistance might be compromised by the use of the disk diffusion or Etest method. PMID:18174304

  9. Treatment of bacteremia by vancomycin-resistant Enterococcus with daptomycin versus linezolid: a systematic review and meta-analyses

    Directory of Open Access Journals (Sweden)

    Caicedo-Ochoa, Edgar Yaset

    2017-01-01

    Full Text Available Introduction: Second-line drugs such as linezolid and daptomycin are used for treatment of vancomycin-resistant Enterococcus (VRE infections. Objective: A systematic review to evaluate treatment of VRE bacteremia with linezolid versus daptomycin. Methods: A search was done in the databases of Pubmed, Embase, Scopus, ScienceDirect, CENTRAL, Lilacs and Google Scholar to identify studies comparing treatment with daptomycin or linezolid of patients infected by VRE up to July 2015. Result: Only 15 studies were included of a total of 1.307 records. There were no differences between daptomycin and linezolid with respect to mortality at 30 days. Microbiological cure was better with daptomycin (OR: 0.64; 95 % CI: 0.45-0.92, whereas there was no difference between the two antibiotics with respect to clinical cure, need to ICU admission, and the occurrence of adverse effects such as thrombocytopenia, neutropenia and renal failure. Conclusions: No significant differences were observed between daptomycin and linezolid in reference to mortality of patients infected with VRE, although daptomycin treatment produced a faster microbiological cure.

  10. Triclosan can select for an AdeIJK-overexpressing mutant of Acinetobacter baumannii ATCC 17978 that displays reduced susceptibility to multiple antibiotics.

    Science.gov (United States)

    Fernando, Dinesh M; Xu, Wayne; Loewen, Peter C; Zhanel, George G; Kumar, Ayush

    2014-11-01

    In order to determine if triclosan can select for mutants of Acinetobacter baumannii ATCC 17978 that display reduced susceptibilities to antibiotics, we isolated a triclosan-resistant mutant, A. baumannii AB042, by serial passaging of A. baumannii ATCC 17978 in growth medium supplemented with triclosan. The antimicrobial susceptibility of AB042 was analyzed by the 2-fold serial dilution method. Expression of five different resistance-nodulation-division (RND) pump-encoding genes (adeB, adeG, adeJ, A1S_2818, and A1S_3217), two outer membrane porin-encoding genes (carO and oprD), and the MATE family pump-encoding gene abeM was analyzed using quantitative reverse transcriptase (qRT) PCR. A. baumannii AB042 exhibited elevated resistance to multiple antibiotics, including piperacillin-tazobactam, doxycycline, moxifloxacin, ceftriaxone, cefepime, meropenem, doripenem, ertapenem, ciprofloxacin, aztreonam, tigecycline, and trimethoprim-sulfamethoxazole, in addition to triclosan. Genome sequencing of A. baumannii AB042 revealed a (116)G→V mutation in fabI, the gene encoding the target enzyme for triclosan. Expression analysis of efflux pumps showed overexpression of the AdeIJK pump, and sequencing of adeN, the gene that encodes the repressor of the adeIJK operon, revealed a 73-bp deletion which would cause a premature termination of translation, resulting in an inactive truncated AdeN protein. This work shows that triclosan can select for mutants of A. baumannii that display reduced susceptibilities to multiple antibiotics from chemically distinct classes in addition to triclosan resistance. This multidrug resistance can be explained by the overexpression of the AdeIJK efflux pump.

  11. In Vitro Antimicrobial Susceptibility of Staphylococcus pseudintermedius Isolates of Human and Animal Origin

    Science.gov (United States)

    Wu, Max T.; Westblade, Lars F.; Robertson, Amy E.; Wallace, Meghan A.; Burd, Eileen M.; Hindler, Janet A.

    2016-01-01

    MIC results for 115 Staphylococcus intermedius group isolates are presented. Of these, 33% were methicillin resistant, among which 51.4% were susceptible to doxycycline, 29.7% to clindamycin, and 21.6% to trimethoprim-sulfamethoxazole. All of the isolates were susceptible to ceftaroline, daptomycin, linezolid, nitrofurantoin, quinupristin-dalfopristin, rifampin, tigecycline, and vancomycin. Of all the isolates, 82.6%, 67.8%, and 23.5% were susceptible to ciprofloxacin, erythromycin, and penicillin, respectively. No isolates harbored mupA or qacA/B genes, which suggested a lack of resistance to mupirocin or chlorhexidine. PMID:26962087

  12. Difference in agr dysfunction and reduced vancomycin susceptibility between MRSA bacteremia involving SCCmec types IV/IVa and I-III.

    Science.gov (United States)

    Jang, Hee-Chang; Kang, Seung-Ji; Choi, Su-Mi; Park, Kyung-Hwa; Shin, Jong-Hee; Choy, Hyon E; Jung, Sook-In; Kim, Hong Bin

    2012-01-01

    Dysfunction of agr, with reduced susceptibility or hetero-resistance to vancomycin, is thought to be associated with a worse outcome of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB). However, the difference in agr dysfunction according to the SCCmec type in MRSA infection is undetermined. We compared the prevalence of agr dysfunction, reduced vancomycin susceptibility and the outcomes of SCCmec IV/IVa and I-III MRSAB. The study included 307 cases of MRSAB. SCCmec types were determined by multiplex PCR. The clinical and microbiological features and outcomes of 58 SCCmec IV/IVa MRSAB were compared with those of 249 SCCmec I-III MRSAB. Compared with SCCmec I-III MRSAB, SCCmec IV/IVa MRSAB was associated with lower rates of agr dysfunction (3% vs. 43%), vancomycin minimum inhibitory concentration (MIC) = 2 µg/mL (3% vs. 15%), and hetero-resistance to vancomycin (0% vs. 8%) (all PIVa MRSAB were not different from those in patients with SCCmec I-III MRSAB in multivariate analyses (HR 1.168, 95% CI 0.705-1.938; HR 1.025, 95% CI 0.556-1.889). SCCmec IV/IVa MRSAB was associated with lower rates of agr dysfunction and hetero-resistance to vancomycin and a lower vancomycin MIC, compared with SCCmec I-III MRSAB. However, the outcomes of SCCmec IV/IVa MRSAB did not differ from those of SCCmec I-III MRSAB.

  13. Functional characterization of a promoter polymorphism in APE1/Ref-1 that contributes to reduced lung cancer susceptibility.

    Science.gov (United States)

    Lu, Juan; Zhang, Shuyu; Chen, Dan; Wang, Huibo; Wu, Wenting; Wang, Xiaotian; Lei, Yunping; Wang, Jiucun; Qian, Ji; Fan, Weiwei; Hu, Zhibin; Jin, Li; Shen, Hongbing; Huang, Wei; Wei, Qingyi; Lu, Daru

    2009-10-01

    Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a ubiquitous multifunctional protein that possesses both DNA-repair and redox regulatory activities. Although it was originally identified as a DNA-repair enzyme, accumulating evidence supports a role of APE1/Ref-1 in tumor development. To investigate association between APE1/Ref-1 polymorphisms and lung cancer risk in Chinese populations, we first genotyped three variants of APE1/Ref-1 and found a -141 T-to-G variant (rs1760944) in the promoter associated with decreased risk of lung cancer [odds ratio (OR) = 0.62 for GG; P=0.043]. Similar results were obtained in a follow-up replication study. Combined data from the two studies comprising a total of 1072 lung cancer patients and 1064 cancer-free control participants generated a more significant association (P=0.002). We observed lower APE1/Ref-1 mRNA levels in the presence of the protective G allele in human peripheral blood mononuclear cells and normal lung tissues. The -141G-allele-promoter construct exhibited decreased luciferase reporter gene expression. Electrophoretic mobility shift assays and surface plasmon resonance analysis showed that the -141G allele impaired the binding affinity of some transcription factor, accounting for lower APE1/Ref-1-promoter activity. Supershift assays further revealed that the protein of interest was octamer-binding transcription factor-1 (Oct-1). Chromatin immunoprecipitation reconfirmed binding of Oct-1 to the APE1/Ref-1 -141-promoter region. We also found that Oct-1 conferred attenuated transactivation capacity toward the -141G variant by exogenously introducing Oct-1. These data indicate that genetic variations in APE1/Ref-1 may modify susceptibility to lung cancer and provide new insights into an unexpected effect of APE1/Ref-1 on lung carcinogenesis.

  14. Reduced Leukocyte Infiltration in Absence of Eosinophils Correlates with Decreased Tissue Damage and Disease Susceptibility in ΔdblGATA Mice during Murine Neurocysticercosis

    Science.gov (United States)

    Mishra, Pramod K.; Li, Qun; Munoz, Luis E.; Mares, Chris A.; Morris, Elizabeth G.; Teale, Judy M.; Cardona, Astrid E.

    2016-01-01

    Neurocysticercosis (NCC) is one of the most common helminth parasitic diseases of the central nervous system (CNS) and the leading cause of acquired epilepsy worldwide. NCC is caused by the presence of the metacestode larvae of the tapeworm Taenia solium within brain tissues. NCC patients exhibit a long asymptomatic phase followed by a phase of symptoms including increased intra-cranial pressure and seizures. While the asymptomatic phase is attributed to the immunosuppressive capabilities of viable T. solium parasites, release of antigens by dying organisms induce strong immune responses and associated symptoms. Previous studies in T. solium-infected pigs have shown that the inflammatory response consists of various leukocyte populations including eosinophils, macrophages, and T cells among others. Because the role of eosinophils within the brain has not been investigated during NCC, we examined parasite burden, disease susceptibility and the composition of the inflammatory reaction in the brains of infected wild type (WT) and eosinophil-deficient mice (ΔdblGATA) using a murine model of NCC in which mice were infected intracranially with Mesocestoides corti, a cestode parasite related to T. solium. In WT mice, we observed a time-dependent induction of eosinophil recruitment in infected mice, contrasting with an overall reduced leukocyte infiltration in ΔdblGATA brains. Although, ΔdblGATA mice exhibited an increased parasite burden, reduced tissue damage and less disease susceptibility was observed when compared to infected WT mice. Cellular infiltrates in infected ΔdblGATA mice were comprised of more mast cells, and αβ T cells, which correlated with an abundant CD8+ T cell response and reduced CD4+ Th1 and Th2 responses. Thus, our data suggest that enhanced inflammatory response in WT mice appears detrimental and associates with increased disease susceptibility, despite the reduced parasite burden in the CNS. Overall reduced leukocyte infiltration due to

  15. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB : systematic review and meta-analysis

    NARCIS (Netherlands)

    Sotgiu, Giovanni; Centis, Rosella; D'Ambrosio, Lia; Alffenaar, Jan-William C.; Anger, Holly A.; Caminero, Jose A.; Castiglia, Paolo; De Lorenzo, Saverio; Ferrara, Giovanni; Koh, Won-Jung; Schecter, Giesela F.; Shim, Tae S.; Singla, Rupak; Skrahina, Alena; Spanevello, Antonio; Udwadia, Zarir F.; Villar, Miquel; Zampogna, Elisabetta; Zellweger, Jean-Pierre; Zumla, Alimuddin; Migliori, Giovanni Battista

    2012-01-01

    Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from t

  16. Antistaphylococcal activity of DX-619 alone and in combination with vancomycin, teicoplanin, and linezolid assessed by time-kill synergy testing.

    Science.gov (United States)

    Credito, Kim; Lin, Genrong; Appelbaum, Peter C

    2007-04-01

    Time-kill synergy studies testing in vitro activity of DX-619 alone and with added vancomycin, teicoplanin, or linezolid against 101 Staphylococcus aureus strains showed synergy between DX-619 and teicoplanin at 12 to 24 h in 72 strains and between DX-619 and vancomycin in 28 strains. No synergy was found with linezolid, and no antagonism was observed with any combination.

  17. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB : systematic review and meta-analysis

    NARCIS (Netherlands)

    Sotgiu, Giovanni; Centis, Rosella; D'Ambrosio, Lia; Alffenaar, Jan-William C.; Anger, Holly A.; Caminero, Jose A.; Castiglia, Paolo; De Lorenzo, Saverio; Ferrara, Giovanni; Koh, Won-Jung; Schecter, Giesela F.; Shim, Tae S.; Singla, Rupak; Skrahina, Alena; Spanevello, Antonio; Udwadia, Zarir F.; Villar, Miquel; Zampogna, Elisabetta; Zellweger, Jean-Pierre; Zumla, Alimuddin; Migliori, Giovanni Battista

    2012-01-01

    Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from t

  18. SiO2-nanocomposite film coating of CAD/CAM composite resin blocks improves surface hardness and reduces susceptibility to bacterial adhesion.

    Science.gov (United States)

    Kamonwanon, Pranithida; Hirose, Nanako; Yamaguchi, Satoshi; Sasaki, Jun-Ichi; Kitagawa, Haruaki; Kitagawa, Ranna; Thaweboon, Sroisiri; Srikhirin, Toemsak; Imazato, Satoshi

    2017-01-31

    Composite resin blocks for computer-aided design/computer-aided manufacturing (CAD/CAM) applications have recently become available. However, CAD/CAM composite resins have lower wear resistance and accumulate more plaque than CAD/CAM ceramic materials. We assessed the effects of SiO2-nanocomposite film coating of four types of CAD/CAM composite resin blocks: Cerasmart, Katana Avencia block, Lava Ultimate, and Block HC on surface hardness and bacterial attachment. All composite blocks with coating demonstrated significantly greater Vickers hardness, reduced surface roughness, and greater hydrophobicity than those without coating. Adhesion of Streptococcus mutans to the coated specimens was significantly less than those for the uncoated specimens. These reduced levels of bacterial adherence on the coated surface were still evident after treatment with saliva. Surface modification by SiO2-nanocomposite film coating has potential to improve wear resistance and susceptibility to plaque accumulation of CAD/CAM composite resin restorations.

  19. Species composition of larvae cultured after anthelmintic treatment indicates reduced moxidectin susceptibility of immature Cylicocyclus species in horses

    NARCIS (Netherlands)

    Kooyman, F N J; van Doorn, D C K; Geurden, T; Mughini-Gras, L; Ploeger, H W; Wagenaar, J A

    2016-01-01

    For the control of cyathostomins in horses, the macrocyclic lactones (MLs), moxidectin (MOX) and ivermectin (IVM) are the most commonly used anthelmintics. However, reduced activity, observed as shortening of the egg reappearance period (ERP) has been described. Shortening of the ERP may be caused b

  20. Comparison of M.I.C.E. and Etest with CLSI agar dilution for antimicrobial susceptibility testing against oxacillin-resistant Staphylococcus spp.

    Directory of Open Access Journals (Sweden)

    Eloiza H Campana

    Full Text Available OBJECTIVE: The main objective of this study was to comparatively evaluate the performance of M.I.C.E. and Etest methodologies to that of agar dilution for determining the antimicrobial susceptibility profile of oxacillin-resistant Staphylococcus spp. METHODS: A total of 100 oxacillin-resistant Staphylococcus spp. isolates were collected from hospitalized patients at a teaching hospital. Antimicrobial susceptibility testing for vancomycin, teicoplanin and linezolid was performed using the reference CLSI agar dilution method (2009, Etest and M.I.C.E. methodologies. The MIC values were interpreted according to CLSI susceptibility breakpoints and compared by regression analysis. RESULTS: In general, the essential agreement (±1-log2 between M.I.C.E. and CLSI agar dilution was 93.0%, 84.0% and 77.0% for linezolid, teicoplanin and vancomycin, respectively. Essential agreement rates between M.I.C.E. and Etest were excellent (>90.0% for all antibiotics tested. Both strips (M.I.C.E. and Etest yielded two very major errors for linezolid. Unacceptable minor rates were observed for teicoplanin against CoNS and for vancomycin against S. aureus. CONCLUSIONS: According to our results, linezolid and teicoplanin MICs against all staphylococci and S. aureus, respectively, were more accurately predicted by M.I.C.E. strips. However, the Etest showed better performance than M.I.C.E. for predicting vancomycin MICs against all staphylococci. Thus, microbiologists must be aware of the different performance of commercially available gradient strips against staphylococci.

  1. Comparison of M.I.C.E. and Etest with CLSI agar dilution for antimicrobial susceptibility testing against oxacillin-resistant Staphylococcus spp.

    Science.gov (United States)

    Campana, Eloiza H; Carvalhaes, Cecilia G; Nonato, Bruna; Machado, Antonia M de O; Gales, Ana C

    2014-01-01

    The main objective of this study was to comparatively evaluate the performance of M.I.C.E. and Etest methodologies to that of agar dilution for determining the antimicrobial susceptibility profile of oxacillin-resistant Staphylococcus spp. A total of 100 oxacillin-resistant Staphylococcus spp. isolates were collected from hospitalized patients at a teaching hospital. Antimicrobial susceptibility testing for vancomycin, teicoplanin and linezolid was performed using the reference CLSI agar dilution method (2009), Etest and M.I.C.E. methodologies. The MIC values were interpreted according to CLSI susceptibility breakpoints and compared by regression analysis. In general, the essential agreement (±1-log2) between M.I.C.E. and CLSI agar dilution was 93.0%, 84.0% and 77.0% for linezolid, teicoplanin and vancomycin, respectively. Essential agreement rates between M.I.C.E. and Etest were excellent (>90.0%) for all antibiotics tested. Both strips (M.I.C.E. and Etest) yielded two very major errors for linezolid. Unacceptable minor rates were observed for teicoplanin against CoNS and for vancomycin against S. aureus. According to our results, linezolid and teicoplanin MICs against all staphylococci and S. aureus, respectively, were more accurately predicted by M.I.C.E. strips. However, the Etest showed better performance than M.I.C.E. for predicting vancomycin MICs against all staphylococci. Thus, microbiologists must be aware of the different performance of commercially available gradient strips against staphylococci.

  2. Immediate hematological toxicity of linezolid in healthy volunteers with different body weight: a phase I clinical trial.

    Science.gov (United States)

    Cai, Yun; Chai, Dong; Falagas, Matthew E; Vouloumanou, Evridiki K; Wang, Rui; Guo, Daihong; Bai, Nan; Liang, Beibei; Liu, Youning

    2012-04-01

    Linezolid is an important therapeutic option for infections from multi-drug resistant Gram-positive pathogens. However, prolonged linezolid treatment (>14 days) is considered to increase the risk of hematological adverse events. We aimed to evaluate the hematological safety profile of an i.v. single dose of linezolid in healthy volunteers of different body weight. We conducted a phase I clinical trial involving 20 healthy male Chinese volunteers that received an i.v. single dose of linezolid (600 mg). The study participants were assigned to two groups: low-weight (LW) group: 50 kg weight ≤55 kg and high-weight (HW) group: ≥80 kg. A significant decrease in the hemoglobin (Hb) levels and red blood cell (RBC) count was observed at the end of administration of the study drug in both groups. White blood cell (WBC) count was simultaneously decreased in the HW group. In the LW group, Hb levels and RBC count were also significantly decreased at 5, 7 and 24 h. In the HW group, both values were significantly decreased at 5 h. At 48 h all values were normal. The observed decreases were numerically higher in the LW group compared with the HW group. Yet, no statistical significance was noted. No difference was observed in the platelet count in both the groups. Our findings suggest that linezolid-associated hematological toxicity may also occur shortly after the i.v. administration of the drug in both LW and HW healthy volunteers. Early initiated continuous monitoring of hematological values and linezolid dosage adjustment for body weight are recommended.

  3. An evidence-based review of linezolid for the treatment of methicillin-resistant Staphylococcus aureus (MRSA: place in therapy

    Directory of Open Access Journals (Sweden)

    Watkins RR

    2012-12-01

    Full Text Available Richard R Watkins,1 Tracy L Lemonovich,2 Thomas M File Jr31Division of Infectious Diseases, Akron General Medical Center, Akron, OH, USA; 2Division of Infectious Diseases and HIV Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA; 3Division of Infectious Diseases, Summa Health System, Akron, OH, USAAbstract: Methicillin-resistant Staphylococcus aureus (MRSA, including community-associated and hospital-associated strains, is a major cause of human morbidity and mortality. Treatment options have become limited due to the emergence of MRSA strains with decreased sensitivity to vancomycin, which has long been the first-line therapy for serious infections. This has prompted the search for novel antibiotics that are efficacious against MRSA. Linezolid, an oxazolidinone class of antibiotic, was approved by the Food and Drug Administration in 2000 for treatment of MRSA infections. Since then, there have been a multitude of clinical trials and research studies evaluating the effectiveness of linezolid against serious infections, including pneumonia (both community- and hospital-acquired, skin and soft-tissue infections such as diabetic foot ulcers, endocarditis, osteomyelitis, prosthetic devices, and others. The primary aim of this review is to provide an up-to-date evaluation of the clinical evidence for using linezolid to treat MRSA infections, with a focus on recently published studies, including those on nosocomial pneumonia. Other objectives are to analyze the cost-effectiveness of linezolid compared to other agents, and to review the pharmokinetics and pharmacodynamics of linezolid, emphasizing the most current concepts.Keywords: linezolid, MRSA, clinical trials, pneumonia, skin infections

  4. Successful treatment of MRSA native valve endocarditis with oral linezolid therapy: a case report.

    Science.gov (United States)

    Nathani, N; Iles, P; Elliott, T S J

    2005-11-01

    Staphylococcal endocarditis is potentially fatal and is now the most common cause of infective endocarditis with a mortality rate of 25-47% [Hecht SR, Berger M. Right-sided endocarditis in intravenous drug users: prognostic features in 102 episodes. Ann Intern Med 1992;117:560-6]. Its treatment requires maintenance of bactericidal level of antibiotics for prolonged periods to attain a culture-negative state. Although intravenous vancomycin is currently the drug of choice for methicillin resistant Staphylococcus aureus (MRSA) endocarditis, we present a case treated successfully with oral linezolid for 4 weeks due to a lack of venous access.

  5. Generation of transgenic cattle expressing human β-defensin 3 as an approach to reducing susceptibility to Mycobacterium bovis infection.

    Science.gov (United States)

    Su, Feng; Wang, Yongsheng; Liu, Guanghui; Ru, Kun; Liu, Xin; Yu, Yuan; Liu, Jun; Wu, Yongyan; Quan, Fusheng; Guo, Zekun; Zhang, Yong

    2016-03-01

    Bovine tuberculosis results from infection with Mycobacterium bovis, a member of the Mycobacterium tuberculosis family. Worldwide, M. bovis infections result in economic losses in the livestock industry; cattle production is especially hard-hit by this disease. Generating M. bovis-resistant cattle may potentially mitigate the impact of this disease by reducing M. bovis infections. In this study, we used transgenic somatic cell nuclear transfer to generate cattle expressing the gene encoding human β-defensin 3 (HBD3), which confers resistance to mycobacteria in vitro. We first generated alveolar epithelial cells expressing HBD3 under the control of the bovine MUC1 promoter, and confirmed that these cells secreted HBD3 and possessed anti-mycobacterial capacity. We then generated and identified transgenic cattle by somatic cell nuclear transfer. The cleavage and blastocyst formation rates of genetically modified embryos provided evidence that monoclonal transgenic bovine fetal fibroblast cells have an integral reprogramming ability that is similar to that of normal cells. Five genetically modified cows were generated, and their anti-mycobacterial capacities were evaluated. Alveolar epithelial cells and macrophages from these cattle expressed higher levels of HBD3 protein compared with non-transgenic cells and possessed effective anti-mycobacterial capacity. These results suggest that the overall risk of M. bovis infection in transgenic cattle is efficiently reduced, and support the development of genetically modified animals as an effective tool to reduce M. bovis infection.

  6. Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry.

    Science.gov (United States)

    Westby, Mike; Smith-Burchnell, Caroline; Mori, Julie; Lewis, Marilyn; Mosley, Michael; Stockdale, Mark; Dorr, Patrick; Ciaramella, Giuseppe; Perros, Manos

    2007-03-01

    Maraviroc is a CCR5 antagonist in clinical development as one of a new class of antiretrovirals targeting human immunodeficiency virus type 1 (HIV-1) coreceptor binding. We investigated the mechanism of HIV resistance to maraviroc by using in vitro sequential passage and site-directed mutagenesis. Serial passage through increasing maraviroc concentrations failed to select maraviroc-resistant variants from some laboratory-adapted and clinical isolates of HIV-1. However, high-level resistance to maraviroc was selected from three of six primary isolates passaged in peripheral blood lymphocytes (PBL). The SF162 strain acquired resistance to maraviroc in both treated and control cultures; all resistant variants were able to use CXCR4 as a coreceptor. In contrast, maraviroc-resistant virus derived from isolates CC1/85 and RU570 remained CCR5 tropic, as evidenced by susceptibility to the CCR5 antagonist SCH-C, resistance to the CXCR4 antagonist AMD3100, and an inability to replicate in CCR5 Delta32/Delta32 PBL. Strain-specific mutations were identified in the V3 loop of maraviroc-resistant CC1/85 and RU570. The envelope-encoding region of maraviroc-resistant CC1/85 was inserted into an NL4-3 background. This recombinant virus was completely resistant to maraviroc but retained susceptibility to aplaviroc. Reverse mutation of gp120 residues 316 and 323 in the V3 loop (numbering from HXB2) to their original sequence restored wild-type susceptibility to maraviroc, while reversion of either mutation resulted in a partially sensitive virus with reduced maximal inhibition (plateau). The plateaus are consistent with the virus having acquired the ability to utilize maraviroc-bound receptor for entry. This hypothesis was further corroborated by the observation that a high concentration of maraviroc blocks the activity of aplaviroc against maraviroc-resistant virus.

  7. Pasteurized whole milk confers reduced susceptibilities to the antimicrobial agents trimethoprim, gatifloxacin, cefotaxime and tetracycline via the marRAB locus in Escherichia coli.

    Science.gov (United States)

    Peng, Yang; Hernandez, Ricardo L; Crow, Robert R; Jones, Suzanna E; Mathews, Sara A; Arnold, Ayanna M; Castillo, Eliseo F; Moseley, Jennifer M; Varela, Manuel F

    2008-11-01

    We inoculated pasteurized whole milk with Escherichia coli strains GC4468 (intact marRAB locus), JHC1096 (Delta marRAB), or AG112 (Delta marR), and incubated each overnight at 37 degrees C. All strains were then recovered from the milk cultures, and susceptibilities to antimicrobial agents were determined by the E-test strip method (CLSI). Cells of strain GC4468, prior to culturing in milk, were susceptible to trimethoprim, gatifloxacin, cefotaxime and tetracycline. After culturing GC4468 in pasteurized milk, however, the minimal inhibitory concentrations (MICs) increased 1.4-fold for trimethoprim (P0.05), 1.5-fold for gatifloxacin (P0.05), 2.0-fold for cefotaxime (P=0.008), and 1.4-fold for tetracycline (P0.05). After culturing GC4468 on milk count agar the MICs were enhanced 3.4-fold for trimethoprim (P0.05), 10-fold for gatifloxacin (P=0.001), 7.1-fold for cefotaxime (P=0.011), and 40.5-fold for tetracycline (P=0.074), but exhibiting tetracycline resistance with a mean MIC of 74.7+/-18.47 microg/ml (CLSI). The MICs of the antimicrobial agents for JHC1096 cells after culturing in pasteurized whole milk were indistinguishable (P0.05) from baseline MICs measured before culturing in the same type of milk. Thus, Esch. coli cells harbouring the marRAB locus exhibit reduced susceptibilities to multiple antimicrobial agents after culturing in pasteurized whole milk.

  8. Linezolid-induced near-fatal serotonin syndrome during escitalopram therapy: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Ranganath R Kulkarni

    2013-01-01

    Full Text Available Linezolid is a synthetic antimicrobial agent of the oxazolidinone class with weak, nonspecific inhibitor of monoamine oxidase enzymes. Concomitant therapy with an adrenergic or serotonergic agent or consuming tyramine (>100 mg/day may induce serotonin syndrome (SS. We present a case report of near-fatal adverse interaction between linezolid and escitalopram inducing SS in a 65-year-old woman with sepsis, under empirical antibiotic treatment. This report also summarizes the current relevant literature as identified via PubMed, EMBASE, and PsycINFO, supplemented with a manual search of cross references.

  9. Success of linezolid therapy for postneurosurgical ventriculitis due to vancomycin-resistant Enterococcus faecium: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    JiaJi Qiu; Jie Tang; DeLing Li

    2016-01-01

    Background:Vancomycin-resistant Enterococcus faecium ventriculitis is one of the most severe events in postneurosurgical intracranial infections.There are no guidelines recommending an appropriate treatment before.Case presentation:This case presents a successful linezolid treatment for post-neurosurgical vancomycin-resistant Enterococcus faecium ventriculitis of a 24-year-old man in the department of neurosurgery,Beijing Tiantan Hospital.Conclusions:Linezolid should be considered as one of the important methods for the treatment of postneurosurgical intracranial infections caused by vancomycin-resistant Enterococcus.

  10. Susceptibility to virus-cell fusion at the plasma membrane is reduced through expression of HIV gp41 cytoplasmic domains.

    Science.gov (United States)

    Malinowsky, Katharina; Luksza, Julia; Dittmar, Matthias T

    2008-06-20

    The cytoplasmic tail of the HIV transmembrane protein plays an important role in viral infection. In this study we analyzed the role of retroviral cytoplasmic tails in modulating the cytoskeleton and interfering with virus-cell fusion. HeLaP4 cells expressing different HIV cytoplasmic tail constructs showed reduced acetylated tubulin levels whereas the cytoplasmic tail of MLV did not alter microtubule stability indicating a unique function for the lentiviral cytoplasmic tail. The effect on tubulin is mediated through the membrane proximal region of the HIV cytoplasmic tail and was independent of membrane localization. Site-directed mutagenesis identified three motifs in the HIV-2 cytoplasmic tail required to effect the reduction in acetylated tubulin. Both the YxxPhi domain and amino acids 21 to 45 of the HIV-2 cytoplasmic tail need to be present to change the level of acetylated tubulin in transfected cells. T-cells stably expressing one HIV-2 cytoplasmic tail derived construct showed also a reduction in acetylated tubulin thus confirming the importance of this effect not only for HeLaP4 and 293T cells. Challenge experiments using transiently transfected HeLaP4 cells and T cells stably expressing an HIV cytoplasmic tail construct revealed both reduced virus-cell fusion and replication of HIV-1(NL4.3) compared to control cells. In the virus-cell fusion assay only virions pseudotyped with either HIV or MLV envelopes showed reduced fusion efficiency, whereas VSV-G pseudotyped virions where not affected by the expression of HIV derived cytoplasmic tail constructs, indicating that fusion at the plasma but not endosomal membrane is affected. Overexpression of human histone-deacetylase 6 (HDAC6) and constitutively active RhoA resulted in a reduction of acetylated tubulin and reduced virus-cell fusion as significant as that observed following expression of HIV cytoplasmic tail constructs. Inhibition of HDAC6 showed a strong increase in acetylated tubulin and increase of

  11. The Role of Vanadium Carbide Traps in Reducing the Hydrogen Embrittlement Susceptibility of High Strength Alloy Steels.

    Science.gov (United States)

    1998-08-01

    A723 steel was not sufficient to induce any appreciable embrittlement. 7.0 4.0 HY80 X 0.0i-r 50 4340 r—,—,—|—i—i—i—r—t—i—i—i—i—I—i—’—’—> l...carbide, V4C3) was identified in the A723 steel by x- ray diffraction. V4C3 traps effectively reduced the hydrogen concentrations at the crack ...ALLOY STEELS G. L. SPENCER D. J. DUQUETTE AUGUST 1998 US ARMY ARMAMENT RESEARCH, DEVELOPMENT AND ENGINEERING CENTER CLOSE COMBAT ARMAMENTS CENTER

  12. 利奈唑胺与万古霉素对耐甲氧西林金黄色葡萄球菌抗生素后效应的研究%Post-antibiotic effect of linezolid and vancomycin against methicillin-resistant Staphyloccus aureus

    Institute of Scientific and Technical Information of China (English)

    梁蓓蓓; 王瑾; 白楠; 周家军; 裴广胜; 王睿

    2013-01-01

    目的 研究利奈唑胺和万古霉素对耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗生素后效应(PAE).方法 用平板菌落计数法测定不同接触浓度、不同接触时间的利奈唑胺和万古霉素对MRSA的PAE;用扫描电镜观察两药PAE期间MRSA形态学的变化.结果 利奈唑胺和万古霉素对MRSA均能产生中度PAE,且随着接触时间的延长、接触浓度的增加,PAE延长.与空白对照组比较,在体外PAE期间没有观察到两药MRSA形态有显著的变化.结论 利奈唑胺和万古霉素在体外对MRSA均能产生中度PAE,两药在体外PAE期间MRSA形态无明显的变化.%Objective To investigate the post - antibiotic effect ( PAE ) of linezolid and vancomycin against methicillin - resistant Staphyloccus aureus (MRS A) . Methods PAE of linezolid and vancomycin against MRSA was determined by plate colony counting at different concentrations (1 × MIC , 2 × MIC , 4 × MIC , 8 × MIC ) and different time points( 1,2,3 h). The morphological changes of MRSA during the PAE period were observed by scanning electron microscopy. Results All strains were susceptible to linezolid and vancomycin. The PAE was greater at higher concentration and longer exposure time. There was no morphological change of MRSA during the PAE. Conclusion It was demonstrated that linezolid and vacomycin had a moderate in vitro PAE against MRSA. There was no morphological change of MRSA during the PAE.

  13. High vancomycin MICs within the susceptible range in Staphylococcus aureus bacteraemia isolates are associated with increased cell wall thickness and reduced intracellular killing by human phagocytes.

    Science.gov (United States)

    Falcón, Rocío; Martínez, Alba; Albert, Eliseo; Madrid, Silvia; Oltra, Rosa; Giménez, Estela; Soriano, Mario; Vinuesa, Víctor; Gozalbo, Daniel; Gil, María Luisa; Navarro, David

    2016-05-01

    Vancomycin minimum inhibitory concentrations (MICs) at the upper end of the susceptible range for Staphylococcus aureus have been associated with poor clinical outcomes of bloodstream infections. We tested the hypothesis that high vancomycin MICs in S. aureus bacteraemia isolates are associated with increased cell wall thickness and suboptimal bacterial internalisation or lysis by human phagocytes. In total, 95 isolates were evaluated. Original vancomycin MICs were determined by Etest. The susceptibility of S. aureus isolates to killing by phagocytes was assessed in a human whole blood assay. Internalisation of bacterial cells by phagocytes was investigated by flow cytometry. Cell wall thickness was evaluated by transmission electron microscopy. Genotypic analysis of S. aureus isolates was performed using a DNA microarray system. Vancomycin MICs were significantly higher (P=0.006) in isolates that were killed suboptimally (killing index 70%) and tended to correlate inversely (P=0.08) with the killing indices. Isolates in both killing groups were internalised by human neutrophils and monocytes with comparable efficiency. The cell wall was significantly thicker (P=0.03) in isolates in the low killing group. No genotypic differences were found between the isolates in both killing groups. In summary, high vancomycin MICs in S. aureus bacteraemia isolates were associated with increased cell wall thickness and reduced intracellular killing by phagocytes.

  14. Improving the efficiency of multisensory integration in older adults: audio-visual temporal discrimination training reduces susceptibility to the sound-induced flash illusion.

    Science.gov (United States)

    Setti, Annalisa; Stapleton, John; Leahy, Daniel; Walsh, Cathal; Kenny, Rose Anne; Newell, Fiona N

    2014-08-01

    From language to motor control, efficient integration of information from different sensory modalities is necessary for maintaining a coherent interaction with the environment. While a number of training studies have focused on training perceptual and cognitive function, only very few are specifically targeted at improving multisensory processing. Discrimination of temporal order or coincidence is a criterion used by the brain to determine whether cross-modal stimuli should be integrated or not. In this study we trained older adults to judge the temporal order of visual and auditory stimuli. We then tested whether the training had an effect in reducing susceptibility to a multisensory illusion, the sound induced flash illusion. Improvement in the temporal order judgement task was associated with a reduction in susceptibility to the illusion, particularly at longer Stimulus Onset Asynchronies, in line with a more efficient multisensory processing profile. The present findings set the ground for more broad training programs aimed at improving older adults׳ cognitive performance in domains in which efficient temporal integration across the senses is required.

  15. Altering the motility of Trypanosoma cruzi with rabbit polyclonal anti-peptide antibodies reduces infection to susceptible mammalian cells.

    Science.gov (United States)

    Finkelsztein, Eli J; Diaz-Soto, Juan C; Vargas-Zambrano, Juan C; Suesca, Elizabeth; Guzmán, Fanny; López, Manuel C; Thomas, M Carmen; Forero-Shelton, Manu; Cuellar, Adriana; Puerta, Concepción J; González, John M

    2015-03-01

    Trypanosoma cruzi's trypomastigotes are highly active and their incessant motility seems to be important for mammalian host cell infection. The kinetoplastid membrane protein-11 (KMP-11) is a protein expressed in all parasite stages, which induces a cellular and humoral immune response in the infected host, and is hypothesized to participate in the parasite's motility. An N-terminal peptide from KMP-11, termed K1 or TcTLE, induced polyclonal antibodies that inhibit parasitic invasion of Vero cells. The goal of this study was to evaluate the motility and infectivity of T. cruzi when exposed to polyclonal anti-TcTLE antibodies. Rabbits were immunized with TcTLE peptide along with FIS peptide as an immunomodulator. ELISA assay results showed that post-immunization sera contained high titers of polyclonal anti-TcTLE antibodies, which were also reactive against the native KMP-11 protein and live parasites as detected by immunofluorescence and flow cytometry assays. Trypomastigotes of T. cruzi were incubated with pre- or post-immunization sera, and infectivity to human astrocytes was assessed by Giemsa staining/light microscope and flow cytometry using carboxyfluorescein diacetate succinimidyl ester (CFSE) labeled parasites. T. cruzi infection in astrocytes decreased approximately by 30% upon incubation with post-immunization sera compared with pre-immunization sera. Furthermore, trypomastigotes were recorded by video microscopy and the parasite's flagellar speed was calculated by tracking the flagella. Trypomastigotes exposed to post-immunization sera had qualitative alterations in motility and significantly slower flagella (45.5 µm/s), compared with those exposed to pre-immunization sera (69.2 µm/s). In summary, polyclonal anti-TcTLE serum significantly reduced the parasite's flagellar speed and cell infectivity. These findings support that KMP-11 could be important for parasite motility, and that by targeting its N-terminal peptide infectivity can be reduced.

  16. Chaperonin GroEL/GroES Over-Expression Promotes Aminoglycoside Resistance and Reduces Drug Susceptibilities in Escherichia coli Following Exposure to Sublethal Aminoglycoside Doses

    DEFF Research Database (Denmark)

    Goltermann, Lise; Sarusie, Menachem V; Bentin, Thomas

    2016-01-01

    Antibiotic resistance is an increasing challenge to modern healthcare. Aminoglycoside antibiotics cause translation corruption and protein misfolding and aggregation in Escherichia coli. We previously showed that chaperonin GroEL/GroES depletion and over-expression sensitize and promote short-ter...... mechanism for emergence of antibiotic resistance.......Antibiotic resistance is an increasing challenge to modern healthcare. Aminoglycoside antibiotics cause translation corruption and protein misfolding and aggregation in Escherichia coli. We previously showed that chaperonin GroEL/GroES depletion and over-expression sensitize and promote short......-term tolerance, respectively, to this drug class. Here, we show that chaperonin GroEL/GroES over-expression accelerates acquisition of streptomycin resistance and reduces susceptibility to several other antibiotics following sub-lethal streptomycin antibiotic exposure. Chaperonin buffering could provide a novel...

  17. Haitian variant ctxB producing Vibrio cholerae O1 with reduced susceptibility to ciprofloxacin is persistent in Yavatmal, Maharashtra, India, after causing a cholera outbreak.

    Science.gov (United States)

    Kumar, P; Mishra, D K; Deshmukh, D G; Jain, M; Zade, A M; Ingole, K V; Yadava, P K

    2014-05-01

    Vibrio cholerae O1 biotype El Tor producing Haitian variant Cholera Toxin (HCT) and showing reduced susceptibility to ciprofloxacin caused a cholera outbreak associated with a high case fatality rate (4.5) in India. HCT-secreting strains responsible for severe cholera epidemics in Orissa (India), Western Africa and Haiti were associated with increased mortality. There is a pressing need for an integrated multidisciplinary approach to combat further spread of newly emerging variant strains. The therapeutic effect of ciprofloxacin was diminished whereas use of doxycycline in moderate to severe cholera patients was found to be effective in outbreak management. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  18. Pharmacologic concentrations of linezolid modify oxidative phosphorylation function and adipocyte secretome

    Directory of Open Access Journals (Sweden)

    Laura Llobet

    2017-10-01

    Full Text Available The oxidative phosphorylation system is important for adipocyte differentiation. Therefore, xenobiotics inhibitors of the oxidative phosphorylation system could affect adipocyte differentiation and adipokine secretion. As adipokines impact the overall health status, these xenobiotics may have wide effects on human health. Some of these xenobiotics are widely used therapeutic drugs, such as ribosomal antibiotics. Because of its similarity to the bacterial one, mitochondrial translation system is an off-target for these compounds. To study the influence of the ribosomal antibiotic linezolid on adipokine production, we analyzed its effects on adipocyte secretome. Linezolid, at therapeutic concentrations, modifies the levels of apolipoprotein E and several adipokines and proteins related with the extracellular matrix. This antibiotic also alters the global methylation status of human adipose tissue-derived stem cells and, therefore, its effects are not limited to the exposure period. Besides their consequences on other tissues, xenobiotics acting on the adipocyte oxidative phosphorylation system alter apolipoprotein E and adipokine production, secondarily contributing to their systemic effects.

  19. A cfr-like gene cfr(C) conferring linezolid resistance is common in Clostridium difficile.

    Science.gov (United States)

    Candela, Thomas; Marvaud, Jean-Christophe; Nguyen, Tiep Khac; Lambert, Thierry

    2017-09-01

    Clostridium difficile T10 and Clostridium bolteae 90B3 were co-resistant to phenicols, lincosamides, oxazolidinones, pleuromutilins and streptogramin A (PhLOPSA) and harbored an unreported cfr-like determinant that may alter the 23S rRNA by m(8)A2503 methylation. The cfr-like cfr(C) gene was cloned in C. difficile 630Δerm in which it conferred PhLOPSA resistance. In C. bolteae 90B3: (i) qRT-PCR analysis indicated that cfr(C) was similarly expressed in the absence or presence of either chloramphenicol or clindamycin or linezolid; and (ii) cfr(C) was part of a putative 24 kb-transposon, which generated a detectable circular intermediate. An element differing by a single nucleotide was found in C. difficile DA00203 from GenBank data, consistent with a recent horizontal transfer. In silico analysis showed cfr(C) in 19 out of 274 C. difficile genomes. This gene was also detected by PCR analysis in 9 out of 80 C. difficile from our laboratory strain collection according to resistance to linezolid and florfenicol. The fact that cfr(C) was mainly confined in C. difficile within polymorphic environments indicates this microorganism is a reservoir for PhLOPSA resistance. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  20. Improved shoot regeneration, salinity tolerance and reduced fungal susceptibility in transgenic tobacco constitutively expressing PR-10a gene

    Directory of Open Access Journals (Sweden)

    Parinita eAgarwal

    2016-02-01

    Full Text Available Plants in ecosystems are simultaneously exposed to abiotic and biotic stresses, which restrict plant growth and development. The complex responses to these stresses are largely regulated by plant hormones, which in turn, orchestrate the different biochemical and molecular pathways to manoeuvre stress tolerance. The PR-10 protein family is reported to be involved in defence regulation, stress response and plant growth and development. The JcPR-10a overexpression resulted in increased number of shoot buds in tobacco (Nicotiana tabacum, which could be due to high cytokinin to auxin ratio in the transgenics. The docking analysis shows the binding of three BAP molecules at the active sites of JcPR-10a protein. JcPR-10a transgenics showed enhanced salt tolerance, as was evident by increased germination rate, shoot and root length, relative water content, proline, soluble sugar and amino acid content under salinity. Interestingly, the transgenics also showed enhanced endogenous cytokinin level as compared to WT, which, further increased with salinity. Exposure of gradual salinity resulted in increased stomatal conductance, water use efficiency, photosynthesis rate and reduced transpiration rate. Furthermore, the transgenics also showed enhanced resistance against Macrophomina fungus. Thus, JcPR-10a might be working in co-ordination with cytokinin signalling in mitigating the stress induced damage by regulating different stress signalling pathways, leading to enhanced stress tolerance.

  1. Dynamic Susceptibility Contrast Perfusion Magnetic Resonance Imaging Demonstrates Reduced Periventricular Cerebral Blood Flow in Dogs with Ventriculomegaly

    Directory of Open Access Journals (Sweden)

    Martin J. Schmidt

    2017-08-01

    Full Text Available The nature of ventriculomegaly in dogs is still a matter of debate. Signs of increased intraventricular pressure and atrophy of the cerebral white matter have been found in dogs with ventriculomegaly, which would imply increased intraventricular pressure and, therefore, a pathological condition, i.e., to some extent. Reduced periventricular blood flow was found in people with high elevated intraventricular pressure. The aim of this study was to compare periventricular brain perfusion in dogs with and without ventriculomegaly using perfusion weighted-magnetic-resonance-imaging to clarify as to whether ventriculomegaly might be associated with an increase in intraventricular pressure. Perfusion was measured in 32 Cavalier King Charles spaniels (CKCS with ventriculomegaly, 10 CKCSs were examined as a control group. Cerebral blood flow (CBF was measured using free-hand regions of interest (ROI in five brain regions: periventricular white matter, caudate nucleus, parietal cortex, hippocampus, and thalamus. CBF was significantly lower in the periventricular white matter of the dogs with ventriculomegaly (p = 0.0029 but not in the other ROIs. Reduction of periventricular CBF might imply increase of intraventricular pressure in ventriculomegaly.

  2. Melatonin promotes Bax sequestration to mitochondria reducing cell susceptibility to apoptosis via the lipoxygenase metabolite 5-hydroxyeicosatetraenoic acid

    KAUST Repository

    Radogna, Flavia

    2015-03-01

    Extra-neurological functions of melatonin include control of the immune system and modulation of apoptosis. We previously showed that melatonin inhibits the intrinsic apoptotic pathway in leukocytes via stimulation of high affinity MT1/MT2 receptors, thereby promoting re-localization of the anti-apoptotic Bcl-2 protein to mitochondria. Here we show that Bcl-2 sequesters pro-apoptotic Bax into mitochondria in an inactive form after melatonin treatment, thus reducing cell propensity to apoptosis. Bax translocation and the anti-apoptotic effect of melatonin are strictly dependent on the presence of Bcl-2, and on the 5-lipoxygenase (5-LOX) metabolite 5-hydroxyeicosatetraenoic acid (5-HETE), which we have previously shown to be produced as a consequence of melatonin binding to its low affinity target calmodulin. Therefore, the anti-apoptotic effect of melatonin requires the simultaneous, independent interaction with high (MT1/MT2) and low (calmodulin) affinity targets, eliciting two independent signal transduction pathways converging into Bax sequestration and inactivation. MT1/MT2 vs. lipoxygenase pathways are activated by 10-9 vs. 10-5M melatonin, respectively; the anti-apoptotic effect of melatonin is achieved at 10-5M, but drops to 10-9M upon addition of exogenous 5-HETE, revealing that lipoxygenase activation is the rate-limiting pathway. Therefore, in areas of inflammation with increased 5-HETE levels, physiological nanomolar concentrations of melatonin may suffice to maintain leukocyte viability.

  3. Urokinase-type plasminogen activator deficiency has little effect on seizure susceptibility and acquired epilepsy phenotype but reduces spontaneous exploration in mice.

    Science.gov (United States)

    Rantala, J; Kemppainen, S; Ndode-Ekane, X E; Lahtinen, L; Bolkvadze, Tamuna; Gurevicius, K; Tanila, H; Pitkänen, A

    2015-01-01

    Urokinase-type plasminogen activator (uPA), a serine protease, converts plasminogen to plasmin. Activation of plasmin leads to degradation of the extracellular matrix, which is critical for tissue recovery, angiogenesis, cell migration, and axonal and synaptic plasticity. We hypothesized that uPA deficiency would cause an abnormal neurophenotype and would lead to exacerbated epileptogenesis after brain injury. Wild-type (Wt) and uPA-/- mice underwent a battery of neurologic behavioral tests evaluating general reactivity, spontaneous exploratory activity, motor coordination, pain threshold, fear and anxiety, and memory. We placed particular emphasis on the effect of uPA deficiency on seizure susceptibility, including the response to convulsants (pentylenetetrazol, kainate, or pilocarpine) and kainate-induced epileptogenesis and epilepsy. The uPA-/- mice showed no motor or sensory impairment compared with the Wt mice. Hippocampus-dependent spatial memory also remained intact. The uPA-/- mice, however, exhibited reduced exploratory activity and an enhanced response to a tone stimulus (p<0.05 compared with the Wt mice). The urokinase-type plasminogen activator deficient mice showed no increase in spontaneous or evoked epileptiform electrographic activity. Rather, the response to pilocarpine administration was reduced compared with the Wt mice (p<0.05). Also, the epileptogenesis and the epilepsy phenotype after intrahippocampal kainate injection were similar to those in the Wt mice. Taken together, uPA deficiency led to diminished interest in the environmental surroundings and enhanced emotional reactivity to unexpected aversive stimuli. Urokinase-type plasminogen activator deficiency was not associated with enhanced seizure susceptibility or worsened poststatus epilepticus epilepsy phenotype.

  4. Difference in agr Dysfunction and Reduced Vancomycin Susceptibility between MRSA Bacteremia Involving SCCmec Types IV/IVa and I–III

    Science.gov (United States)

    Choi, Su-Mi; Park, Kyung-Hwa; Shin, Jong-Hee; Choy, Hyon E.; Jung, Sook-In; Kim, Hong Bin

    2012-01-01

    Background Dysfunction of agr, with reduced susceptibility or hetero-resistance to vancomycin, is thought to be associated with a worse outcome of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB). However, the difference in agr dysfunction according to the SCCmec type in MRSA infection is undetermined. We compared the prevalence of agr dysfunction, reduced vancomycin susceptibility and the outcomes of SCCmec IV/IVa and I–III MRSAB. Methods The study included 307 cases of MRSAB. SCCmec types were determined by multiplex PCR. The clinical and microbiological features and outcomes of 58 SCCmec IV/IVa MRSAB were compared with those of 249 SCCmec I–III MRSAB. Results Compared with SCCmec I–III MRSAB, SCCmec IV/IVa MRSAB was associated with lower rates of agr dysfunction (3% vs. 43%), vancomycin minimum inhibitory concentration (MIC) = 2 µg/mL (3% vs. 15%), and hetero-resistance to vancomycin (0% vs. 8%) (all PIVa MRSAB were not different from those in patients with SCCmec I–III MRSAB in multivariate analyses (HR 1.168, 95% CI 0.705–1.938; HR 1.025, 95% CI 0.556–1.889). Conclusions SCCmec IV/IVa MRSAB was associated with lower rates of agr dysfunction and hetero-resistance to vancomycin and a lower vancomycin MIC, compared with SCCmec I–III MRSAB. However, the outcomes of SCCmec IV/IVa MRSAB did not differ from those of SCCmec I–III MRSAB. PMID:23152862

  5. Antimicrobial Susceptibility Pattern of Enterococci Isolated From Patients in Tehran

    Directory of Open Access Journals (Sweden)

    Saderi

    2015-11-01

    Full Text Available Background Enterococci are one of the most common nosocomial pathogens and the emergence of multidrug-resistant strains has been increasing. Objectives We studied the antimicrobial susceptibility of enterococci isolated from different clinical specimens of patients in Tehran. Materials and Methods From the beginning of April 2013 to the end of June 2013, a total of 146 enterococci were isolated from the Pars General Hospital in Tehran. The antimicrobial susceptibility pattern of the isolates against ampicillin, clindamaycin, ciprofloxacin, erythromycin, levofloxacin, linezolid, nitrofurantoin, tetracycline, and vancomycin was determined using the disk diffusion method according to the guidelines of clinical laboratory standards institute (CLSI. Results The rates of resistance were high to clindamycin, tetracycline, and erythromycin (97.2%, 89%, and 74.5%, respectively; moderate to ciprofloxacilin and levofloxacilin (40.6% and 36.4%, respectively; and low to ampicillin and nitrofurantoin (13.8% and 3.5%, respectively. All isolates were linezolid sensitive. Vancomycin-resistant enterococci (VRE accounted for 9.6% of the isolates. Conclusions VRE and a high rate of resistance to some of antimicrobial agents were found among the enterococci isolated from patients in Tehran. These findings highlight the importance of regular supervision of antimicrobial susceptibilities.

  6. Antimicrobial Susceptibility Pattern of Enterococci Isolated From Patients in Tehran

    Directory of Open Access Journals (Sweden)

    Horieh Saderi

    2015-11-01

    Full Text Available Background: Enterococci are one of the most common nosocomial pathogens and the emergence of multidrug-resistant strains has been increasing. Objectives: We studied the antimicrobial susceptibility of enterococci isolated from different clinical specimens of patients in Tehran. Materials and Methods: From the beginning of April 2013 to the end of June 2013, a total of 146 enterococci were isolated from the Pars General Hospital in Tehran. The antimicrobial susceptibility pattern of the isolates against ampicillin, clindamaycin, ciprofloxacin, erythromycin, levofloxacin, linezolid, nitrofurantoin, tetracycline, and vancomycin was determined using the disk diffusion method according to the guidelines of clinical laboratory standards institute (CLSI. Results: The rates of resistance were high to clindamycin, tetracycline, and erythromycin (97.2%, 89%, and 74.5%, respectively; moderate to ciprofloxacilin and levofloxacilin (40.6% and 36.4%, respectively; and low to ampicillin and nitrofurantoin (13.8% and 3.5%, respectively. All isolates were linezolid sensitive. Vancomycin-resistant enterococci (VRE accounted for 9.6% of the isolates. Conclusions: VRE and a high rate of resistance to some of antimicrobial agents were found among the enterococci isolated from patients in Tehran. These findings highlight the importance of regular supervision of antimicrobial susceptibilities.

  7. Front-loaded linezolid regimens result in increased killing and suppression of the accessory gene regulator system of Staphylococcus aureus.

    Science.gov (United States)

    Tsuji, Brian T; Brown, Tanya; Parasrampuria, Ridhi; Brazeau, Daniel A; Forrest, Alan; Kelchlin, Pamela A; Holden, Patricia N; Peloquin, Charles A; Hanna, Debra; Bulitta, Jurgen B

    2012-07-01

    Front loading is a strategy used to optimize the pharmacodynamic profile of an antibiotic through the administration of high doses early in therapy for a short duration. Our aims were to evaluate the impact of front loading of linezolid regimens on bacterial killing and suppression of resistance and on RNAIII, the effector molecule of the accessory gene regulator system (encoded by agr) in methicillin-resistant Staphylococcus aureus (MRSA). Time-killing experiments over 48 h were utilized for linezolid against four strains of MRSA: USA100, USA300, USA400, and ATCC 29213. A hollow-fiber infection model simulated traditional and front-loaded human therapeutic regimens of linezolid versus USA300 at 10(6) CFU/ml over 240 h. Over 48 h in time-kill experiments, linezolid displayed bacteriostatic activity, with reductions of >1 log(10) CFU/ml for all strains. Front-loaded regimens that were administered over 5 days, 1,200 mg every 12 h (q12h) (total, 10 doses) and 2,400 mg q12h (total, 10 doses) followed by 300 mg q12h thereafter, resulted in sustained bactericidal activity, with reductions of the area under the CFU curve of -6.15 and -6.03, respectively, reaching undetectable limits at the 10-day study endpoint. All regimens displayed a reduction in RNAIII relative expression at 24 h and 240 h compared with that of the growth control. Monte Carlo simulations predicted a infections, where early aggressive therapy is necessary.

  8. Enriched Housing Reduces Disease Susceptibility to Co-Infection with Porcine Reproductive and Respiratory Virus (PRRSV) and Actinobacillus pleuropneumoniae (A. pleuropneumoniae) in Young Pigs.

    Science.gov (United States)

    van Dixhoorn, Ingrid D E; Reimert, Inonge; Middelkoop, Jenny; Bolhuis, J Elizabeth; Wisselink, Henk J; Groot Koerkamp, Peter W G; Kemp, Bas; Stockhofe-Zurwieden, Norbert

    2016-01-01

    Until today, anti-microbial drugs have been the therapy of choice to combat bacterial diseases. Resistance against antibiotics is of growing concern in man and animals. Stress, caused by demanding environmental conditions, can reduce immune protection in the host, influencing the onset and outcome of infectious diseases. Therefore psychoneuro-immunological intervention may prove to be a successful approach to diminish the impact of diseases and antibiotics use. This study was designed to investigate the effect of social and environmental enrichment on the impact of disease, referred to as "disease susceptibility", in pigs using a co-infection model of PRRSV and A. pleuropneumoniae. Twenty-eight pigs were raised in four pens under barren conditions and twenty-eight other pigs were raised in four pens under enriched conditions. In the enriched pens a combination of established social and environmental enrichment factors were introduced. Two pens of the barren (BH) and two pens of the enriched housed (EH) pigs were infected with PRRSV followed by A. pleuropneumoniae, the other two pens in each housing treatment served as control groups. We tested if differences in disease susceptibility in terms of pathological and clinical outcome were related to the different housing regimes and if this was reflected in differences in behavioural and immunological states of the animals. Enriched housed pigs showed a faster clearance of viral PRRSV RNA in blood serum (p = 0.014) and histologically 2.8 fold less interstitial pneumonia signs in the lungs (p = 0.014). More barren housed than enriched housed pigs developed lesions in the lungs (OR = 19.2, p = 0.048) and the lesions in the barren housed pigs showed a higher total pathologic tissue damage score (ppleuropneumoniae in pigs. Enrichment positively influences behavioural state, immunological response and clinical outcome in pigs.

  9. Biofilms of Candida spp. from the ocular conjunctiva of horses with reduced azole susceptibility: a complicating factor for the treatment of keratomycosis?

    Science.gov (United States)

    Brilhante, Raimunda Sâmia Nogueira; Bittencourt, Paula Vago; de Souza Collares Castelo-Branco, Débora; de Melo Guedes, Glaucia Morgana; de Oliveira, Jonathas Sales; Alencar, Lucas Pereira; de Aguiar Cordeiro, Rossana; Pinheiro, Mariana; Nogueira-Filho, Evilázio Fernandes; de Aquino Pereira-Neto, Waldemiro; Sidrim, José Júlio Costa; Rocha, Marcos Fábio Gadelha

    2017-04-18

    This study aimed to assess the biofilm-forming ability of Candida spp. from the ocular conjunctiva of horses and to investigate the antifungal susceptibility of these biofilms. Initially, the biofilm-forming ability of 15 strains was assessed by crystal violet staining, which reveals the fungal biomass adhered to the polystyrene plates, and scanning electron microscopy. Then, the minimum inhibitory concentrations (MICs) of amphotericin B, fluconazole, itraconazole, and caspofungin were initially determined against strains in planktonic form. Afterward, antifungal susceptibility of mature biofilms was evaluated by exposing them to 10 × MIC and 50 × MIC of the tested drugs, followed by the assessment of their metabolic activity, using the oxidoreduction indicator XTT. Results were analyzed through ANOVA and Tukey's post-test, and P-values below 5% led to significant conclusions. Eight strains produced biofilms and were classified as strong (1/15), moderate (3/15) and weak (4/15) producers, according to the amount of crystal violet retained by the adhered fungal biomass. Biofilm metabolic activity of one C. tropicalis did not decrease after exposure to the tested antifungals, while biofilm metabolic activity of five strains was reduced by amphotericin B, but not the other drugs. One C. parapsilosis sensu stricto and one C. glabrata showed significant reduction in biofilm metabolic activity after exposure to fluconazole, itraconazole, and caspofungin, but not amphotericin B. The results demonstrate that Candida from the ocular conjunctiva of horses can pose as a risk to animal health as they are capable of forming biofilms, which are commonly involved in fungal keratitis. © 2017 American College of Veterinary Ophthalmologists.

  10. Bumetanide reduce the seizure susceptibility induced by pentylenetetrazol via inhibition of aberrant hippocampal neurogenesis in neonatal rats after hypoxia-ischemia.

    Science.gov (United States)

    Hu, Jiang-Jian; Yang, Xing-Liang; Luo, Wen-Di; Han, Song; Yin, Jun; Liu, Wan-Hong; He, Xiao-Hua; Peng, Bi-Wen

    2017-02-02

    Hypoxia-ischemia brain damage (HIBD) is one of prevalent causes of neonatal mortality and morbidity. Our data demonstrated that hypoxia-ischemia (HI) induced Na(+)-K(+)-Cl(-)-co-transporter 1 (NKCC1) increasing in hippocampus. Previous studies demonstrated that NKCC1 regulates various stages of neurogenesis. In this study, we studied the role of increased NKCC1 in regulating of HI-induced neurogenesis. HIBD model was established in 7days old Sprague-Dawley rat pup, and the expression of NKCC1 was detected by western blot and qPCR. Brain electrical activity in freely rats was monitored by electroencephalography (EEG) recordings. HI-induced neurogenesis was detected by immunofluorescence staining. Neurobehavioral test was to investigate the neuro-protective role of bumetanide, an inhibitor of NKCC1, on neonatal rats after HI. The results showed that bumetanide treatment significantly reduced brain electrical activity and the seizure stage of epilepsy induced by pentylenetetrazol (PTZ) in vivo after HI. In addition, bumetanide restored aberrant hippocampal neurogenesis and associated cognitive function. Our data demonstrated that bumetanide reduces the susceptibility of epilepsy induced by PTZ in rats suffering from HI injury during neonatal period via restoring the ectopic newborn neurons in dentate gyrus (DG) and cognitive function.

  11. Linezolid Injection

    Science.gov (United States)

    ... It works by stopping the growth of bacteria. Antibiotics will not kill viruses that can cause colds, ... raisins; bananas; sour cream; pickled herring; liver (especially chicken liver); dried meats and sausage (including hard salami ...

  12. ANTIMICROBIAL SUSCEPTIBILITY PATTERN OF ORGANISMS CAUSING SURGICAL SITE INFECTIONS (SSI

    Directory of Open Access Journals (Sweden)

    Rohini Murlidhar Gajbhiye

    2017-02-01

    Full Text Available BACKGROUND CDC defines surgical site infection as ‘Infections related to operative procedure that occurs at or near surgical incision within 30 days of operative procedure or within one year if the implant is left in situ’. Surgical site infection (SSI is 3 rd most frequently reported nosocomial infection (12%-16% as per National Nosocomial Infection Surveillance (NNIS. The aim of this study was to investigate the antimicrobial susceptibility pattern of organisms causing SSI. MATERIALS AND METHODS During a two year study period in a tertiary care hospital, 19,127 patients underwent surgeries in various surgical departments. Of these 517 (2.7% developed surgical site infection. The surgical wounds were classified by CDC & NNIS criteria into 4 classes. Two wound swabs were taken and processed by standard microbiological techniques. Antimicrobial susceptibility along with testing of ESBLs, MBLs, AmpCβ lactamases was done for all isolates causing SSI. RESULTS Among 19,127 patients, 517 (2.7% developed SSI. It was highest in patients of perforation peritonitis (11.99%.Among 517 specimens, 340 (65.76% showed growth and 177 (34.23% were culture negative. E.coli (23.33% was the commonest organism isolated followed by Acinetobacter spp. (16%, Klebsiella spp. (15.66%, Pseudomonas spp. (15.33%, S. aureus (10.33%, S. epidermidis(7.3%, Proteus spp. (6.00% and Citrobacter spp. (2.66%.Staphylococcus spp. were 100 % sensitive to Vancomycin & Linezolid. (27.5% S. aureus were MRSA and (17.5% were Inducible Clindamycin resistant (ICR. Enterobacteriaceae isolates showed maximum sensitivity towards Imipenem, Piperacillin-Tazobactam and Amikacin. Klebsiella spp. (40.62%, E.coli (35.89%, Citrobacter spp. (33.33%, Proteus spp. (26.08% were ESBL producers. Klebsiella spp. (17.18%, E.coli (10.25%, Proteus spp. (11.11% and Citrobacter spp. (8.69% were AmpC producers. Acinetobacter spp. (28.57% was commonest MBL producer followed by Klebsiella spp. (20

  13. Semi-national surveillance of fungaemia in Denmark 2004-2006: increasing incidence of fungaemia and numbers of isolates with reduced azole susceptibility

    DEFF Research Database (Denmark)

    Arendrup, M.C.; Fuursted, K.; Gahrn-Hansen, B.;

    2008-01-01

    .0%) isolates in 2006 (p 0.03). Overall, the proportion of isolates with decreased susceptibility to fluconazole exceeded 30% in 2006. The incidence of fungaemia in Denmark was three-fold higher than that reported from other Nordic countries and is increasing. Decreased susceptibility to fluconazole is frequent...

  14. A propensity score analysis shows that empirical treatment with linezolid does not increase the thirty-day mortality rate in patients with Gram-negative bacteremia.

    Science.gov (United States)

    Ternavasio-de la Vega, Hugo-Guillermo; Mateos-Díaz, Ana-María; Martinez, Jose-Antonio; Almela, Manel; Cobos-Trigueros, Nazaret; Morata, Laura; De-la-Calle, Cristina; Sala, Marta; Mensa, Josep; Marcos, Miguel; Soriano, Alex

    2014-12-01

    The role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patients with Gram-negative bacteremia in the Hospital Clinic of Barcelona from 2000 to 2012 were included in this study. In order to compare the mortality rates between patients who received linezolid or glycopeptides, the propensity scores on baseline variables were used to balance the treatment groups, and both propensity score matching and propensity-adjusted logistic regression were used to compare the 30-day mortality rates between the groups. The overall 30-day mortality rate was 16.0% during the study period. Sixty-eight patients received empirical treatment with linezolid, and 1,058 received glycopeptides. The propensity score matching included 64 patients in each treatment group. After matching, the mortality rates were 14.1% (9/64) in patients who received glycopeptides and 21.9% (14/64) in those who received linezolid, and a nonsignificant association between empirical linezolid treatment and mortality rate (odds ratio [OR], 1.63; 95% confidence interval [CI], 0.69 to 3.82; P = 0.275, McNemar's test) was found. This association remained nonsignificant when variables that remained unbalanced after matching were included in a conditional logistic regression model. Further, the stratified propensity score analysis did not show any significant relationship between empirical linezolid treatment and the mortality rate after adjustment by propensity score quintiles or other variables potentially associated with mortality. In conclusion, the propensity score analysis showed that empirical treatment with linezolid compared with that with glycopeptides was not associated with 30-day mortality rates in patients with Gram-negative bacteremia.

  15. Antistaphylococcal Activity of DX-619 Alone and in Combination with Vancomycin, Teicoplanin, and Linezolid Assessed by Time-Kill Synergy Testing▿ †

    Science.gov (United States)

    Credito, Kim; Lin, Genrong; Appelbaum, Peter C.

    2007-01-01

    Time-kill synergy studies testing in vitro activity of DX-619 alone and with added vancomycin, teicoplanin, or linezolid against 101 Staphylococcus aureus strains showed synergy between DX-619 and teicoplanin at 12 to 24 h in 72 strains and between DX-619 and vancomycin in 28 strains. No synergy was found with linezolid, and no antagonism was observed with any combination. PMID:17261625

  16. Activities of the Oxazolidinones Linezolid and Eperezolid in Experimental Intra-Abdominal Abscess Due to Enterococcus faecalis or Vancomycin-Resistant Enterococcus faecium

    OpenAIRE

    1999-01-01

    The in vivo effectiveness of oxazolidinones eperezolid (U-100592) and linezolid (U-100766) against one strain each of Enterococcus faecalis and vancomycin-resistant Enterococcus faecium was examined in a rat model of intra-abdominal abscess. MICs of both drugs were 2 μg/ml for each strain. At doses of 25 mg/kg of body weight twice daily intravenously or orally, linezolid produced small but statistically significant reductions in abscess bacterial density for E. faecalis. The reduction in viab...

  17. A functional variant in the cystathionine β-synthase gene promoter significantly reduces congenital heart disease susceptibility in a Han Chinese population

    Institute of Scientific and Technical Information of China (English)

    Jian-Yuan Zhao; Xue-Yan Yang; Kai-Hu Shi; Shu-Na Sun; Jia Hou; Zhi-Zhou Ye; Jue Wang

    2013-01-01

    Homocysteine is an independent risk factor for various cardiovascular diseases.There are two ways to remove homocysteine from embryonic cardiac cells:remethylation to form methionine or transsulfuration to form cysteine.Cystathionine β-synthase (CBS) catalyzes the first step of homocysteine transsulfuration as a rate-limiting enzyme.In this study,we identified a functional variant-4673C>G (rs2850144) in the CBS gene promoter region that significantly reduces the susceptibility to congenital heart disease (CHD) in a Han Chinese population consisting of 2 340 CHD patients and 2 270 controls.Individuals carrying the heterozygous CG and homozygous GG genotypes had a 15% (odds ratio (OR) =0.85,95% confidence interval (CI) =0.75-0.96,P =0.011) and 40% (OR =0.60,95% CI =0.49-0.73,P =1.78 × 10-7) reduced risk to develop CHD than the wild-type CC genotype carriers in the combined samples,respectively.Additional stratified analyses demonstrated that CBS-4673C>G is significantly related to septation defects and conotruncal defects.In vivo detection of CBS mRNA levels in human cardiac tissues and in vitro luciferase assays consistently showed that the minor G allele significantly increased CBS transcription.A functional analysis revealed that both the attenuated transcription suppressor SP1 binding affinity and the CBS promoter hypomethylation specifically linked with the minor G allele contributed to the remarkably upregulated CBS expression.Consequently,the carriers with genetically increased CBS expression would benefit from the protection due to the low homocysteine levels maintained by CBS in certain cells during the critical heart development stages.These results shed light on unexpected role of CBS and highlight the importance of homocysteine removal in cardiac development.

  18. Unbound fraction of fluconazole and linezolid in human plasma as determined by ultrafiltration: Impact of membrane type.

    Science.gov (United States)

    Kratzer, Alexander; Kees, Frieder; Dorn, Christoph

    2016-12-15

    Ultrafiltration is a rapid and convenient method to determine the free concentrations of drugs in plasma. Several ultrafiltration devices based on Eppendorf cups are commercially available, but are not validated for such use by the manufacturer. Plasma pH, temperature and relative centrifugal force as well as membrane type can influence the results. In the present work, we developed an ultrafiltration method in order to determine the free concentrations of linezolid or fluconazole, both neutral and moderately lipophilic antiinfective drugs for parenteral as well as oral administration, in plasma of patients. Whereas both substances behaved relatively insensitive in human plasma regarding variations in pH (7.0-8.5), temperature (5-37°C) or relative centrifugal force (1000-10.000xg), losses of linezolid were observed with the Nanosep Omega device due to adsorption onto the polyethersulfone membrane (unbound fraction 75% at 100mg/L and 45% at 0.1mg/L, respectively). No losses were observed with Vivacon which is equipped with a membrane of regenerated cellulose. With fluconazole no differences between Nanosep and Vivacon were observed. Applying standard conditions (pH 7.4/37°C/1000xg/20min), the mean unbound fraction of linezolid in pooled plasma from healthy volunteers was 81.5±2.8% using Vivacon, that of fluconazole was 87.9±3.5% using Nanosep or 89.4±3.3% using Vivacon. The unbound fraction of linezolid was 85.4±3.7% in plasma samples from surgical patients and 92.1±6.2% in ICU patients, respectively. The unbound fraction of fluconazole was 93.9±3.3% in plasma samples from ICU patients.

  19. Front-Loaded Linezolid Regimens Result in Increased Killing and Suppression of the Accessory Gene Regulator System of Staphylococcus aureus

    OpenAIRE

    Tsuji, Brian T.; Brown, Tanya; Parasrampuria, Ridhi; Daniel A Brazeau; Forrest, Alan; Kelchlin, Pamela A.; Holden, Patricia N.; Peloquin, Charles A.; Hanna, Debra; Bulitta, Jurgen B.

    2012-01-01

    Front loading is a strategy used to optimize the pharmacodynamic profile of an antibiotic through the administration of high doses early in therapy for a short duration. Our aims were to evaluate the impact of front loading of linezolid regimens on bacterial killing and suppression of resistance and on RNAIII, the effector molecule of the accessory gene regulator system (encoded by agr) in methicillin-resistant Staphylococcus aureus (MRSA). Time-killing experiments over 48 h were utilized for...

  20. Rapid and sensitive LC-MS/MS method for the analysis of antibiotic linezolid on dried blood spot.

    Science.gov (United States)

    la Marca, Giancarlo; Villanelli, Fabio; Malvagia, Sabrina; Ombrone, Daniela; Funghini, Silvia; De Gaudio, Marina; Fallani, Stefania; Cassetta, Maria Iris; Novelli, Andrea; Chiappini, Elena; de Martino, Maurizio; Galli, Luisa

    2012-01-01

    Linezolid is a new drug from the oxazolidinone class of antibiotics used against mycobacteria and multi-drug resistant (MDR) Gram-positive bacterial infections, which may are also glycopeptide-resistant. The drug usage in pediatric age needs an accurate drug monitoring for effective patient management. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to determinate linezolid levels during treatment. Advantages of DBS include short collection time, low invasiveness, ease and low cost of sample collection, transport and storage. The analysis was performed in LC-MS/MS operating in positive ion mode and multiple reaction monitoring (MRM) mode. The calibration curve in matrix was linear in the concentration range of 1-100 mg/L with correlation coefficient value of 0.9987. Intraday and interday coefficients of variation were within 3.6% and 13.0%, respectively. We also tested the thermal and temporal drug stability in dried blood spots at four different temperatures to evaluate the risks of sample delivery in different conditions. The short term stability studies showed that linezolid concentration remained stable for at least one month under all the conditions tested. This new assay has favorable characteristics being highly precise and accurate and allows a fast linezolid analysis with a total run time 22 min long, in gradient analysis. Concentration data for plasma and DBS samples from patients after treatment were compared showing a good correlation. Correlation between DBS data and serum samples measured by HPLC-UV was satisfactory. The benefit for patients is the ability to monitor the treatment with a simple and convenient sample collection at home.

  1. Proper use of antibiotics: situation of linezolid at the intensive care unit of the Tunisian Military Hospital

    Science.gov (United States)

    Safa, Louhichi; Afif, Neffati; Zied, Hajjej; Mehdi, Dridi; Ali, Yousfi Mohamed

    2016-01-01

    Linezolid was introduced in clinical practice in the early 2000s. It was considered to be an ideal reserve drug for treatment of vancomycin-resistant Enterococcus spp. (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA). The aim of our study was to describe and evaluate the use of linezolid in clinical practice at the intensive care unit (ICU) of the Tunisian military hospital. This is a thirty-month retrospective study including patients treated with linezolid at the ICU of the Tunisian military hospital. Data collection was realized using the patients’ medical files and prescriptions. A pharmacist conducted an extended medication history and checked if an advice from an infectious disease-physician and a microbiological documentation were requested. A total of 80 patients were included. Forty-one per cent of indications were outside the Marketing Authorization (MA) criteria, and were mainly sepsis and postoperative mediastinitis (32% and 4% of total prescriptions, respectively). This antibiotic was used as a first-line therapy in 58% of cases. The advice from an infectious-disease physician was requested for 33% of prescriptions. Only 20% of infections were documented microbiologically, of which 35% were caused by methicillin resistant coagulase-negative Staphylococcus. Linezolid is an interesting therapeutic alternative in case of infections due to multi-resistant bacteria and/or complex clinical situations. Therefore, its prescription must be rationalized in order to slow down the emergence of resistance to this antibiotic. The high frequency of its use outside the MA criteria shows the importance of carrying out more clinical trials to evaluate its effectiveness and safety for new indications.

  2. Characterization of Enterococcus faecium with macrolide resistance and reduced susceptibility to quinupristin/dalfopristin in a Japanese hospital: detection of extensive diversity in erm(B)-regulator regions.

    Science.gov (United States)

    Isogai, Nayuta; Urushibara, Noriko; Kawaguchiya, Mitsuyo; Ghosh, Souvik; Suzaki, Keisuke; Watanabe, Naoki; Quiñones, Dianelys; Kobayashi, Nobumichi

    2013-08-01

    Cross-resistance to macrolide, lincosamide, and streptogramin B (MLSB) antibiotics is mainly mediated by the erm (erythromycin ribosome methylation) genes that encode 23S rRNA methylases in enterococi, and various mechanisms are involved in the streptogramin B resistance. Prevalence of MLSB resistance and its genetic mechanisms were analyzed for a total of 159 strains of Enterococcus faecium isolated from clinical specimens in a university hospital in Japan from 1997 to 2006. Resistance to erythromycin (EM) and clindamycin was detected in 88.1% and 89.9% of all the strains examined, respectively, and expression of resistance was totally constitutive. Although none of the strain was resistant to quinupristin/dalfopristin (Q/D), 28 strains (17.6%) showed intermediate resistance to Q/D (MIC: 2 μg/ml). The erm(B) gene was detected in 139 strains (87.4%), and msrC was found in all the strains examined, whereas no other known MLSB resistance genes were identified. The erm(B) regulator region (RR) containing a coding region of the leader peptide was classified into 13 genetic variations (L1-L3, M, S1-S7, D, and R genotypes) in 56 strains. However, no relatedness was identified between the erm(B) RR genotype and EM resistance, or reduced susceptibility to Q/D, although most of Q/D-intermediate strains were assigned to the L1, L2, and S1 genotypes. Q/D-intermediate strains were classified into five multiple-locus variable-number tandem-repeat analysis (MLVA) types, including four types of clonal complex (CC)-C1, five sequence types (STs), including four STs of CC-17, and several resistance gene/virulence factor profiles. The present study revealed the occurrence of Q/D-intermediate E. faecium, which are composed of heterogeneous strains in Japan, and more genetic diversity in the erm(B) RRs than those reported previously.

  3. Biofilm inhibition of linezolid-like Schiff bases: synthesis, biological activity, molecular docking and in silico ADME prediction.

    Science.gov (United States)

    Sangshetti, Jaiprakash N; Khan, Firoz A Kalam; Patil, Rajendra H; Marathe, Sayali D; Gade, Wasudev N; Shinde, Devanand B

    2015-02-15

    Herein, we report the synthesis and screening of linezolid-like Schiff bases as inhibitors of biofilm formation. The result of biofilm inhibition of Pseudomonas aeruginosa suggested that compounds 5h (IC50 value=12.97±0.33μM) and 5i (IC50 value=15.63±0.20μM) had more inhibitory activity when compared with standard linezolid (IC50=15.93±0.18μM) without affecting the growth of cells (and thus behave as anti-quorum sensing agents). The compounds 5h (MIC range=2.5-10μg/mL) and 5i (MIC range=3.5-10μg/mL) with 2-chloroquinolinyl and 2-chloro-8-methylquinolinyl motif, respectively, showed antibacterial activity in comparable range of linezolid (MIC range=2-3μg/mL) and were more potent when compared with ciprofloxacin (MIC range=25-50μg/mL). Thus, the active derivatives were not only potent inhibitors of P. aeruginosa biofilm growth but also efficient antibacterial agents. The docking study of most active compounds 5h and 5i against PqsD enzyme of P. aeruginosa exhibited good binding properties. In silico ADME properties of synthesized compounds were also analyzed and showed potential to develop as good oral drug candidates.

  4. Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of cavitary pulmonary tuberculosis: preparation and in vitro characterization

    Directory of Open Access Journals (Sweden)

    Huang J

    2017-03-01

    Full Text Available Jieyun Huang,1,* Zhi Chen,2,* Ying Li,3 Li Li,2 Guangyu Zhang2 1The Second Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Institute for Tuberculosis Research, The 309th Hospital of Chinese PLA, Beijing, People’s Republic of China; 3Department of Drug Delivery Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: In this study, we aimed to design controlled-release microspheres for the treatment of cavitary pulmonary tuberculosis (TB for solving the issues of poor drug delivery and short duration maintained at effective drug concentration during bronchoscopic interventional therapy. We fabricated rifapentine-linezolid-loaded poly(lactic acid-co-glycolic acid microspheres (RLPMs using the oil-in-water emulsion solvent evaporation method and assessed their in vitro release as well as the bronchial mucosal retention characteristics. The microspheres are spherical in shape with a circular concave on the surface. The particle size of RLPMs was 27.38±1.28 µm. The drug loading of rifapentine and linezolid was 18.51±0.26 and 8.42%±0.24%, respectively, while the encapsulation efficiencies were 55.53±0.78 and 16.87%±0.47%, respectively (n=3. During the burst release phase of the in vitro release test, 21.37%±0.68% rifapentine was released in 3 days and 43.56%±2.54% linezolid was released in 1 day. Then, both the drugs entered the sustained release phase. Finally, the cumulative percentage release of rifapentine and linezolid in 14 days was 27.61±1.52 and 51.01%±3.31%, respectively (n=3. Bronchoscopic observation revealed that the controlled-release microspheres could slowly release the drugs and retain them on the surface of bronchial mucosa of canines for 20 days. These results indicated that the fabricated microspheres exhibited

  5. Cost-effectiveness of linezolid versus vancomycin in mechanical ventilation-associated nosocomial pneumonia caused by methicillin-resistant staphylococcus aureus

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    Adão R. L. Machado

    Full Text Available Linezolid, an oxazolidinone-class antimicrobial agent, is a new drug; its use has frequently been questioned due to its high price. However, recent trials have demonstrated that the use of linezolid in mechanical ventilation-associated nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (VAP-MRSA may be justified due to its improved efficacy compared to vancomycin. Price and cost have different magnitudes, and clinical efficacy should always be considered in the decision-making process. Our objective was to determine whether linezolid treatment was more cost-effective than vancomycin for treating VAP-MRSA. METHODOLOGY: Elaboration of an economic model from a metanalysis of previous clinical trials comparing both drugs, through a cost-effectiveness analysis. Costs of the treatments were calculated using Brazilian parameters and were compared to the results obtained in the metanalysis. In order to compare the results with real life conditions, costs were calculated for both name brand and for generic vancomycin. RESULTS: The cost (May/2004 per unit (vial, ampoule or bag was R$ 47.73 for the name-brand vancomycin, R$ 14.45 for generic vancomycin and R$ 214.04 for linezolid. Linezolid's efficacy in VAP-MRSA according to the metanalysis was 62.2% and vancomycin's efficacy was 21.2%. The total cost per cured patient was R$ 13,231.65 for the name-brand vancomycin, R$ 11,277.59 for generic vancomycin and R$ 7,764.72 for linezolid. CONCLUSION: Despite the higher price per unit, linezolid was more cost-effective than vancomycin.

  6. Prevalence and Antimicrobial Susceptibility of Enterococcus Species Isolated from Different Clinical Samples in a Tertiary Care Hospital of North India

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    Preeti Srivastava

    2013-08-01

    Result: Among the 100 isolates of Enterococcus from various clinical samples maximum isolates were from urine sample 70% and E. faecalis 92% constituted the predominant isolate. They were found to be susceptible to linezolid and vancomycin with least sensitive to ciprofloxacin and tetracycline. Conclusion: Routine speciation and in vitro antimicrobial susceptibility testing of Enterococcus in various clinical samples is emphasized due to the prevalence of wide variety of Enterococcus species and also appearance of high resistant strains. [Natl J Med Res 2013; 3(4.000: 389-391

  7. Economic impact and formulary positioning of linezolid: a new anti-Gram-positive antimicrobial.

    Science.gov (United States)

    Nathwani, D

    2001-12-01

    Gram-positive bacteria have emerged as major causes of colonization and serious infection within the nosocomial and increasingly also within the community setting. These infections have significantly contributed to patient morbidity and mortality as well as prolongation of hospital stay, a key determinant of the cost of an episode of infection in hospital. In many countries globally, infections due to methicillin-resistant Staphylococcus aureus (MRSA) are providing the greatest burden of clinical infection, often occurring in vulnerable patients or "high risk" therapeutic settings. Combined with this scenario is the increasing requirement for health care organizations to provide cost-effective health care as well as care that is delivered on evidence-based practice delivered through formularies or guidelines. This article aims to: 1) summarize the key economic considerations pertinent to these multiresistant infections but with an emphasis on MRSA, 2) discuss the current therapeutic options of managing MRSA infections, and 3) discuss the formulary positioning of linezolid by means of outlining its core strengths, weaknesses and the opportunity it provides to hospital infection management.

  8. Pharmacokinetics and relative bioavailability evaluation of linezolid suspension and tablet formulations.

    Science.gov (United States)

    Helmy, S A

    2013-09-01

    The oral liquid formulations poses an alternative way in providing medications to pediatric patients, geriatric patients, patients with feeding tubes, and patients who cannot swallow solid dosage forms. This study was conducted to evaluate the pharmacokinetics (PKs) and relative bioavailability of suspension (reference) and tablet (test) formulations of Linezolid (LZD). In vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2 Way, Cross-Over Study with a washout period of 1-week. Under fasting conditions, 28 healthy Egyptian male volunteers were randomly allocated to receive a single oral dose of either 30 ml LZD or 1 tablet (600 mg LZD) of marketed suspension and tablet formulations. Plasma samples were obtained over a 48-h interval and analyzed for LZD by reversed phase liquid chromatography with ultraviolet detection. The 90% confidence intervals for the ratio of log transformed values of Cmax, AUC0-t, and AUCt-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, in this small study in healthy Egyptian adult male volunteers, a single 600 mg dose of the tablet formulation demonstrated comparable rate and extent of absorption to a single 600 mg dose of the suspension formulation based on the US FDA's regulatory definition. No adverse events occurred or were reported after a single 600 mg LZD and both formulations were well tolerated.

  9. Can counter-advertising reduce pre-adolescent children's susceptibility to front-of-package promotions on unhealthy foods? Experimental research.

    Science.gov (United States)

    Dixon, Helen; Scully, Maree; Kelly, Bridget; Chapman, Kathy; Wakefield, Melanie

    2014-09-01

    This study aimed to test whether counter-advertisements (i.e. messages contesting industry marketing) make pre-adolescent children less susceptible to the influence of food promotions. Since children have lower media literacy levels due to their immature cognitive abilities, specific research questions explored were: (1) whether the effectiveness of counter-ads is contingent on children having understood them; and (2) whether counter-ads may be detrimental when they are misinterpreted. A between-subjects experimental design using a web-based methodology was employed. 1351 grade 5-6 students (mean age 11 years) from schools located in metropolitan Melbourne, Australia participated. Participants were randomly shown an animated web banner advertisement (counter-ad challenging front-of-package promotion or control ad) and a pair of food packages from the same product category comprising an unhealthy product featuring a front-of-package promotion (nutrient content claim or sports celebrity endorsement) and a healthier control pack without a front-of-package promotion. Responses to the assigned advertisement, choice of product (healthy versus unhealthy) and ratings of the unhealthy product and front-of-package promotion on various nutritional and image-related attributes were recorded for each child. Sixty-six percent of children who viewed a counter-ad understood its main message. These children rated the front-of-package promotion as less believable and rated the unhealthy product bearing the front-of-package promotion as less healthy compared to the control group. However, children who misunderstood the counter-ad rated the unhealthy product bearing a front-of-package promotion as more healthy and rated the front-of-package promotion more favourably than those who correctly understood the counter-ad. Counter-advertising may have unintended consequences when misunderstood. If public health organizations or government pursue counter-advertising as a strategy to reduce

  10. Beijing genotype of Mycobacterium tuberculosis is significantly associated with linezolid resistance in multidrug-resistant and extensively drug-resistant tuberculosis in China.

    Science.gov (United States)

    Zhang, Zhijian; Pang, Yu; Wang, Yufeng; Liu, Changting; Zhao, Yanlin

    2014-03-01

    Linezolid (LNZ) is a promising antimicrobial agent for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). To investigate the efficacy of LNZ among MDR-TB and XDR-TB in China, the LNZ susceptibility of 158 MDR-TB isolates from the national drug resistance survey was determined by the minimum inhibitory concentration method. The 158 MDR-TB isolates were also sequenced in the 23S rRNA, rplC and rplD genes conferring LNZ resistance and were typed using spoligotyping to identify the Beijing genotype of Mycobacterium tuberculosis. Overall, the prevalence of LNZ-resistant isolates was 10.8% (17/158) among MDR-TB isolates circulating in China. Beijing genotype was significantly associated with LNZ resistance in MDR-TB and XDR-TB (odds ratio=4.66, 95% confidence interval 1.03-21.16; P=0.033). In addition, a higher frequency of LNZ-resistant isolates was observed among XDR-TB strains (60%) compared with the MDR (5.6%; PMutations in 23S rRNA and rplC were responsible for only 29.4% of LNZ-resistant M. tuberculosis among MDR-TB isolates, and a novel non-synonymous substitution His155Asp in rplC was first identified to be contributing to low-level LNZ resistance (2μg/mL) in M. tuberculosis. The unsatisfactory correlation between mutant genotypes highlights the urgent need to investigate another mechanism for LNZ resistance that has not yet been described.

  11. Brown dog tick, Rhipicephalus sanguineus sensu lato, infestation ofsusceptible dog hosts is reduced by slow release of semiochemicalsfrom a less susceptible host

    Science.gov (United States)

    Domestic dog breeds are hosts for the tick Rhipicephalus sanguineus sensu lato, but infestation levels vary among breeds. Beagles are less susceptible to tick infestations than English cocker spaniels due to enhanced production of 2-hexanone and benzaldehyde that act as tick repellents. We report th...

  12. Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis

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    Taeksun Song

    2015-11-01

    Full Text Available Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs. Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3·10, 95% CI 1·23–7 · 86. Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0·004 or 600 mg (P 2 μg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use.

  13. Prosystemin overexpression induces transcriptional modifications of defense-related and receptor-like kinase genes and reduces the susceptibility to Cucumber mosaic virus and its satellite RNAs in transgenic tomato plants

    Science.gov (United States)

    Bubici, Giovanni; Carluccio, Anna Vittoria; Stavolone, Livia

    2017-01-01

    Systemin is a plant signal peptide hormone involved in the responses to wounding and insect damage in the Solanaceae family. It works in the same signaling pathway of jasmonic acid (JA) and enhances the expression of proteinase inhibitors. With the aim of studying a role for systemin in plant antiviral responses, a tomato (Solanum lycopersicum) transgenic line overexpressing the prosystemin cDNA, i.e. the systemin precursor, was inoculated with Cucumber mosaic virus (CMV) strain Fny supporting either a necrogenic or a non-necrogenic satellite RNA (satRNA) variant. Transgenic plants showed reduced susceptibility to both CMV/satRNA combinations. While symptoms of the non-necrogenic inoculum were completely suppressed, a delayed onset of lethal disease occurred in about half of plants challenged with the necrogenic inoculum. RT-qPCR analysis showed a correlation between the systemin-mediated reduced susceptibility and the JA biosynthetic and signaling pathways (e.g. transcriptional alteration of lipoxygenase D and proteinase inhibitor II). Moreover, transgenically overexpressed systemin modulated the expression of a selected set of receptor-like protein kinase (RLK) genes, including some playing a known role in plant innate immunity. A significant correlation was found between the expression profiles of some RLKs and the systemin-mediated reduced susceptibility to CMV/satRNA. These results show that systemin can increase plant defenses against CMV/satRNA through transcriptional reprogramming of diverse signaling pathways. PMID:28182745

  14. Reduced susceptibility effects in perfusion fMRI with single-shot spin-echo EPI acquisitions at 1.5 Tesla.

    Science.gov (United States)

    Wang, Jiongjiong; Li, Lin; Roc, Anne C; Alsop, David C; Tang, Kathy; Butler, Norman S; Schnall, Mitchell D; Detre, John A

    2004-01-01

    Arterial spin labeling (ASL) perfusion contrast is not based on susceptibility effects and can therefore be used to study brain function in regions of high static inhomogeneity. As a proof of concept, single-shot spin-echo echo-planar imaging (EPI) acquisition was carried out with a multislice continuous ASL (CASL) method at 1.5T. A bilateral finger tapping paradigm was used in the presence of an exogenously induced susceptibility artifact over left motor cortex. The spin-echo CASL technique was compared with a regular gradient-echo EPI sequence with the same slice thickness, as well as other imaging methods using thin slices and spin-echo acquisitions. The results demonstrate improved functional sensitivity and efficiency of the spin-echo CASL approach as compared with gradient-echo EPI techniques, and a trend of improved sensitivity as compared with spin-echo EPI approach in the brain regions affected by the susceptibility artifact. ASL images, either with or without subtraction of the control, provide a robust alternative to blood oxygenation level dependant (BOLD) methods for activation imaging in regions of high static field inhomogeneity.

  15. Comparing the cost-effectiveness of linezolid to trimethoprim/sulfamethoxazole plus rifampicin for the treatment of methicillin-resistant Staphylococcus aureus infection: a healthcare system perspective.

    Science.gov (United States)

    von Dach, E; Morel, C M; Murthy, A; Pagani, L; Macedo-Vinas, M; Olearo, F; Harbarth, S

    2017-09-01

    Few industry-independent studies have been conducted to compare the relative costs and benefits of drugs to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. We performed a stochastic cost-effectiveness analysis comparing two treatment strategies-linezolid versus trimethoprim-sulfamethoxazole plus rifampicin-for the treatment of MRSA infection. We used cost and effectiveness data from a previously conducted clinical trial, complementing with other data from published literature, to compare the two regimens from a healthcare system perspective. Effectiveness was expressed in terms of quality-adjusted life-years (QALYs). Several sensitivity analyses were performed using Monte Carlo simulation, to measure the effect of potential parameter changes on the base-case model results, including potential differences related to type of infection and drug toxicity. Treatment of MRSA infection with trimethoprim-sulfamethoxazole plus rifampicin and linezolid were found to cost on average €146 and €2536, and lead to a gain of 0.916 and 0.881 QALYs, respectively. Treatment with trimethoprim-sulfamethoxazole plus rifampicin was found to be more cost-effective than linezolid in the base case and remained dominant over linezolid in most alternative scenarios, including different types of MRSA infection and potential disadvantages in terms of toxicity. With a willingness-to-pay threshold of €0, €50 000 and €200 000 per QALY gained, trimethoprim-sulfamethoxazole plus rifampicin was dominant in 100%, 96% and 85% of model iterations. A 95% discount on the current purchasing price of linezolid would be needed when it goes off-patent for it to represent better value for money compared with trimethoprim-sulfamethoxazole plus rifampicin. Combined treatment of trimethoprim-sulfamethoxazole plus rifampicin is more cost-effective than linezolid in the treatment of MRSA infection. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus treated with linezolid or vancomycin: A secondary economic analysis of resource use from a Spanish perspective.

    Science.gov (United States)

    Rello, J; Nieto, M; Solé-Violán, J; Wan, Y; Gao, X; Solem, C T; De Salas-Cansado, M; Mesa, F; Charbonneau, C; Chastre, J

    2016-11-01

    Adopting a unique Spanish perspective, this study aims to assess healthcare resource utilization (HCRU) and the costs of treating nosocomial pneumonia (NP) produced by methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized adults using linezolid or vancomycin. An evaluation is also made of the renal failure rate and related economic outcomes between study groups. An economic post hoc evaluation of a randomized, double-blind, multicenter phase 4 study was carried out. Nosocomial pneumonia due to MRSA in hospitalized adults. The modified intent to treat (mITT) population comprised 224 linezolid- and 224 vancomycin-treated patients. Costs and HCRU were evaluated between patients administered either linezolid or vancomycin, and between patients who developed renal failure and those who did not. Analysis of HCRU outcomes and costs. Total costs were similar between the linezolid- (€17,782±€9,615) and vancomycin-treated patients (€17,423±€9,460) (P=.69). The renal failure rate was significantly lower in the linezolid-treated patients (4% vs. 15%; P<.001). The total costs tended to be higher in patients who developed renal failure (€19,626±€10,840 vs. €17,388±€9,369; P=.14). Among the patients who developed renal failure, HCRU (days on mechanical ventilation: 13.2±10.7 vs. 7.6±3.6 days; P=.21; ICU stay: 14.4±10.5 vs. 9.9±6.6 days; P=.30; hospital stay: 19.5±9.5 vs. 16.1±11.0 days; P=.26) and cost (€17,219±€8,792 vs. €20,263±€11,350; P=.51) tended to be lower in the linezolid- vs. vancomycin-treated patients. There were no statistically significant differences in costs per patient-day between cohorts after correcting for mortality (€1000 vs. €1,010; P=.98). From a Spanish perspective, there were no statistically significant differences in total costs between the linezolid and vancomycin pneumonia cohorts. The drug cost corresponding to linezolid was partially offset by fewer renal failure adverse events. Copyright © 2016

  17. Linezolid-associated thrombocytopenia: prevention and treatment%利奈唑胺致血小板减少及其防治

    Institute of Scientific and Technical Information of China (English)

    王博雅; 闫素英

    2011-01-01

    Linezolid is an oxazolidinone antibacterial used for the treatment of Gram-positive infection of the respiratory tract and skin, including those due to vancomycin resistant enterocooci. The common adverse reactions are diarrhea, nausea, vomiting, headache, and rash. Linezolid may cause thrombocytopenia, and the risk factors for thrombocytopenia are prolonged use of linezolid, advanced age, and renal insufficiency. The mechanism of thrombocytopenia induced by linezolid might be linked to bone marrow suppression or immune-mediated platelet decrease. The measures for prevention and treatment of thrombocytopenia are as follows: high-dose and prolonged use of linezolid should be avoided; platelet count should be closely monitored during linezolid therapy; linezolid combined with drugs that produce bone marrow suppression should be avoided; linezolid therapy should be discontinued in patients who developed thrombocytopenia, and transfusion of platelets should be considered in patients having severe thrombocytopenia.%利奈唑胺为恶唑烷酮类抗生素,主要用于革兰阳性细菌引起的呼吸道和皮肤感染以及耐万古霉素肠球菌引起的感染.利奈唑胺的常见不良反应为腹泻、恶心、呕吐、头痛、皮疹等.利奈唑胺可致血小板减少,其危险因素为长时间治疗、高龄以及肾功能不全.利奈唑胺所致血小板减少的机制可能与骨髓抑制或免疫介导致血小板减少有关.防治血小板减少的措施:避免大剂量和长时间应用利奈唑胺;用药期间严密监测血小板水平;避免将利奈唑胺与抑制骨髓的药物联用;患者出现血小板减少应立即停药,严重患者可考虑输注血小板.

  18. Loading of atorvastatin and linezolid in β-cyclodextrin–conjugated cadmium selenide/silica nanoparticles: A spectroscopic study

    Energy Technology Data Exchange (ETDEWEB)

    Antony, Eva Janet; Shibu, Abhishek [Department of Nanosciences & Technology, Karunya University, Coimbatore 641114, Tamil Nadu (India); Ramasamy, Sivaraj; Paulraj, Mosae Selvakumar [Department of Chemistry, Karunya University, Coimbatore 641114, Tamil Nadu (India); Enoch, Israel V.M.V., E-mail: drisraelenoch@gmail.com [Department of Nanosciences & Technology, Karunya University, Coimbatore 641114, Tamil Nadu (India); Department of Chemistry, Karunya University, Coimbatore 641114, Tamil Nadu (India)

    2016-08-01

    The preparation of β–cyclodextrin–conjugated cadmium selenide–silica nanoparticles, the loading of two drugs viz., Atorvastatin and linezolid in the cyclodextrin cavity, and the fluorescence energy transfer between CdSe/SiO{sub 2} nanoparticles and the drugs encapsulated in the cyclodextrin cavity are reported in this paper. IR spectroscopy, X-ray diffractometry, transmission electron microscopy, and particle size analysis by light–scattering experiment were used as the tools of characterizing the size and the crystal system of the nanoparticles. The nanoparticles fall under hexagonal system. The silica–shell containing CdSe nanoparticles were functionalized by reaction with aminoethylamino–β–cyclodextrin. Fluorescence spectra of the nanoparticles in their free and drug–encapsulated forms were studied. The FÖrster distances between the encapsulated drugs and the CdSe nanoparticles are below 3 nm. The change in the FÖrster resonance energy parameters under physiological conditions may aid in tracking the release of drugs from the cavity of the cyclodextrin. - Highlights: • CdSe/SiO{sub 2} nanoparticles of crystallite size 15 nm are prepared. • β-Cyclodextrin is attached to the surface of the nanoparticles. • Atorvastatin and linezolid get encapsulated in the cyclodextrin cavity. • FRET efficiency between the nanoparticles and the loaded drugs are determined.

  19. Linezolid pharmacokinetics/pharmacodynamics and the development of dosage regimen design optimization%利奈唑胺的PK/PD与给药方案优化设计研究进展

    Institute of Scientific and Technical Information of China (English)

    金砚杰; 张晶; 卢克鹏; 刘倩; 林立敏; 宋洪涛

    2014-01-01

    To provide reference for clinical reasonable application by introducing linezolid pharmacokinetics and pharmacodynamics characteristics in different diseases.The data from CNKI,PUBMED were analyzed.On the basis of PK/PD parameters,the dosage regimen was optimized,which could better improve the curative effect of antimicrobial drugs,and reduce the incidence of adverse reactions,drug resistance and the patients' economic burden.Linezolid had strong antibacterial effect against gram-positive bacteria.It is meaningful to study on the optimum dosage regimen and promote the rational drug use due to the different pathological physiological factors instead of PK/PD characteristics.%通过CNKI、PUBMED等文献库查阅相关文献进行分析,介绍利奈唑胺在不同疾病中PK/PD特点,从而为临床合理应用提供参考.以PK/PD参数为依据,对给药方案进行优化,可以更好地发挥抗菌药物的临床治疗效果,降低不良反应和耐药性的发生率,减轻患者经济负担.利奈唑胺具有强大的抗革兰阳性菌活性,由于不同病理生理因素与其PK/PD特点,研究优化给药方案、促进合理用药具有重大意义.

  20. Antimicrobial Susceptibility of Bloodstream Isolates of Staphylococcus aureus: Global Results from the Tigecycline Evaluation and Surveillance Trial, 2004-2008

    Directory of Open Access Journals (Sweden)

    Daniel Amsterdam

    2010-01-01

    Full Text Available Problem statement: The Tigecycline Evaluation and Surveillance Trial (TEST commenced in 2004 to monitor the activity of tigecycline, a new glycylcycline and numerous comparators against major hospital-and community-associated pathogens. In this report we examine the efficacy of tigecycline and comparators against isolates of Staphylococcus aureus collected from blood. Approach: Almost 4000 blood-derived isolates of Staphylococcus aureus were collected from participating centers globally between 2004-2008. Results: All isolates were susceptible to tigecycline (MIC90 0.25 mg L-1 and linezolid (MIC90 4 mg L-1; 99.9% of isolates were susceptible to vancomycin (MIC90 1 mg L-1. Tigecycline and linezolid activity were unaffected by resistance to methicillin, ICU vs non-ICU isolate collection or the age of patients from which the isolates were collected. Although 95.3% of MSSA were levofloxacin susceptible, only 14.4% of MRSA isolates were susceptible to levofloxacin in this study. Conclusion: Tigecycline is shown here to be active against S. aureus isolates collected from blood and is unaffected by methicillin resistance. However, tigecycline is not as yet approved for the treatment of bacteremic infections.

  1. High Susceptibility to Cry1Ac and Low Resistance Allele Frequency Reduce the Risk of Resistance of Helicoverpa armigera to Bt Soybean in Brazil

    Science.gov (United States)

    Bacalhau, Fabiana B.; Amado, Douglas; Carvalho, Renato A.; Martinelli, Samuel; Head, Graham P.; Omoto, Celso

    2016-01-01

    The Old World bollworm, Helicoverpa armigera (Hübner), was recently introduced into Brazil, where it has caused extensive damage to cotton and soybean crops. MON 87701 × MON 89788 soybean, which expresses the Bt protein Cry1Ac, was recently deployed in Brazil, providing high levels of control against H. armigera. To assess the risk of resistance to the Cry1Ac protein expressed by MON 87701 × MON 89788 soybean in Brazil, we conducted studies to evaluate the baseline susceptibility of H. armigera to Cry1Ac, in planta efficacy including the assessment of the high-dose criterion, and the initial resistance allele frequency based on an F2 screen. The mean Cry1Ac lethal concentration (LC50) ranged from 0.11 to 1.82 μg·mL−1 of diet among all H. armigera field populations collected from crop seasons 2013/14 to 2014/15, which indicated about 16.5-fold variation. MON 87701 × MON 89788 soybean exhibited a high level of efficacy against H. armigera and most likely met the high dose criterion against this target species in leaf tissue dilution bioassays up to 50 times. A total of 212 F2 family lines of H. armigera were established from field collections sampled from seven locations across Brazil and were screened for the presence of MON 87701 × MON 89788 soybean resistance alleles. None of the 212 families survived on MON 87701 × MON 89788 soybean leaf tissue (estimated allele frequency = 0.0011). The responses of H. armigera to Cry1Ac protein, high susceptibility to MON 87701 × MON 89788 soybean, and low frequency of resistance alleles across the main soybean-producing regions support the assumptions of a high-dose/refuge strategy. However, maintenance of reasonable compliance with the refuge recommendation will be essential to delay the evolution of resistance in H. armigera to MON 87701 × MON 89788 soybean in Brazil. PMID:27532632

  2. Molecular characterization and antimicrobial susceptibility of nasal Staphylococcus aureus isolates from a Chinese medical college campus.

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    Jimei Du

    Full Text Available Staphylococcus aureus colonization and infection occur more commonly among persons living or working in crowded conditions, but characterization of S. aureus colonization within medical communities in China is lacking. A total of 144 (15.4%, 144/935 S. aureus isolates, including 28 (3.0%, 28/935 MRSA isolates, were recovered from the nares of 935 healthy human volunteers residing on a Chinese medical college campus. All S. aureus isolates were susceptible to vancomycin, quinupristin/dalfopristin and linezolid but the majority were resistant to penicillin (96.5%, ampicillin/sulbactam (83.3% and trimethoprim/sulfamethoxazole (93.1%. 82%, (23/28 of the MRSA isolates and 66% (77/116 of the MSSA isolates were resistant to multiple antibiotics, and 3 MRSA isolates were resistant to mupirocin--an agent commonly used for nasal decolonization. 16 different sequence types (STs, as well as SCCmec genes II, III, IVd, and V, were represented among MRSA isolates. We also identified, for the first time, two novel STs (ST1778 and ST1779 and 5 novel spa types for MRSA. MRSA isolates were distributed in different sporadic clones, and ST59-MRSA-VId- t437 was found within 3 MRSA isolates. Moreover, one isolate with multidrug resistance belonging to ST398-MRSA-V- t571 associated with animal infections was identified, and 3 isolates distributed in three different clones harbored PVL genes. Collectively, these data indicate a high prevalence of nasal MRSA carriage and molecular heterogeneity of S. aureus isolates among persons residing on a Chinese medical college campus. Identification of epidemic MRSA clones associated with community infection supports the need for more effective infection control measures to reduce nasal carriage and prevent dissemination of MRSA to hospitalized patients and health care workers in this community.

  3. Successful Treatment of Disseminated Bacillus Calmette-Guérin Disease in an HIV-Infected Child with a Linezolid-Containing Regimen

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    Srđan Roglić

    2016-01-01

    Full Text Available Upon HIV infection diagnosis, an 8-month-old boy was transferred for evaluation of worsening respiratory distress requiring mechanical ventilation. Pneumocystis jirovecii pneumonia (PCP was diagnosed; the boy also had a nonhealing ulcer at the site of vaccination with Statens Serum Institut (Danish strain Bacillus Calmette-Guérin (BCG vaccine and associated axillary lymphadenopathy. PCP treatment resulted in weaning from mechanical ventilation. Antimycobacterial treatment was immediately attempted but was discontinued because of hepatotoxicity. Over several months, he developed splenic lesions and then disseminated skin and cystic bone lesions. M. bovis was repeatedly cultured from both skin and bone lesions despite various multidrug antimycobacterial regimens which included linezolid. Eventually, treatment with a regimen of rifabutin, isoniazid, ethambutol, and linezolid led to definitive cure. Clinicians should consider a linezolid-containing regimen for treatment of severe disseminated BCG infection, especially if other drug regimens have failed. Although drug toxicity is a particular concern for young children, this patient received linezolid for 13 months without serious toxicity. This case also highlights the need for universal screening among pregnant women to prevent vertical transmission of HIV. Finally, routine immunization with BCG vaccine at birth should be questioned in countries with low and declining burden of tuberculosis.

  4. Mutations in 23S rRNA at the Peptidyl Transferase Center and Their Relationship to Linezolid Binding and Cross-Resistance

    DEFF Research Database (Denmark)

    Long, Katherine; Munck, Christian

    2010-01-01

    The oxazolidinone antibiotic linezolid targets the peptidyl transferase center (PTC) on the bacterial ribosome. Thirteen single and four double 23S rRNA mutations were introduced into a Mycobacterium smegmatis strain with a single rRNA operon. Converting bacterial base identity by single mutations...

  5. Comparison of the Pharmacokinetics of Two Dosage Regimens of Linezolid in Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis Patients

    NARCIS (Netherlands)

    Alffenaar, Jan-Willem C.; van Altena, Richard; Harmelink, Ilse M.; Filguera, Patricia; Molenaar, Esther; Wessels, A. Mireille A.; van Soolingen, Dick; Kosterink, Jos G. W.; Uges, Donald R. A.; van der Werf, Tjip S.

    2010-01-01

    Background and Objectives: For the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), potent new drugs are urgently needed. Linezolid is a promising drug, but its use is limited by adverse effects with prolonged administration of 600 mg twice daily. In

  6. Effects of linezolid in the treatment of patients with tuberculous meningitis%利奈唑胺治疗结核性脑膜炎临床疗效

    Institute of Scientific and Technical Information of China (English)

    吴彪; 符娟; 符健; 贾杰

    2012-01-01

    OBJECTIVE To investigate the efficacy of linezolid against tuberculous meningitis infection. METHODS Carried on case-series report and systematic review about linezolid for the treatment of patients with tuberculous meningitis. RESULTS Three patients with tuberculous meningitis were treated by conventional anti—tuberculous treatment and use of linezolid, 600mg intravenous drip bid. The clinical symptoms, including headache, high fever, etc, were all relieved. Abnormality of cere-brospinal fluid was improved.The CT/MRI scan of two cases showed the shadow in the lung and brain obviously absorbed after treatment. CONCLUSION Linezolid has the efficacy against tuberculosis. Linezolid has very good penetration ability in CSF, it can be used in the treatment of tuberculous meningitis.%目的 介绍利奈唑胺(曝唑烷酮类抗菌药)治疗结核性脑膜炎的临床疗效.方法 观察利奈唑胺治疗3例结核性脑膜炎的临床疗效,并系统性对相关文献进行综述.结果 3例临床诊断结核性脑膜炎患者,在接受常规抗结核药物治疗基础上加用利奈唑胺600 mg,每日2次静脉滴注,头痛、发热等症状均在短期内缓解,脑脊液得到改善,2例合并肺部及颅脑内结核者病灶明显吸收.结论 利奈唑胺具有抗结核作用,具有良好的脑脊液的穿透率,可用子治疗结核性脑膜炎.

  7. Influence of oviposition preference in reduced susceptibility of Ottawa Valley white spruce (picea glauce) to spruce budmoth (zeiraphera canadensis) in New Brunswick: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Quiring, D.T.; Butterworth, E.W.

    1995-12-31

    In New Brunswick, efforts to control populations of spruce budmoth by spraying adults with insecticides or pheromones have produced encouraging results. An alternative technique, the selection of less-susceptible spruce, would aid in the development of an integrated management program for this insect pest. Differences in spruce damage as revealed in previous studies could be due to oviposition choice and/or to host suitability. However, researchers must determine the distribution of eggs laid by the spruce budmoth before they can determine whether some families of spruce have low levels of damage because they are avoided by ovipositing females and/or because they are less suitable for egg and larval development. This report presents results from studies carried out to quantify the number of eggs laid on trees from different families. Investigators collected tree branch samples from plantations and a seed orchard in May, before bud burst or egg hatching commenced. They analysed variations in oviposition parameters (such as number of eggs and egg masses, number of eggs parasitized by Trichogramma minutum, and number of viable eggs) using analysis of variance. To determine whether differences in egg density were related to plant morphology, they also measured such parameters as shoot length and diameter, needle length, shot type, and needle density.

  8. Reduced susceptibility to eccentric exercise-induced muscle damage in resistance-trained men is not linked to resistance training-related neural adaptations

    Science.gov (United States)

    Beck, TW; Wages, NP

    2015-01-01

    The purpose of this study was to examine the acute effects of maximal concentric vs. eccentric exercise on the isometric strength of the elbow flexor, as well as the biceps brachii muscle electromyographic (EMG) responses in resistance-trained (RT) vs. untrained (UT) men. Thirteen RT men (age: 24 ± 4 years; height: 180.2 ± 7.7 cm; body weight: 92.2 ± 16.9 kg) and twelve UT men (age: 23 ± 4 years; height: 179.2 ± 5.0 cm; body weight: 81.5 ± 8.6 kg) performed six sets of ten maximal concentric isokinetic (CON) or eccentric isokinetic (ECC) elbow flexion exercise in two separate visits. Before and after the exercise interventions, maximal voluntary contractions (MVCs) were performed for testing isometric strength. In addition, bipolar surface EMG signals were detected from the biceps brachii muscle during the strength testing. Both CON and ECC caused isometric strength to decrease, regardless of the training status. However, ECC caused greater isometric strength decline than CON did for the UT group (p = 0.006), but not for the RT group. Both EMG amplitude and mean frequency significantly decreased and increased, respectively, regardless of the training status and exercise intervention. Resistance-trained men are less susceptible to eccentric exercise-induced muscle damage, but this advantage is not likely linked to the chronic resistance training-induced neural adaptations. PMID:26424922

  9. I223R mutation in influenza A(H1N1pdm09 neuraminidase confers reduced susceptibility to oseltamivir and zanamivir and enhanced resistance with H275Y.

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    Jérome LeGoff

    Full Text Available BACKGROUND: Resistance of pandemic A(H1N12009 (H1N1pdm09 virus to neuraminidase inhibitors (NAIs has remained limited. A new mutation I223R in the neuraminidase (NA of H1N1pdm09 virus has been reported along with H275Y in immunocompromised patients. The aim of this study was to determine the impact of I223R on oseltamivir and zanamivir susceptibility. METHODS: The NA enzymatic characteristics and susceptibility to NAIs of viruses harbouring the mutations I223R and H275Y alone or in combination were analyzed on viruses produced by reverse genetics and on clinical isolates collected from an immunocompromised patient with sustained influenza H1N1pdm09 virus shedding and treated by oseltamivir (days 0-15 and zanamivir (days 15-25 and 70-80. RESULTS: Compared with the wild type, the NA of recombinant viruses and clinical isolates with H275Y or I223R mutations had about two-fold reduced affinity for the substrate. The H275Y and I223R isolates showed decreased susceptibility to oseltamivir (246-fold and oseltamivir and zanamivir (8.9- and 4.9-fold, respectively. Reverse genetics assays confirmed these results and further showed that the double mutation H275Y and I223R conferred enhanced levels of resistance to oseltamivir and zanamivir (6195- and 15.2-fold. In the patient, six days after initiation of oseltamivir therapy, the mutation H275Y conferring oseltamivir resistance and the I223R mutation were detected in the NA. Mutations were detected concomitantly from day 6-69 but molecular cloning did not show any variant harbouring both mutations. Despite cessation of NAI treatment, the mutation I223R persisted along with additional mutations in the NA and the hemagglutinin. CONCLUSIONS: Reduced susceptibility to both oseltamivir and zanamivir was conferred by the I223R mutation which potentiated resistance to both NAIs when associated with the H275Y mutation in the NA. Concomitant emergence of the I223R and H275Y mutations under oseltamivir treatment

  10. Drug Resistance in ICU by Meticillin-resistant Staphylococcus aureus Infection and Effect of Linezolid%耐甲氧西林金黄色葡萄球菌感染的耐药性分析及利奈唑胺治疗效果的研究

    Institute of Scientific and Technical Information of China (English)

    何志捷

    2009-01-01

    OBJECTIVE To explore the drug resistance of the infection caused by meticillin-resistant Staphylococcus aureus (MRSA) in ICU and the effect of linezolid in the treatment on MRSA. METHODS The collection of sputum, blood, urine, cerebrospinal fluid, the top and local drainage of central venous needle in 3 years(2006 to 2009) in ICU was carried out, and the bacteriological culture and drug susceptibility testing were executed. Fifteen cases of MRSA infection patients were treated with linezolid. RESULTS There were 72 cases of MRSA infection in 3 years in ICU,most of them were drug-resistant. The sensitivity for MRSA infection was high to 100% by used with vancomycin, teicoplanin and linezolid. The trend of MRSA infection in ICU had increased in the past 3 years. The efficiency and recovery rates of linezolid group (73.3% and 33.3%, respectively) were higher than the vancomycin group (66.7% and 28.6%, respectively)(P<0.05). CONCLUSIONS The infection rates of MRSA are high in ICU, so we must pay attention to it. Linezolid is an effective drug for MRSA infection, and the adverse reactions were few.%目的 通过对重症监护病房(ICU)耐甲氧西林金黄色葡萄球菌(MRSA)感染的分析,探讨其耐药性;并观察利奈唑胺在MRSA感染中的治疗效果.方法 收集ICU 2006年3月-2009年3月入住ICU患者的痰、血、尿、脑脊液、中心静脉穿刺针顶端及局部引流物进行细菌学培养及药物敏感性试验,其中15例MRSA感染患者应用利奈唑胺治疗.结果 ICU 3年共发生MRSA感染72例,绝大多数为耐药菌;万古霉素、替考拉宁和利奈唑胺对MRSA感染的敏感率高,均为100%,ICU近3年MRSA有逐年升高的趋势,利奈唑胺组的有效率和痊愈率分别为73.3%和33.3%,均高于万古霉素组(66.7%和28.6%)(P<0.05).结论 ICU中MRSA的感染率较高,必须引起重视,利奈唑胺是MRSA感染的有效药物,且不良反应较少.

  11. Transmission of chimeric HIV by mating in conventional mice: prevention by pre-exposure antiretroviral therapy and reduced susceptibility during estrus.

    Science.gov (United States)

    Hadas, Eran; Chao, Wei; He, Hongxia; Saini, Manisha; Daley, Eleen; Saifuddin, Mohammed; Bentsman, Galina; Ganz, Eric; Volsky, David J; Potash, Mary Jane

    2013-09-01

    Heterosexual transmission accounts for the majority of new human immunodeficiency virus (HIV) cases worldwide. The current approach to investigate HIV heterosexual transmission in animals involves application of virus stock to the vaginal surface, a method that does not reproduce the physiological conditions of vaginal intercourse that influence the rate of transmission. We have previously described efficient infection of conventional mice using EcoHIV/NL4-3 and EcoHIV/NDK, chimeric HIV molecular clones constructed to express all HIV structural and regulatory genes except envelope, which is replaced by a rodent-tropic envelope gene. Here we investigated whether EcoHIV/NDK-infected male mice transmit virus to females during coitus, and the sensitivity of this transmission to HIV pre-exposure prophylaxis and the estrus state. Our general approach was to allow mating between EcoHIV/NDK-infected male mice and uninfected females for 1-7 nights. At 1-6 weeks after mating, mice were euthanized and virus burdens were measured by quantitative PCR (qPCR) amplification of HIV RNA or DNA in peritoneal macrophages, inguinal lymph node cells, spleen cells or vas deferens, or by ELISA for antibodies to HIV Gag. We found that 70-100% of female mice mated to EcoHIV/NDK-infected males acquired infection. Pericoital treatment of females with either 2',3'-dideoxcytidine (ddC) or tenofovir largely prevented their EcoHIV/NDK infection by mating (P<0.05 and P<0.003, respectively). In males, T cells were dispensable for virus transmission. The rate of EcoHIV/NDK sexual transmission to females in estrus declined sharply (P=0.003) but their infection by injection was unaffected, indicating that the local environment in the female reproductive tract influences susceptibility to HIV. We conclude that this system of EcoHIV/NDK transmission during mouse mating reproduces key features of heterosexual transmission of HIV in humans and can be used to investigate its biology and control.

  12. Transmission of chimeric HIV by mating in conventional mice: prevention by pre-exposure antiretroviral therapy and reduced susceptibility during estrus

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    Eran Hadas

    2013-09-01

    Heterosexual transmission accounts for the majority of new human immunodeficiency virus (HIV cases worldwide. The current approach to investigate HIV heterosexual transmission in animals involves application of virus stock to the vaginal surface, a method that does not reproduce the physiological conditions of vaginal intercourse that influence the rate of transmission. We have previously described efficient infection of conventional mice using EcoHIV/NL4-3 and EcoHIV/NDK, chimeric HIV molecular clones constructed to express all HIV structural and regulatory genes except envelope, which is replaced by a rodent-tropic envelope gene. Here we investigated whether EcoHIV/NDK-infected male mice transmit virus to females during coitus, and the sensitivity of this transmission to HIV pre-exposure prophylaxis and the estrus state. Our general approach was to allow mating between EcoHIV/NDK-infected male mice and uninfected females for 1–7 nights. At 1–6 weeks after mating, mice were euthanized and virus burdens were measured by quantitative PCR (qPCR amplification of HIV RNA or DNA in peritoneal macrophages, inguinal lymph node cells, spleen cells or vas deferens, or by ELISA for antibodies to HIV Gag. We found that 70–100% of female mice mated to EcoHIV/NDK-infected males acquired infection. Pericoital treatment of females with either 2′,3′-dideoxcytidine (ddC or tenofovir largely prevented their EcoHIV/NDK infection by mating (P<0.05 and P<0.003, respectively. In males, T cells were dispensable for virus transmission. The rate of EcoHIV/NDK sexual transmission to females in estrus declined sharply (P=0.003 but their infection by injection was unaffected, indicating that the local environment in the female reproductive tract influences susceptibility to HIV. We conclude that this system of EcoHIV/NDK transmission during mouse mating reproduces key features of heterosexual transmission of HIV in humans and can be used to investigate its biology and control.

  13. Emergence of linezolid- and vancomycin-resistant Enterococcus faecium in a department for hematologic stem cell transplantation

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    M. Krull

    2016-09-01

    Full Text Available Abstract Background Prevalence of vancomycin-resistant enterococci has increased in Germany. Here, we report the cluster of linezolid- and vancomycin-resistant Enterococcus faecium (LVRE in a German department for hematologic stem cell transplantation (HSCT. Methods In this retrospective analysis we included all patients with LVRE in a university-based department for HSCT in 2014 and 2015. Patients chart reviews were used to investigate the epidemiology and clinical outcome. Available LVRE isolates underwent detailed microbiological characterization and genotyping by pulsed-field gel electrophoresis (PFGE. Results In total, 20 patients with LVRE were identified within the observed time period. All except two patients underwent allogeneic HSCT. Surveillance culture results from incoming patients and chart review revealed that 10 of 20 patients were colonized at hospital admission. Eight of 10 patients with in-hospital acquired LVRE had previous linezolid treatment. Analysis of spatio-temporal patterns showed no evidence for LVRE patient-to-patient or environment-to-patient transmission within the HSCT department. In five cases (25 % LVRE bloodstream infection occurred. Nine LVRE isolates could be saved for characterization. Eight isolates carried vanA, one isolate vanB. PFGE analysis showed that four different LVRE clones were responsible for the cluster. One single genotype was present in six LVRE isolates whereupon the corresponding patients were all referred from the same hospital to the HSCT department. Conclusions This is the first report demonstrating the emergence of LVRE in a German HSCT department. (LVRE screening at patients’ admission and appropriate infection control strategies were sufficient to prevent any transmission. Further studies in this predisposed patient collective are warranted.

  14. BACTERIOLOGICAL PROFILE AND ANTIBIOTIC SUSCEPTIBILITY PATTERN OF NEONATAL SEPTICAEMIA

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    Shilpy

    2016-06-01

    Full Text Available Neonatal sepsis is one of the most common causes of neonatal mortality and morbidity, particularly in the developing countries. Appropriate clinical diagnosis and empirical treatment is crucial as pathogens causing sepsis and their antibiotic susceptibility pattern varies in different settings. The objective of this study was to determine the causative bacteria and pattern of susceptibility to antibiotics in NICU, which in turn may help in implementation of empirical therapy. MATERIALS AND METHOD A total of 100 blood samples were screened for sepsis in newborns less than 28 days old in this prospective study. The blood cultures of suspected cases were detected by using BACTEC blood culture systems and antibiotic susceptibility testing was done by using Kirby-Bauer disk diffusion method. This prospective observational study was conducted in the Department of Microbiology and Level III NICU in the Department of Paediatrics of D. Y. Patil Hospital and Research Centre during the period of two years 2013 to 2015. RESULTS In this study out of 100 neonates 38 (38% showed sepsis and 62 (62% showed no sepsis. Most common organisms responsible for the sepsis were CONS followed by Klebsiella pneumonia and Acinetobacter sp. Gram negative organisms were 100% sensitive to Colistin, Imipenem and Meropenem while Gram positive organisms were 100% sensitive to Azithromycin, Linezolid and Vancomycin. CONCLUSION The diagnostic capabilities of blood culture systems have improved over the last decade with the advent of automated continuous blood culture monitoring systems. BACTEC is a sensitive method and lead to earlier detection of bacterial growth

  15. An economic model to compare linezolid and vancomycin for the treatment of confirmed methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany

    Directory of Open Access Journals (Sweden)

    Patel DA

    2014-10-01

    Full Text Available Dipen A Patel,1 Andre Michel,2 Jennifer Stephens,1 Bertram Weber,3 Christian Petrik,4 Claudie Charbonneau5 1Health Economic and Outcomes Research, Pharmerit International, Bethesda, MD, USA; 2Klinikum Hanau GmbH, Hanau, Germany; 3Health Technology Assessment and Outcomes Research, 4Anti-infectives, Pfizer, Berlin, Germany; 5Pfizer International Operations, Pfizer France, Paris, France Background: Across Europe, methicillin-resistant Staphylococcus aureus (MRSA is considered to be the primary cause of nosocomial pneumonia (NP. In Germany alone, approximately 14,000 cases of MRSA-associated NP occur annually, which may have a significant impact on health care resource use and associated economic costs. The objective of this study was to investigate the economic impact of linezolid compared with that of vancomycin in the treatment of hospitalized patients with MRSA-confirmed NP in the German health care system. Methods: A 4-week decision tree model incorporated published data and expert opinion on clinical parameters, resource use, and costs (2012 euros was constructed. The base case first-line treatment duration for patients with MRSA-confirmed NP was 10 days. Treatment success (survival, failure due to lack of efficacy, serious adverse events, and mortality were possible outcomes that could impact costs. Alternate scenarios were analyzed, such as varying treatment duration (7 or 14 days or treatment switch due to a serious adverse event/treatment failure (at day 5 or 10. Results: The model calculated total base case inpatient costs of €15,116 for linezolid and €15,239 for vancomycin. The incremental cost-effectiveness ratio favored linezolid (versus vancomycin, with marginally lower costs (by €123 and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA NP. Approximately 85%–87% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit

  16. Antibiotic susceptibility patterns and prevalence of group B Streptococcus isolated from pregnant women in Misiones, Argentina.

    Science.gov (United States)

    Quiroga, M; Pegels, E; Oviedo, P; Pereyra, E; Vergara, M

    2008-04-01

    This study was performed to determine the susceptibility patterns and the colonization rate of Group B Streptococcus (GBS) in a population of pregnant women. From January 2004 to December 2006, vaginal-rectal swabs were obtained from 1105 women attending Dr. Ramón Madariaga Hospital, in Posadas, Misiones, Argentina. The carriage rate of GBS among pregnant women was 7.6%. A total of 62 GBS strains were randomly selected for in vitro susceptibility testing to penicillin G, ampicillin, tetracycline, levofloxacin, gatifloxacin, ciprofloxacin, quinupristin-dalfopristin, linezolid, vancomycin, rifampicin, trimethoprim- sulfametoxazol, nitrofurantoin, gentamicin, clindamycin and erythromycin, and determination of resistance phenotypes. No resistance to penicillin, ampicillin, quinupristin-dalfopristin, linezolid, and vancomycin was found. Of the isolates examined 96.8%, 98.3%, 46.8%, and 29.0% were susceptible to rifampicin, nitrofurantoin, trimethoprim-sulfametoxazol and tetracycline, respectively. Rank order of susceptibility for the quinolones was: gatifloxacin (98.4%) > levofloxacin (93.5%) > ciprofloxacin (64.5%). The rate of resistance to erythromycin (9.7%) was higher than that of other reports from Argentina. High-level resistance to gentamicin was not detected in any of the isolates. Based on our finding of 50% of GBS isolates with MIC to gentamicin equal o lower than 8 μg/ml, a concentration used in one of the selective media recommended for GBS isolation, we suggested, at least in our population, the use of nalidixic acid and colistin in selective media with the aim to improve the sensitivity of screening cultures for GBS carriage in women.

  17. Silencing of flavanone-3-hydroxylase in apple (Malus × domestica Borkh.) leads to accumulation of flavanones, but not to reduced fire blight susceptibility.

    Science.gov (United States)

    Flachowsky, Henryk; Halbwirth, Heidi; Treutter, Dieter; Richter, Klaus; Hanke, Magda-Viola; Szankowski, Iris; Gosch, Christian; Stich, Karl; Fischer, Thilo C

    2012-02-01

    Transgenic antisense flavanone-3-hydroxylase apple plants were produced to mimic the effect of the agrochemical prohexadione-Ca on apple leaves. This enzyme inhibitor for 2-oxoglutarate dependent dioxygenases is used as a growth retardant and for control of secondary fire blight of leaves. Like using the agent, silencing of flavanone-3-hydroxylase leads to an accumulation of flavanones in leaves, but in contrast not to the formation of 3-deoxyflavonoids. In prohexadione-Ca treated leaves the 3-deoxyflavonoid luteoforol is formed from accumulating flavanones, acting as an antimicrobial compound against the fire blight pathogen Erwinia amylovora. Seemingly, the silencing of just one of the 2-oxoglutarate dependent dioxygenases (in apple also flavonol synthase and anthocyanidin synthase take part downstream in the pathway) does not provide a sufficiently high ratio of flavanones to dihydroflavonols. This seems to be needed to let the dihydroflavonol-4-reductase/flavanone-4-reductase enzyme reduce flavanones to luteoforol, and to let this be reduced by the leucoanthocyanidin-4-reductase/3-deoxyleucoanthocyanidin-4-reductase, each acting with their respective weak secondary activities. Accordingly, also the intended inducible resistance to fire blight by prohexadione-Ca is not observed with the antisense flavanone-3-hydroxylase apple plants. On the other hand, for most transgenic lines with strong flavanone-4-reductase down-regulation, up-regulation of gene expression for the other flavonoid genes was found. This provides further evidence for the feedback regulation of flavonoid gene expression having been previously reported for the prohexadione-Ca inhibited apple plants. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  18. Electoral Susceptibility

    CERN Document Server

    Levine, G C; Cerise, J E

    2012-01-01

    In the United States electoral system, a candidate is elected indirectly by winning a majority of electoral votes cast by individual states, the election usually being decided by the votes cast by a small number of "swing states" where the two candidates historically have roughly equal probabilities of winning. The effective value of a swing state in deciding the election is determined not only by the number of its electoral votes but by the frequency of its appearance in the set of winning partitions of the electoral college. Since the electoral vote values of swing states are not identical, the presence or absence of a state in a winning partition is generally correlated with the frequency of appearance of other states and, hence, their effective values. We quantify the effective value of states by an {\\sl electoral susceptibility}, $\\chi_j$, the variation of the winning probability with the "cost" of changing the probability of winning state $j$. We study $\\chi_j$ for realistic data accumulated for the 201...

  19. Manipulation of two α-endo-β-1,4-glucanase genes, AtCel6 and GmCel7, reduces susceptibility to Heterodera glycines in soybean roots.

    Science.gov (United States)

    Woo, Mi-Ok; Beard, Hunter; MacDonald, Margaret H; Brewer, Eric P; Youssef, Reham M; Kim, Hyunsoon; Matthews, Benjamin F

    2014-12-01

    Plant endo-β-1,4-glucanases (EGases) include cell wall-modifying enzymes that are involved in nematode-induced growth of syncytia (feeding structures) in nematode-infected roots. EGases in the α- and β-subfamilies contain signal peptides and are secreted, whereas those in the γ-subfamily have a membrane-anchoring domain and are not secreted. The Arabidopsis α-EGase At1g48930, designated as AtCel6, is known to be down-regulated by beet cyst nematode (Heterodera schachtii) in Arabidopsis roots, whereas another α-EGase, AtCel2, is up-regulated. Here, we report that the ectopic expression of AtCel6 in soybean roots reduces susceptibility to both soybean cyst nematode (SCN; Heterodera glycines) and root knot nematode (Meloidogyne incognita). Suppression of GmCel7, the soybean homologue of AtCel2, in soybean roots also reduces the susceptibility to SCN. In contrast, in studies on two γ-EGases, both ectopic expression of AtKOR2 in soybean roots and suppression of the soybean homologue of AtKOR3 had no significant effect on SCN parasitism. Our results suggest that secreted α-EGases are likely to be more useful than membrane-bound γ-EGases in the development of an SCN-resistant soybean through gene manipulation. Furthermore, this study provides evidence that Arabidopsis shares molecular events of cyst nematode parasitism with soybean, and confirms the suitability of the Arabidopsis-H. schachtii interaction as a model for the soybean-H. glycines pathosystem.

  20. Improved Xenobiotic Metabolism and Reduced Susceptibility to Cancer in Gluten-Sensitive Macaques upon Introduction of a Gluten-Free Diet

    Science.gov (United States)

    Sestak, Karol; Conroy, Lauren; Aye, Pyone P.; Mehra, Smriti; Doxiadis, Gaby G.; Kaushal, Deepak

    2011-01-01

    Background A non-human primate (NHP) model of gluten sensitivity was employed to study the gene perturbations associated with dietary gluten changes in small intestinal tissues from gluten-sensitive rhesus macaques (Macaca mulatta). Methodology Stages of remission and relapse were accomplished in gluten-sensitive animals by administration of gluten-free (GFD) and gluten-containing (GD) diets, as described previously. Pin-head-sized biopsies, obtained non-invasively by pediatric endoscope from duodenum while on GFD or GD, were used for preparation of total RNA and gene profiling, using the commercial Rhesus Macaque Microarray (Agilent Technologies),targeting expression of over 20,000 genes. Principal Findings When compared with normal healthy control, gluten-sensitive macaques showed differential gene expressions induced by GD. While observed gene perturbations were classified into one of 12 overlapping categories - cancer, metabolism, digestive tract function, immune response, cell growth, signal transduction, autoimmunity, detoxification of xenobiotics, apoptosis, actin-collagen deposition, neuronal and unknown function - this study focused on cancer-related gene networks such as cytochrome P450 family (detoxification function) and actin-collagen-matrix metalloproteinases (MMP) genes. Conclusions/Significance A loss of detoxification function paralleled with necessity to metabolize carcinogens was revealed in gluten-sensitive animals while on GD. An increase in cancer-promoting factors and a simultaneous decrease in cancer-preventing factors associated with altered expression of actin-collagen-MMP gene network were noted. In addition, gluten-sensitive macaques showed reduced number of differentially expressed genes including the cancer-associated ones upon withdrawal of dietary gluten. Taken together, these findings indicate potentially expanded utility of gluten-sensitive rhesus macaques in cancer research. PMID:21533263

  1. Improved xenobiotic metabolism and reduced susceptibility to cancer in gluten-sensitive macaques upon introduction of a gluten-free diet.

    Directory of Open Access Journals (Sweden)

    Karol Sestak

    Full Text Available BACKGROUND: A non-human primate (NHP model of gluten sensitivity was employed to study the gene perturbations associated with dietary gluten changes in small intestinal tissues from gluten-sensitive rhesus macaques (Macaca mulatta. METHODOLOGY: Stages of remission and relapse were accomplished in gluten-sensitive animals by administration of gluten-free (GFD and gluten-containing (GD diets, as described previously. Pin-head-sized biopsies, obtained non-invasively by pediatric endoscope from duodenum while on GFD or GD, were used for preparation of total RNA and gene profiling, using the commercial Rhesus Macaque Microarray (Agilent Technologies,targeting expression of over 20,000 genes. PRINCIPAL FINDINGS: When compared with normal healthy control, gluten-sensitive macaques showed differential gene expressions induced by GD. While observed gene perturbations were classified into one of 12 overlapping categories--cancer, metabolism, digestive tract function, immune response, cell growth, signal transduction, autoimmunity, detoxification of xenobiotics, apoptosis, actin-collagen deposition, neuronal and unknown function--this study focused on cancer-related gene networks such as cytochrome P450 family (detoxification function and actin-collagen-matrix metalloproteinases (MMP genes. CONCLUSIONS/SIGNIFICANCE: A loss of detoxification function paralleled with necessity to metabolize carcinogens was revealed in gluten-sensitive animals while on GD. An increase in cancer-promoting factors and a simultaneous decrease in cancer-preventing factors associated with altered expression of actin-collagen-MMP gene network were noted. In addition, gluten-sensitive macaques showed reduced number of differentially expressed genes including the cancer-associated ones upon withdrawal of dietary gluten. Taken together, these findings indicate potentially expanded utility of gluten-sensitive rhesus macaques in cancer research.

  2. In Vivo Assessment of Phage and Linezolid Based Implant Coatings for Treatment of Methicillin Resistant S. aureus (MRSA Mediated Orthopaedic Device Related Infections.

    Directory of Open Access Journals (Sweden)

    Sandeep Kaur

    Full Text Available Staphylococcus comprises up to two-thirds of all pathogens in orthopaedic implant infections with two species respectively Staphylococcus aureus and Staphylococcus epidermidis, being the predominate etiological agents isolated. Further, with the emergence of methicillin-resistant S. aureus (MRSA, treatment of S. aureus implant infections has become more difficult, thus representing a devastating complication. Use of local delivery system consisting of S.aureus specific phage along with linezolid (incorporated in biopolymer allowing gradual release of the two agents at the implant site represents a new, still unexplored treatment option (against orthopaedic implant infections that has been studied in an animal model of prosthetic joint infection. Naked wire, hydroxypropyl methylcellulose (HPMC coated wire and phage and /or linezolid coated K-wire were surgically implanted into the intra-medullary canal of mouse femur bone of respective groups followed by inoculation of S.aureus ATCC 43300(MRSA. Mice implanted with K-wire coated with both the agents i.e phage as well as linezolid (dual coated wires showed maximum reduction in bacterial adherence, associated inflammation of the joint as well as faster resumption of locomotion and motor function of the limb. Also, all the coating treatments showed no emergence of resistant mutants. Use of dual coated implants incorporating lytic phage (capable of self-multiplication as well as linezolid presents an attractive and aggressive early approach in preventing as well as treating implant associated infections caused by methicillin resistant S. aureus strains as assessed in a murine model of experimental joint infection.

  3. Structure-Activity Relationships of Diverse Oxazolidinones for Linezolid-Resistant Staphylococcus aureus Strains Possessing the cfr Methyltransferase Gene or Ribosomal Mutations▿

    OpenAIRE

    Locke, Jeffrey B.; Finn, John; Hilgers, Mark; Morales, Gracia; Rahawi, Shahad; Kedar, G. C.; Picazo, Juan José; Im, Weonbin; Shaw, Karen Joy; Stein, Jeffrey L.

    2010-01-01

    Staphylococcal resistance to linezolid (LZD) is mediated through ribosomal mutations (23S rRNA or ribosomal proteins L3 and L4) or through methylation of 23S rRNA by the horizontally transferred Cfr methyltransferase. To investigate the structural basis for oxazolidinone activity against LZD-resistant (LZDr) strains, we compared structurally diverse, clinically relevant oxazolidinones, including LZD, radezolid (RX-1741), TR-700 (torezolid), and a set of TR-700 analogs (including novel CD-ring...

  4. Linezolid in the treatment of vancomycin-resistant Enterococcus faecium in solid organ transplant recipients: report of a multicenter compassionate-use trial.

    Science.gov (United States)

    El-Khoury, J; Fishman, J A

    2003-09-01

    Vancomycin-resistant Enterococcus faecium (VRE) is increasing in incidence in solid organ transplant recipients and has a high (up to 83%) associated mortality rate. Until recently, there have been no consistently effective antimicrobial therapies for VRE infection. Linezolid is a new antibiotic that belongs to the class of oxazolidinones approved by the FDA for the treatment of VRE infections, including those with bacteremia. Here, we report the experience with linezolid in an open-label, compassionate-use trial at 53 US centers for the treatment of documented VRE infections in patients with solid organ transplants. Eighty-five patients with solid organ transplants and documented VRE infections were studied. Blood cultures were positive for VRE in 43 patients, while 42 patients had other, non-rectal, sites of infection. Fifty-three patients responded well to treatment, with clinical resolution of the infection (62.4% survival rate). Of these, 47 had documented negative cultures post therapy. The mean duration of therapy for cured patients was 23.5 days. Thirty-two (37.6%) patients died, 28 due to sepsis and organ failure (32.9% failure rate), and 4 due to unrelated causes. Mortality rates for patients with bacteremia were comparable to mortality rates observed with patients who had positive cultures from other sites. Adverse reactions to linezolid included thrombocytopenia (4.7%), decreased leukocyte count (3.5%), and an increase in blood pressure (1.2%), none of which led to discontinuation of therapy. Linezolid appears to be a safe and effective treatment option for VRE, even in the presence of bacteremia, and may lead to decreased mortality in solid organ transplant recipients with VRE infection.

  5. Linezolid Is Associated with Serotonin Syndrome in a Patient Receiving Amitriptyline, and Fentanyl: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Lampros Samartzis

    2013-01-01

    Full Text Available We report a unique case of an adverse interaction between the oxazolidinone antibiotic linezolid, the tricyclic antidepressant amitriptyline and the opioid analgesic fentanyl in a 68-year-old woman with advanced ischemic peripheral arterial disease and sepsis, under empirical antibiotic treatment. We also summarize the current relevant literature as identified via PubMed, EMBASE, and PsycINFO as well as reference sections of selected articles.

  6. European perspective and update on the management of nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus after more than 10 years of experience with linezolid.

    Science.gov (United States)

    Chastre, J; Blasi, F; Masterton, R G; Rello, J; Torres, A; Welte, T

    2014-04-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of antimicrobial-resistant hospital-acquired infections worldwide and remains a public health priority in Europe. Nosocomial pneumonia (NP) involving MRSA often affects patients in intensive care units with substantial morbidity, mortality and associated costs. A guideline-based approach to empirical treatment with an antibacterial agent active against MRSA can improve the outcome of patients with MRSA NP, including those with ventilator-associated pneumonia. New methods may allow more rapid or sensitive diagnosis of NP or microbiological confirmation in patients with MRSA NP, allowing early de-escalation of treatment once the pathogen is known. In Europe, available antibacterial agents for the treatment of MRSA NP include the glycopeptides (vancomycin and teicoplanin) and linezolid (available as an intravenous or oral treatment). Vancomycin has remained a standard of care in many European hospitals; however, there is evidence that it may be a suboptimal therapeutic option in critically ill patients with NP because of concerns about its limited intrapulmonary penetration, increased nephrotoxicity with higher doses, as well as the emergence of resistant strains that may result in increased clinical failure. Linezolid has demonstrated high penetration into the epithelial lining fluid of patients with ventilator-associated pneumonia and shown statistically superior clinical efficacy versus vancomycin in the treatment of MRSA NP in a phase IV, randomized, controlled study. This review focuses on the disease burden and clinical management of MRSA NP, and the use of linezolid after more than 10 years of clinical experience.

  7. Bacillus cereus from blood cultures: virulence genes, antimicrobial susceptibility and risk factors for blood stream infection.

    Science.gov (United States)

    Horii, Toshinobu; Notake, Shigeyuki; Tamai, Kiyoko; Yanagisawa, Hideji

    2011-11-01

    We characterized the profiles of virulence genes and antimicrobial susceptibility of Bacillus cereus isolates from blood cultures as well as the risk factors for blood stream infections (BSIs). The diversity of virulence gene patterns was found to be wide among 15 B. cereus isolates from BSIs and also among 11 isolates from contaminated blood cultures. The MicroScan broth microdilution method yielded results corresponding with those of the agar dilution (reference) method for levofloxacin, linezolid, and vancomycin, while the Etest results were consistent with the reference results for clindamycin, gentamicin, imipenem, levofloxacin, and linezolid. Compared with the reference values, however, some isolates showed marked differences of the minimum inhibitory concentrations (MICs) for ampicillin and clindamycin when determined using the MicroScan method, or the MICs for ampicillin, meropenem, and vancomycin when determined using the Etest method. Significantly more patients were treated with antimicrobials for more than 3 days during the 3-month period before isolation in the BSI group. Prior antimicrobial therapy may be a risk factor for BSIs due to B. cereus.

  8. Mechanisms underlying the resistance and reduced susceptibility to ceftriaxone in Neisseria gonorrhoeae%淋病奈瑟菌对头孢曲松耐药性及敏感性降低机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    张丽君; 李国明

    2012-01-01

    头孢曲松为目前治疗淋病的首选药物之一,国内外淋球菌耐药监测均发现淋球菌对头孢曲松敏感性降低,并已发现少数散发的头孢曲松耐药株.淋球菌对头孢曲松敏感性降低主要由染色体介导,目前大多数研究主要关注三个方面:一是抗生素作用靶位点的改变,影响抗生素与淋球菌的结合产生耐药;二是细菌细胞膜孔蛋白的改变,导致膜通透性降低产生耐药;三是外排系统的改变,导致细菌外排作用增强产生耐药.涉及的基因有penA、ponA、porB和mtrR等.%Ceftriaxone is one of the first-line drugs for gonorrhea treatment.In vitro antimicrobial susceptibility studies have shown Neisseria gonorrhoeae strains with reduced susceptibility or resistance to ceftriaxone,which is mainly mediated by chromosomes.Current studies on ceftriaxone resistance are mainly focused on three aspects,i.e.,changes in antibiotic target sites affecting the combination of antibiotics and Neisseria gonorrhoeae,bacterial cell membrane porin changes resulting in decreased membrane permeability,and efflux system changes enhancing the bacterial efflux capacity,It has been demonstrated that penA,ponA,porB and mtrR genes are associated with Neisseria gonorrhoeae resistance.

  9. Effect of Linezolid on the 50% Lethal Dose and 50% Protective Dose in Treatment of Infections by Gram-Negative Pathogens in Naive and Immunosuppressed Mice and on the Efficacy of Ciprofloxacin in an Acute Murine Model of Septicemia

    Science.gov (United States)

    Marra, Andrea; Lamb, Lucinda; Medina, Ivette; George, David; Gibson, Glenn; Hardink, Joel; Rugg, Jady; Van Deusen, Jeffrey

    2012-01-01

    Murine models of infection were used to study the effect of linezolid on the virulence of Gram-negative bacteria and to assess potential pharmacodynamic interactions with ciprofloxacin in the treatment of these infections, prompted by observations from a recent clinical trial. Naive and immunosuppressed mice were challenged with Klebsiella pneumoniae 53A1109, K. pneumoniae GC6658, and Pseudomonas aeruginosa UC12120 in acute sepsis and pulmonary infection models, using different serial dilutions of these pathogens (groups of 8 animals each). Linezolid (100 mg/kg/dose) was administered orally at 0.5 and 4.0 h postchallenge in the sepsis model and at 4 h postchallenge followed by 2 days of twice-daily treatment in the pulmonary model. Further, ciprofloxacin alone and in combination with oral linezolid was investigated in the sepsis model. Survival was assessed for 4 and 10 days postchallenge in the systemic and respiratory models, respectively. The data were fitted to a nonlinear regression analysis to determine 50% lethal doses (LD50s) and 50% protective doses (PD50s). A clinically relevant, high-dose regimen of linezolid had no significant effect on LD50 in these models. This lack of effect was independent of immune status. A combination of oral ciprofloxacin with linezolid yielded lower PD50s than oral ciprofloxacin alone (ciprofloxacin in combination, 8.4 to 32.7 mg/kg; oral ciprofloxacin, 39.4 to 88.3 mg/kg). Linezolid did not improve the efficacy of subcutaneous ciprofloxacin (ciprofloxacin in combination, 2.0 to 2.4 mg/kg; subcutaneous ciprofloxacin, 2.0 to 2.8 mg/kg). In conclusion, linezolid does not seem to potentiate infections caused by Gram-negative pathogens or to interact antagonistically with ciprofloxacin. PMID:22710118

  10. Forewarning reduces fraud susceptibility in vulnerable consumers

    NARCIS (Netherlands)

    Scheibe, Susanne; Notthoff, Nanna; Menkin, Josephine; Ross, Lee; Shadel, Doug; Deevy, Martha; Carstensen, Laura L.

    2014-01-01

    Telemarketing fraud is pervasive, and older consumers are disproportionally targeted. We conducted a field experiment to test whether forewarning could protect people who were victimized in the past. A telemarketer pitched a mock scam 2 or 4 weeks after participants were warned about the same scam o

  11. 利奈唑胺耐药肠球菌的分子流行病学和感染危险因素分析%The molecular epidemiology and infections risk factors of clinical linezolid-resistant Enterococci isolates

    Institute of Scientific and Technical Information of China (English)

    贾晓炯; 徐绣宇; 马维佳; 史静; 张莉萍

    2015-01-01

    目的 探究利奈唑胺耐药肠球菌(LRE)的分子流行病学特点和感染危险因素.方法 2011至2013年共收集重庆医科大学附属第一医院13株利奈唑胺耐药肠球菌,采用微量肉汤稀释法对菌株进行验证,并通过法国生物梅里埃Vitek 2对12种抗生素进行MIC检测;多位点序列分型(MLST)、脉冲场凝胶电泳(PFGE)、Diversilab进行分子流行病学调查;对患者病例资料进行回顾性分析,采用Logistic回归模型来明确利奈唑胺耐药肠球菌的独立危险因素.结果 13株利奈唑胺耐药肠球菌均对利奈唑胺呈现低水平耐药,对四环素、红霉素、环丙沙星多表现耐药,对青霉素、氨苄西林、替加环素等多表现敏感;我院以ST480型别为主,其中2013年7至9月有3株菌(菌株3~5)具有相同的序列分型(ST)型别、PFGE条带和rep-PCR分型结果,属于同一耐药克隆群;入住ICU、周围血管疾病、男性、低蛋白血症、肠道灌洗和利奈唑胺使用等是利奈唑胺耐药肠球菌的主要危险因素,其中,入住ICU(OR=8.74;P =0.008)、肠道灌洗(OR=8.39;P=0.015)、利奈唑胺使用(OR=10.19;P =0.039)是其独立危险因素.结论 13株LRE均为多重耐药菌株,2013年下半年存在小规模的LRE流行,应重视LRE的监管工作,从而减少利奈唑胺耐药菌株的出现.%Objective To investigate the molecular epidemiology and infectious risk factors of linezolid-resistant Enterococci (LRE) isolates in the First Affiliated Hospital of Chongqing Medical University.Methods Thirteen LRE isolates were collected from 2011 to 2013 and confirmed by broth dilution susceptibility testing.The minimum inhibitory concentrations (MIC) of twelve antimicrobial agents were analyzed using Vitek 2 compact.The molecular epidemiology of LRE isolates was determined by multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and the Diversilab.A casecontrol study was conducted for the analysis of risk factors, and

  12. 利奈唑胺致全血细胞减少%Pancytopenia following treatment with linezolid

    Institute of Scientific and Technical Information of China (English)

    谢诚; 高杰; 赵玉琴; 缪丽燕

    2011-01-01

    1例75岁男性患者因房宣传导阻滞行永久起搏器植入术,术后出现感染性心内膜炎.首先单独给予头孢哌酮钠-舒巴坦钠3.0g、1次/12 h静脉滴注4d,然后改为万古霉素1.0g、1次/12h静脉滴注3d,最后单独应用利奈唑胺600mg,1次/12 h静脉滴注44d.应用利奈唑胺前实验室检查示患者外周血白细胞12.00×109/L,红细胞3.92×1012/L,血小板158×109/L,血红蛋白115 g/L.用药第19天血常规示白细胞2.81×109/L,红细胞3.39×1012/L,血小板74×109/L,血红蛋白102 g/L.其后血常规检查显示各项指标均低于正常范围,最低值如下:白细胞2.69×109/L,红细胞2.51×1012/L,血小板48×109/L,血红蛋白69g/L.由于病情需要未停用利奈唑胺,给予重组人粒细胞集落刺激因子、琥珀酸亚铁及红细胞悬液等对症治疗.患者应用利奈唑胺共44d.停药后18 d血常规恢复正常:白细胞5.07×109/L,红细胞3.02×1012/L,血小板156×109/L,血红蛋白102 g/L.%A 75-year-old male patient developed infective endocarditis after a permanent pacemaker implantation for atrioventricular block. He received initially an Ⅳ infusion of cefoperazone sodium/sulbactam sodium 3.0 g every 12 hours for 4 days alone which was replaced by an Ⅳ infusion of vancomycin 1. 0 g every 12 hours for 3 days and then finally was treated with an Ⅳ infusion of linezolid 600 mg every 12 hours for 44 days alone. Before administration of linezolid, laboratory tests revealed a WBC count of 12.00×109/L, a RBC count of 3.92×1012/L, a platelet (PLT) count of 158 × 109/L, and a Hb level of 115 g/L. However, on day 19 of treatment, routine blood testing showed the following values; WBC count 2. 81 × 109/L, RBC count 3. 39 × 1012/L, PLT count 74 × 109/L, and Hb 102 g/L. The following routine blood tests showed that complete blood cells count values were below normal and the lowest values were as follows; WBC count 2.69 × 109/L, RBC count 2.51 × 1012/L, PLT count 48 × 109/L, and Hb

  13. Linezolid plasma concentrations and occurrence of drug-related haematological toxicity in patients with gram-positive infections.

    Science.gov (United States)

    Cattaneo, Dario; Orlando, Giovanna; Cozzi, Valeria; Cordier, Laura; Baldelli, Sara; Merli, Stefania; Fucile, Serena; Gulisano, Cecilia; Rizzardini, Giuliano; Clementi, Emilio

    2013-06-01

    Retrospective studies have documented a significant association between linezolid (LNZ) plasma concentrations and drug-related haematological toxicity. However, the safe upper threshold level for LNZ plasma trough concentrations (Cmin values) has not been defined with certainty. A prospective observational study was performed aimed at comparing LNZ Cmin values in patients developing drug-related side effects with those measured in patients not experiencing LNZ toxicity. LNZ Cmin values were measured from the first week after starting therapy and were repeated periodically up to the end of treatment. Fifty patients, for a total of 210 LNZ Cmin evaluations, were considered. All patients (n=9) who developed drug-related haematological toxicity also had significantly higher plasma LNZ Cmin values during the first week of therapy (9.0±6.4 mg/L vs. 4.9±3.7 mg/L; P<0.01) and thereafter (9.3±5.4 mg/L vs. 4.4±3.4 mg/L; P<0.01). The significant association between LNZ plasma concentrations and haematological toxicity was also confirmed by multivariate logistic regression analysis including age, serum creatinine and concomitant medications as independent variables. A causal relationship between LNZ concentrations and the risk of developing drug-related haematological toxicity was observed. Accordingly, application of therapeutic drug monitoring may improve the safety outcome of patients receiving LNZ therapy.

  14. Linezolid-induced pure red cell aplasia in a patient with Staphylococcus epidermidis infection after allogeneic stem cell transplantation.

    Science.gov (United States)

    Waki, F; Ohnishi, H; Shintani, T; Uemura, M; Matsumoto, K; Fukumoto, T; Kitanaka, A; Kubota, Y; Tanaka, T; Ishida, T; Matsunaga, T

    2012-08-01

    Linezolid (LZD) is the first oxazolidinone antibiotic that is effective against drug-resistant gram-positive organisms. Hematological toxicities such as thrombocytopenia, anemia, and leukocytopenia are common in LZD therapy. However, LZD-induced pure red cell aplasia (PRCA) is very rare. A 56-year-old man with myelodysplastic syndrome underwent allogeneic bone marrow transplantation from a human leukocyte antigen-matched and ABO blood type-matched unrelated male donor. He had bacteremia caused by Staphylococcus epidermidis after engraftment of neutrophils and red blood cells. We first administered vancomycin, but then changed to intravenous LZD because of kidney damage. Two weeks after LZD therapy, the patient's hemoglobin and reticulocyte levels were 6.8 g/dL and 0.3%, respectively. Bone marrow examination revealed red blood cell aplasia (myeloid/erythroid ratio was 402). The patient showed rapid recovery of normal erythropoiesis within 2 weeks of LZD cessation. It is important to be aware of the hematological effects associated with LZD in the setting of stem cell transplantation,particularly for those with pre-existing myelosuppression, renal insufficiency, and those receiving concomitant drugs that produce bone marrow suppression. We advocate that a reticulocyte count be performed periodically for detecting bone marrow suppression, including PRCA, during LZD therapy.

  15. In vitro antimicrobial susceptibility in clinical isolates of Enterococcus species

    Directory of Open Access Journals (Sweden)

    Calderón-Jaimes Ernesto

    2003-01-01

    Full Text Available OBJECTIVE: To describe the antimicrobial activity of several antimicrobial agents against 97 clinical significant isolates of Enterococcus spp. MATHERIAL AND METHODS: During a 2-year prospective study at Instituto Nacional de Pediatria (National Institute of Pediatrics in Mexico City. Ninety seven strains of Enterococcus spp. (60 E. faecalis and 37 E. faecium were tested against 11 antibiotics. Susceptibility tests were performed with agar, according to the standards of the sNational Committee for Clinical Laboratory Standards (NCCLS. Isolates were screened for high-level resistance (HLR to beta-lactams, aminoglycosides, glycopeptides and other antibiotics, as well as for vancomycin-phenotypes. Differences between proportions were evaluated with chi2 of Fisher exact fest. RESULTS: Overall resistance rates to the antibiotics tested were: 17/97 (17.5% to penicillin, ampicillin, amoxicillin-clavulanate and imipenem. There was neither HLR nor beta-lactamase production; 74/97 (48.4% were resistant to erythromycin; 60% to ciprofloxacin; 31/97 (32% to gentamicin, and 55/97 (56.7% to streptomycin. Seven strains were vancomycin-resistant enterococci (VRE, all of them identified as E. faecium; 5/7 with Van A and 2/7 with Van B phenotypes. All the isolates were susceptible to linezolid. The difference in susceptibility among species was significant. CONCLUSIONS: Mutidrug-resistant enterococci is a real problem and continuous surveillance is necessary. The microbiology laboratory is the first line of defense against the spread of multiantibiotic-resistan enterococci in the hospital environment . All the strains recovered should be tested for susceptibility to ampicillin, streptomycin, gentamicin and glycopeptides.

  16. Single-Dose Oral Amoxicillin or Linezolid for Prophylaxis of Experimental Endocarditis Due to Vancomycin-Susceptible and Vancomycin-Resistant Enterococcus faecalis▿

    OpenAIRE

    Moreillon, Philippe; Wilson, Walter R.; Leclercq, Roland; Entenza, José M,

    2007-01-01

    Endocarditis prophylaxis following genitourinary or gastrointestinal procedures targets Enterococcus faecalis. Prophylaxis recommendations advocate oral amoxicillin (2 g in the United States and 3 g in the United Kingdom) in moderate-risk patients and intravenous amoxicillin (2 g) or vancomycin (1 g) plus gentamicin in high-risk patients. While ampicillin-resistant (or amoxicillin-resistant) E. faecalis is still rare, there is a concern that these regimens might fail against vancomycin-resist...

  17. Long aculeus and behavior of Anastrepha ludens render gibberellic acid ineffective as an agent to reduce 'ruby red' grapefruit susceptibility to the attack of this pestiferous fruit fly in commercial groves.

    Science.gov (United States)

    Birke, Andrea; Aluja, Martín; Greany, Patrick; Bigurra, Everardo; Pérez-Staples, Diana; McDonald, Roy

    2006-08-01

    Treating Mexican grapefruit with gibberellic acid (GA3) before color break, significantly delayed peel color change and increased peel puncture resistance, but it did not reduce grapefruit susceptibility to Mexican fruit fly, Anastrepha ludens (Loew) attack under natural conditions. Despite GA3 treatments, larval infestation levels increased with higher fruit fly populations, which also increased as the season progressed. Late in the season, infestation levels were even higher in GA3-treated fruit compared with untreated fruit, possibly because treated fruit were in better condition at that stage. Egg clutch size was significantly greater in very unripe, hard, GA3-treated fruit at the beginning of the harvest season and in December, compared with control fruit. Under laboratory conditions, egg injection into different regions of the fruit suggested that A. ludens eggs are intoxicated by peel oil content in the flavedo region. However, A. ludens' long aculeus allows females to oviposit eggs deeper into the peel (i.e., albedo), avoiding toxic essential oils in the flavedo. This makes A. ludens a particularly difficult species to control compared with other citrus-infesting species such as Anastrepha suspensa (Loew), Anastrepha fraterculus (Wiedemann), and Ceratitis capitata (Wiedemann) (fly species with significantly shorter aculei), which can be effectively managed with GA3 sprays. We discuss our findings in light of their practical implications and with respect to the oviposition behavior of various fruit flies attacking citrus.

  18. Endocarditis due to vancomycin-resistant Enterococcus raffinosus successfully treated with linezolid: case report and review of literature Endocarditis por Enterococcus raffinosus resistente a vancomicina exitosamente tratada con linezolid: caso clínico y revisión de la literatura

    Directory of Open Access Journals (Sweden)

    A. Jasovich

    2008-12-01

    Full Text Available Enterococcus raffinosus is scarcely found in clinical samples and even less frequently as etiologic agent of endocarditis. We are herein presenting one case of mitral prosthetic-valve endocarditis in a 77-y-o male due to a vancomycinresistant Enterococcus raffinosus isolate, successfully treated with 6 weeks of linezolid, and a two-year follow up.Enterococcus raffinosus es una especie poco frecuente en materiales clínicos y menos aún como agente etiológico de endocarditis. En este trabajo se presenta un caso de endocarditis de válvula mitral protésica en un paciente de 77 años debida a Enterococcus raffinosus resistente a vancomicina y que fue exitosamente tratada con linezolid durante 6 semanas, con un seguimiento de 2 años.

  19. Antimicrobial susceptibility pattern of bacterial isolates from surgical wound infections in Tertiary Care Hospital in Allahabad, India

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    A K Kapoor

    2012-01-01

    Full Text Available The aim of present study to analyze the occurrence and in-vitro antimicrobial susceptibility of bacterial pathogens isolated from surgical wound infections. Specimens from a total of 129 patients undergoing either emergency or elective surgery were collected from infected sites or stitch lines and inoculated onto appropriate media. The bacterial cultures were identified utilizing standard microbiological and biochemical methods. Isolates were tested for susceptibility to antimicrobials using the Kirby Bauer disk diffusion method. Statistical analysis was performed using the chi-square test. Of 129 patients investigated (62 emergency and 67 elective surgery cases, bacterial isolates were isolated with almost equal frequency both from emergency and elective surgery cases. Of 108 (83.72% culture positive samples, 62 (57.41% were Gram negative, 39 (36.11% Gram positive, and 7 (6.48% showed multiple organisms. Of total 115 bacteria isolated (101 single and 7 double organisms culture positive, 33 (28.69% were Escherichia coli and were also the commonest; followed by Staphylococcus aureus, 30 (26.09% cases. S. aureus and Streptococcus spp. showed maximum susceptibility (100% to linezolid and vancomycin. Maximum susceptibility of E. coli was observed to ciprofloxacin (75.7%, followed by gentamicin (54.5%; of Klebsiella spp. to ceftriaxone and gentamicin (66.6% each, of Proteus spp. to gentamicin (70% followed by ciprofloxacin (60%, and of Pseudomonas aeruginosa to piperacillin (100% and tobramycin (71.4%. E. coli and S. aureus were the most common and Salmonella spp. and Acinetobacter spp. were the least common organism causing surgical site infections. The definitive therapy included ciprofloxacin and gentamicin for E. coli; linezolid and vancomycin for S. aureus and Streptococcus spp; ceftriaxone and ciprofloxacin for Klebsiella spp., Citrobacter spp., acinetobacter spp and Salmonella spp.

  20. Co-therapy using lytic bacteriophage and linezolid: effective treatment in eliminating methicillin resistant Staphylococcus aureus (MRSA from diabetic foot infections.

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    Sanjay Chhibber

    Full Text Available BACKGROUND: Staphylococcus aureus remains the predominant pathogen in diabetic foot infections and prevalence of methicillin resistant S.aureus (MRSA strains further complicates the situation. The incidence of MRSA in infected foot ulcers is 15-30% and there is an alarming trend for its increase in many countries. Diabetes acts as an immunosuppressive state decreasing the overall immune functioning of body and to worsen the situation, wounds inflicted with drug resistant strains represent a morbid combination in diabetic patients. Foot infections caused by MRSA are associated with an increased risk of amputations, increased hospital stay, increased expenses and higher infection-related mortality. Hence, newer, safer and effective treatment strategies are required for treating MRSA mediated diabetic foot infections. The present study focuses on the use of lytic bacteriophage in combination with linezolid as an effective treatment strategy against foot infection in diabetic population. METHODOLOGY: Acute hindpaw infection with S.aureus ATCC 43300 was established in alloxan induced diabetic BALB/c mice. Therapeutic efficacy of a well characterized broad host range lytic bacteriophage, MR-10 was evaluated alone as well as in combination with linezolid in resolving the course of hindpaw foot infection in diabetic mice. The process of wound healing was also investigated. RESULTS AND CONCLUSIONS: A single administration of phage exhibited efficacy similar to linezolid in resolving the course of hindpaw infection in diabetic animals. However, combination therapy using both the agents was much more effective in arresting the entire infection process (bacterial load, lesion score, foot myeloperoxidase activity and histopathological analysis. The entire process of tissue healing was also hastened. Use of combined agents has been known to decrease the frequency of emergence of resistant mutants, hence this approach can serve as an effective strategy in

  1. Development, Optimization, and Validation of a Microplate Bioassay for Relative Potency Determination of Linezolid Using a Design Space Concept, and its Measurement Uncertainty.

    Science.gov (United States)

    Saviano, Alessandro Morais; Francisco, Fabiane Lacerda; Ostronoff, Celina Silva; Lourenço, Felipe Rebello

    2015-01-01

    The aim of this study was to develop, optimize, and validate a microplate bioassay for relative potency determination of linezolid in pharmaceutical samples using quality-by-design and design space approaches. In addition, a procedure is described for estimating relative potency uncertainty based on microbiological response variability. The influence of culture media composition was studied using a factorial design and a central composite design was adopted to study the influence of inoculum proportion and triphenyltetrazolium chloride in microbial growth. The microplate bioassay was optimized regarding the responses of low, medium, and high doses of linezolid, negative and positive controls, and the slope, intercept, and correlation coefficient of dose-response curves. According to optimization results, design space ranges were established using: (a) low (1.0 μg/mL), medium (2.0 μg/mL), and high (4.0 μg/mL) doses of pharmaceutical samples and linezolid chemical reference substance; (b) Staphylococcus aureus ATCC 653 in an inoculum proportion of 10%; (c) antibiotic No. 3 culture medium pH 7.0±0.1; (d) 6 h incubation at 37.0±0.1ºC; and (e) addition of 50 μL of 0.5% (w/v) triphenyltetrazolium chloride solution. The microplate bioassay was linear (r2=0.992), specific, precise (repeatability RSD=2.3% and intermediate precision RSD=4.3%), accurate (mean recovery=101.4%), and robust. The overall measurement uncertainty was reasonable considering the increased variability inherent in microbiological response. Final uncertainty was comparable with those obtained with other microbiological assays, as well as chemical methods.

  2. Comparative in vitro activity of penicillin G, levofloxacin, moxifloxacin, telithromycin, pristinamycin, quinupristin-dalfopristin and linezolid against ofloxacin-intermediate and -resistant Streptococcus pneumoniae.

    Science.gov (United States)

    Frédénucci, I; Chomarat, M; Bercion, R; Carricajo, A; Celard, M; Croizé, J; Delubac, F; Fèvre, D; Fuhrmann, C; Helfre, M; Letouzey, M N; Lelièvre, H; Mandjee, A; Marthelet, P; Meley, R; Perrier-Gros-Claude, J D; Ros, A; Roure, C; Smati, S; Thierry, J; Tous, J

    2002-10-01

    Screening by ofloxacin disk was carried out on 1158 strains of Streptococcus pneumoniae in order to investigate the in vitro bacteriostatic activity of penicillin G, levofloxacin, moxifloxacin, telithromycin, linezolid, pristinamycin and quinupristin-dalfopristin against ofloxacin-intermediate and -resistant S. pneumoniae strains. It was concluded that these new antimicrobial agents could be useful for the treatment of pneumococcal infections caused by penicillin-sensitive and -resistant S. pneumoniae, and would represent a valid therapeutic option for patients allergic to beta-lactams, should they prove to be potent in vivo.

  3. Synthesis of novel tricyclic oxazolidinones by a tandem SN2 and SNAr reaction: SAR studies on conformationally constrained analogues of Linezolid.

    Science.gov (United States)

    Selvakumar, N; Yadi Reddy, B; Sunil Kumar, G; Khera, Manoj Kumar; Srinivas, D; Sitaram Kumar, M; Das, Jagattaran; Iqbal, Javed; Trehan, Sanjay

    2006-08-15

    A series of conformationally constrained analogues of Linezolid were synthesised by employing a tandem SN(2) and SNAr reaction as the key step and tested for antibacterial activity. While the hexahydroazolo-quinoxaline compounds were inactive, the tetrahydroazolo-benzothiazine compounds exhibited interesting antibacterial activity. The introduction of fluorine in the aromatic ring further made the compounds more potent in acetamide compounds resulting in an interesting analogue 32. However, the introduction of fluorine (analogue 34) on the already potent non-fluorine thiocarbamate 21 did not have any influence on the activity.

  4. To comparatively evaluate the antimicrobial efficacy of chlorhexidine, nisin and linezolid as an intracanal medicament on Enterococcus faecalis: An in vitro study

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    Geethu Somanath

    2015-01-01

    Results: In group Nisin, the mean CFU was 10.6250 at 24 hrs, 6.6250 at 72 hrs and 6.2500 after 1 week respectively (statistically significant. In group Chlorhexidine, mean CFU was found to be the lowest of 10.5000 at 24 hrs, with further gradual increase to 13.7500 at 72 hrs and further increase to 15.8750 by 1 week. Similarly, in group linezolid , the mean CFU was found to decrease from 49.0000 at 24 hrs to 29.8750 at 72hrs and then increase to 34.8750 in 1 week

  5. Interspecies transfer of the penicillin-binding protein 3-encoding gene ftsI between Haemophilus influenzae and Haemophilus haemolyticus can confer reduced susceptibility to β-lactam antimicrobial agents.

    Science.gov (United States)

    Søndergaard, Annette; Witherden, Elizabeth A; Nørskov-Lauritsen, Niels; Tristram, Stephen G

    2015-07-01

    Mutations in ftsI, encoding penicillin-binding protein 3, can cause decreased β-lactam susceptibility in Haemophilus influenzae. Sequencing of ftsI from clinical strains has indicated interspecies recombination of ftsI between H. influenzae and Haemophilus haemolyticus. This study documented apparently unrestricted homologous recombination of ftsI between H. influenzae and H. haemolyticus in vitro. Transfer of ftsI from resistant isolates conferred similar but not identical increases in the MICs of susceptible strains of H. influenzae and H. haemolyticus.

  6. Susceptibility profiles of Nocardia spp. to antimicrobial and antituberculotic agents detected by a microplate Alamar Blue assay

    Science.gov (United States)

    Zhao, Pan; Zhang, Xiujuan; Du, Pengcheng; Li, Guilian; Li, Luxi; Li, Zhenjun

    2017-01-01

    Nocardia species are ubiquitous in natural environments and can cause nocardiosis. Trimethoprim-sulfamethoxazole has long been the monotherapy treatment of choice, but resistance to this treatment has recently emerged. In this study, we used microplate Alamar Blue assays to determine the antimicrobial susceptibility patterns of 65 standard Nocardia isolates, including 28 type strains and 20 clinical Nocardia isolates, to 32 antimicrobial agents, including 13 little studied drugs. Susceptibility to the most commonly used drug, trimethoprim-sulfamethoxazole, was observed in 98% of the isolates. Linezolid, meropenem, and amikacin were also highly effective, with 98%, 95%, and 90% susceptibility, respectively, among the isolates. The isolates showed a high percentage of resistance or nonsusceptibility to isoniazid, rifampicin, and ethambutol. For the remaining antimicrobials, resistance was species-specific among isolates and was observed in traditional drug pattern types. In addition, the antimicrobial susceptibility profiles of a variety of rarely encountered standard Nocardia species are reported, as are the results for rarely reported clinical antibiotics. We also provide a timely update of antimicrobial susceptibility patterns that includes three new drug pattern types. The data from this study provide information on antimicrobial activity against specific Nocardia species and yield important clues for the optimization of species-specific Nocardia therapies. PMID:28252662

  7. Genotypically Different Clones of Staphylococcus aureus Are Diverse in the Antimicrobial Susceptibility Patterns and Biofilm Formations

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    Salman Sahab Atshan

    2013-01-01

    Full Text Available This study evaluated whether genotypically different clinical isolates of S. aureus have similar susceptibilities to individual antibiotics. It further aims to check the impact of biofilm on the in vitro activity of vancomycin, daptomycin, linezolid, and tigecycline against S. aureus clones. The study used a total of 60 different clinical MSSA and MRSA isolates. Susceptibilities were performed in planktonic cultures by macrobroth dilution and epsilon-test (E test system. Biofilm production was determined using an adherent plate assay. The efficacy of antimicrobial activities against biofilms formation was checked using confocal laser scanning microscopy (CLSM. The study found that similar and different spa, MLST, and SCCmec types displayed high variation in their susceptibilities to antibiotics with tigecycline and daptomycin being the most effective. The biofilms were found resistant to high concentrations of most antibiotics tested with daptomycin being the most effective drug used in adhesive biofilms. A considerable difference exists among similar and various clone types against antibiotics tested. This variation could have contributed to the degree of virulence even within the same clonal genotype and enhanced heterogeneity in the infection potential. Thus, the development of a rapid and precise identification profile for each clone in human infections is important.

  8. Antimicrobial susceptibility pattern of Staphylococcus aureus isolated from clinical specimens in Northern area of Jordan

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    Mazhar Salim Al Zoubi

    2015-12-01

    Full Text Available Background and Objectives: The global spread of methicillin resistant Staphylococcus aureus (MRSA constitutes one of the most serious contemporary challenges to the treatment of hospital-acquired infections. We aimed to screen and assess the antibiotic susceptibility pattern of Staphylococcus aureus isolated from clinical specimens in local hospitals of Northern province in Jordan.Materials and Methods: Staphylococcus aureus was isolated and identified using standard methods from various clinical specimens of different infected body sites from 358 patients during the period from January 2005 to November 2008.Results: Our analysis showed that 31.6% of S. aureus infections were MRSA, while 31% were multidrug resistance (MDR and 42.7% were Oxacillin-resistant (ORSA. Most of these strains were isolated from wound specimens. All isolates were susceptible to vancomycin (100%. They were also susceptible to chloramphenicol, linezolid, nitrofurantoin, rifampicin and teicoplanin (>80%, but showed resistance to erythromycin and penicillin.Conclusion: Vancomycin was the most effective antimicrobial agent against S. aureus. We recommend regular surveillance of hospital associated infections and monitoring antibiotic sensitivity pattern and strict drug policy for antibiotics used within and outside the hospital environments. Keywords: Staphylococcus aureus, MRSA, MDR

  9. Invasive isolates of Streptococcus pneumoniae in Serbia: Antimicrobial susceptibility and serotypes

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    Gajić Ina

    2013-01-01

    Full Text Available Introduction. Streptococcus pneumoniae is one of the leading causes of bacterial meningitis and sepsis. Invasive pneumococcal disease is a significant medical problem worldwide, particularly in children, due to a huge increase of pneumococcal resistance to antibiotics. Objective. The aim of the study was to investigate the antimicrobial susceptibility pattern of invasive pneumococcal isolates, as well as to determine whether decreased S. pneumoniae susceptibility to antibiotics was related to a particular serotype. Methods. Antimicrobial susceptibility to 19 antibiotics was determined in 58 invasive pneumococcal strains that were collected from seven regional centers during the period July 2009 to February 2011 in the National Reference Laboratory for streptococci and pneumococci. Results. The overall nonsusceptibility rate to penicillin was detected in 34% of pneumococcal isolates and to erythromycin in 36%. Higher resistance rates were observed among children than among adults. Penicillin resistance rate was 65% in children versus 22% in adults, while erythromycin nonsusceptibility rate was 47% in children versus 32% in adults. Co-resistance to penicillin and erythromycin was detected in 21% strains, mostly isolated from children. Multiresistance was found in one third of isolates. All strains were susceptible to vancomycin, linezolid, fluoroquinolones, telithromycin and rifampicin, while 23 (40% isolates were susceptible to all tested antibiotics. The most common resistant serotypes were 19F and 14. Conclusion. The study has revealed that penicillin and macrolide resistance among invasive pneumococcal isolates is very high in Serbia. This emphasizes the need for continuous monitoring for invasive pneumococcal disease to document the serotype distribution and antimicrobial susceptibility pattern. [Projekat Ministarstva nauke Republike Srbije, br. 175039: Bakterije rezistentne na antibiotike u Srbiji - fenotipska i genotipska karakterizacija

  10. 10例利奈唑胺不敏感肠球菌血流感染的临床特征及药敏分析%The clinical features and drug resistance of 10 patients with linezolid-nonsusceptible Enterococcal blood stream infection

    Institute of Scientific and Technical Information of China (English)

    徐慧; 周华; 杨青; 沈毅弘; 周建英

    2016-01-01

    antibacterial drug exposure within 2 weeks;none had linezolid exposure within 1 year.4 patients received glycopeptides therapy,4 patients received carbapenems therapy,1 patient received tigecycline and piperacillin/tazobactam combination therapy,and 1 patient received quinolone and aminoglycoside combination therapy.After treatment,there were 7 cases of bacteria removal,6 cases of clinical improvement;4 cases died of MODS.6 linezolid-resistant strains and 4 linezolid-mediated strains were detected,all of which were sensitive to vancomycin,tigecycline and teicoplanin,while resistant to most of the other antibiotics.Conclusion Linezolid-nonsusceptible Enterococcal BSI are often complicated with severe basic diseases,and the patients had a history of repeated hospitalization and antibiotic exposure.Due to multidrug-resistance,the infections of these patients are refractory,which causes high mortality among them.Appropriate antibiotic use and normative nosocomial infection control are important measures to effectively reduce the emergence of drug-resistant strains.

  11. Amino acid substitution or insertion patterns in penicillin-binding protein 2 in Neisseria gonorrhoeae isolates with reduced susceptibility to ceftriaxone%头孢曲松低敏的淋球菌中青霉素结合蛋白2氨基酸替代或插入模式研究

    Institute of Scientific and Technical Information of China (English)

    蒋法兴; 其木格; 钱革; 郑波; 叶顺章; 苏晓红; 胡白; 王千秋

    2008-01-01

    Objective To investigate the amino acid patterns in penicillin-binding protein 2(PBP2)in Neisseria gonorrhoeae isolates with reduced susceptibility to ceftriaxonc.and the relationship between the amino acid patterns and reduced ceftriaxone susceptibility.Methods DNA was extracted from 13 clinical isolates of N.gonorrhoeae.including 11 strains with decreased susceptibility to ceftriaxone and 2 sensitive isolates.The full-length penA gene encoding the penicillin-binding protein 2 was amplified and sequenced.BLASTn and BLASTx programs were used to assess the insertion and substitution patterns of nucleotides in penA gene and of amino acids in PBP2,respectively.Results BLASTn analysis revealed insertion or substitution of 18-38 nucleotides in the penA gene of gonococcal isolates with reduced ceftriaxone susceptibility.As shown by BLASTX analysis.there were five patterns of amino acid substitution or insertion in PBP2 of the 11 isolates with reduced ceftriaxone susceptibility.However.mosaic structure of PBP2 was not found in any of these isolates.Conclusion Mosaic PBP2 seems not to be the major factor contributing to the decrease in susceptibility of N.gonorrhoeae to ceftriaxone.%目的 检测头孢曲松低敏的淋球菌中青霉素结合蛋白2(PBP2)模式,探讨其是否与淋球菌对头孢曲松敏感性降低有关.方法 将11株头孢曲松低敏和2株头孢曲松敏感的淋球菌penA基因全基因测序,通过BLASTn与BLASTx分析,研究penA基因的碱基插入和置换情况及PBP2中氨基酸插入和置换模式.结果 13株淋球菌的penA基因中有多个碱基置换或插入,PBP2中共发现5种模式的氨基酸插入或置换模式,没有发现PBP2镶嵌状结构模式.结论 PBP2的镶嵌状结构可能不是导致淋球菌对头孢曲松敏感性下降的主要因素.

  12. Retrospective Analysis of Clinical and Cost Outcomes Associated with Methicillin-Resistant Staphylococcus aureus Complicated Skin and Skin Structure Infections Treated with Daptomycin, Vancomycin, or Linezolid

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    Bradley M. Wright

    2011-01-01

    Full Text Available Objective. The objective of this analysis was to compare clinical and cost outcomes associated with patients who had suspected or documented methicillin-resistant Staphylococcus aureus (MRSA infections treated with daptomycin, vancomycin, or linezolid in complicated skin and skin structure infections (cSSSIs. Design. This was a retrospective analysis conducted from February to June of 2007. Appropriate data was collected, collated, and subsequently evaluated with the purpose of quantifying length of stay, antibiotic therapy duration, clinical cure rates, adverse drug events, and cost of hospitalization. Results. All 82 patients included in the analysis experienced clinical cure. The duration of antibiotic therapy was similar among the three groups yet the length of hospitalization was slightly shorter in the daptomycin group. Conclusions. The incidence of resistant staphylococcal infections is increasing; therefore, judicious use of MRSA active agents is paramount. Future studies are necessary to determine if MRSA treatment options can be stratified based on the severity of the infectious process.

  13. A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalisation.

    Science.gov (United States)

    Nicholson, Susan C; Welte, Tobias; File, Thomas M; Strauss, Richard S; Michiels, Bart; Kaul, Pratibha; Balis, Dainius; Arbit, Deborah; Amsler, Karen; Noel, Gary J

    2012-03-01

    Community-acquired pneumonia (CAP) is a serious infection requiring hospitalisation in 20% of cases. The novel cephalosporin ceftobiprole has microbiological activity against the major bacterial pathogens causing CAP, including Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae, as well as against Staphylococcus aureus, including meticillin-resistant S. aureus (MRSA). This was a multicentre, double-blind study in which 706 patients with CAP severe enough to require hospitalisation were randomised to ceftobiprole or to an expert-recommended course of ceftriaxone ± linezolid (comparator group). Clinical and microbiological outcomes were determined 7-14 days after completion of therapy (test-of-cure visit). For the 469 clinically evaluable patients, cure rates were 86.6% vs. 87.4% for ceftobiprole and comparator, respectively [95% confidence interval (CI) of the difference, -6.9% to 5.3%]; in the intention-to-treat (ITT) analysis of 638 CAP patients, these cure rates were 76.4% vs. 79.3%, respectively (95% CI of the difference, -9.3% to 3.6%). A typical bacterial pathogen was identified in 29% of the ITT population. Microbiological eradication rates in the 144 microbiologically evaluable patients were 88.2% and 90.8% for the respective treatment groups (95% CI of the difference, -12.6% to 7.5%). Both study drugs were well tolerated, with but a minority of patients requiring premature discontinuation due to an adverse event (6% in the ceftobiprole group and 4% in the comparator group). The overall incidence of treatment-related adverse events was higher in the ceftobiprole group, primarily owing to differences in rates of self-limited nausea (7% vs. 2%) and vomiting (5% vs. 2%). In summary, ceftobiprole was non-inferior to the comparator (ceftriaxone ± linezolid) in all clinical and microbiological analyses conducted, suggesting that ceftobiprole has a potential role in treating hospitalised patients with CAP. [ClinicalTrials.gov identifier

  14. Real-time PCR using mycobacteriophage DNA for rapid phenotypic drug susceptibility results for Mycobacterium tuberculosis.

    Science.gov (United States)

    Pholwat, Suporn; Ehdaie, Beeta; Foongladda, Suporn; Kelly, Kimberly; Houpt, Eric

    2012-03-01

    Managing drug-resistant Mycobacterium tuberculosis requires drug susceptibility testing, yet conventional drug susceptibility testing is slow, and molecular testing does not yield results for all antituberculous drugs. We addressed these challenges by utilizing real-time PCR of mycobacteriophage D29 DNA to evaluate the drug resistance of clinical M. tuberculosis isolates. Mycobacteriophages infect and replicate in viable bacterial cells faster than bacterial cells replicate and have been used for detection and drug resistance testing for M. tuberculosis either by using reporter cells or phages with engineered reporter constructs. Our primary protocol involved culturing M. tuberculosis isolates for 48 h with and without drugs at critical concentrations, followed by incubation with 10(3) PFU/ml of D29 mycobacteriophage for 24 h and then real-time PCR. Many drugs could be incubated instantly with M. tuberculosis and phage for 24 h alone. The change in phage DNA real-time PCR cycle threshold (C(T)) between control M. tuberculosis and M. tuberculosis treated with drugs was calculated and correlated with conventional agar proportion drug susceptibility results. Specifically, 9 susceptible clinical isolates, 22 multidrug-resistant (MDR), and 1 extensively drug-resistant (XDR) M. tuberculosis strains were used and C(T) control-C(T) drug cutoffs of between +0.3 and -6.0 yielded 422/429 (98%) accurate results for isoniazid, rifampin, streptomycin, ethambutol, amikacin, kanamycin, capreomycin, ofloxacin, moxifloxacin, ethionamide, para-aminosalicylic acid, cycloserine, and linezolid. Moreover, the ΔC(T) values correlated with isolate MIC for most agents. This D29 quantitative PCR assay offers a rapid, accurate, 1- to 3-day phenotypic drug susceptibility test for first- and second-line drugs and may suggest an approximate MIC.

  15. Epidemic extinction in a generalized susceptible-infected-susceptible model

    Science.gov (United States)

    Chen, Hanshuang; Huang, Feng; Zhang, Haifeng; Li, Guofeng

    2017-01-01

    We study the extinction of epidemics in a generalized susceptible-infected-susceptible model, where a susceptible individual becomes infected at the rate λ when contacting m infective individual(s) simultaneously, and an infected individual spontaneously recovers at the rate μ. By employing the Wentzel-Kramers-Brillouin approximation for the master equation, the problem is reduced to finding the zero-energy trajectories in an effective Hamiltonian system, and the mean extinction time depends exponentially on the associated action S and the size of the population N, ˜ \\exp ≤ft(NS\\right) . Because of qualitatively different bifurcation features for m  =  1 and m≥slant 2 , we derive independently the expressions of S as a function of the rescaled infection rate λ /μ . For the weak infection, S scales to the distance to the bifurcation with an exponent 2 for m  =  1 and 3/2 for m≥slant 2 . Finally, a rare-event simulation method is used to validate the theory.

  16. MR susceptibility imaging

    Science.gov (United States)

    Duyn, Jeff

    2013-04-01

    This work reviews recent developments in the use of magnetic susceptibility contrast for human MRI, with a focus on the study of brain anatomy. The increase in susceptibility contrast with modern high field scanners has led to novel applications and insights into the sources and mechanism contributing to this contrast in brain tissues. Dedicated experiments have demonstrated that in most of healthy brain, iron and myelin dominate tissue susceptibility variations, although their relative contribution varies substantially. Local variations in these compounds can affect both amplitude and frequency of the MRI signal. In white matter, the myelin sheath introduces an anisotropic susceptibility that has distinct effects on the water compartments inside the axons, between the myelin sheath, and the axonal space, and renders their signals dependent on the angle between the axon and the magnetic field. This offers opportunities to derive tissue properties specific to these cellular compartments.

  17. Antimicrobial susceptibility of Staphylococcus pseudintermedius colonizing healthy dogs in Saskatoon, Canada.

    Science.gov (United States)

    Priyantha, Roshan; Gaunt, Mathew C; Rubin, Joseph E

    2016-01-01

    This study reports antimicrobial susceptibility of Staphylococcus pseudintermedius carried by healthy dogs in Saskatoon, and describes changes in antimicrobial resistance since a 2008 study. One hundred healthy dogs presenting to the wellness service at the Western College of Veterinary Medicine were screened for S. pseudintermedius by culturing rectal and pharyngeal swabs. Staphylococcus pseudintermedius was identified biochemically and antimicrobial minimum inhibitory concentrations were determined by broth microdilution. Methicillin resistance was confirmed by polymerase chain reaction (PCR) and sequencing of the mecA gene. Of 221 S. pseudintermedius isolates from 78 dogs, 7 were methicillin resistant. No resistance to the fluoroquinolones, nitrofurantoin, tigecycline, vancomycin, quinupristin-dalfopristin, linezolid, or daptomycin was identified. Of the 78 positive dogs, isolates resistant to penicillin were found in 78%, to ampicillin in 61% and to tetracycline in 26%; resistance to oxacillin, erythromycin, clindamycin, trimethoprim + sulfamethoxazole, chloramphenicol, and gentamicin was found in < 10% of dogs. Compared to the 2008 study, the frequency of resistance to all drugs increased, and the frequency of colonization with pan-susceptible isolates decreased from 46% to 30%.

  18. Effects of Linezolid on Platelet during Treatment of Elderly Patients with Lung Infection%利奈唑胺治疗老年肺部感染对血小板的影响

    Institute of Scientific and Technical Information of China (English)

    李娟; 马容莉; 张艳

    2012-01-01

    目的 评价利奈唑胺对住院老年肺部感染患者血小板的影响.方法 回顾性分析13例住院老年患者肺部感染后应用利奈唑胺治疗的临床资料.结果 13例应用利奈唑胺抗感染治疗的患者,7例发生血小板减少,发生率为53.85%,在用药第3~12天,平均(6.4±2.5)d开始出现血小板下降,第6~12天,平均(9.4±2.6)d降至最低,有2例出血,7例患者均停用利奈唑胺,其中2例输注血小板,1例输注血浆,停药后3~6 d,平均(4.1±1.1)d血小板开始回升,停药后6~12 d,平均(10.0±3.2)d恢复至正常水平.结论 利奈唑胺在治疗住院老年肺部感染患者时,血小板减少发生率较高;临床选用利奈唑胺要慎重,治疗期间和治疗后严密监测血小板.%Objective To evaluate the effects of linezolid on platelet in the process of treating elderly patients with gram-negative bacteria affected lung infection. Methods Clinical data of 13 elderly patients with lung infection who were treated with linezolid were analyzed retrospectively. Results There were 7 elderly patients developed thrombocytopenia, and the incidence of which was 53. 85%. The reduction of platelet developed on the third to twelfth day of linezolid usage, and the lowest platelets count occurred on the sixth to twelfth day. There were 2 cases of thrombocytopenia with bleeding complications. All the 7 cases terminated using linezolid, in which there were 2 cases infused with platelet and 1 with plasma. The platelets counts rose a-gain on the third to sixth day after linezolid withdrawn, and the platelet resumed to the normal level on the sixth to fourteenth day. Conclusion When elderly in-patients with lung infection receive linezolid against gram-negative bacteria, the incidence of thrombocytopenia turns high. In clinical settings, we should choose linezolid carefully and monitor platelet counts closely in the course of using linezolid and post-treatment.

  19. Clinical analysis of infective endocarditis treated with linezolid%利奈唑胺治疗感染性心内膜炎临床分析

    Institute of Scientific and Technical Information of China (English)

    卢芬; 何朝生; 胡湘明; 张莉滟; 李晓明; 廖火生; 林蔡弟

    2016-01-01

    目的:探讨利奈唑胺治疗感染性心内膜炎(IE)的疗效及安全性。方法纳入2009年1月~2015年3月间于广东省人民医院平洲分院收治的诊断为感染性心内膜炎并使用利奈唑胺抗感染治疗的住院患者11例,分析其临床特点及使用利奈唑胺治疗IE的临床疗效及不良反应。结果入选患者男性6例,女性5例,平均年龄(47.0±19.4)岁;既往心脏病史:二尖瓣脱垂3例,风湿性心脏病瓣膜置换术后3例(其中1例安装起搏器),既往感染性心内膜炎病史2例,先天性心脏病史1例,无心脏病史2例;心脏瓣膜损害情况:左心自体瓣膜4例,右心自体瓣膜1例,左右心自体瓣膜1例,人工瓣膜5例;病原菌:粪肠球菌3例,丙酸丙酸杆菌1例,路邓葡萄球菌1例,金黄色葡萄球菌2例,表皮葡萄球菌1例,血链球菌1例,血培养阴性2例;血培养阳性细菌对糖肽类及噁唑酮类抗菌药物均敏感;心脏超声情况:单纯瓣膜赘生物形成5例,赘生物并穿孔3例,赘生物并瓣周脓肿1例,单纯瓣膜脓肿2例;治疗情况:急诊手术1例,择期手术4例,保守治疗6例,治愈10例,治愈率达90.90%;使用利奈唑胺时间5~56 d,平均(23.6±16.2)d;随访时间最短6个月,最长4年无复发;主要不良反应为血小板减少,总共有6例,占54.55%,患者停药和输注血小板或予重组人血小板生成素治疗后均恢复正常。结论利奈唑胺治疗IE临床疗效好,主要不良反应为血小板减少,是一种可逆性不良反应。%Objective To investigate the curative effect and safety of linezolid in treatment of infective endocarditis (IE).Methods The patients (n=11) diagnose with IE and treated with linezolid in the Pingzhou Branch of Guangdong Provincial People’s Hospital were chosen from Jan. 2009 to Mar. 2015. The clinical characteristics of the patients, and curative effect and adverse

  20. Antimicrobial susceptibility of bacteria, isolated from patients treated at Jesenice General hospital in the period between 2004 and 2006

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    Helena Ribič

    2007-11-01

    Full Text Available Background: Antimicrobial resistance of bacteria is still one of the mayor problems in medicine. In the year 2006, microbiologists of the Institute of Public Health Kranj together with clinicians and pharmacist of Jesenice General Hospital prepared the programm of antimicrobial resistance surveillance of patients treated in the hospital. Some of the results are presented in this article.Methods: In the retrospective study, bacterial strains, isolated from different samples were analysed. The strains were isolated and studied during the routine work of microbiology laboratory of IPH Kranj in the period between 2004 and 2006.Results: The most frequently isolated bacteria from haemocultures was Escherichia coli (35.4 %. In the years 2004 and 2006, susceptibility of strains for ciprofloxacin was 95.7 % and 97.2 %, for parenteral cefuroxime (95.7 % and 94.4 %, for cefotaxime and gentamicin in both years 100 %. Susceptibility of E. coli strains from urine samples in patients from the department for internal medicine was in 2004 and 2006 for co-amoxiclav 88.5 % and 70.1 %, for co-trimoxazole 60.3 % and 81.3 %, for cefaclor 94.9 % and 89.7 %, for ciprofloxacin 83.3 % and 82.2 %. Among strains of Staphylococcus aureus, 100 % were sensitive to vancomycin and 99.3 % to linezolid in 2006. Among methicillin susceptible strains, sensitivity to erythromycin, clindamycin and ciprofloxacin lowered slightely in the three years period; in 2006 it was 87.6 %, 90.6 % and 89.1 %. Susceptibility of strains Pseudomonas aeruginosa was in 2006 similar comparing to 2004; it was 92 % for ceftazidime, 75 % for gentamicin, 64.6 % for ciprofloxacin and 96 % for imipenem. Among strains of Acinetobacter spp., sensitivity rate to ciprofloxacin, ceftazidime, piperacillin with tazobactam and gentamicin significantly fell in the year 2005 and stayed low in 2006.Conclusions: The results of antimicrobial susceptibility surveillance and trends of susceptibility are intended to guide

  1. Inoculum effects of ceftobiprole, daptomycin, linezolid, and vancomycin with Staphylococcus aureus and Streptococcus pneumoniae at inocula of 10(5) and 10(7) CFU injected into opposite thighs of neutropenic mice.

    Science.gov (United States)

    Lee, Dong-Gun; Murakami, Yoichi; Andes, David R; Craig, William A

    2013-03-01

    Reduced bactericidal efficacy at a high inoculum is known as the inoculum effect (IE). We used neutropenic mice to compare the IEs of ceftobiprole (CFB), daptomycin (DAP), linezolid (LZD), and vancomycin (VAN) against 6 to 9 strains of Staphylococcus aureus and 4 strains of Streptococcus pneumoniae at 2 inocula in opposite thighs of the same mice. Neutropenic mice had 10(4.5) to 10(5.7) CFU/thigh (low inoculum [LI]) in one thigh and 10(6.4) to 10(7.2) CFU/thigh (high inoculum [HI]) in the opposite thigh when treated for 24 h with subcutaneous (s.c.) doses every 12 h of DAP at 0.024 to 100 mg/kg of body weight and LZD at 0.313 to 320 mg/kg and s.c. doses every 6 h of CFB at 0.003 to 160 mg/kg and VAN at 0.049 to 800 mg/kg. Dose-response data were analyzed by a maximum effect (E(max)) model using nonlinear regression. Static doses for each drug and at each inoculum were calculated, and the difference between HI and LI (IE index) gave the magnitude of IE for each drug-organism combination. Mean (range) IE indexes of S. aureus were 2.9 (1.7 to 4.6) for CFB, 4.1 (2.6 to 9.3) for DAP, 4.6 (1.7 to 7.1) for LZD, and 10.1 (6.3 to 20.3) for VAN. In S. pneumoniae, the IE indexes were 2.5 (1.3 to 3.3) for CFB, 2.0 (1.6 to 2.8) for DAP, 1.9 (1.7 to 2.2) for LZD, and 1.5 (0.8 to 3.2) for VAN; these values were similar for all drugs. In S. aureus, the IE was much larger with VAN than with CFB, DAM, and LZD (P < 0.05). An in vivo time course of vancomycin activity showed initiation of killing at 4- to 16-fold-higher doses at HI than at LI despite similar initial growth of controls.

  2. Climate change and corn susceptibility to mycotoxins

    Science.gov (United States)

    Maize is an essential part of the world’s grain supply, but climate change has the potential to increase maize susceptibility to mycotoxigenic fungal pathogens and reduce food security and safety. While rising atmospheric [CO2] is a driving force of climate change, our understanding of how elevated ...

  3. Genetic susceptibility of periodontitis

    NARCIS (Netherlands)

    Laine, M.L.; Crielaard, W.; Loos, B.G.

    2012-01-01

    In this systematic review, we explore and summarize the peer-reviewed literature on putative genetic risk factors for susceptibility to aggressive and chronic periodontitis. A comprehensive literature search on the PubMed database was performed using the keywords ‘periodontitis’ or ‘periodontal dise

  4. Evaluation on efficacy and safety of vancomycin and linezolid for treatment of pulmonary infections%万古霉素与利奈唑胺治疗肺部感染的有效性及安全性评价

    Institute of Scientific and Technical Information of China (English)

    王昱; 张红瑾; 安爱军

    2015-01-01

    目的:比较万古霉素与利奈唑胺治疗耐甲氧西林金黄色葡萄球菌(M RS A )肺部感染的疗效及安全性。方法选取2012年5月-2013年5月109例M RS A肺部感染患者为研究对象,将其分为万古霉素组73例及利奈唑胺组36例,万古霉素组予以万古霉素1.0g,每12h1次进行治疗,利奈唑胺组予以利奈唑胺0.6g,每12h 1次进行治疗,观察两组患者治疗后的临床效果及安全性。结果治疗总有效率万古霉素组为76.71%、利奈唑胺组为61.11%,两组比较差异有统计学意义( P<0.05);而两组患者治疗后白细胞计数、C‐反应蛋白、中性粒细胞比值、降钙素原及并发症发生率比较差异无统计学意义。结论对M RS A肺部感染患者,万古霉素与利奈唑胺敏感性均较高,总体疗效万古霉素略高,且安全性和耐受性较利奈唑胺略高。%OBJECTIVE To compare efficacy and safety of vancomycin and linezolid for treatment of pulmonary infections caused by methicillin‐resistant Staphylococcus aureus (MRSA ) .METHODS Totally 109 cases of pulmonary MRSA infections during May 2012 to May 2013 were enrolled and divided into two groups , the vancomycin group (n=73) and the linezolid group (n=36) .The vancomycin group received vancomycin 1 .0 g , administrated every 12 hours ,and the linezolid group received linezolid 0 .6 g ,administrated every 12 hours .The clinical efficacy and safety after treatment were observed .RESULTS The total effective rate was 76 .71% in the vancomycin group and 61 .11% in the linezolid group ,the difference was significant (P<0 .05) .And there was no significant difference in white blood cell count ,C‐reactive protein ,neutrophil ratio ,PCT and the incidence of complications after treatment between the two groups .CONCLUSION Vancomycin and linezolid were sensitive for patients with pulmonary MRSA infection and the overall efficacy , safety and tolerability of

  5. 替考拉宁与利奈唑胺治疗MRSA感染的临床比较%Clinical efficacy of teicoplanin and linezolid for MRSA infections: a comparative study

    Institute of Scientific and Technical Information of China (English)

    姚孟英; 邢丽华; 张庆宪; 许爱国; 张伟宏

    2012-01-01

    OBJECTIVE To compare the therapeutic effect and safety of teicoplanin and linezolid used for the treatment of the patients with MRSA infections in TCU. METHODS The open-label control test was performed for 68 patients with MRSA infections was performed,35 cases were treated with teicoplanin for 400mg/per time and 12h once, after 3 doses,once per dayi 33 patients with MRSA infections were treated with linezolid for 600mg per time.l2h once, which were all the intravenous drip with 14-18d a course; the therapeutic effect, bacterial clearance, and APACHE D score before and after the medication between the two groups were compared. RESULTS The clinical effective rates of teicoplanin and linezolid for treatment of severe MRSA infections were 88. 6 % and 90. 9 %, respectively (P>0. 05), the bacterial clearance rates were 86. 8 % and 88. 2 % , respectively the differences were not statistically significant) the APACHE Ⅱ score of the patients on the 14th day were (10. 17 ±3. 32) and (13. 66±5. 98), respectively, the teicoplanin group was superior to the linezolid group,the difference was statistically significant (P<0. 05); the incidence rates of the adverse reactions were 11. 4% and 18. 2%, the incidence rate of the adverse reactions was lower in the teicoplanin group than in the linezolid group, the difference was statistically significant (P<0. 05). CONCLUSION Both teicoplanin and linezolid exhibit a similar clinical efficacy on the treatment of patients with MRSA infections, but the teicoplanin is superior to linezolid in the safety of clinical medication.%目的 评价替考拉宁与利奈唑胺随机对照治疗重症监护室MRSA感染患者的疗效和安全性.方法 对68例MRSA重症感染患者进行随机对照开放试验,分为替考拉宁组35例,剂量400mg/次,1次/12 h,3个剂量后,1次/d;利奈唑胺组33例,剂量600mg/次,1次/12 h,均为静脉滴注,疗程14~18 d;比较两组病例的疗效、细菌清除率、用药前

  6. Characterisation of clinical meticillin-resistant Staphylococcus epidermidis demonstrating high levels of linezolid resistance (>256 μg/ml) resulting from transmissible and mutational mechanisms.

    Science.gov (United States)

    Gabriel, Emma M; Fitzgibbon, Siobhan; Clair, James; Coffey, Aidan; O'Mahony, Jim M

    2015-07-01

    Staphylococcus epidermidis (S. epidermidis), one of the leading etiological agents of nosocomial infections poses a significant economic burden globally. Introduced in 2000, linezolid (LZD) has become an important antibiotic, used in nearly seventy countries worldwide to treat infections caused by Gram-positive pathogens such as meticillin-resistant Staphylococcus and Streptococcus species along with vancomycin-resistant enterococci. Resistance to LZD in clinical settings remains rare. Here, we report the emergence of meticillin resistant S. epidermidis (MRSE) clinical isolates from two voluntary general acute hospitals exhibiting higher than typically reported levels of LZD resistance (MIC>256 μg/ml). The MRSE ST-2 clone isolated from eight patients (2010-2011) not only possessed resistance-conferring mutations such as G2576T in domain V of 23S rRNA gene (as determined by HRM-PCR analysis) and R172C substitution in the ribosomal protein L3, but also carried the cfr gene (the only known transmissible mechanism of LZD resistance). All isolates possessed several key biofilm-associated genes (such as icaA, icaD, aap and atlE) and resistance to multiple clinically significant antibiotics was recorded. This study reports the earliest incidence (2010) of clinical MRSE in the Republic of Ireland demonstrating multiple LZD resistance mechanisms both mutational and potentially transmissible, and characterises this emerging resistance from a molecular perspective.

  7. A 5-year survey of antimicrobial susceptibility profiles of methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients with bloodstream infections in Northeast Italy.

    Science.gov (United States)

    Cojutti, Piergiorgio; Scarparo, Claudio; Sartor, Assunta; Coato, Paola; Rigoli, Roberto; Pea, Federico

    2015-01-01

    A 5-year survey (2009-2013) of antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients with bloodstream infections was carried out in Northeast Italy. No upward creep of glycopeptides MICs was documented among 582 nonduplicate MRSA blood isolates, which were tested in accordance with broth microdilution and interpreted in accordance with EUCAST recommendations. Teicoplanin showed stably a lower MIC50 in comparison with vancomycin (0.25-0.5 versus 1 mg/L). The activities of newer anti-MRSA antibacterials stratified by glycopeptides MICs showed similar trends in MICs of either vancomycin or teicoplanin with those of daptomycin, linezolid, and tigecycline. We hypothesize that in centers with different distribution of glycopeptides MICs, downward for teicoplanin and upward for vancomycin, teicoplanin could be a more effective alternative to vancomycin for empirical treatment of MRSA-related bacteremia.

  8. Ciprofloxacin susceptibility reduction of Salmonella strains isolated from outbreaks

    Directory of Open Access Journals (Sweden)

    Roberta B. Souza

    2010-06-01

    Full Text Available The antimicrobial susceptibility of 212 Salmonella strains isolated from patients and foods was evaluated and 45% were found to be resistant to nalidixic acid. Nalidixic acid resistant strains showed a higher minimal inhibitory concentration for ciprofloxacin than sensitive strains. During the study an increase of strains with reduced susceptibility to ciprofloxacin was also observed.

  9. 碳青霉烯类抗生素敏感性下降肺炎克雷伯菌耐药机制及分子流行病学研究%Study on the antibiotic resistance mechanism and the molecular epidemiology of Klebsiella Pneumoniae with reduced susceptibility to Carbapenems

    Institute of Scientific and Technical Information of China (English)

    裘莉佩; 常燕子; 孙珺; 魏泽庆; 周华; 俞云松

    2012-01-01

    目的:研究临床分离对碳青霉烯类抗生素敏感性下降肺炎克雷伯菌的耐药机制及同源性分析.方法:收集对碳青霉烯类抗生素敏感性下降肺炎克雷伯菌25株.E test法测定10种抗菌药物的MIC值;脉冲场凝胶电泳分析菌株同源性;PCR及克隆测序分析耐药基因型.结果:25株菌株对β-内酰胺类抗生素呈多重耐药,但对多黏菌素E和替加环素敏感.PFGE分型除一株外均为同一克隆(暗示医院内感染).25株菌株均产KPC-2碳青霉烯酶基因,并同时携带CTX-M、SHV、DHA等多种耐药基因.结论:携带KPC-2基因的肺炎克雷伯菌同时携带多种耐药基因.此类菌株对碳青霉烯类抗生素敏感性下降并对除多黏菌素E和替加环素外抗生素多重耐药.%Objective:To investigate antibiotic resistance mechanism and clonal relatedness of Klebsiella pneumoniae with reduced susceptibility to Carbapenems. Methods; 25 strains of Klebsiella pneumoniae with reduced susceptibility to Carbapenems were collected. The minimum inhibitory concentrations of these strains to 10 kinds of antibiotics were examined by E test. The homology of these isolates was analyzed by pulse — field gel electrophoresis. The encoding gene of β - lactamases were analyzed by PCR and verified by DNA sequencing. Results; All strains of Klebsiella pneumoniae were rmllti - resistant to β — lactam antibiotics, while susceptible to Colistin and Tigecycline. They were classified into the same clone (suggest nosocomial infection) except one based on PFGE pattern. All of the 25 strains produced Carbapenemases which were confirmed as KPC - 2 by PCR and sequencing. These isolates with positive KPC -2 also carried other resistance genes such as CTX - M, SHV, DHA. Conclusion; All of the positive KPC — 2 Klebsiella pneumoniae carried other resistance genes. These strains were low susceptibility to Carbapenems and multi — resistant to other antibiotics except Colistin and Tigecycline.

  10. Genetic Susceptibility to Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sanja Kovacic

    2012-01-01

    Full Text Available Atherosclerosis is a complex multifocal arterial disease involving interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic ground significantly influences susceptibility to atherosclerotic vascular diseases. Besides further investigations of monogenetic diseases, candidate genes, genetic polymorphisms, and susceptibility loci associated with atherosclerotic diseases have been identified in recent years, and their number is rapidly increasing. This paper discusses main genetic investigations fields associated with human atherosclerotic vascular diseases. The paper concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on prospective prediction from an early age of individuals who are predisposed to develop premature atherosclerosis as well as to facilitate the discovery of novel drug targets.

  11. Efficacies of teicoplanin,vancomycin,and linezolid in treatment of patients with MRSA infections%替考拉宁与万古霉素及利奈唑胺治疗MRSA感染患者的疗效评价

    Institute of Scientific and Technical Information of China (English)

    王明强; 张思森; 刘小军; 祁绍艳; 徐彦立

    2015-01-01

    目的:评价替考拉宁、万古霉素及利奈唑胺治疗ICU耐甲氧西林金黄色葡萄球菌(MASA)感染的疗效与安全性。方法选取2013年5月-2014年7月入住医院的96例ICUMRSA重症感染患者,将其随机分为3组,替考拉宁组33例、万古霉素组32例、利奈唑胺组31例,比较3组患者的临床疗效、细菌清除率及不良反应发生率。结果替考拉宁、万古霉素及利奈唑胺治疗MASA感染患者的临床有效率分别为87.88%、81.25%、87.10%,细菌清除率分别为84.85%、81.25%、83.87%,不良反应发生率分别为6.06%、12.50%、9.68%,临床有效率及细菌清除率3组对比差异无统计学意义;不良反应发生率3组对比差异有统计学意义(P<0.05)。结论替考拉宁、万古霉素和利奈唑胺治疗ICUMRSA感染的临床疗效可靠,替考拉宁的不良反应较少,治疗时可优先选择替考拉宁。%OBJECTIVE To evaluate the efficacies and safety of teicoplanin ,vancomycin ,and linezolid in treatment of methicillin‐resistant Staphylococcus aureus (MRSA) infections in ICUs .METHODS A total of 96 patients with severe MRSA infection who were hospitalized the ICUs from May 2013 to Jul 2014 were enrolled in the study and randomly divided into three groups :the teicoplanin group with 33 cases ,the vancomycin group with 32 cases ,and the linezolid group with 31 cases .The clinical efficacies ,bacterial clearance rates ,and incidence of adverse reac‐tions were observed and compared among the three groups .RESULTS The effective rate of clinical treatment of the patients with MRSA infection was 87 .88% in the teicoplanin group ,81 .25% in the vancomycin group ,87 .10%in the linezolid group .The bacterial clearance rate was 84 .85% in the teicoplanin group ,81 .25% in the vancomy‐cin group ,83 .87% in the linezolid group .The incidence of adverse reactions was 6 .06% in the teicoplanin group , 12 .50% in the

  12. Virulence factors, antimicrobial susceptibility and molecular characterization of Streptococcus agalactiae isolated from pregnant women.

    Science.gov (United States)

    Beigverdi, Reza; Jabalameli, Fereshteh; Mirsalehian, Akbar; Hantoushzadeh, Sedigheh; Boroumandi, Shahram; Taherikalani, Morovat; Emaneini, Mohammad

    2014-12-01

    Forty-one Streptococcus agalactiae isolates collected from pregnant women at 35-37 weeks of gestation were analysed for their capsular types, antimicrobial resistance determinants, distribution of virulence factors and genetic relatedness using PCR and multiplex PCR. Capsular type III was predominant (65.8%), followed by capsular type II (14.6%), Ib (7.3%), and V(4.9%). All isolates were susceptible to penicillin, vancomycin, linezolid and quinupristin-dalfopristin. Resistance to tetracycline, erythromycin and clindamycin were found in 97.6%, 24.4%, and 14.6% of isolates, respectively. The most common antimicrobial resistance gene was tetM found in 97.6% of the isolates followed by ermTR and ermB found in 12% and 7.3% of isolates, respectively. The most common virulence gene was hly (100%), followed by scpB (97.6%), bca (97.6%), rib (53.65%) and bac (4.9%). The insertion sequence IS1548 was found in 63.4% of isolates. By multi locus variable number of tandem repeat analysis (MLVA) typing, 30 different allelic profiles or MLVA types (MTs) were identified. The most frequent was the MT1 (5/41, 12.2%) and followed by MT2 (4/41, 9.75%). Our data revealed that population structure of these isolates is highly diverse and indicates different MLVA types.

  13. Effect of habituation to tea tree (Melaleuca alternifolia) oil on the subsequent susceptibility of Staphylococcus spp. to antimicrobials, triclosan, tea tree oil, terpinen-4-ol and carvacrol.

    Science.gov (United States)

    Thomsen, Natalie A; Hammer, Katherine A; Riley, Thomas V; Van Belkum, Alex; Carson, Christine F

    2013-04-01

    The aim of this study was to seek additional data on the antimicrobial susceptibility of Staphylococcus spp. after habituation to low levels of the topical antimicrobial agent tea tree (Melaleuca alternifolia) oil. Meticillin-susceptible Staphylococcus aureus (MSSA), meticillin-resistant S. aureus (MRSA) and coagulase-negative staphylococci (CoNS) were habituated to 0.075% tea tree oil for 3 days. Subsequently, the susceptibility of five isolates each of MSSA, MRSA and CoNS to fusidic acid, mupirocin, chloramphenicol, linezolid and vancomycin was determined by Etest, and susceptibility to tea tree oil, terpinen-4-ol, carvacrol and triclosan was determined by agar dilution. Following habituation to 0.075% tea tree oil, antimicrobial MICs differed between control and habituated isolates on 33 occasions (out of a possible 150), with MICs being higher in habituated isolates on 22 occasions. Using clinical breakpoint criteria, one MSSA isolate changed susceptibility category from vancomycin-susceptible (MIC=2 μg/mL) to intermediate susceptibility (MIC=3 μg/mL) after habituation in one of two replicates. For the non-antibiotic antimicrobial agents, MICs of habituated and control isolates differed on 12 occasions (out of a possible 120); 10 occasions in MRSA and 2 occasions in MSSA. MICs were higher for habituated isolates on five occasions. However, all the differences were one serial dilution only and were not regarded as significant. Habituation to sublethal concentrations of tea tree oil led to minor changes in MICs of antimicrobial agents, only one of which may have been clinically relevant. There is no evidence to suggest that tea tree oil induces resistance to antimicrobial agents.

  14. Identification of the gene mutation conferring resistance to linezolid in a strain of Enterococcus faecalis%1株利奈唑胺耐药粪肠球菌的基因突变检测

    Institute of Scientific and Technical Information of China (English)

    潘伟光; 李一凡; 邓启文; 张健华

    2013-01-01

    Objective To investigate the mechanism of linezolid resistance in a strain of Enterococcus faecalis. Methods We isolated a linezolid-resistant Enterococcus faecalis from the sputum in a patient with heamtological disease. The 23S rRNA V-re-gion and 4 copies of 23S rRNA gene fragments of the linezolid-resistant Enterococcus faecalis strain were amplified using poly-merase chain reaction (PCR), followed by DNA sequencing and sequence alignment analysis. Results One G→U mutation at the 2576 nucleotide (G2576U) was identified in the V-region of 23S rRNA of this drug-resistant strain. A G2576U mutation was also found in three out of the four copies of gene fragments of 23S rRNA. Conclusions G2576U point mutation may be the cause of resistance of this strain to linezolid.%目的 探讨1株对利奈唑胺耐药的粪肠球菌的耐药机制.方法 从广东医学院附属深圳南山医院1例血液病患者痰标本分离出1株对利奈唑胺耐药的粪肠球菌,采用聚合酶链反应(PCR)法,对该菌利奈唑胺耐药的粪肠球菌23S rRNA V区域和23S rRNA 4个拷贝基因片段进行扩增和测序比对分析.结果 耐药菌株23S rRNA V区域第2576位核苷酸发生G→U突变(G2576U),4个拷贝基因片段中,除拷贝1外,其他3个拷贝均发生G2576U突变.结论 G2576U点突变是该菌株的耐药机制.

  15. DNA methyltransferase 1/3a overexpression in sporadic breast cancer is associated with reduced expression of estrogen receptor-alpha/breast cancer susceptibility gene 1 and poor prognosis.

    Science.gov (United States)

    Yu, Zhaojin; Xiao, Qinghuan; Zhao, Lin; Ren, Jie; Bai, Xuefeng; Sun, Mingli; Wu, Huizhe; Liu, Xiaojian; Song, Zhiguo; Yan, Yuanyuan; Mi, Xiaoyi; Wang, Enhua; Jin, Feng; Wei, Minjie

    2015-09-01

    DNA methyltransferases (DNMTs), including DNMT1, 3a, and 3b, play an important role in the progression of many malignant tumors. However, it remains unclear whether expression of DNMTs is associated with the development of breast cancer. This study aimed to explore the clinical significance of DNMT proteins in sporadic breast cancer. We investigated the expression of DNMT1, 3a, and 3b in 256 breast cancer and 36 breast fibroadenoma, using immunohistochemistry. The expression of DNMT1 and 3a was significantly higher in breast cancer than in fibroadenoma. In breast cancer, the expression of DNMT1 was significantly correlated with lymph node metastasis (P = 0.020), and the expression of DNMT3a and 3b was significantly correlated with advanced clinical stages (P = 0.046 and 0.012, respectively). Overexpression of DNMT1/3a was correlated with promoter hypermethylation and reduced expression of ERα and BRCA1. The expression levels of DNMT1 or DNMT3a were associated with a significantly shorter DFS or OS in a subgroup of breast cancer patients (patients with the age ≤50 years old, ERα-negative status, or HER2-postive status). The expression of DNMT1 or a combined expression of DNMT1 and 3a was associated with poor prognosis in patients who received chemotherapy and endocrine therapy, but not in patients who received chemotherapy alone. These findings suggest that DNMT1 and 3a may be involved in the progression and prognosis of sporadic breast cancer.

  16. Network susceptibilities: Theory and applications

    Science.gov (United States)

    Manik, Debsankha; Rohden, Martin; Ronellenfitsch, Henrik; Zhang, Xiaozhu; Hallerberg, Sarah; Witthaut, Dirk; Timme, Marc

    2017-01-01

    We introduce the concept of network susceptibilities quantifying the response of the collective dynamics of a network to small parameter changes. We distinguish two types of susceptibilities: vertex susceptibilities and edge susceptibilities, measuring the responses due to changes in the properties of units and their interactions, respectively. We derive explicit forms of network susceptibilities for oscillator networks close to steady states and offer example applications for Kuramoto-type phase-oscillator models, power grid models, and generic flow models. Focusing on the role of the network topology implies that these ideas can be easily generalized to other types of networks, in particular those characterizing flow, transport, or spreading phenomena. The concept of network susceptibilities is broadly applicable and may straightforwardly be transferred to all settings where networks responses of the collective dynamics to topological changes are essential.

  17. Topological Susceptibility from Slabs

    CERN Document Server

    Bietenholz, Wolfgang; Gerber, Urs

    2015-01-01

    In quantum field theories with topological sectors, a non-perturbative quantity of interest is the topological susceptibility chi_t. In principle it seems straightforward to measure chi_t by means of Monte Carlo simulations. However, for local update algorithms and fine lattice spacings, this tends to be difficult, since the Monte Carlo history rarely changes the topological sector. Here we test a method to measure chi_t even if data from only one sector are available. It is based on the topological charges in sub-volumes, which we denote as slabs. Assuming a Gaussian distribution of these charges, this method enables the evaluation of chi_t, as we demonstrate with numerical results for non-linear sigma-models.

  18. Susceptibility to anchoring effects

    Directory of Open Access Journals (Sweden)

    Todd McElroy

    2007-02-01

    Full Text Available Previous research on anchoring has shown this heuristic to be a very robust psychological phenomenon ubiquitous across many domains of human judgment and decision-making. Despite the prevalence of anchoring effects, researchers have only recently begun to investigate the underlying factors responsible for how and in what ways a person is susceptible to them. This paper examines how one such factor, the Big-Five personality trait of openness-to-experience, influences the effect of previously presented anchors on participants' judgments. Our findings indicate that participants high in openness-to-experience were significantly more influenced by anchoring cues relative to participants low in this trait. These findings were consistent across two different types of anchoring tasks providing convergent evidence for our hypothesis.

  19. Nutrition affects insect susceptibility to Bt toxins

    Science.gov (United States)

    Deans, Carrie A.; Behmer, Spencer T.; Tessnow, Ashley E.; Tamez-Guerra, Patricia; Pusztai-Carey, Marianne; Sword, Gregory A.

    2017-01-01

    Pesticide resistance represents a major challenge to global food production. The spread of resistance alleles is the primary explanation for observations of reduced pesticide efficacy over time, but the potential for gene-by-environment interactions (plasticity) to mediate susceptibility has largely been overlooked. Here we show that nutrition is an environmental factor that affects susceptibility to Bt toxins. Protein and carbohydrates are two key macronutrients for insect herbivores, and the polyphagous pest Helicoverpa zea self-selects and performs best on diets that are protein-biased relative to carbohydrates. Despite this, most Bt bioassays employ carbohydrate-biased rearing diets. This study explored the effect of diet protein-carbohydrate content on H. zea susceptibility to Cry1Ac, a common Bt endotoxin. We detected a 100-fold increase in LC50 for larvae on optimal versus carbohydrate-biased diets, and significant diet-mediated variation in survival and performance when challenged with Cry1Ac. Our results suggest that Bt resistance bioassays that use ecologically- and physiologically-mismatched diets over-estimate susceptibility and under-estimate resistance. PMID:28045087

  20. Nutrition affects insect susceptibility to Bt toxins

    Science.gov (United States)

    Deans, Carrie A.; Behmer, Spencer T.; Tessnow, Ashley E.; Tamez-Guerra, Patricia; Pusztai-Carey, Marianne; Sword, Gregory A.

    2017-01-01

    Pesticide resistance represents a major challenge to global food production. The spread of resistance alleles is the primary explanation for observations of reduced pesticide efficacy over time, but the potential for gene-by-environment interactions (plasticity) to mediate susceptibility has largely been overlooked. Here we show that nutrition is an environmental factor that affects susceptibility to Bt toxins. Protein and carbohydrates are two key macronutrients for insect herbivores, and the polyphagous pest Helicoverpa zea self-selects and performs best on diets that are protein-biased relative to carbohydrates. Despite this, most Bt bioassays employ carbohydrate-biased rearing diets. This study explored the effect of diet protein-carbohydrate content on H. zea susceptibility to Cry1Ac, a common Bt endotoxin. We detected a 100-fold increase in LC50 for larvae on optimal versus carbohydrate-biased diets, and significant diet-mediated variation in survival and performance when challenged with Cry1Ac. Our results suggest that Bt resistance bioassays that use ecologically- and physiologically-mismatched diets over-estimate susceptibility and under-estimate resistance.

  1. 母亲还原叶酸载体1基因80G/A多态性与子女唐氏综合症易感性关系的meta分析%Correlation between maternal reduced folate carrier 1 gene 80G/A polymorphism and offspring down syndrome susceptibility: A meta-Analysis

    Institute of Scientific and Technical Information of China (English)

    何大莉; 曾照芳

    2013-01-01

    目的:探讨母亲还原叶酸载体1(RFC1)基因80G/A多态性与子女唐氏综合症(DS)易感性的相关性.方法:计算机检索PubMed、MEDLINE 、Web of Science、CNKI、CBM数据库,收集从建库至2012年9月间关于母亲RFC1基因80G/A多态性与子女DS易感性相关性的病例对照研究,对符合纳入标准的文献进行Meta分析.结果:共纳入7个研究,包括病例625例,对照767例.Meta分析结果显示:母亲RFC1基因80G/A多态性与子女DS易感性的相关性在各比较模型中差异无统计学意义[A Vs.G:OR=0.85,95%CI(0.73,1.00);AA Vs.GG:OR=0.73,95%CI(0.53,0.99);AA Vs.AG+ GG:OR=0.82,95%CI(0.63,1.06);AA+ AG Vs.GG:OR=0.81,95%CI(0.64,1.03)].基于人种的亚组分析结果显示,两者相关性无统计学意义.结论:目前的研究结果显示,母亲RFC1基因80G/A多态性与子女DS易感性无明显相关性.%Objective:To evaluate the correlation between maternal reduced folate carrier 1 (RFCl)gene 80G/A polymorphism and offspring Down syndrome susceptibility.Methods: We searched PubMed,MEDL!NE,Web of Science, CNKK CBM database and collected all the publications about the correlation between maternal reduced folate carrier 1 gene 80G/A polymorphism and offspring Down syndrome susceptibility. Results: A total of 7 studies involving 625 mothers who had children affected by DS and 767 controls mothers who had no miscarriages or children affected by genetic disorders in their life. The results of meta - analyses showed no significant difference was found in the correlation between maternal RFC1 80G/A polymorphism and offspring Down syndrome susceptibility( A Vs. G: OR = 0.85,95%CI(0.73,1.00); AAVs.GG: OR = 0.73,95%CI(0.53,0.99); AA Vs. AG+GG: OR = 0.82,95%CI(0.63,1.06); AA+AGVs. GG: OR = 0.81,95%CI(0.64,1.03) ]. In the subgroup analyses on ethnicity, no significant correlation was found. Conclusion:The present meta - analysis suggests that the correlation between maternal RFC1 80G/A polymorphism and

  2. Clinical evaluation of Linezolid in the treatment of MRSA infections in ICU%利奈唑胺治疗ICU耐甲氧西林金黄色葡萄球菌感染的临床评价

    Institute of Scientific and Technical Information of China (English)

    陈畅; 张彧

    2012-01-01

    Objective To evaluate the efficacy and safety of Unezolid in the treatment of methicillin-resistant ataphylococcus aureiu ( MRSA) infections in ICU. Methods A retrospective analysis of the clinical data was conducted for 42 patients with MRSA infections and treated with Linezolid in ICU of our hospital. Results Hie results showed that the total effective rate was 78.57 % (33/ 42) , among the 42 cases, 28 cases cured, 5 cases had positive responses, 6 cases unproved, and 3 cases had no efficacy, the drug-related side effect rate was 16.61%. Conclusion Linezolid is an effective and safe drug for MRSA infections in ICU.%目的 评价利奈唑胺治疗ICU耐甲氧西林金黄色葡萄球菌(MRSA)感染的疗效与安全性.方法 回顾性分析我院急诊ICU接受利奈唑胺治疗的42例MRSA感染患者的临床资料.结果 42例MRsA感染患者治愈28例,显效5例,进步6例,无效3例,治疗总有效率78.57%( 33/42),不良反应发生率为16.67%.结论 利奈唑胺是治疗ICU MRSA感染有效、安全的药物.

  3. 43株利奈唑胺耐药葡萄球菌耐药机制研究%The mechanisms of linezolid resistance in 43 strains of Staphylococcus

    Institute of Scientific and Technical Information of China (English)

    陈宏斌; 张雅薇; 李曙光; 王启; 张菲菲; 王辉; 黄加铭; 杨青; 马晓波; 张嵘; 夏菲; 赵峰; 曹俊明; 王晓娟

    2016-01-01

    目的:了解我国耐利奈唑胺葡萄球菌的耐药形势,探讨耐利胺唑胺菌株的耐药形成机制,为临床合理使用抗生素提供理论依据。方法收集2009至2012年全国9家医院分离的所有非重复的利奈唑胺耐药葡萄球菌共43株。通过微量肉汤稀释法测其MIC值,PCR方法检测是否携带cfr基因以及是否发生23S rRNA基因Ⅴ区突变,Southern blot验证cfr基因是否在质粒上,质粒全基因组测序分析cfr基因周围环境。结果43株利奈唑胺耐药葡萄球菌大部分为多重耐药菌株,大部分菌株携带cfr基因和发生23S rRNA G2576T突变,cfr基因位于质粒上且其周围基因环境存在IS256或IS21-558插入序列、Tn558转座子可移动基因元件。结论获得cfr基因或23S rRNA G2576T突变是导致葡萄球菌对利奈唑胺耐药的主要机制,cfr基因位于质粒上,并且其周围存在可移动基因元件,可导致cfr基因在不同菌株或菌种间传播。(中华检验医学杂志,2016,39:848-851)%Objective To investigate the prevalence of linezolid-resistant Staphylococcus in China and analyze the resistance mechanism of linezolid-resistant isolates to provide the evidence of rational use of antibiotics.Methods Forty-three non-duplicate linezolid-resistant isolates were collected from 9 hospitals throughout China over a period of 4 years ( 2009 -2012 ) .The MIC of each antimicrobial agent was determined by the broth microdilution method .Presence of cfr and mutations in 23S rRNA were detected by PCR and sequencing .Presence of cfr in plasmid was determined by Southern blot .The genetic environment of the cfr was determined by whole plasmid genome sequencing and analysis .Results Most of the 43 linezolid-resistant Staphylococcus isolates showed a multidrug-resistant phenotype , and most of isolates harboured the cfr gene and mutation of 23S rRNA G2576T.Southern blott indicated that the cfr gene of these isolates resided on

  4. Arbuscular mycorrhiza reduces susceptibility of tomato to Alternaria solani.

    Science.gov (United States)

    Fritz, Maendy; Jakobsen, Iver; Lyngkjaer, Michael Foged; Thordal-Christensen, Hans; Pons-Kühnemann, Jörn

    2006-09-01

    Mycorrhiza frequently leads to the control of root pathogens, but appears to have the opposite effect on leaf pathogens. In this study, we studied mycorrhizal effects on the development of early blight in tomato (Solanum lycopersicum) caused by the necrotrophic fungus Alternaria solani. Alternaria-induced necrosis and chlorosis of all leaves were studied in mycorrhizal and non-mycorrhizal plants over time course and at different soil P levels. Mycorrhizal tomato plants had significantly less A. solani symptoms than non-mycorrhizal plants, but neither plant growth nor phosphate uptake was enhanced by mycorrhizas. An increased P supply had no effect on disease severity in non-mycorrhizal plants, but led to a higher disease severity in mycorrhizal plants. This was parallel to a P-supply-induced reduction in mycorrhiza formation. The protective effect of mycorrhizas towards development of A. solani has some parallels to induced systemic resistance, mediated by rhizobacteria: both biocontrol agents are root-associated organisms and both are effective against necrotrophic pathogens. The possible mechanisms involved are discussed.

  5. Reduced susceptibility of Plasmodium falciparum to artesunate in southern Myanmar.

    Directory of Open Access Journals (Sweden)

    Myat P Kyaw

    Full Text Available BACKGROUND: Plasmodium falciparum resistance to artemisinins, the first line treatment for malaria worldwide, has been reported in western Cambodia. Resistance is characterized by significantly delayed clearance of parasites following artemisinin treatment. Artemisinin resistance has not previously been reported in Myanmar, which has the highest falciparum malaria burden among Southeast Asian countries. METHODS: A non-randomized, single-arm, open-label clinical trial of artesunate monotherapy (4 mg/kg daily for seven days was conducted in adults with acute blood-smear positive P. falciparum malaria in Kawthaung, southern Myanmar. Parasite density was measured every 12 hours until two consecutive negative smears were obtained. Participants were followed weekly at the study clinic for three additional weeks. Co-primary endpoints included parasite clearance time (the time required for complete clearance of initial parasitemia, parasite clearance half-life (the time required for parasitemia to decrease by 50% based on the linear portion of the parasite clearance slope, and detectable parasitemia 72 hours after commencement of artesunate treatment. Drug pharmacokinetics were measured to rule out delayed clearance due to suboptimal drug levels. RESULTS: The median (range parasite clearance half-life and time were 4.8 (2.1-9.7 and 60 (24-96 hours, respectively. The frequency distributions of parasite clearance half-life and time were bimodal, with very slow parasite clearance characteristic of the slowest-clearing Cambodian parasites (half-life longer than 6.2 hours in approximately 1/3 of infections. Fourteen of 52 participants (26.9% had a measurable parasitemia 72 hours after initiating artesunate treatment. Parasite clearance was not associated with drug pharmacokinetics. CONCLUSIONS: A subset of P. falciparum infections in southern Myanmar displayed markedly delayed clearance following artemisinin treatment, suggesting either emergence of artemisinin resistance in southern Myanmar or spread to this location from its site of origin in western Cambodia. Resistance containment efforts are underway in Myanmar. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000896077.

  6. Reduced Susceptibility of Plasmodium falciparum to Artesunate in Southern Myanmar

    Science.gov (United States)

    Kyaw, Myat P.; Nyunt, Myat H.; Chit, Khin; Aye, Moe M.; Aye, Kyin H.; Aye, Moe M.; Tarning, Joel; Imwong, Mallika; Jacob, Christopher G.; Rasmussen, Charlotte; Perin, Jamie; Ringwald, Pascal; Nyunt, Myaing M.

    2013-01-01

    Background Plasmodium falciparum resistance to artemisinins, the first line treatment for malaria worldwide, has been reported in western Cambodia. Resistance is characterized by significantly delayed clearance of parasites following artemisinin treatment. Artemisinin resistance has not previously been reported in Myanmar, which has the highest falciparum malaria burden among Southeast Asian countries. Methods A non-randomized, single-arm, open-label clinical trial of artesunate monotherapy (4 mg/kg daily for seven days) was conducted in adults with acute blood-smear positive P. falciparum malaria in Kawthaung, southern Myanmar. Parasite density was measured every 12 hours until two consecutive negative smears were obtained. Participants were followed weekly at the study clinic for three additional weeks. Co-primary endpoints included parasite clearance time (the time required for complete clearance of initial parasitemia), parasite clearance half-life (the time required for parasitemia to decrease by 50% based on the linear portion of the parasite clearance slope), and detectable parasitemia 72 hours after commencement of artesunate treatment. Drug pharmacokinetics were measured to rule out delayed clearance due to suboptimal drug levels. Results The median (range) parasite clearance half-life and time were 4.8 (2.1–9.7) and 60 (24–96) hours, respectively. The frequency distributions of parasite clearance half-life and time were bimodal, with very slow parasite clearance characteristic of the slowest-clearing Cambodian parasites (half-life longer than 6.2 hours) in approximately 1/3 of infections. Fourteen of 52 participants (26.9%) had a measurable parasitemia 72 hours after initiating artesunate treatment. Parasite clearance was not associated with drug pharmacokinetics. Conclusions A subset of P. falciparum infections in southern Myanmar displayed markedly delayed clearance following artemisinin treatment, suggesting either emergence of artemisinin resistance in southern Myanmar or spread to this location from its site of origin in western Cambodia. Resistance containment efforts are underway in Myanmar. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12610000896077 PMID:23520478

  7. Influence of conductive additive on temperature susceptibility of asphalt binders

    Institute of Scientific and Technical Information of China (English)

    吴少鹏; 李波; 陈筝; 黄旭

    2008-01-01

    The effects of graphite on temperature susceptibility of asphalt binders were investigated by penetration test,Ring & Ball softening point test and viscosity test.And penetration index(IP),viscosity-temperature susceptibility(SVT),and penetration-viscosity numbers(NPV) were introduced to evaluate the effects.The results show that the penetration,softening point and viscosity of asphalt binder increase with the increase of content of graphite.This means that the addition of graphite makes asphalts stiffer.The results from IP,NPV and SVT show that temperature susceptibility is reduced by the addition of graphite.

  8. The screening of Staphylococcus with reduced susceptibility to vancomycin and the detection of the clinically relevant antibiotic resistant genes%万古霉素敏感性减低葡萄球菌筛选及抗生素耐药相关基因检测

    Institute of Scientific and Technical Information of China (English)

    茅挺; 王敬华; 邹静雯

    2011-01-01

    Objective To determine the existence of the clinically relevant antibiotic resistant genes in clinical isolates of Staphylococcus with reduced susceptibility to vancomycin.Methods 100 stains of clinical isolates staphylococci were subjected to Brain Heart Infusion (BHI) vancomycin screen agar to screen vancomycin intermediate Staphylococcus or vancomycin resistant Staphylococcus, and then performed population analysis to detect heterogeneous vancomycin-resistant staphylococci (hVRS).MICs of the staphylococci with reduced susceptibility to vancomycin were detected by E-test and by Mueller-Hinton agar Micro-dilution; Antibiotic resistant genes including mecaA, aac(6’)/aph(2″) aph(3’)-Ⅲ, tetM, vanA, vanB and vanC were detected by PCR, and PCR products were sequenced.Results No vancomycin intermediate or resistant Staphylococcus was detected, but 7 strains of heterogeneous vancomycin-resistant staphylococci were isolated; the detective rates of mecaA and aph(3’)-Ⅲ were both 85.7%, but 57.1% for aac(6’)/aph(2″); no vanA, vanB, vanC or terM gene was detected from hVRS by PCR.Conclusions It is similar to methicillin resistant Staphylococcus aureus that heterogeneous vancomycin-resistant staphylococci carry many clinically relevant antibiotic resistant genes and resistant to most of antibiotics.So, furtherstudy of the antibiotics resistance mechanism of Staphylococcus with reduced susceptibility to vancomycin should be kept focus on.%目的 了解万古霉素敏感性减低葡萄球菌临床分离株对-内酰胺类、氨基糖苷类、四环素以及万古霉素耐药相关基因存在状况.方法 采用含61tg/mL万古霉素脑心浸液琼脂从临床分离的葡萄球菌中筛选万古霉素中介葡萄球菌和万古霉素耐药葡萄球菌;采用菌谱分析法筛选异质性万古霉素耐药葡萄球菌:E-test法和琼脂稀释法检测其MIC值;PCR技术扩增mecA,aac(6')/aph(2'),aph(3)-Ⅲ,tetM,vanA.vanB和vanC基因,并对阳性

  9. Osseointegration in periodontitis susceptible individuals.

    Science.gov (United States)

    Cecchinato, Denis; Bressan, Eriberto A; Toia, Marco; Araújo, Mauricio G; Liljenberg, Birgitta; Lindhe, Jan

    2012-01-01

    The aim of the present study was to examine tissue integration of implants placed (i) in subjects who had lost teeth because of advanced periodontal disease or for other reasons, (ii) in the posterior maxilla exhibiting varying amounts of mineralized bone. Thirty-six subjects were enrolled; 19 had lost teeth because of advanced periodontitis (group P) while the remaining 17 subjects had suffered tooth loss from other reasons (group NP). As part of site preparation for implant placement, a 3 mm trephine drill was used to remove one or more 2 mm wide and 5-6 mm long block of hard tissue [biopsy site; Lindhe et al. (2011). Clinical of Oral Implants Research, DOI: 10.1111/j.1600-0501.2011.02205.x]. Lateral to the biopsy site a twist drill (diameter 2 mm) was used to prepare the hard tissue in the posterior maxilla for the placement of a screw-shaped, self-tapping micro-implant (implant site). The implants used were 5 mm long, had a diameter of 2.2 mm. After 3 months of healing, the micro-implants with surrounding hard tissue cores were retrieved using a trephine drill. The tissue was processed for ground sectioning. The blocks were cut parallel to the long axis of the implant and reduced to a thickness of about 20 μm and stained in toluidine blue. The percentage of (i) implant surface that was in contact with mineralized bone as well as (ii) the amount of bone present within the threads of the micro-implants (percentage bone area) was determined. Healing including hard tissue formation around implants placed in the posterior maxilla was similar in periodontitis susceptible and non-susceptible subjects. Thus, the degree of bone-to-implant contact (about 59%) as well as the amount of mineralized bone within threads of the micro-implant (about 45-50%) was similar in the two groups of subjects. Pearson's coefficient disclosed that there was a weak negative correlation (-0.49; P < 0.05) between volume of fibrous tissue (biopsy sites) and the length of bone to implant

  10. [Serotypes and antimicrobial susceptibilities of invasive group A streptococci identified in eastern Black Sea region of Turkey].

    Science.gov (United States)

    Bayramoğlu, Gülçin; Topkaya, Aynur E; Balıkcı, Ahmet; Aydın, Faruk

    2011-07-01

    Frequency of invasive group A streptococcus (GAS) infections is increasing worldwide in recent 20 years. Serotypes responsible for these clinical manifestations and their antibiotic susceptibilities should be known in order to establish preventive measures and initiate appropriate treatment. This study was aimed to determine the serotypes, antibiotic susceptibilities and inducible clindamycin resistance among invasive GAS isolated between 2006-2009 period. A total of 22 GAS strains isolated from clinical samples [sterile body fluids (peritoneal, pleural, pericardial, joint and cerebrospinal fluids), blood, tissue biopsy] of the patients (14 male, 8 female; age range: 3-82 years, median age: 59) who admitted to Karadeniz Technical University Faculty of Medicine, Farabi Hospital located in Trabzon province (Eastern Black Sea Region of Turkey), between March 2006 and March 2009 were included in the study. GAS serotypes were determined by the investigation of serum opacity factors (SOF), T proteins and M proteins. SOF production was investigated by microplate method using human serum and SOF types were determined by SOF-inhibition test using specific antisera. T protein types were detected by agglutination method using polyvalent anti-T sera, and M serotypes were detected by capillary precipitation method using M antisera. Antimicrobial susceptibility tests were performed by disk-diffusion method according to CLSI recommendations. SOF were positive in 9 (41%) samples. Use of T antiserum yielded T (n= 8) and U (n= 7) types and M antiserum M1 (n= 4) and M2 (n= 3) types. The overall antibiotic susceptibility rate of the isolates was 68% (15/22) and overall resistance rate was 32% (7/22). All of the GAS strains were found susceptible to benzylpenicillin, ceftriaxone, vancomycin, levofloxacine and linezolid, however 9 (41%) were intermediate susceptible to tetracycline and 1 (4.5%) was intermediate susceptible to erythromycin. Four (18%) strains were found resistant to

  11. Routine disc diffusion antimicrobial susceptibility testing of Clostridium difficile and association with PCR ribotype 027

    DEFF Research Database (Denmark)

    Holt, H M; Danielsen, T K; Justesen, U S

    2015-01-01

    Reduced susceptibility to metronidazole and vancomycin in Clostridium difficile has been reported, which emphasises the need for simple antimicrobial susceptibility testing methods. The aim of this study was to apply a published disc diffusion method and zone diameter breakpoint correlates...... diameters than non-027 isolates. The disc diffusion method is very simple and inexpensive, and the published zone diameter breakpoints will detect C. difficile isolates with reduced susceptibility to metronidazole and vancomycin....

  12. Antimicrobial susceptibility survey of pathogens isolated from selected patients in Northern Italy

    Directory of Open Access Journals (Sweden)

    Elisabetta Maioli

    2005-03-01

    Full Text Available The Clinical Microbiology Laboratory of the University of Genoa participated, during the year 2003, in an international antimicrobial surveillance program.The collection of isolates was done according to the site of infection and/or type of patient. Four hundred twenty (420 clinical isolates were analyzed during this year and the frequencies of the different pathogens were investigated. A reference centre carried out susceptibility tests. Oxacillin-resistant Staphylococcus aureus represented 47.6% of all S. aureus isolates from blood stream infections and 33.3% of all S. aureus isolated from skin and soft tissue infections in hospitalised patients.These strains showed resistance to most of the antimicrobial agents evaluated, except vancomycin, teicoplanin, quinupristin/dalfopristin and linezolid which registered 100% of susceptibility. Some isolates from blood stream infections such as E. coli demonstrated resistance to ciprofloxacin (23.3%, levofloxacin (20%, and gatifloxacin (16.6%, and Klebsiella pneumoniae was resistant (18% to all fluoroquinolones tested. Pseudomonas aeruginosa manifested resistance to ciprofloxacin (16.6%, while 27.7% of these strains were resistant both to levofloxacin and gatifloxacin. All the Enterobacter cloacae isolated from blood were susceptible to ciprofloxacin, levofloxacin and gatifloxacin. Haemophilus influenzae and Moraxella catarrhalis collected from community-acquired respiratory tract infections were all inhibited by ciprofloxacin, levofloxacin and gatifloxacin. E. coli isolated from urinary tract infections in hospitalised patients were resistant to ciprofloxacin, levofloxacin and gatifloxacin (2.7%. All Salmonella spp. collected from samples of patients affected by infections of the gastro-intestinal tract were susceptible to all fluoroquinolones. Penicillin resistance in Streptococcus pneumoniae was found in 21.4% of isolates from patients with respiratory tract infections. Fluoroquinolone resistance was

  13. Toward Modelling Topsoil Magnetic Susceptibility for Demining Activities

    Science.gov (United States)

    Hannam, J. A.; Dearing, J. A.

    2003-12-01

    The Landmine Monitor estimates that landmines cause up to 20,000 fatalities and casualties worldwide every year, in over 100 countries affected by landmine contamination. Although detection technologies have become more sophisticated, the metal detector still remains the most widely employed detection system in landmine affected regions. With increased use of minimum metal mines, the performance and sensitivity of metal detectors are increasingly challenged. In addition to mine constituents, depth of burial and orientation, soil properties significantly affect metal detection capabilities. Soils with high magnetic susceptibility, in particular those dominated by viscous components, interfere with the response signal in both frequency and time domain metal detection systems. Using Bosnia and Herzegovina (BiH) as a pilot region, we created an expert system to predict topsoil susceptibility from environmental information within a SOTER data base. Initially, the knowledge base is constructed from published relationships of environmental parameters and magnetic susceptibility and knowledge of experts in the field of soil magnetism. The knowledge base is underpinned by environmental conditions that are known to enhance or reduce magnetic susceptibility in topsoils. Where semi-quantitative data exists, transfer-functions are used to provide first approximations of susceptibility classes and offer a basis for a probability score for the susceptibility class. As a first approximation, susceptibility values are categorized into five continuous classes delimited by published magnetic susceptibility ranges in topsoils. The predicted susceptibility maps result in regional contrasts, delineated by the spatial scale of the environmental information. Further development of the model using a Baysean rule-based system with fuzzy boundaries is anticipated. Validation of the model is proposed using archived soil survey samples from BiH. In addition to providing essential data for

  14. Serotyping, Antibiotic Susceptibility and Related Risk Factors Aspects of Nasopharyngeal Carriage of Streptococcus pneumoniae in Healthy School Students.

    Directory of Open Access Journals (Sweden)

    Hamed Mirzaei Ghazikalayeh

    2014-09-01

    Full Text Available Streptococcus pneumoniae is an important problem worldwide and nasopharyngeal colonization plays significant role in pneumococcal infections. The aims of this study were to determine the nasopharyngeal colonization rate, serotyping, antibiotics susceptibility and study the risk factors for nasopharyngeal colonization with S. pneumoniae in students in Kashan, Iran.A cross-sectional study was conducted on children aged 7 to 19 years from December 2011 to November 2012. Nasopharyngeal swabs were plated onto brain heart infusion agar plates with 5% sheep blood and 4µg/ml of gentamycin. Antimicrobial susceptibility profiles were determined on Mueller-Hinton agar in accordance with CLSI. S. pneumoniae strains were investigated for the presence of the most common pneumococcal serotypes using a multiplex polymerase chain reaction.13.9% were found to be carriers. The most prevalent serogroups were 19F (30%, 6A/B (18.9%, 15A (16.5%, 11 (11.3%, 23F (8.2%, 1 (6.2%, 19A (3.4%, and 35B (2.4%. Nine strains (3.1% were non-typeable. The carrier rate was significantly higher in 12 to15 year old age group. Upper respiratory tract infections within the last month (OR=1.5, P<0.011, previous hospitalization (OR=1.6, P<0.001, previous antibiotic usage last two weeks (OR=1.89, P<0.001, rhinorea (OR=1.9 P<0.001, male sex (OR=3.5 P< 0.001 and passive smoking (OR=1.56, P< 0.001 have been determined to be risk factors for S. pneumoniae carriage. The highest pneumococcal resistance was to tetracycline (25.4%. All strains were susceptible to linezolid and levofloxacin.Our information leads to an important source to screen the future impact of pneumococcal vaccination on bacterial colonization.

  15. Japanese nationwide surveillance in 2011 of antibacterial susceptibility patterns of clinical isolates from complicated urinary tract infection cases.

    Science.gov (United States)

    Ishikawa, Kiyohito; Hamasuna, Ryoichi; Uehara, Shinya; Yasuda, Mitsuru; Yamamoto, Shingo; Hayami, Hiroshi; Takahashi, Satoshi; Matsumoto, Tetsuro; Minamitani, Shinichi; Kadota, Jun-ichi; Iwata, Satoshi; Kaku, Mitsuo; Watanabe, Akira; Sunakawa, Keisuke; Sato, Junko; Hanaki, Hideaki; Tsukamoto, Taiji; Kiyota, Hiroshi; Egawa, Shin; Deguchi, Takashi; Matsumoto, Minori; Tanaka, Kazushi; Arakawa, Soichi; Fujisawa, Masato; Kumon, Hiromi; Kobayashi, Kanao; Matsubara, Akio; Wakeda, Hironobu; Amemoto, Yoshinosuke; Onodera, Shoichi; Goto, Hirokazu; Komeda, Hisao; Yamashita, Masuo; Takenaka, Tadasu; Fujimoto, Yoshinori; Tsugawa, Masaya; Takahashi, Yoshito; Maeda, Hiroshi; Onishi, Hiroyuki; Ishitoya, Satoshi; Nishimura, Kazuo; Mitsumori, Kenji; Ito, Toru; Togo, Yoshikazu; Nakamura, Ichiro; Ito, Noriyuki; Kanamaru, Sojun; Hirose, Takaoki; Muranaka, Takashi; Yamada, Daisuke; Ishihara, Satoshi; Oka, Hiroya; Inatomi, Hisato; Matsui, Takashi; Kobuke, Makoto; Kunishima, Yasuharu; Kimura, Takahiro; Ichikawa, Takaharu; Kagara, Ichiro; Matsukawa, Masanori; Takahashi, Koichi; Mita, Koji; Kato, Masao; Okumura, Kazuhiro; Kawanishi, Hiroaki; Hashimura, Takayuki; Aoyama, Teruyoshi; Shigeta, Masanobu; Koda, Shuntaro; Taguchi, Keisuke; Matsuda, Yohei

    2015-09-01

    To investigate antimicrobial susceptibility patterns of various bacterial pathogens isolated from complicated urinary tract infection (UTI) cases, the Japanese Society of Chemotherapy, the Japanese Association of Infectious Disease, and the Japanese Society of Clinical Microbiology conducted the second nationwide surveillance from January to September 2011. With the cooperation of 42 medical institutions throughout Japan, 1036 strains belonging to 8 clinically relevant bacterial species were collected. Among methicillin-resistant Staphylococcus aureus (MRSA) strain, the vancomycin (VCM) MIC for 5.5% (3/55) of the strains was 2 μg/mL. Ampicillin, VCM, and linezolid were relatively active against 209 Enterococcus faecalis strains. The proportion of fluoroquinolone (FQ)-resistant strains was >20%. The MIC90 of FQs against the 382 Escherichia coli strains was 2-64 mg/L and the proportion resistant to FQs was approximately 30%. However, susceptibility of E. coli to sitafloxacin was still high (MIC90 = 2 mg/L). Fifty-eight (15.2%) of 382 E. coli, 6 (4.5%) of 132 Klebsiella pneumoniae, 1 (2.4%) of 41 Klebsiella oxytoca and 4 (6.8%) of 59 Proteus mirabilis strains were suspected of producing extended-spectrum beta-lactamase. Of 93 Pseudomonas aeruginosa strains, the proportions resistant to imipenem, amikacin, and ciprofloxacin were 21.5%, 4.3%, and 20.4%, respectively. Four strains (4.3%) were found to be multidrug-resistant. In complicated UTI cases, all of MRSA and E. faecalis were susceptible to all anti-MRSA agents. Sitafloxacin was active against other FQ-resistant E. coli strains. The isolation of extended-spectrum beta-lactamase-producing and multidrug-resistant strains increased.

  16. Prevalence and antimicrobial susceptibility pattern of coagulase-negative staphylococci (CoNS isolated from clinical specimens in Northern of Jordan

    Directory of Open Access Journals (Sweden)

    Ibrahim Ali Al Tayyar

    2016-01-01

    Full Text Available Background: Coagulase negative Staphylococci (CoNS are one of the most common bacteria found on human skin and on mucous membranes as a component of normal flora. The presence of CoNS in clinical specimens is frequently associated with an infectious aetiology or contamination.Objectives: We aimed to evaluate CoNS species distribution and susceptibility patterns in specimens obtained from clinics and hospitals in the Northern area of Jordan.Methods: Standard identification methods showed the presence of CoNS in 223 specimens at different local hospitals. Susceptibility testing was performed using 18 antibiotics in accordance with the Clinical and Laboratory Standards Institute (CLSI recommendations.Results: Staphylococcus epidermidis and S. haemolyticus were found to be the most common species isolated from all spec- imens representing 122 (54.7% and 52 (23.4% of all CoNS species, respectively. Antibiotic susceptibility testing of CoNS species revealed their sensitivity to vancomycin, linozolid, rifampin and nitrofurantin, while showing a highly resistant pattern to ampicillin, penicillin, ceftriaxone, cefazolin, amoxicillin-clavulanic acid and erythromycin. Some variation of the susceptibility pattern of CoNS species were identified in specimens isolated from the ICU and paediatric hospital wards as well as from clinical specimens of urine, blood and catheter tips.Conclusion: The most common CoNS isolates were found to be S. epidermidis and S. haemolyticus with variable percentag- es according to the specimen source. Moreover, a high susceptibility CoNS to vancomycin, rifampin, and linezolid showed resistance to amoxicillin and penicillin. Keywords: CoNS, Antibiotic, Hospital, Intensive Care Units, Hospital Wards, Nosocomial Infection

  17. [Antimicrobial susceptibility in Chile 2012].

    Science.gov (United States)

    Cifuentes-D, Marcela; Silva, Francisco; García, Patricia; Bello, Helia; Briceño, Isabel; Calvo-A, Mario; Labarca, Jaime

    2014-04-01

    Bacteria antimicrobial resistance is an uncontrolled public health problem that progressively increases its magnitude and complexity. The Grupo Colaborativo de Resistencia, formed by a join of experts that represent 39 Chilean health institutions has been concerned with bacteria antimicrobial susceptibility in our country since 2008. In this document we present in vitro bacterial susceptibility accumulated during year 2012 belonging to 28 national health institutions that represent about 36% of hospital discharges in Chile. We consider of major importance to report periodically bacteria susceptibility so to keep the medical community updated to achieve target the empirical antimicrobial therapies and the control measures and prevention of the dissemination of multiresistant strains.

  18. 利奈唑胺体外诱导粪肠球菌中介耐药及机制研究%Intermediate resistance of Enterococcus faecali induced induced by linezolid in vitro and the mechanism

    Institute of Scientific and Technical Information of China (English)

    郑金鑫; 马桂红; 潘伟光; 李多云; 陈重; 刘晓军; 邓启文; 余治健

    2013-01-01

    目的 研究利奈唑胺对粪肠球菌中介耐药的体外诱导作用并探讨其耐药机制.方法 采用多步诱导法对4株临床分离粪肠球菌以及质控菌株进行体外诱导耐药试验,采用琼脂平皿二倍稀释法测定诱导前后的MIC值,采用PCR测序法检测粪肠球菌4个23S rRNA V区基因的变异.结果 4株临床分离粪肠球菌和质控菌株均诱导出中介株和稳定耐药株,在中介株和耐药株中均检测到了G2576U、G2505A和C2424U变异,2株中介株和耐药株还同时存在G2576U和C2424U变异.结论 利奈唑胺可体外诱导粪肠球菌产生中介株和稳定性耐药株,粪肠球菌中介株即可出现23S rRNA V区基因变异.%Objective To explore the in vitro linezolid-induced intermediate resistance of Enterococcus faecalis and its mechanism.Methods Multi-step in vitro induction by using linezolid was conducted with 4 Enterococcus faecalis isolates and 1 reference strain.The minimum inhibitory concentrations (MICs) were determined by agar dilution method.And the variations of 23S rRNA V region gene of Enterococcus faecalis were detected by PCR sequencing.Results The intermediate-resistant strains from 4 Enterococcus faecalis isolates and 1 reference isolate.were successfully induced The G2576U,G2505A and C2424U mutations were detected in the intermediate-resistant strains.The G2576U and C2424U mutations were both detected in 2 intermediary and resistant strains.Conclusion Linezolid can induce intermediate resistance in Enterococcus faecalis in vitro,23S rRNA V region gene mutations can be dteteced in the intermediate-resistant strains of Enterococcus faecalis.

  19. 利奈唑胺治疗结核性脑膜炎的效果研究%Study on the Curative Effect of Linezolid in the Treatment of Tuberculosis Meningitis

    Institute of Scientific and Technical Information of China (English)

    刘岩

    2016-01-01

    目的:探究结核性脑膜炎患者采取利奈唑胺治疗的方法和效果。方法选取2014年11月~2015年11月收治的37例结核性脑膜炎患者进行治疗研究,随机分组,实验组20例采取利奈唑胺治疗,对照组17例采取常规治疗,比较患者的治疗效果。结果实验组治疗总有效率为90.0%,对照组治疗总有效率为76.47%。实验组患者得到更加有效的治疗效果,差异有统计学意义(P<0.05)。结论结核性脑膜炎患者采取利奈唑胺治疗,抗结核效果较好,脑脊液穿透率较好,结核性脑膜炎患者可得到显著的治疗效果。%Objective Linezolid treatment method and its effect for tuberculosis meningitis are to be studied.Methods Chose 37 patients of tuberculosis meningitis who were treated in hospital from November 2014 to November 2015 and separated them into two groups at random; 20 patients in study group were given Linezolid treatment,while 17 patients in control group were given conventional treatment,and then compared treatment effects between two groups.Results Patients’ treatment efficacy in study group was 90.0% and it was 76.47% in control group,treatment efficacy in study group was much higher and better,there was a differential between two groups and such a differential had statistic value(P<0.05).Conclusion Linezolid is quite effective in treatment of patients with tuberculosis meningitis,such a treatment is of favorable cerebrospinal fluid(CSF) penetration rate and treatment efficiency.

  20. Serological Characterization and Antimicrobial Susceptibility ...

    African Journals Online (AJOL)

    300L Coordinator

    identified and antibiotic susceptibility test was performed using standard procedures. The total .... serotypes and their antimicrobial resistivity patterns from patients ..... the best of our knowledge). ... Testing of Bacterial Pathogens of Public.

  1. Genetic diversity and disease susceptibility.

    OpenAIRE

    Bodmer, W F

    1997-01-01

    The range of genetic diversity within human populations is enormous. Genetic susceptibility to common chronic disease is a significant part of this genetic diversity, which also includes a variety of rare clear-cut inherited diseases. Modern DNA-based genomic analysis can now routinely lead to the identification of genes involved in disease susceptibility, provides the basis for genetic counselling in affected families, and more widely for a genetically targeted approach to disease prevention...

  2. Magnetic Susceptibilities as they appeared to me - An Amperian approach

    Energy Technology Data Exchange (ETDEWEB)

    Van den Bosch, A.

    2008-08-15

    Starting from scratch, the book narrates a systematic story of the basic ideas you need for understanding quasi static magnetic susceptibilities. The story leans on the authors 25 year experience measuring susceptibilities following the Faraday technique (related with solid state physics, radiation effects, materials and magneto chemistry). The base of magnetism, the current-current interaction, is the linkage between the topics treated. The number of mathematical equations are reduced to a minimum and can be skipped without losing the thread of the story. The story is positive towards the sound bases of magnetism. However, room is left for the interpretation of measuring data. As the word susceptibility covers different meanings, the story answers for different situations the question: what is susceptible to what for creating what?

  3. Trends in the susceptibility of methicillin-resistant Staphylococcus aureus to nine antimicrobial agents, including ceftobiprole, nemonoxacin, and tyrothricin: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006-2010.

    Science.gov (United States)

    Chen, Y-H; Liu, C-Y; Ko, W-C; Liao, C-H; Lu, P-L; Huang, C-H; Lu, C-T; Chuang, Y-C; Tsao, S-M; Chen, Y-S; Liu, Y-C; Chen, W-Y; Jang, T-N; Lin, H-C; Chen, C-M; Shi, Z-Y; Pan, S-C; Yang, J-L; Kung, H-C; Liu, C-E; Cheng, Y-J; Liu, J-W; Sun, W; Wang, L-S; Yu, K-W; Chiang, P-C; Lee, M-H; Lee, C-M; Hsu, G-J; Hsueh, P-R

    2014-02-01

    This study investigated the in vitro susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) to nine antimicrobial agents in Taiwan. A total of 1,725 isolates were obtained from 20 hospitals throughout Taiwan from 2006 to 2010. The minimum inhibitory concentrations (MICs) of the nine agents were determined by the agar dilution method. The MICs of mupirocin and tyrothricin were determined for 223 MRSA isolates collected from 2009 to 2010. For vancomycin, 99.7 % were susceptible; however, 30.0 % (n = 517) exhibited MICs of 2 μg/ml and 0.3 % (n = 6) demonstrated intermediate susceptibility (MICs of 4 μg/ml). Nearly all isolates (≥ 99.9 %) were susceptible to teicoplanin, linezolid, and daptomycin. The MIC90 values were 2 μg/ml for ceftobiprole and 1 μg/ml for nemonoxacin. The MIC90 values of mupirocin and tyrothricin were 0.12 and 4 μg/ml, respectively. MIC creep was noted for daptomycin during this period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For isolates with vancomycin MICs of 2 μg/ml, the MIC90 values were 2 μg/ml for teicoplanin, 0.5 μg/ml for daptomycin, and 0.5 μg/ml for tigecycline. Those values were four- to eight-fold higher than those among isolates with vancomycin MICs of 0.5 μg/ml (2, 0.06, and 0.12 μg/ml, respectively). Of the nine MRSA isolates exhibiting non-susceptibility to vancomycin (n = 6), teicoplanin (n = 1), daptomycin (n = 2), or tigecycline (n = 1), all had different pulsotypes, indicating the absence of intra-hospital or inter-hospital spread. The presence of a high proportion of MRSA isolates with elevated MICs (2 μg/ml) and MIC creep of daptomycin might alert clinicians on the therapy for serious MRSA infections in Taiwan.

  4. Antimicrobial susceptibility and susceptibility testing of Mycoplasma hominis: a review.

    Science.gov (United States)

    Bygdeman, S M; Mårdh, P A

    1983-01-01

    The determination of the minimal growth-inhibiting concentration (MIC), the minimal metabolism-inhibiting concentration (MMC), and the minimal mycoplasmacidal concentration (MCC) of various antimicrobial compounds for Mycoplasma hominis is influenced by the pH of the test media, the inoculum size, and the incubation time, although each of these factors generally do not affect the minimal concentration more than fourfold. M. hominis is resistant to beta-lactam antibiotics, vancomycin, sulfonamides, trimethoprim, and polymyxin B. There are great differences in the susceptibility of M. hominis to various macrolide antibiotics. Thus the organism is resistant to erythromycin and oleandomycin, moderately resistant to tylosin and spiramycin, susceptible to josamycin as well as to another macrolide drug, labelled M-4365G. M. hominis is also highly susceptible to the macrolide-like compound rosaramicin and to the tetracyclines (although resistant strains occur). It is susceptible to lincomycin and clindamycin, and moderately susceptible to chloramphenicol and rifampicin. The aminoglycosides have limited activity against M. hominis.

  5. Surveillance of tedizolid activity and resistance: In vitro susceptibility of Gram-positive pathogens collected over 5 years from the United States and Europe.

    Science.gov (United States)

    Bensaci, Mekki; Sahm, Daniel

    2017-02-01

    In vitro activity of tedizolid and comparators against 11,231 Gram-positive clinical isolates from the United States (84 centers) and Europe (115 centers) were summarized as part of the Surveillance of Tedizolid Activity and Resistance program between 2009 and 2013. Susceptibility testing was performed according to Clinical Laboratory and Standards Institute (CLSI) guidelines. Minimum inhibitory concentration (MIC) interpretations were based on CLSI and European Committee on Antimicrobial Susceptibility Testing criteria. Tedizolid inhibited 99.7% of all isolates at MIC ≤0.5 mg/L; activity was similar regardless of methicillin or vancomycin resistance phenotypes of Staphylococcus aureus and enterococci, respectively. Tedizolid MIC >1 mg/L was reported for 3 S. aureus, 4 coagulase-negative staphylococci, and 2 enterococcal isolates; all streptococci were inhibited at MIC ≤0.5 mg/L. Tedizolid was ≥4-fold more potent than linezolid against all groups, including resistant phenotypes. Tedizolid had potent/stable activity against a large, contemporary collection of Gram-positive clinical isolates, with low rates of resistance.

  6. Landslide Susceptibility Assessment Through Fuzzy Logic Inference System (flis)

    Science.gov (United States)

    Bibi, T.; Gul, Y.; Rahman, A. Abdul; Riaz, M.

    2016-09-01

    Landslide is among one of the most important natural hazards that lead to modification of the environment. It is a regular feature of a rapidly growing district Mansehra, Pakistan. This caused extensive loss of life and property in the district located at the foothills of Himalaya. Keeping in view the situation it is concluded that besides structural approaches the non-structural approaches such as hazard and risk assessment maps are effective tools to reduce the intensity of damage. A landslide susceptibility map is base for engineering geologists and geomorphologists. However, it is not easy to produce a reliable susceptibility map due to complex nature of landslides. Since 1980s, several mathematical models have been developed to map landslide susceptibility and hazard. Among various models this paper is discussing the effectiveness of fuzzy logic approach for landslide susceptibility mapping in District Mansehra, Pakistan. The factor maps were modified as landslide susceptibility and fuzzy membership functions were assessed for each class. Likelihood ratios are obtained for each class of contributing factors by considering the expert opinion. The fuzzy operators are applied to generate landslide susceptibility maps. According to this map, 17% of the study area is classified as high susceptibility, 32% as moderate susceptibility, 51% as low susceptibility and areas. From the results it is found that the fuzzy model can integrate effectively with various spatial data for landslide hazard mapping, suggestions in this study are hope to be helpful to improve the applications including interpretation, and integration phases in order to obtain an accurate decision supporting layer.

  7. LANDSLIDE SUSCEPTIBILITY ASSESSMENT THROUGH FUZZY LOGIC INFERENCE SYSTEM (FLIS

    Directory of Open Access Journals (Sweden)

    T. Bibi

    2016-09-01

    Full Text Available Landslide is among one of the most important natural hazards that lead to modification of the environment. It is a regular feature of a rapidly growing district Mansehra, Pakistan. This caused extensive loss of life and property in the district located at the foothills of Himalaya. Keeping in view the situation it is concluded that besides structural approaches the non-structural approaches such as hazard and risk assessment maps are effective tools to reduce the intensity of damage. A landslide susceptibility map is base for engineering geologists and geomorphologists. However, it is not easy to produce a reliable susceptibility map due to complex nature of landslides. Since 1980s, several mathematical models have been developed to map landslide susceptibility and hazard. Among various models this paper is discussing the effectiveness of fuzzy logic approach for landslide susceptibility mapping in District Mansehra, Pakistan. The factor maps were modified as landslide susceptibility and fuzzy membership functions were assessed for each class. Likelihood ratios are obtained for each class of contributing factors by considering the expert opinion. The fuzzy operators are applied to generate landslide susceptibility maps. According to this map, 17% of the study area is classified as high susceptibility, 32% as moderate susceptibility, 51% as low susceptibility and areas. From the results it is found that the fuzzy model can integrate effectively with various spatial data for landslide hazard mapping, suggestions in this study are hope to be helpful to improve the applications including interpretation, and integration phases in order to obtain an accurate decision supporting layer.

  8. Is Streptococcus pyogenes resistant or susceptible to trimethoprim-sulfamethoxazole?

    Science.gov (United States)

    Bowen, Asha C; Lilliebridge, Rachael A; Tong, Steven Y C; Baird, Robert W; Ward, Peter; McDonald, Malcolm I; Currie, Bart J; Carapetis, Jonathan R

    2012-12-01

    Streptococcus pyogenes is commonly believed to be resistant to trimethoprim-sulfamethoxazole (SXT), resulting in reservations about using SXT for skin and soft tissue infections (SSTI) where S. pyogenes is involved. S. pyogenes' in vitro susceptibility to SXT depends on the medium's thymidine content. Thymidine allows S. pyogenes to bypass the sulfur-mediated inhibition of folate metabolism and, historically, has resulted in apparently reduced susceptibility of S. pyogenes to sulfur antibacterials. The low thymidine concentration in Mueller-Hinton agar (MHA) is now regulated. We explored S. pyogenes susceptibility to SXT on various media. Using two sets of 100 clinical S. pyogenes isolates, we tested for susceptibility using SXT Etests on MHA containing defibrinated horse blood and 20 mg/liter β-NAD (MHF), MHA with sheep blood (MHS), MHA alone, MHA with horse blood (MHBA), and MHA with lysed horse blood (MHLHBA). European Committee on Antibacterial Susceptibility Testing (EUCAST) breakpoints defined susceptibility (MIC, ≤ 1 mg/liter) and resistance (MIC, >2 mg/liter). In study 1, 99% of S. pyogenes isolates were susceptible to SXT on MHA, MHBA, and MHLHBA, with geometric mean MICs of 0.04, 0.04, and 0.05 mg/liter, respectively. In study 2, all 100 S. pyogenes isolates were susceptible to SXT on MHF, MHS, MHA, and MHLHBA with geometric mean MICs of 0.07, 0.16, 0.07, and 0.09 mg/liter, respectively. This study confirms the in vitro susceptibility of S. pyogenes to SXT, providing support for the use of SXT for SSTIs. A clinical trial using SXT for impetigo is ongoing.

  9. 利奈唑胺与万古霉素治疗耐甲氧西林金黄色葡萄球菌感染疗效及安全性荟萃分析%Meta-analysis of efficacy and safety of linezolid and vancomycin in treatment of methicillin-resistant Staphylococcus aureus infection

    Institute of Scientific and Technical Information of China (English)

    柯邵鹏; 刘江福; 苏智军; 郭如意; 陈素梅; 林琪

    2015-01-01

    目的:系统评价利奈唑胺和万古霉素治疗耐甲氧西林金黄色葡萄球菌(MRSA)感染的临床疗效及安全性。方法计算机检索 Cochrane 图书馆、PubMed 、Embase 、CNKI 全文数据库、维普中文科技期刊数据库中2013年6月前发表关于利奈唑胺和万古霉素治疗 MRSA 感染的随机对照试验文献,并应用 STATA 软件进行统计分析。结果共纳入11篇文献,合计5567例患者,MRSA 所致肺炎者利奈唑胺组临床治愈率、细菌清除率均高于万古霉素组(P<0.05);MRSA 所致复杂性皮肤软组织感染(cSTTI)者采用利奈唑胺治疗临床治愈率、细菌清除率均高于万古霉素组(P<0.05);利奈唑胺的肾功能不全、不良反应发生率均低于万古霉素(P<0.05),消化系统不良反应高于万古霉素(P<0.01)。结论对于 MRSA 所致的肺炎、cSTTI 感染,利奈唑胺的临床及微生物疗效优于万古霉素。%OBJECTIVE To systematically evaluate the clinical efficacy and safety of linezolid and vancomycin in treatment of methicillin-resistant Staphylococcus aureus (MRSA ) infection .METHODS The Cochrane Library , PubMed ,Embase ,CNKI full-text database ,and VIP Chinese scientific journals database were retrieved to collect the literatures regarding the randomized controlled trials for linezolid and vancomycin in treatment of MRSA infec -tion that were published before Jun 2013 ,and the statistical analysis was performed with the use of stata software . RESULTS Totally 11 literatures were included ,with 5 567 patients involved .The clinical cure rate of the patients with MRSA pneumonia was higher in the linezolid group than in the vancomycin group ;the bacterial clearance rate of the linezolid group was higher than that of the vancomycin group (P< 0 .05) .The clinical cure rate of the pa-tients with MRSA complicated skin and soft tissue infection (cSSTI) was higher in the linezolid group than in the

  10. Biofilm Formation and Antimicrobial Susceptibility of Staphylococcus epidermidis Strains from a Hospital Environment

    Directory of Open Access Journals (Sweden)

    Robert D. Wojtyczka

    2014-04-01

    Full Text Available The hospital environment microflora comprise a wide variety of microorganisms which are more or less pathogenic and where staphylococci are one of the most common types. The aim of the presented study was to evaluate the prevalence of the biofilm forming coagulase-negative staphylococci (CoNS in a hospital environment as a risk factor for nosocomial infections. Among 122 isolated and tested strains of CoNS the most frequent were: S. epidermidis—32 strains, S. haemolyticus—31 strains, S. capitis subsp. capitis— 21 strains, S. hominis—11 strains, S. cohnii subsp. cohnii—nine strains. In case of CoNS, the main molecule responsible for intercellular adhesion is a polysaccharide intercellular adhesin (PIA, encoded on the ica gene operon. The analysis revealed the presence of the icaADBC operon genes in 46.88% of S. epidermidis isolates. IcaA and icaD were present in 34.38% and 28.13% of strains respectively while IcaC gene was present in 37.50% of strains. IcaB gene was found in 21.88% of S. epidermidis strains. In 15 (63% strains all icaADBC operon genes were observed. The assessment of antibacterial drugs susceptibility demonstrated that analyzed CoNS strains were highly resistant to macrolides and lincosamides and more sensitive to rifampicin and linezolid. Our data indicates that the hospital environment can be colonized by biofilm forming coagulase-negative staphylococci and transmission of these strains can cause an increased risk of serious nosocomial infections.

  11. Susceptibility Genes in Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban

    2005-01-01

    Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

  12. Susceptibility to Frost-Bite

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    Bal Krishna

    1966-11-01

    Full Text Available The body protects its susceptible parts e.g. hands and feet from cold injury by allowing a surge of blood to flow through them on exposure to severe cold. This occurs through alternate vasodilatation and vasoconstriction known as Lewis Hunting Reaction. This phenomenon is influenced by several factors, which indirectly may also affect individual susceptibility to cold injury. The role of nutrition, adequate insulation of the body and positive heat balance in relation to the protective mechanism have been reviewed and discussed. Available literature on various factors has been surveyed and discussed in the light of recent advances in the physiology of cold exposure. Certain tests based on the present knowledge, to be developed and standardised for screening susceptible individuals to frost-bite have been suggested.

  13. Inherited susceptibility and radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B. [Harvard School of Public Health, Boston, MA (United States)

    1997-03-01

    There is continuing concern that some people in the general population may have genetic makeups that place them at particularly high risk for radiation-induced cancer. The existence of such a susceptible subpopulation would have obvious implications for the estimation of risks of radiation exposure. Although it has been long known that familial aggregations of cancer do sometimes occur, recent evidence suggests that a general genetic predisposition to cancer does not exist; most cancers occur sporadically. On the other hand, nearly 10% of the known Mendelian genetic disorders are associated with cancer. A number of these involve a familial predisposition to cancer, and some are characterized by an enhanced susceptibility to the induction of cancer by various physical and chemical carcinogens, including ionizing radiation. Such increased susceptibility will depend on several factors including the frequency of the susceptibility gene in the population and its penetrance, the strength of the predisposition, and the degree to which the cancer incidence in susceptible individuals may be increased by the carcinogen. It is now known that these cancer-predisposing genes may be responsible not only for rare familial cancer syndromes, but also for a proportion of the common cancers. Although the currently known disorders can account for only a small fraction of all cancers, they serve as models for genetic predisposition to carcinogen-induced cancer in the general population. In the present report, the author describes current knowledge of those specific disorders that are associated with an enhanced predisposition to radiation-induced cancer, and discusses how this knowledge may bear on the susceptibility to radiation-induced cancer in the general population and estimates of the risk of radiation exposure.

  14. Effects of linezolid on proinflammatory cytokines in rabbits with serious burn injury%利奈唑胺对严重烧伤家兔炎症因子水平的影响

    Institute of Scientific and Technical Information of China (English)

    马建丽; 高磊; 褚万立; 冯永强; 姚飞; 王晓青; 李翔; 张清哲; 马晓晖

    2013-01-01

    Objective:To study the effects of linezolid (LZD) on proinflammatory cytokines including tumor necrosis factor-α (TNF-a),interleukin-1 β (IL-1β)and interleukin-6 (IL-6) in rabbits with severe burns.Methods:Twenty-four rabbits were randomly divided into four groups:sham-scald group,scald group,sham-scald with LZD treatment group,and scald with LZD treatment group,with 6 animals in each group.Full thickness scald involving 30% total body surface area was replicated by dipping rabbits back in 98 ℃ water for 18 seconds in the two scald groups.In the two sham-scald groups,37 C water was used instead of 98 ℃ water.LZD was administered intravenously in a dose of 10 mg/kg in two LZD treatment groups.The pathological changes were observed,and the blood concentrations of TNF-α,IL-1β and IL-6 were determined by radioimmunoassay method.Results:Compared with the sham-scald group,levels of TNF-α,IL-1β and IL-6 in the scald groups elevated significantly.The IL-1β concentration reached the peak at 12 hours,and the levels of TNF-α and IL-6 reached the peak at 24 hours after burn.LZD could significantly reduce these three cytokines by 28.19%,38.54% and 28.48% in burn rabbits (P<0.05),but it showed no influence in sham injured rabbits (P>0.05).Conclusions:LZD could significantly reduce the levels of proinflammatory cytokines in rabbits with severe burn,but it showed no influence on the proinflammatory cytokines level in normal rabbits.%目的:研究利奈唑胺(LZD)对严重烧伤家兔促炎症因子肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)水平的影响.方法:随机将24只家兔分为假烫组、烫伤组、假烫+LZD治疗组、烫伤+LZD治疗组4组,每组6只.将两烫伤组家兔背部皮肤置于98℃热水18 s制备30% TBSAⅢ度烫伤模型;假烫组用37℃温水代替热水.两LZD治疗组家兔静脉注射10 mg/kg利奈唑胺.组织病理学观察烫伤深度,采用放射免疫分析方法检测烧

  15. Heck's disease: diagnosis and susceptibility.

    Science.gov (United States)

    Bennett, Lindsey K; Hinshaw, Molly

    2009-01-01

    Focal epithelial hyperplasia, or Heck's disease, is an uncommon proliferation of oral mucosa that presents primarily in Native Central and South American populations. It presents as asymptomatic papules or nodules on the oral mucosa, gingiva, tongue, and lips. In the majority of cases, human papilloma virus 13 or 32 is detected. Factors that determine disease susceptibility are unclear, but genetics, and having the human lymphocytic antigen-DR4 (DRB1*0404) allele in particular, are thought to play a major role in disease vulnerability. We report another case of focal epithelial hyperplasia, hypothesize on disease susceptibility, and review the current understanding of this uncommon disorder.

  16. In vitro susceptibilities of Brucella melitensis isolates to eleven antibiotics

    Directory of Open Access Journals (Sweden)

    Loukaides Feidias

    2006-10-01

    Full Text Available Abstract Background Brucellosis is an endemic disease present in many countries worldwide, but it is rare in Europe and North America. Nevertheless brucella is included in the bacteria potentially used for bioterrorism. The aim of this study was the investigation of the antibiotic susceptibility profile of brucella isolates from areas of the eastern Mediterranean where it has been endemic. Methods The susceptibilities of 74 Brucella melitensis isolates derived from clinical samples (57 and animal products (17 were tested in vitro. The strains originate from Crete (59, Cyprus (10, and Syria (5. MICs of tetracycline, rifampicin, streptomycin, gentamicin, norfloxacin, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole, ampicillin, amoxicillin/clavulanic acid, and erythromycin were detected by E-test method. The NCCLS criteria for slow growing bacteria were considered to interpret the results. Results All the isolates were susceptible to tetracycline, streptomycin, gentamicin, ciprofloxacin, norfloxacin, and levofloxacin. Two isolates presented reduced susceptibility to rifampicin (MIC value: 1.5 mg/l and eight to SXT (MIC values: 0.75–1.5 mg/l. Erythromycin had the highest (4 mg/l MIC90value and both norfloxacin and erythromycin the highest (1.5 mg/l MIC50 value. Conclusion Brucella isolates remain susceptible in vitro to most antibiotics used for treatment of brucellosis. The establishment of a standardized antibiotic susceptibility method for Brucella spp would be useful for resistance determination in these bacteria and possible evaluation of bioterorism risks.

  17. 还原型叶酸载体基因多态性与急性白血病易感性的相关性%Association of single nucleotide polymorphism of reduced folate carrier gene with susceptibility to acute leukemia

    Institute of Scientific and Technical Information of China (English)

    赵玮; 岳丽杰; 陈小文

    2011-01-01

    目的 研究还原型叶酸载体(reduced folate carrier,RFC)80G/A单核苷酸多态性(single nucleotide polymorphism,SNP)与急性白血病(acute leukemia,AL)之间的关联性.方法 采用逆转录-聚合酶链反应-变性梯度凝胶电泳(reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis,RT-PCR-DGGE)结合DNA直接测序,对98例AL患儿和135名正常儿童进行RFC第80位点SNP筛查.结果 在AL组和正常儿童组中发现RFC 80 GA基因型的例数分别为53和52,AA基因型例数分别为24和30,两组A等位基因频率分别为0.515和0.415.应用x2分析发现RFC 80G/A与AL存在交互作用.结论 确定了中国儿童RFC 80G/A的等位基因频率,并初步认为RFC 80G/A与AL发生存在一定的相关性.%Objective To investigate the allele and genotype frequencies of reduced folate carrier gene (RFC) 80G/A polymorphism in Chinese patients with acute leukemia (AL) and healthy control children,and to provide clue for association between the single nucleotide polymorphism (SNP) of RFC and the occurrence of AL. Methods Bone marrow samples from 98 childhood patients with AL and peripheral blood samples from 135 healthy children were obtained to prepare complementary DNAs (cDNAs). The cDNAs were analyzed for the polymorphisms in RFC 80G/A by reverse transcriptase-polymerase chain reactiondenaturing gradient gel electrophoresis (RT-PCR-DGGE) and direct sequencing. Results The A allele frequencies of the AL patients and control children were 0. 515 and 0. 415, respectively (P<0. 05). Chisquare test confirmed a statistical significance of the association between RFC80 G/A and AL. Conclusion RFC 80AA or GA genotype may contribute to increasing the susceptibility to AL.

  18. Current Microbial Isolates from Wound Swab and Their Susceptibility Pattern in a Private Medical College Hospital in Dhaka city

    Directory of Open Access Journals (Sweden)

    Shahin Sultana

    2015-03-01

    Full Text Available Background: Wound infection is one of the major health problems that are caused and aggravated by the invasion of pathogenic organisms where empiric treatment is routine. Objective: To isolate and identify the bacteria causing wound infection and to determine the antimicrobial susceptibility pattern. Materials and method: A total of 263 wound swab and pus samples were collected during the period of January to December 2012 from Delta Medical College and Hospital, Dhaka, Bangladesh. Swabs from the wound were inoculated on appropriate media and cultured and the isolates were identified by standard procedures as needed. Antimicrobial susceptibility testing was performed by disk diffusion method according to ‘The Clinical Laboratory Standard Institute’ guidelines. Results: In this study 220 bacterial isolates were recovered from 263 samples showing an isolation rate of 83.65%. The predominant bacteria isolated from infected wounds were Staphylococcus aureus 89 (40.45% followed by Escherichia coli 62 (28.18%, Pseudomonas aeruginosa 34 (15.45%, Enterococci 18 (8.18%, Acinetobacter 5 (2.27%, Klebsiella 9 (4.09% and Proteus 3 (3.36%. Staphylococcus aureus was sensitive to linezolid (94.38%, fusidic acid (91.01%, vancomycin (87.64%, amikacin (74.15% and gentamicin (73.03%. Among the Gram negative isolates Escherichia coli was predominant and showed sensitivity to imipenem (93.54% amikacin (83.87% colistin (53.22% and piperacillin and tazobactum (53.22% and pseudomonas showed sensitivity to amikacin (73.52%, imipenem (70.58% and colistin (70.58%. Conclusion: Staphylococcus aureus was the most frequently isolated pathogen from wound swab and the antibiotic sensitivity pattern of various isolates help to assist the clinician in appropriate selection of empirical antibiotics against wound infection.

  19. Mapping landslide susceptibility using data-driven methods.

    Science.gov (United States)

    Zêzere, J L; Pereira, S; Melo, R; Oliveira, S C; Garcia, R A C

    2017-07-01

    Most epistemic uncertainty within data-driven landslide susceptibility assessment results from errors in landslide inventories, difficulty in identifying and mapping landslide causes and decisions related with the modelling procedure. In this work we evaluate and discuss differences observed on landslide susceptibility maps resulting from: (i) the selection of the statistical method; (ii) the selection of the terrain mapping unit; and (iii) the selection of the feature type to represent landslides in the model (polygon versus point). The work is performed in a single study area (Silveira Basin - 18.2km(2) - Lisbon Region, Portugal) using a unique database of geo-environmental landslide predisposing factors and an inventory of 82 shallow translational slides. The logistic regression, the discriminant analysis and two versions of the information value were used and we conclude that multivariate statistical methods perform better when computed over heterogeneous terrain units and should be selected to assess landslide susceptibility based on slope terrain units, geo-hydrological terrain units or census terrain units. However, evidence was found that the chosen terrain mapping unit can produce greater differences on final susceptibility results than those resulting from the chosen statistical method for modelling. The landslide susceptibility should be assessed over grid cell terrain units whenever the spatial accuracy of landslide inventory is good. In addition, a single point per landslide proved to be efficient to generate accurate landslide susceptibility maps, providing the landslides are of small size, thus minimizing the possible existence of heterogeneities of predisposing factors within the landslide boundary. Although during last years the ROC curves have been preferred to evaluate the susceptibility model's performance, evidence was found that the model with the highest AUC ROC is not necessarily the best landslide susceptibility model, namely when terrain

  20. Prion protein and scrapie susceptibility

    NARCIS (Netherlands)

    Smits, M.A.; Bossers, A.; Schreuder, B.E.C.

    1997-01-01

    This article presents briefly current views on the role of prion protein (PrP) in Transmissible Spongiform Encephalopathies or prion diseases and the effect of PrP polymoryhisms on the susceptibility to these diseases, with special emphasis on sheep scrapie. The PrP genotype of sheep apears to be a

  1. Topological susceptibility from overlap fermion

    Institute of Scientific and Technical Information of China (English)

    应和平; 张剑波

    2003-01-01

    We numerically calculate the topological charge of the gauge configurations on a finite lattice by the fermionic method with overlap fermions. By using the lattice index theorem, we identify the index of the massless overlap fermion operator to the topological charge of the background gauge configuration. The resulting topological susceptibility X is in good agreement with the anticipation made by Witten and Veneziano.

  2. Pyrazinamide susceptibility testing: proposed new standard with the BACTECTM MGITTM 960 system.

    Science.gov (United States)

    Piersimoni, C; Mustazzolu, A; Iacobino, A; Giannoni, F; Santoro, G; Gherardi, G; Del Giudice, A; Perna, R; Fattorini, L

    2016-12-01

    The susceptibility of 253 Mycobacterium tuberculosis complex isolates to pyrazinamide (PZA) was assessed using the BACTECTM MGITTM 960 (M960) system. Resistant strains underwent paired repeat testing using 1) a critical concentration of 200 g/ml (PZA-200), and 2) a reduced inoculum of 0.25 ml. They were also examined using the BACTEC 460 (B460) reference method and investigated for pncA mutations. On M960, 37 isolates were resistant. In the PZA-200 assay, 20 of these were resistant and 17 susceptible, while 18 were resistant and 19 susceptible with reduced inoculum. The B460 assay and pncA sequencing confirmed results with reduced inoculum.

  3. Antifungal Susceptibility of Candida Biofilms: Unique Efficacy of Amphotericin B Lipid Formulations and Echinocandins

    OpenAIRE

    Kuhn, D M; T. George; CHANDRA, J; P. K. Mukherjee; Ghannoum, M A

    2002-01-01

    Biofilms, likely the predominant mode of device-related microbial infection, exhibit resistance to antimicrobial agents. Evidence suggests that Candida biofilms have dramatically reduced susceptibility to antifungal drugs. We examined antifungal susceptibilities of Candida albicans and Candida parapsilosis biofilms grown on a bioprosthetic model. In addition to conventional agents, we determined if new antifungal agents (triazoles, amphotericin B lipid formulations, and echinocandins) have ac...

  4. 利奈唑胺与替考拉宁治疗高龄患者重症MRSA感染的回顾性分析%Restrospective Analysis of Linezolid and Teicoplanin in the Treatment of Elderly Patients with Severe MRSA Infection

    Institute of Scientific and Technical Information of China (English)

    施珍; 康建强

    2015-01-01

    OBJECTIVE:To investigate therapeutic efficacy and safety of linezolid and teicoplanin in the elderly patients with severe MRSA infection. METHODS:97 elderly patients with severe MRSA infection were collected and divided into linezolid group (42 patients) and teicoplanin group (55 patients). Linezolid group was given linezolid 600 mg intravenously,bid;teico-planin group was given teicoplanin 400 mg intravenously,qd,double dose for the first day. Treatment course lasted for 7-21 d. Clin-ical effective rate,bacterium clearance rate and ADR were compared between 2 groups after treatment. RESULTS:The bacterium clearance rate of teicoplanin group was 52.6%,and that of linezolid group was 73.5%;the linezolid group was significantly higher than the teicoplanin group,with statistical significance(χ2=12.57,P=0.034). Clinical effective rate was 78.6% in linezolid group and 58.2% in teicoplanin group;the linezolid group was significantly higher than the teicoplanin group,with statistical significance (χ2=9.56,P=0.018). After 14 days of treatment,APACHEⅡ score of teicoplanin group and linezolid group were (14.56±3.04) and(10.29±4.84),respectively;the teicoplanin group was lower than the linezolid group,with statistical significance(t=10.97, P=0.014). The incidence of ADR was 11.9% in linezolid group and 20.0% in teicoplanin group,with statistical significance(χ2=1.13,P=0.287). CONCLUSIONS:Linezolid has superior curative effect to teicoplanin in the treatment of severe MRSA infection in elderly patients with good safety.%目的:探讨利奈唑胺与替考拉宁治疗高龄患者院内重症耐甲氧西林金黄色葡萄球菌(MRSA)感染的疗效及安全性。方法:收集高龄男性重症MRSA感染患者临床资料97例,根据使用药物分为利奈唑胺组(42例)和替考拉宁组(55例)。利奈唑胺组给予利奈唑胺600 mg,ivgtt,bid;替考拉宁组给予替考拉宁400 mg,ivgtt,qd,治疗首日剂量加倍。两组疗程均为7

  5. Susceptibility level of cucumber downy mildew (Pseudoperonospora cubensis to metalaxyl

    Directory of Open Access Journals (Sweden)

    Bagi Ferenc F.

    2009-01-01

    Full Text Available Level of susceptibility of Pseudoperonospora cubensis isolate from Ratkovo to metalaxyl in concentrations 50, 100, 200, 400 and 800 μg/ml was investigated. The trials were conducted on cotyledon and fully developed young leaves using cucumber cultivar Haroš. Reduced level of susceptibility was detected in metalaxyl concentrations of 50, 100 and 200 μg/ml because the intensity of sporulation in these treatments was on the same level as in control. Sporulation was also observed on developed leaves treated with metalaxyl in concentrations of 400 and 800 μg/ml.

  6. Rifampicin-containing combinations are superior to combinations of vancomycin, linezolid and daptomycin against Staphylococcus aureus biofilm infection in vivo and in vitro

    DEFF Research Database (Denmark)

    Jørgensen, Nis Pedersen; Skovdal, Sandra M; Meyer, Rikke L;

    2016-01-01

    implants does not reflect the actual susceptibility, and the optimal antibiotic strategy for treating implant-associated infections is not established. In this study of biofilm formation in implant-associated osteomyelitis, we compared thein vitroandin vivoefficacy of selected antibiotics alone...... combinations were tested in a murine model of implant-associated osteomyelitis. Mice were infected by inserting implants colonized withS. aureustrough their tibia. After 11 days, the animals were divided into different groups (five animals/group) and given 14 days of antibiotic therapy. All antibiotics...

  7. Universal locality of quantum thermal susceptibility

    Science.gov (United States)

    De Palma, Giacomo; De Pasquale, Antonella; Giovannetti, Vittorio

    2017-05-01

    The ultimate precision of any measurement of the temperature of a quantum system is the inverse of the local quantum thermal susceptibility [A. De Pasquale et al., Nat. Commun. 7, 12782 (2016), 10.1038/ncomms12782] of the subsystem with which the thermometer interacts. If this subsystem can be described with the canonical ensemble, such quantity reduces to the variance of the local Hamiltonian, which is proportional to the heat capacity of the subsystem. However, the canonical ensemble might not apply in the presence of interactions between the subsystem and the rest of the system. In this work, we address this problem in the framework of locally interacting quantum systems. We prove that the local quantum thermal susceptibility of any subsystem is close to the variance of its local Hamiltonian, provided the volume-to-surface ratio of the subsystem is much larger than the correlation length. This result greatly simplifies the determination of the ultimate precision of any local estimate of the temperature and rigorously determines the regime where interactions can affect this precision.

  8. FLOOD SUSCEPTIBILITY ASSESSMENT IN THE NIRAJ BASIN

    Directory of Open Access Journals (Sweden)

    SANDA ROŞCA

    2012-03-01

    Full Text Available Flood susceptibility assessment in the Niraj basin. In the context of global warming and the increasing frequency of extreme weather events, it becomes evident that we have to face natural hazards, such as floods. In the area of Niraj basin this phenomenon is specific both in the spring, because of the snow melting and of the precipitations which come along with the season, and then in the summer because of the torrential precipitations but rarely in autumn and winter. The aim of this paper is to determinate the susceptibility of the zone and obtain a map which will take into consideration the possibility of a flooding. Defining vulnerability can help us understand this type of natural disasters and find the best ways to reduce it. For this purpose we use thematic layers, morphological characteristics (slope and depth fragmentation, hydrological characteristics, geology, pedology (permeability and soil texture, landuse, precipitation data, and human interventions because in this way we have the possibility to use data mining for this purpose. Data mining will allow us to extract new information based on the existing sets of data.The final result will be a thematic map that highlights the areas which are exposed to the flood. Therefore, this map can be used as a support decision for local government or business purposes.

  9. Field susceptibility of 13 scab-resistant apple cultivars to apple powdery mildew [Podosphaera leucotricha (Ell. et Ev. Salmon

    Directory of Open Access Journals (Sweden)

    Zbigniew Borecki

    2013-12-01

    Full Text Available Field susceptibility of 13 scab-resistant apple cultivars to apple powdery mildew was evaluated in 1983-1986. Four groups of susceptibility were distinguished. None of the 13 tested scab-resistant apple trees exhibited complete field immunity to apple powdery mildew. Two cultivars, 'Prima' and 'Primula', were practically resistant. 'Liberty' and two numbered selections, NY-140-9 and NY-158-2, belonged to the group of lower susceptibility. Moderate susceptibility was shown by: 'Novamac', 'Freedom', 'Gavin', 'Prima' and 'Florina'. The group of apple trees most susceptible to Podosphaera leucotricha included: 'Macfree', 'Priscilla' and 'Nova Easygro'. It is not necessary to use chemical sprays to control powdery mildew on 'Prima' and 'Primula'. A reduced spraying program may be recommended only under high disease pressure on less susceptible apple cultivars. A regular spray schedule is needed on moderately susceptible apple trees, but improved chemical control is necessary on the most susceptible ones.

  10. Biofilm susceptibility to metal toxicity.

    Science.gov (United States)

    Harrison, Joe J; Ceri, Howard; Stremick, Carol A; Turner, Raymond J

    2004-12-01

    This study compared bacterial biofilm and planktonic cell susceptibility to metal toxicity by evaluating the minimum inhibitory concentration (MIC), the planktonic minimum bactericidal concentration (MBC), and minimum biofilm eradication concentration (MBEC) using the MBEC device. In total, 17 metal cations and oxyanions, chosen to represent groups VIB to VIA of the periodic table, were each tested on biofilm and planktonic cultures of Escherichia coli JM109, Staphylococcus aureus ATCC 29213, and Pseudomonas aeruginosa ATCC 27853. In contrast to control antibiotic assays, where biofilm cultures were 2 to 64 times less susceptible to killing than logarithmically growing planktonic bacteria, metal compounds killed planktonic and biofilm cultures at the same concentration in the vast majority of combinations. Our data indicate that, under the conditions reported, growth in a biofilm does not provide resistance to bacteria against killing by metal cations or oxyanions.

  11. Topological susceptibility from the overlap

    CERN Document Server

    Del Debbio, L; Debbio, Luigi Del; Pica, Claudio

    2004-01-01

    The chiral symmetry at finite lattice spacing of Ginsparg-Wilson fermionic actions constrains the renormalization of the lattice operators; in particular, the topological susceptibility does not require any renormalization, when using a fermionic estimator to define the topological charge. Therefore, the overlap formalism appears as an appealing candidate to study the continuum limit of the topological susceptibility while keeping the systematic errors under theoretical control. We present results for the SU(3) pure gauge theory using the index of the overlap Dirac operator to study the topology of the gauge configurations. The topological charge is obtained from the zero modes of the overlap and using a new algorithm for the spectral flow analysis. A detailed comparison with cooling techniques is presented. Particular care is taken in assessing the systematic errors. Relatively high statistics (500 to 1000 independent configurations) yield an extrapolated continuum limit with errors that are comparable with ...

  12. Topological susceptibility from the overlap

    DEFF Research Database (Denmark)

    Del Debbio, Luigi; Pica, Claudio

    2003-01-01

    The chiral symmetry at finite lattice spacing of Ginsparg-Wilson fermionic actions constrains the renormalization of the lattice operators; in particular, the topological susceptibility does not require any renormalization, when using a fermionic estimator to define the topological charge....... Therefore, the overlap formalism appears as an appealing candidate to study the continuum limit of the topological susceptibility while keeping the systematic errors under theoretical control. We present results for the SU(3) pure gauge theory using the index of the overlap Dirac operator to study...... the topology of the gauge configurations. The topological charge is obtained from the zero modes of the overlap and using a new algorithm for the spectral flow analysis. A detailed comparison with cooling techniques is presented. Particular care is taken in assessing the systematic errors. Relatively high...

  13. Antimycotics susceptibility testing of dermatophytes

    Directory of Open Access Journals (Sweden)

    Arsić-Arsenijević Valentina

    2010-01-01

    Full Text Available Dermatophytes are moulds that produce infections of the skin, hair and nails of humans and animals. The most common forms among these infections are onychomycosis and tinea pedis affecting 20% of world population. These infections are usually chronic. The treatment of dermatophytoses tends to be prolonged partly because available treatments are not very effective. Antifungal drug consumption and public health expenditure are high worldwide, as well as in Serbia. For adequate therapy, it is necessary to prove infection by isolation of dermatophytes and to test the antifungal susceptibility of isolates. Susceptibility testing is important for the resistance monitoring, epidemiological research and to compare in vitro activities of new antifungal agents. The diffusion and dilution methods of susceptibility tests are used, and technical issues of importance for the proper performance and interpretation of test results are published in the document E.DEF 9.1 (EUCAST and M38-A2 (CLSI. The aim of our paper is to promptly inform the public about technical achievements in this area, as well as the new organization of laboratory for medical mycology in our country. The formation of laboratory networks coordinated by the National Reference Laboratory for the cause of mycosis need to enable interlaboratory studies and further standardization of methods for antifungal susceptibility testing of dermatophytes, reproducibility of tests and clinical correlation monitoring (MIK values and clinical outcome of dermatophytosis. The importance of the new organization is expected efficient improvement in the dermatophytosis therapy at home, better quality of patient's life and the reduction of the cost of treatment.

  14. A New Approach for Calculating Vacuum Susceptibility

    Institute of Scientific and Technical Information of China (English)

    宗红石; 平加伦; 顾建中

    2004-01-01

    Based on the Dyson-Schwinger approach, we propose a new method for calculating vacuum susceptibilities. As an example, the vector vacuum susceptibility is calculated. A comparison with the results of the previous approaches is presented.

  15. Enumeration, Isolation and Antibiotic Susceptibility Profile of ...

    African Journals Online (AJOL)

    Antibiotic susceptibility testing of the isolates indicated that S. aureus species had the highest susceptibility of 14(93.3%) .... which sterile forceps were used to carefully remove the disc from its ..... micro-organisms found in public telephones.

  16. Landslide Susceptibility Statistical Methods: A Critical and Systematic Literature Review

    Science.gov (United States)

    Mihir, Monika; Malamud, Bruce; Rossi, Mauro; Reichenbach, Paola; Ardizzone, Francesca

    2014-05-01

    Landslide susceptibility assessment, the subject of this systematic review, is aimed at understanding the spatial probability of slope failures under a set of geomorphological and environmental conditions. It is estimated that about 375 landslides that occur globally each year are fatal, with around 4600 people killed per year. Past studies have brought out the increasing cost of landslide damages which primarily can be attributed to human occupation and increased human activities in the vulnerable environments. Many scientists, to evaluate and reduce landslide risk, have made an effort to efficiently map landslide susceptibility using different statistical methods. In this paper, we do a critical and systematic landslide susceptibility literature review, in terms of the different statistical methods used. For each of a broad set of studies reviewed we note: (i) study geography region and areal extent, (ii) landslide types, (iii) inventory type and temporal period covered, (iv) mapping technique (v) thematic variables used (vi) statistical models, (vii) assessment of model skill, (viii) uncertainty assessment methods, (ix) validation methods. We then pulled out broad trends within our review of landslide susceptibility, particularly regarding the statistical methods. We found that the most common statistical methods used in the study of landslide susceptibility include logistic regression, artificial neural network, discriminant analysis and weight of evidence. Although most of the studies we reviewed assessed the model skill, very few assessed model uncertainty. In terms of geographic extent, the largest number of landslide susceptibility zonations were in Turkey, Korea, Spain, Italy and Malaysia. However, there are also many landslides and fatalities in other localities, particularly India, China, Philippines, Nepal and Indonesia, Guatemala, and Pakistan, where there are much fewer landslide susceptibility studies available in the peer-review literature. This

  17. Life style factors and acquired susceptibility to environmental disease.

    Science.gov (United States)

    Au, W W

    2001-10-01

    Multifactorial risk factors are responsible for many diseases. They can be broadly categorized as environmental, genetic and life style factors. Much attention has been focused on the first two categories, e.g. the identification of environmental toxicants/carcinogens and the elucidation of genetic susceptibility to disease. Life style risk factors such as aging, poor nutrition, infection and exposure to toxicants can also increase susceptibility to illnesses. These life style factors can therefore be considered to cause acquired susceptibility for increased risk for environmental disease. Among Egyptians, infection with the parasite, Schistosoma, is the primary risk factor for bladder cancer and the risk is enhanced by exposure to mutagenic chemicals. We have shown that inheritance of susceptible metabolizing genes that can increase body burden of mutagenic chemicals enhances the risk. We have also hypothesized that chronic exposure to mutagenic chemicals causes cellular abnormalities that can reduce the capacity of cells to repair DNA damage and thus increase the risk for environmental disease. We have used a challen