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Sample records for affects beta-lactam resistance

  1. The in-vitro antimicrobial activity of some medicinal plants against beta-lactam-resistant bacteria

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    Gangoue Pieboji, Joseph; Eze, N.; Ngongang Djintchui, A.; Ngameni, B; Tsabang, N.; Pegnyemb, D. E.; Biyiti, L.; Ngassam, P.; Koulla-Shiro, S.; Galleni, Moreno

    2009-01-01

    BACKGROUND: In effort to identify novel bacterial agents, this study was initiated to evaluate the antimicrobial properties of 17 crude extracts from 12 medicinal plants against beta-lactam-resistant bacteria. METHODOLOGY: The antimicrobial activities of plant extracts were evaluated against clinically proved beta-lactam-resistant bacteria (Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Serratia marcescens, Acinetobacter baumannii, Staphylococcus aureus and Enterococcus sp.)...

  2. Resistance patterns to beta-lactams and quinolones in clinical isolates of bacteria from Cuban hospitals.

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    Gonzáles, I; Niebla, A; Vallin, C

    1995-01-01

    The resistance patterns to 26 beta-lactams and 8 quinolones of clinical isolates from Cuban hospitals were evaluated using the disk susceptibility test, according to the NCCLS guidelines (1992). The genera studied were Escherichia sp (320), Enterobacter sp (10), Klebsiella sp (90), Proteus sp (10), Pseudomonas sp (90), Serratia sp (20), and Staphylococcus sp (80). Higher resistance to beta-lactams was observed in the genera Pseudomonas, Escherichia and Klebsiella. For fluoroquinolones we found no significant resistance, with the exception of the genus Klebsiella. The most effective antibiotics were cephalosporins of the second and third generations, fluoroquinolones, and non-classical beta-lactams (cephamycins, moxalactam and monobactams). On the contrary, a pronounced resistance was found to penicillin, oxacillin, ticarcillin, ampicillin, methicillin, nalidixic acid and cinoxacin. These resistance patterns correspond to the high consumption of these antibiotics throughout the country.

  3. Comprehensive identification of single nucleotide polymorphisms associated with beta-lactam resistance within pneumococcal mosaic genes.

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    Claire Chewapreecha

    2014-08-01

    Full Text Available Traditional genetic association studies are very difficult in bacteria, as the generally limited recombination leads to large linked haplotype blocks, confounding the identification of causative variants. Beta-lactam antibiotic resistance in Streptococcus pneumoniae arises readily as the bacteria can quickly incorporate DNA fragments encompassing variants that make the transformed strains resistant. However, the causative mutations themselves are embedded within larger recombined blocks, and previous studies have only analysed a limited number of isolates, leading to the description of "mosaic genes" as being responsible for resistance. By comparing a large number of genomes of beta-lactam susceptible and non-susceptible strains, the high frequency of recombination should break up these haplotype blocks and allow the use of genetic association approaches to identify individual causative variants. Here, we performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs and indels that could confer beta-lactam non-susceptibility using 3,085 Thai and 616 USA pneumococcal isolates as independent datasets for the variant discovery. The large sample sizes allowed us to narrow the source of beta-lactam non-susceptibility from long recombinant fragments down to much smaller loci comprised of discrete or linked SNPs. While some loci appear to be universal resistance determinants, contributing equally to non-susceptibility for at least two classes of beta-lactam antibiotics, some play a larger role in resistance to particular antibiotics. All of the identified loci have a highly non-uniform distribution in the populations. They are enriched not only in vaccine-targeted, but also non-vaccine-targeted lineages, which may raise clinical concerns. Identification of single nucleotide polymorphisms underlying resistance will be essential for future use of genome sequencing to predict antibiotic sensitivity in clinical microbiology.

  4. [Pathogenesis of beta-lactam-resistant Haemophilus influenzae isolated from sputum].

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    Watanuki, Yuji; Odagiri, Shigeki; Takahashi, Hiroshi; Ogura, Takashi; Tomioka, Toshiaki

    2004-10-01

    Haemophlus influenzae persists in the respiratory tract and sometimes causes respiratory tract infections. To evaluate the pathogenesis of beta-lactam-resistant Haemophilus influenzae, we classified 193 Haemophilus influenzae strains isolated from sputum of patients with respiratory tract disease in 24 beta-lactamase positive (BLP) strains, 65 beta-lactamase negative ampicillin resistant (BLNAR) strains and 104 beta-lactamase negative ampicillin sensitive (BLNAS) strains and reviewed the pathogenesis of the strains. The pathogenesis of the strains was evaluated as definite pathogen, presumptive pathogen, colonization and contamination. It was judged to be the definite pathogen that many bacteria isolated from high quality sputum of the patients with respiratory tract infections. Presumptive pathogen was considered to be the bacteria provided from the patient with respiratory infections when the quality of the sputum or quantity of bacteria did not satisfy superscription basis. We considered the bacteria to be colonization or contamination isolated from patients without infections. The breakdown of definite pathogen/presumptive pathogen/colonization/contamination in each by groups was BLP (8/4/8/4), BLNAR (26/14/15/10), BLNAS (36/20/31/17). The ratio of definite or presumptive pathogen was 50% in BLP, 62% in BLNAR and 54% in BLNAS and the significant difference was not recognized in these. Pathogenesis of beta-lactam-resistant Haemophilus influenzae is estimated to be equal with beta-lactam-sensitive Haemophilus influenzae.

  5. Structural basis for the beta lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus.

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    Lim, Daniel; Strynadka, Natalie C J

    2002-11-01

    The multiple antibiotic resistance of methicillin-resistant strains of Staphylococcus aureus (MRSA) has become a major clinical problem worldwide. The key determinant of the broad-spectrum beta-lactam resistance in MRSA strains is the penicillin-binding protein 2a (PBP2a). Because of its low affinity for beta-lactams, PBP2a provides transpeptidase activity to allow cell wall synthesis at beta-lactam concentrations that inhibit the beta-lactam-sensitive PBPs normally produced by S. aureus. The crystal structure of a soluble derivative of PBP2a has been determined to 1.8 A resolution and provides the highest resolution structure for a high molecular mass PBP. Additionally, structures of the acyl-PBP complexes of PBP2a with nitrocefin, penicillin G and methicillin allow, for the first time, a comparison of an apo and acylated resistant PBP. An analysis of the PBP2a active site in these forms reveals the structural basis of its resistance and identifies features in newly developed beta-lactams that are likely important for high affinity binding.

  6. Biofilm production and beta-lactamic resistance in Brazilian Staphylococcus aureus isolates from bovine mastitis

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    Viviane Figueira Marques

    Full Text Available Abstract Staphylococcus spp. play an important role in the etiology of bovine mastitis. Staphylococcus aureus is considered the most relevant species due to the production of virulence factors such as slime, which is required for biofilm formation. This study aimed to evaluate biofilm production and its possible relation to beta-lactamic resistance in 20 S. aureus isolates from bovine mastitic milk. The isolates were characterized by pheno-genotypic and MALDI TOF-MS assays and tested for genes such as icaA, icaD, bap, agr RNAIII, agr I, agr II, agr III, and agr IV, which are related to slime production and its regulation. Biofilm production in microplates was evaluated considering the intervals determined along the bacterial growth curve. In addition, to determine the most suitable time interval for biofilm analysis, scanning electron microscopy was performed. Furthermore, genes such as mecA and blaZ that are related to beta-lactamic resistance and oxacillin susceptibility were tested. All the studied isolates were biofilm producers and mostly presented icaA and icaD. The Agr type II genes were significantly prevalent. According to the SEM, gradual changes in the bacterial arrangement were observed during biofilm formation along the growth curve phases, and the peak was reached at the stationary phase. In this study, the penicillin resistance was related to the production of beta-lactamase, and the high minimal bactericidal concentration for cefoxitin was possibly associated with biofilm protection. Therefore, further studies are warranted to better understand biofilm formation, possibly contributing to our knowledge about bacterial resistance in vivo.

  7. Meropenem in cystic fibrosis patients infected with resistant Pseudomonas aeruginosa or Burkholderia cepacia and with hypersensitivity to beta-lactam antibiotics

    DEFF Research Database (Denmark)

    Ciofu, Oana; Jensen, Tim; Pressler, Tacjana

    1996-01-01

    OBJECTIVE: To assess the efficacy and safety of meropenem, administered on a compassionate basis to 62 cystic fibrosis (CF) patients (age: 24plus minus6 years) with hypersensitivity reactions to beta-lactam antibiotics and/or infection by bacteria resistant to other antibiotics. METHODS: Fifty...... reactions to other beta-lactam drugs....

  8. CesRK, a two-component signal transduction system in Listeria monocytogenes, responds to the presence of cell wall-acting antibiotics and affects beta-lactam resistance

    DEFF Research Database (Denmark)

    Kallipolitis, Birgitte H; Ingmer, Hanne; Gahan, Cormac G

    2003-01-01

    Listeria monocytogenes is a food-borne pathogen that can cause a variety of illnesses ranging from gastroenteritis to life-threatening septicemia. The beta-lactam antibiotic ampicillin remains the drug of choice for the treatment of listeriosis. We have previously identified a response regulator...... of L. monocytogenes to tolerate ethanol and cell wall-acting antibiotics of the beta-lactam family. Furthermore, CesRK controls the expression of a putative extracellular peptide encoded by the orf2420 gene, located immediately downstream from cesRK. Inactivation of orf2420 revealed that it contributes...

  9. Impact of mecA promoter mutations on mecA expression and beta-lactam resistance levels.

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    Ender, Miriam; McCallum, Nadine; Berger-Bächi, Brigitte

    2008-10-01

    The reason for the extremely low-level oxacillin resistance in a so-called 'drug clone', a methicillin-resistant Staphylococcus aureus circulating among injection drug users in Zurich, Switzerland, could be traced back to the mecA promoter sequence and particularly to the strain's genetic background. Sequencing of its mec complex identified a point mutation (TATACT to TATATT), creating a perfect palindrome in the -10 region of the mecA promoter/operator region containing the binding sites for the mecA repressors MecI and BlaI. Two strains with vastly different beta-lactam resistance phenotypes, the low-level resistant drug clone type strain CHE482 and the highly homogeneously resistant strain COLn, were cured of their SCCmec elements and subsequently transformed with plasmids containing mecA under the control of either the wild-type or mutant promoter. Expression studies showed that this mutation had significant effects on both mecA transcription and corresponding PBP2a production, but only small effects on beta-lactam resistance levels within a given genetic background. A further mutation in the mecA ribosomal binding site (GGAGG to GGAGT), common to SCCmec type IV strains, was found to have no discernable effect on mecA transcription and PBP2a content, and only minimal effects on beta-lactam resistance. Factors associated with the genetic backgrounds into which these differently controlled mecA genes were introduced had a much higher impact on beta-lactam resistance levels than the rates of mecA transcription. The tight repression of mecA expression in this drug clone in the absence of beta-lactams could contribute to the apparent fitness of this fast growing strain.

  10. Molecular epidemiology of penicillin-susceptible non-beta-lactam-resistant Streptococcus pneumoniae isolates from Greek children

    NARCIS (Netherlands)

    D. Bogaert (Debby); P.W.M. Hermans (Peter); I.N. Grivea; G.S. Katopodis; T.J. Mitchell; M. Sluijter (Marcel); R. de Groot (Ronald); N.G. Beratis; G.A. Syrogiannopoulos

    2003-01-01

    textabstractA total of 128 Streptococcus pneumoniae isolates that were susceptible to penicillin but resistant to non-beta-lactam agents were isolated from young carriers in Greece and analyzed by antibiotic susceptibility testing, serotyping, restriction fragment end labeling (RFE

  11. The mechanism of heterogeneous beta-lactam resistance in MRSA: key role of the stringent stress response.

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    Choonkeun Kim

    Full Text Available All methicillin resistant S. aureus (MRSA strains carry an acquired genetic determinant--mecA or mecC--which encode for a low affinity penicillin binding protein -PBP2A or PBP2A'--that can continue the catalysis of peptidoglycan transpeptidation in the presence of high concentrations of beta-lactam antibiotics which would inhibit the native PBPs normally involved with the synthesis of staphylococcal cell wall peptidoglycan. In contrast to this common genetic and biochemical mechanism carried by all MRSA strains, the level of beta-lactam antibiotic resistance shows a very wide strain to strain variation, the mechanism of which has remained poorly understood. The overwhelming majority of MRSA strains produce a unique--heterogeneous--phenotype in which the great majority of the bacteria exhibit very poor resistance often close to the MIC value of susceptible S. aureus strains. However, cultures of such heterogeneously resistant MRSA strains also contain subpopulations of bacteria with extremely high beta-lactam MIC values and the resistance level and frequency of the highly resistant cells in such strain is a characteristic of the particular MRSA clone. In the study described in this communication, we used a variety of experimental models to understand the mechanism of heterogeneous beta-lactam resistance. Methicillin-susceptible S. aureus (MSSA that received the mecA determinant in the laboratory either on a plasmid or in the form of a chromosomal SCCmec cassette, generated heterogeneously resistant cultures and the highly resistant subpopulations that emerged in these models had increased levels of PBP2A and were composed of bacteria in which the stringent stress response was induced. Each of the major heterogeneously resistant clones of MRSA clinical isolates could be converted to express high level and homogeneous resistance if the growth medium contained an inducer of the stringent stress response.

  12. Antibodies against Pseudomonas aeruginosa chromosomal beta-lactamase inpatients with cystic fibrosis are markers of the development of resistance of P. aeruginosa to beta-lactams

    DEFF Research Database (Denmark)

    Ciofu, O; Giwercman, B; Walter-Rasmussen, J

    1995-01-01

    Chromosomal beta-lactamase production is considered to be the most important resistance mechanism of Pseudomonas aeruginosa against beta-lactams. Recently we have detected serum and sputum antibodies against P. aeruginosa chromosomal beta-lactamase (a beta ab), using immunoblotting techniques...... infection and was significantly higher (P beta-lactam courses. A 14 fold increase in a beta ab...... levels occurred during the 14 year period covered by the longitudinal study. The results of this study show that a beta ab to P. aeruginosa is a specific marker for resistance development of P. aeruginosa to beta-lactams....

  13. Preincubation of pneumococci with beta-lactams alone or combined with levofloxacin prevents quinolone-induced resistance without increasing intracellular levels of levofloxacin.

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    Cottagnoud, Philippe; Johnson, Maggie; Cottagnoud, Marianne; Piddock, Laura

    2005-08-01

    Preincubation of pneumococci with sub-MIC concentrations of ceftriaxone (1/16x MIC), cefotaxime (1/8x MIC), and meropenem (1/4x MIC) alone or combined with levofloxacin (1/8x MIC) over 6 h prevents the emergence of levofloxacin-resistant mutants after 96 h of incubation but does not affect the intracellular accumulation of levofloxacin in two penicillin-resistant pneumococcal strains, suggesting a link between the mechanism of action of beta-lactams and the emergence of quinolone-induced resistance in pneumococci.

  14. Evaluation and updating of the Osiris expert system for identification of Escherichia coli beta-lactam resistance phenotypes.

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    Bert, Frédéric; Juvin, Manette; Ould-Hocine, Zahia; Clarebout, Gervais; Keller, Emmanuelle; Lambert, Nicole; Arlet, Guillaume

    2005-04-01

    Osiris is a video zone size reader for disk diffusion tests that includes a built-in extended expert system (EES). We evaluated the efficacy of the Osiris EES for the identification of beta-lactam susceptibility phenotypes of Escherichia coli isolates. Fifteen beta-lactam agents and three beta-lactam-beta-lactamase inhibitor combinations were tested by the disk diffusion method against 50 E. coli strains with well-characterized resistance mechanisms. The strains were screened for the production of extended-spectrum beta-lactamase (ESBL) by the double-disk synergy test using a disk of amoxicillin-clavulanic acid with disks of the extended-spectrum cephalosporins and aztreonam. Overall, the EES accurately identified the phenotype for 78% of the strains, indicated an inexact phenotype for 17% of the strains, and could not find a matching phenotype for the remaining 5% of the strains. The percentage of correct identification for each resistance mechanism was 100% for inhibitor-resistant TEM and for TEM plus cephalosporinase, 88.9% for TEM and for ESBL, 70.8% for cephalosporinase overproduction, and 25% for oxacillinase. The main cause of discrepancy was the misidentification of oxacillinase as inhibitor-resistant TEM. The conventional double-disk synergy test failed to detect ESBL production in two strains (one producing VEB-1 and one producing CTX-M-14), but synergy between cefepime and amoxicillin-clavulanic acid was visible after the distance between the disks was reduced to 20 mm. After the interpretative guidelines of the EES were updated according to our results, the percentage of correct phenotype identification increased from 78 to 96%.

  15. Metallo-beta-lactamases of Pseudomonas aeruginosa--a novel mechanism resistance to beta-lactam antibiotics.

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    Dorota Olszańska

    2008-06-01

    Full Text Available Since about twenty years, following the introduction into therapeutic of news beta-lactam antibiotics (broad-spectrum cephalosporins, monobactams and carbapenems, a very significant number of new beta-lactamases appeared. These enzymes confer to the bacteria which put them, the means of resisting new molecules. The genetic events involved in this evolution are of two types: evolution of old enzymes by mutation and especially appearance of new genes coming for some, from bacteria of the environment. Numerous mechanisms of enzymatic resistance to the carbapenems have been described in Pseudomonas aeruginosa. The important mechanism of inactivation carbapenems is production variety of b-lactam hydrolysing enzymes associated to carbapenemases. The metallo-beta-enzymes (IMP, VIM, SPM, GIM types are the most clinically significant carbapenemases. P. aeruginosa posses MBLs and seem to have acquired them through transmissible genetic elements (plasmids or transposons associated with integron and can be transmission to other bacteria. They have reported worldwide but mostly from South East Asia and Europe. The enzymes, belonging to the molecular class B family, are the most worrisome of all beta-lactamases because they confer resistance to carbapenems and all the beta-lactams (with the exception of aztreonam and usually to aminoglycosides and quinolones. The dissemination of MBLs genes is thought to be driven by regional consumption of extended--spectrum antibiotics (e.g. cephalosporins and carbapenems, and therefore care must be taken that these drugs are not used unnecessarily.

  16. Resistance to beta-lactams among blood isolates of Salmonella spp. in European hospitals : results from the SENTRY Antimicrobial Surveillance Program 1997-98

    NARCIS (Netherlands)

    Tzouvelekis, LS; Lukova, [No Value; Tassios, PT; Fluit, AC; Jones, RN; Legakis, NJ

    2003-01-01

    The susceptibility to beta -lactams and the beta -lactamase content of 110 Salmonella spp. blood isolates collected during 1997-98 in 19 European centers participating in the SENTRY Surveillance Program were studied. Thirty-one isolates (28%) were resistant to penicillins, due to production of TEM-1

  17. [Allergy to beta-lactam antibiotics].

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    Comte, D; Petitpierre, S; Spertini, F; Bart, P-A

    2012-04-18

    Beta-lactam antibiotics allergies are common. Up to 10% of the population describe a former allergy to penicillins. However only 10 to 15% of these individuals are actually allergic. In most cases, beta-lactam antibiotics will be avoided and replaced by other antibiotics such as quinolones. This fear of a serious allergic reaction has an economic impact and may lead to the emergence of antibiotic resistance. A thorough allergic work-up can accurately determine true allergic patients. Most of the patients with a proven allergy will be able to tolerate other antibiotics belonging to the beta-lactam family. This article focuses on the management of beta-lactam allergic patients.

  18. Streptococcus pneumoniae: the evolution of antimicrobial resistance to beta-lactams, fluoroquinolones and macrolides.

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    Cornick, J E; Bentley, S D

    2012-07-01

    Multi drug resistant Streptococcus pneumoniae constitute a major public health concern worldwide. In this review we discuss how the transformable nature of the pneumococcus, in parallel with antimicrobial induced stress, contributes to the evolution of antimicrobial resistance; and how the introduction of the pneumococcal conjugate vaccine has affected the situation.

  19. The Survey of Genes Encoding Beta-Lactamases, in Escherichia Coli Resistant to Beta-Lactam and Non-Beta-Lactam Antibiotics

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    Fereshteh Shahcheraghi

    2010-01-01

    Full Text Available Resistance to the new generation of cephalosporins which is mediated by Extended-Spectrum beta-lactamases (ESBLs has been found amongEscherichia coli isolates throughout the world. These resistance genes and their producers, the micro-organisms carrying beta-lactamases, are responsible for serious clinical and therapeutic problems among inpatients and it is necessary to pay more attention to detection of ESBLs producing organisms.Materiasl and MethodsCollectively 260 isolates of E. coli were obtained from 6 hospitals in Tehran (Iran during April-2006 to April-2007. The antibiotic susceptibility patterns of isolates were determined by disk diffusion method. phenotypic confirmatory test (PCT was carried out for screening of ESBLs. Microbroth dilution assay was used to determine the minimum inhibitory concentration (MIC of ceftazidime. Isolates showing MIC≥2 μg/ml were subjected to polymerase chain reaction (PCR targeting blaTEM, blaSHV, blaCTX and blaPER genes. ResultsThe PCT showed that 48.08% of isolates are ESBL producers (125 of 260. The majority of cefotaxime resistant (90.8% and ceftazidime resistant (92.5% isolates were ESBL producers. The obtained results by PCR revealed that 5.77% (n=15 of 260 and 24.23 (n=63 of isolates can produce SHV and TEM type enzymes respectively. blaCTX was detected in 20.38% of isolates (n=53 and none of them could produce blaPER type beta-lactamases. ConclusionThe results of our study showed that the ESBL genes have high prevalence among clinical isolates of E. coli. Such high dissemination of ESBLs is a serious problem for public health and therefore, it's necessary to seek a program for monitoring ESBLs in hospitals.

  20. Abundances of tetracycline, sulphonamide and beta-lactam antibiotic resistance genes in conventional wastewater treatment plants (WWTPs) with different waste load

    DEFF Research Database (Denmark)

    Laht, Mailis; Karkman, Antti; Voolaid, Veiko

    2014-01-01

    Antibiotics and antibiotic resistant bacteria enter wastewater treatment plants (WWTPs), an environment where resistance genes can potentially spread and exchange between microbes. Several antibiotic resistance genes (ARGs) were quantified using qPCR in three WWTPs of decreasing capacity located...... conclude that there is neither considerable enrichment nor purification of antibiotic resistance genes in studied conventional WWTPs....... in Helsinki, Tallinn, and Tartu, respectively: sulphonamide resistance genes (sul1 and sul2), tetracycline resistance genes (tetM and tetC), and resistance genes for extended spectrum beta-lactams (blaoxa-58, blashv-34, and blactx-m-32). To avoid inconsistencies among qPCR assays we normalised the ARG...

  1. Natural lipopeptide antibiotic tripropeptin C revitalizes and synergistically potentiates the activity of beta-lactams against methicillin-resistant Staphylococcus aureus.

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    Hashizume, Hideki; Takahashi, Yoshiaki; Harada, Shigeko; Nomoto, Akio

    2015-06-01

    Tripropeptin C (TPPC) is a natural calcium-ion-dependent lipopeptide antibiotic that inhibits peptidoglycan biosynthesis by binding to prenyl pyrophosphate. It displays very potent antimicrobial activity both in vitro and in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) septicemia. The combination of TPPC with all classes of beta-lactams tested (including penam, carbapenem, cephem and oxacephem) showed highly synergistic (SYN) effects against MRSA strains, but not against methicillin-sensitive S. aureus strains. These SYN effects were observed with both a checkerboard methodology and a time-kill analysis. The TPPC analog, bis-methyl ester-TPPC, which has neither antimicrobial activity nor the ability to bind prenyl pyrophosphate, also potentiated the activity of beta-lactams. This result indicates that the mechanism of the SYN activity of TPPC is independent of its binding to prenyl pyrophosphate. Therefore, synergistically enhancing the anti-MRSA activities of TPPC and beta-lactams by combining them is a novel and potentially powerful therapeutic strategy for MRSA infections.

  2. Occurrence of quinolone- and beta-lactam-resistant Escherichia coli in danish broiler flocks

    DEFF Research Database (Denmark)

    Bortolaia, Valeria; Guardabassi, Luca; Bisgaard, Magne;

    resistant to quinolones or ß-lactams. Sock samples were collected from 10 broiler parent flocks and 10 broiler offspring flocks. Five pairs of socks were collected from each house. Samples were enriched in McConkey broth and streaked on McConkey agar added with nalidixic acid (32 µg/ml), ciprofloxacin (2 µg...... and nalidixic acid resistances were detected in all flocks. The numbers of E. coli resistant to these drugs were higher in plates from parent flocks than in those from offspring flocks. A broiler parent flock without any history of quinolone usage tested positive for ciprofloxacin-resistant E. coli, although......, these types of resistance are widespread in Danish broiler flocks. The observed high prevalence of nalidixic acid-resistant E. coli is surprising since the use of quinolones in poultry is restricted in Denmark. The low prevalence (5%) of flocks positive for ciprofloxacin resistance and the absence...

  3. Haemophilus influenzae with Non-Beta-Lactamase-Mediated Beta-Lactam Resistance: Easy To Find but Hard To Categorize.

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    Skaare, Dagfinn; Lia, Astrid; Hannisdal, Anja; Tveten, Yngvar; Matuschek, Erika; Kahlmeter, Gunnar; Kristiansen, Bjørn-Erik

    2015-11-01

    Haemophilus influenzae is a major pathogen, and beta-lactams are first-line drugs. Resistance due to altered penicillin-binding protein 3 (rPBP3) is frequent, and susceptibility testing of such strains is challenging. A collection of 154 beta-lactamase-negative isolates with a large proportion of rPBP3 (67.5%) was used to evaluate and compare Etest (Haemophilus test medium [HTM]) and disk diffusion (EUCAST method) for categorization of susceptibility to aminopenicillins and cefuroxime, using MICs generated with broth (HTM) microdilution and clinical breakpoints from CLSI and EUCAST as the gold standards. In addition, the proficiency of nine disks in screening for the rPBP3 genotype (N526K positive) was evaluated. By Etest, both essential and categorical agreement were generally poor (<70%), with high very major errors (VME) (CLSI, 13.0%; EUCAST, 34.3%) and falsely susceptible rates (FSR) (CLSI, 87.0%; EUCAST, 88.3%) for ampicillin. Ampicillin (2 μg) with adjusted (+2 mm) zone breakpoints was superior to Etest for categorization of susceptibility to ampicillin (agreement, 74.0%; VME, 11.0%; FSR, 28.3%). Conversely, Etest was superior to 30 μg cefuroxime for categorization of susceptibility to cefuroxime (agreement, 57.1% versus 60.4%; VME, 2.6% versus 9.7%; FSR, 7.1% versus 26.8%). Benzylpenicillin (1 unit) (EUCAST screening disk) and cefuroxime (5 μg) identified rPBP3 isolates with highest accuracies (95.5% and 92.2%, respectively). In conclusion, disk screening reliably detects rPBP3 H. influenzae, but false ampicillin susceptibility is frequent with routine methods. We suggest adding a comment recommending high-dose aminopenicillin therapy or the use of other agents for severe infections with screening-positive isolates that are susceptible to aminopenicillins by gradient or disk diffusion.

  4. Haemophilus influenzae with Non-Beta-Lactamase-Mediated Beta-Lactam Resistance: Easy To Find but Hard To Categorize

    Science.gov (United States)

    Lia, Astrid; Hannisdal, Anja; Tveten, Yngvar; Matuschek, Erika; Kahlmeter, Gunnar; Kristiansen, Bjørn-Erik

    2015-01-01

    Haemophilus influenzae is a major pathogen, and beta-lactams are first-line drugs. Resistance due to altered penicillin-binding protein 3 (rPBP3) is frequent, and susceptibility testing of such strains is challenging. A collection of 154 beta-lactamase-negative isolates with a large proportion of rPBP3 (67.5%) was used to evaluate and compare Etest (Haemophilus test medium [HTM]) and disk diffusion (EUCAST method) for categorization of susceptibility to aminopenicillins and cefuroxime, using MICs generated with broth (HTM) microdilution and clinical breakpoints from CLSI and EUCAST as the gold standards. In addition, the proficiency of nine disks in screening for the rPBP3 genotype (N526K positive) was evaluated. By Etest, both essential and categorical agreement were generally poor (<70%), with high very major errors (VME) (CLSI, 13.0%; EUCAST, 34.3%) and falsely susceptible rates (FSR) (CLSI, 87.0%; EUCAST, 88.3%) for ampicillin. Ampicillin (2 μg) with adjusted (+2 mm) zone breakpoints was superior to Etest for categorization of susceptibility to ampicillin (agreement, 74.0%; VME, 11.0%; FSR, 28.3%). Conversely, Etest was superior to 30 μg cefuroxime for categorization of susceptibility to cefuroxime (agreement, 57.1% versus 60.4%; VME, 2.6% versus 9.7%; FSR, 7.1% versus 26.8%). Benzylpenicillin (1 unit) (EUCAST screening disk) and cefuroxime (5 μg) identified rPBP3 isolates with highest accuracies (95.5% and 92.2%, respectively). In conclusion, disk screening reliably detects rPBP3 H. influenzae, but false ampicillin susceptibility is frequent with routine methods. We suggest adding a comment recommending high-dose aminopenicillin therapy or the use of other agents for severe infections with screening-positive isolates that are susceptible to aminopenicillins by gradient or disk diffusion. PMID:26354813

  5. An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance

    OpenAIRE

    Nadia Abed; Fatouma Saïd-Hassane; Fatima Zouhiri; Julie Mougin; Valérie Nicolas; Didier Desmaële; Ruxandra Gref; Patrick Couvreur

    2015-01-01

    The “Golden era” of antibiotics is definitely an old story and this is especially true for intracellular bacterial infections. The poor intracellular bioavailability of antibiotics reduces the efficency of many treatments and thereby promotes resistances. Therefore, the development of nanodevices coupled with antibiotics that are capable of targeting and releasing the drug into the infected-cells appears to be a promising solution to circumvent these complications. Here, we took advantage of ...

  6. An efficient system for intracellular delivery of beta-lactam antibiotics to overcome bacterial resistance.

    Science.gov (United States)

    Abed, Nadia; Saïd-Hassane, Fatouma; Zouhiri, Fatima; Mougin, Julie; Nicolas, Valérie; Desmaële, Didier; Gref, Ruxandra; Couvreur, Patrick

    2015-08-27

    The "Golden era" of antibiotics is definitely an old story and this is especially true for intracellular bacterial infections. The poor intracellular bioavailability of antibiotics reduces the efficency of many treatments and thereby promotes resistances. Therefore, the development of nanodevices coupled with antibiotics that are capable of targeting and releasing the drug into the infected-cells appears to be a promising solution to circumvent these complications. Here, we took advantage of two natural terpenes (farnesyl and geranyl) to design nanodevices for an efficient intracellular delivery of penicillin G. The covalent linkage between the terpene moieties and the antibiotic leads to formation of prodrugs that self-assemble to form nanoparticles with a high drug payload between 55-63%. Futhermore, the addition of an environmentally-sensitive bond between the antibiotic and the terpene led to an efficient antibacterial activity against the intracellular pathogen Staphylococcus aureus with reduced intracellular replication of about 99.9% compared to untreated infected cells. Using HPLC analysis, we demonstrated and quantified the intracellular release of PenG when this sensitive-bond (SB) was present on the prodrug, showing the success of this technology to deliver antibiotics directly into cells.

  7. The molecular phenomena of the blaZ genes forming betalactamase enzymes structure in Staphylococcus aureus resistant to beta-lactam antibiotics (ampicillin

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    Mieke Satari

    2010-09-01

    Full Text Available Background: Nowadays, infectious disease still an important problem. One of the bacteria causing infectious diseases is Staphylococcus aureus (S. aureus. In the effort to deal with infections caused by S. aureus, beta-lactam antibiotics, such as ampicillin, are used. In fact, it is unfortunately known that many of S. aureus bacteria are resistant to this group of antibiotics. Because of nucleotide base changes in the structure of the genes blaZ which encode beta-lactamase enzymes in S. aureus. Purpose: The objective of this study was to analyze the nucleotide base changes in the structure of the genes blaZ forming beta-lactamase enzymes in S. aureus resistant to ampicillin based on molecular point of view. Methods: Molecular examinations was conducted by isolating the genes, forming beta-lactamase enzyme, which length was 845bp, from 7 isolates of S. aureus resistant to ampicillin by using PCR technique. The results of blaZ amplification were then subjected to homology by using Tn 552 of S. aureus obtained from bank of genes. Results: Based on the result of the homology, it was found that there was a change in purine base TG, which was a pyrimidine base at the -37 position of the initial codon of blaZ. This change, however, did not affect the strength of the promoter since the number of A and T is still more than the number of G and C. In the structure of the blaZ gene there was even no mutation or deletion or nucleotide base substitution found, so it would not affect the effectiveness of beta-lactamase enzyme. Conclusion: It can be concluded that the resistance of S. aureus towards ampicillin was not caused by nucleotide base deletion/substation. It is suspected that there were other causes leading to the resistance, including the overproduction of beta-lactamase enzyme of the blaZ gene, causing the degradation of beta-lactam antibiotics.Latar belakang: Penyakit infeksi sampai saat ini masih merupakan masalah. Salah satu bakteri penyebab

  8. An Investigation of beta-lactam antibiotics resistance in Escherichia coli isolates and molecular detection of Escherichia coli O157:H7 in cage birds from Shahrekord, Iran

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    Hossein Tahmasby

    2014-04-01

    Full Text Available Introduction: Cage birds can harbor human pathogens and contribute to the transmission and spread of drug resistant infectious agents to human. Since many people are interested in keeping cage birds, present study was conducted in cage birds from Shahrekord to investigate the beta-lactam antibiotics resistant E. coli and molecular detection of E. coli O157:H7 that is responsible for outbreaks of human intestinal diseases and fatal haemolytic-uraemic syndrome worldwide. Materials and methods: Altogether 256 samples of cage birds (lovebirds, quails, nightingales, parrots, mynahs, goldfinchs, finches, kingbirds, peacocks, and pheasants faeces were collected with sterile cotton swabs from different areas of Shahrekord, Iran. Swabs were placed directly into Tryptone Soya Broth (TSB. In the laboratory, samples were streaked onto MacConkey agar and also Sorbitol MacConkey agar as selective plating media. Then, antibiogram tests were performed using disc diffusion method. Suspected colonies to E. coli O157:H7 were tested by polymerase chain reaction (PCR. Results: E. coli was isolated from 31 (12.1% out of 256 the samples. Resistance of isolates to Imipenem, Cefotaxime, Cefixime, Cefalexin, Amoxicillin, Penicillin G and Oxacillin was 0, 3.2, 16.1, 90.3, 100, 100 and 100% respectively. E. coli O157:H7 was not found in any samples. Discussion and conclusion: Although cage birds were not sourcee or carriers of E. coli O157:H7 in the studied region, they harbored beta-lactam antibiotics resistant E. coli and could be an important component of drug-resistant infections transmission from cage-birds to human, especially to kids and can pose a potential risk to human health. For this reason, it is recommended to make pet birds owners and general public aware of potential dangers of cage bird keeping.

  9. In vitro activity of beta-lactams, macrolides, telithromycin, and fluoroquinolones against clinical isolates of Streptococcus pneumoniae: correlation between drug resistance and genetic characteristics.

    Science.gov (United States)

    Yamaguchi, Toshiyuki; Hashikita, Giichi; Takahashi, Shun; Itabashi, Akira; Yamazaki, Tsutomu; Maesaki, Shigefumi

    2005-10-01

    The in vitro activity of antimicrobial agents against Streptococcus pneumoniae was determined using 16 strains of penicillin-susceptible S. pneumoniae (PSSP) and 26 strains of penicillin intermediately resistant S. pneumoniae (PISP) + penicillin-resistant S. pneumoniae (PRSP) in Japan. The minimum inhibitory concentrations (MICs) of potent antibiotics, including eight beta-lactams (benzylpenicillin, ampicillin, cefotiam, cefepime, cefditoren, faropenem, panipenem, and biapenem), three macrolides (erythromycin, clarithromycin, and azithromycin), telithromycin, and three fluoroquinolones (ciprofloxacin, levofloxacin, and gatifloxacin), were determined. Twenty-three strains exhibited genetic variations at pbp1a + pbp2x + pbp2b, which are genetic-PRSP (g-PRSP). g-PISP strains accounted for 62.5% (10/16) of the PSSP strains. The existence of an abnormal pbp gene conferred not only penicillin resistance but resistance to cephems; however, panipenem and biapenem had potent in vitro efficacy against alterations. Regarding the macrolide resistance mechanisms (mefA or ermB): 16 isolates had only mefA, 18 isolates had ermB, and 2 isolates had both mefA and ermB. There was no correlation between the existence of an abnormal pbp gene and the existence of the mefA gene or the ermB gene.

  10. Amino acid sequence requirements at residues 69 and 238 for the SME-1 beta-lactamase to confer resistance to beta-lactam antibiotics.

    Science.gov (United States)

    Majiduddin, Fahd K; Palzkill, Timothy

    2003-03-01

    Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring beta-lactamases and extended-spectrum beta-lactamases. Four enzymes from the class A group of beta-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these beta-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of beta-lactam antibiotics.

  11. Abundances of tetracycline, sulphonamide and beta-lactam antibiotic resistance genes in conventional wastewater treatment plants (WWTPs) with different waste load.

    Science.gov (United States)

    Laht, Mailis; Karkman, Antti; Voolaid, Veiko; Ritz, Christian; Tenson, Tanel; Virta, Marko; Kisand, Veljo

    2014-01-01

    Antibiotics and antibiotic resistant bacteria enter wastewater treatment plants (WWTPs), an environment where resistance genes can potentially spread and exchange between microbes. Several antibiotic resistance genes (ARGs) were quantified using qPCR in three WWTPs of decreasing capacity located in Helsinki, Tallinn, and Tartu, respectively: sulphonamide resistance genes (sul1 and sul2), tetracycline resistance genes (tetM and tetC), and resistance genes for extended spectrum beta-lactams (blaoxa-58, blashv-34, and blactx-m-32). To avoid inconsistencies among qPCR assays we normalised the ARG abundances with 16S rRNA gene abundances while assessing if the respective genes increased or decreased during treatment. ARGs were detected in most samples; sul1, sul2, and tetM were detected in all samples. Statistically significant differences (adjusted p<0.01) between the inflow and effluent were detected in only four cases. Effluent values for blaoxa-58 and tetC decreased in the two larger plants while tetM decreased in the medium-sized plant. Only blashv-34 increased in the effluent from the medium-sized plant. In all other cases the purification process caused no significant change in the relative abundance of resistance genes, while the raw abundances fell by several orders of magnitude. Standard water quality variables (biological oxygen demand, total phosphorus and nitrogen, etc.) were weakly related or unrelated to the relative abundance of resistance genes. Based on our results we conclude that there is neither considerable enrichment nor purification of antibiotic resistance genes in studied conventional WWTPs.

  12. Abundances of tetracycline, sulphonamide and beta-lactam antibiotic resistance genes in conventional wastewater treatment plants (WWTPs with different waste load.

    Directory of Open Access Journals (Sweden)

    Mailis Laht

    Full Text Available Antibiotics and antibiotic resistant bacteria enter wastewater treatment plants (WWTPs, an environment where resistance genes can potentially spread and exchange between microbes. Several antibiotic resistance genes (ARGs were quantified using qPCR in three WWTPs of decreasing capacity located in Helsinki, Tallinn, and Tartu, respectively: sulphonamide resistance genes (sul1 and sul2, tetracycline resistance genes (tetM and tetC, and resistance genes for extended spectrum beta-lactams (blaoxa-58, blashv-34, and blactx-m-32. To avoid inconsistencies among qPCR assays we normalised the ARG abundances with 16S rRNA gene abundances while assessing if the respective genes increased or decreased during treatment. ARGs were detected in most samples; sul1, sul2, and tetM were detected in all samples. Statistically significant differences (adjusted p<0.01 between the inflow and effluent were detected in only four cases. Effluent values for blaoxa-58 and tetC decreased in the two larger plants while tetM decreased in the medium-sized plant. Only blashv-34 increased in the effluent from the medium-sized plant. In all other cases the purification process caused no significant change in the relative abundance of resistance genes, while the raw abundances fell by several orders of magnitude. Standard water quality variables (biological oxygen demand, total phosphorus and nitrogen, etc. were weakly related or unrelated to the relative abundance of resistance genes. Based on our results we conclude that there is neither considerable enrichment nor purification of antibiotic resistance genes in studied conventional WWTPs.

  13. The biosynthetic gene cluster for the beta-lactam carbapenem thienamycin in Streptomyces cattleya.

    Science.gov (United States)

    Núñez, Luz Elena; Méndez, Carmen; Braña, Alfredo F; Blanco, Gloria; Salas, José A

    2003-04-01

    beta-lactam ring formation in carbapenem and clavam biosynthesis proceeds through an alternative mechanism to the biosynthetic pathway of classic beta-lactam antibiotics. This involves the participation of a beta-lactam synthetase. Using available information from beta-lactam synthetases, we generated a probe for the isolation of the thienamycin cluster from Streptomyces cattleya. Genes homologous to carbapenem and clavulanic acid biosynthetic genes have been identified. They would participate in early steps of thienamycin biosynthesis leading to the formation of the beta-lactam ring. Other genes necessary for the biosynthesis of thienamycin have also been identified in the cluster (methyltransferases, cysteinyl transferases, oxidoreductases, hydroxylase, etc.) together with two regulatory genes, genes involved in exportation and/or resistance, and a quorum sensing system. Involvement of the cluster in thienamycin biosynthesis was demonstrated by insertional inactivation of several genes generating thienamycin nonproducing mutants.

  14. Effects of reducing beta-lactam antibiotic pressure on intestinal colonization of antibiotic-resistant gram-negative bacteria

    NARCIS (Netherlands)

    S. Nijssen (Saskia); A.C. Fluit (Ad); D.A.M.C. van de Vijver (David); J. Top (Janetta); R.J.L. Willems (Rob); M.J.M. Bonten (Marc)

    2010-01-01

    textabstractBackground: We determined the effects of two antibiotic policies (predominance of either β-lactam antibiotics or fluroquinolones) on acquisition with third-generation cephalosporin-resistant Enterobacteriaceae (CRE) and fluoroquinolone-resistant CRE (FCRE) in two ICUs, with monitoring of

  15. In-vitro profile of a new beta-lactam, ceftobiprole, with activity against methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Jones, M E

    2007-06-01

    Ceftobiprole is a novel, broad-spectrum cephalosporin with in-vitro activity against common Gram-positive and Gram-negative organisms. It forms a stable inhibitory complex with Staphylococcus aureus penicillin-binding protein (PBP) 2' (2a), resulting in enhanced activity against methicillin-resistant S. aureus (MRSA). In recent studies of methicillin-susceptible S. aureus, the ceftobiprole MIC(90) value was most frequently Ceftobiprole is active against Enterococcus faecalis (MIC(90) = 4 mg/L), but not generally active against Enterococcus faecium (MIC(90) > 16 mg/L). Ceftobiprole displayed bactericidal activity against Gram-negative pathogens comparable to that of cefepime, ceftazidime or piperacillin-tazobactam in early studies. However, recent data show activity against Pseudomonas aeruginosa similar to that of cefepime but less than that of ceftazidime. Ceftobiprole, like cefepime, is stable in the presence of most class A non-extended spectrum beta-lactamases and inducible class C beta-lactamases. Ceftobiprole is a poor inducer of AmpC beta-lactamase and a poor substrate for hydrolysis by AmpC beta-lactamase. Studies of ceftobiprole in several animal models have demonstrated potent in-vivo efficacy against infections caused by MRSA, including strains intermediately resistant to vancomycin. It was also efficacious in murine infections caused by Gram-negative bacteria with MIC values ceftobiprole in vitro and in vivo suggests that it may have potential for empirical treatment of suspected Gram-negative and Gram-positive infections, including those caused by MRSA.

  16. Molecular Analysis of Gene Frequencies of TEM, CTX-M and SHV in Beta-Lactam Antibiotic-Resistant Strains of E. Coli Isolated from Urinary Tract Infections in Yasuj Hospitals

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    R Mortezavi

    2014-06-01

    Full Text Available Background & aim: Urinary tract infections is one of the most common infectious diseases which many factors are involved, but bacteria such as E.coli is the most important agent of urinary tract infections. Antibiotic resistance as a major problem in the treatment and control of these infections is considered. The aim of this study was to determine the genes that cause resistance to beta-lactam family of antibiotics on E.coli isolated from urinary tract infections in Yasuj city. Methods: In the present Cross-sectional study which was conducted over a period of seven months in 2013, 123 samples of E.coli were collected from Yasuj hospitals for molecular analysis of TEM, SHV CTX-M genes, causing antibiotic resistance by (PCR method.Data were analyzed using SPSS statistical test. Results: PCR showed that the gene frequency of TEM (50.94%, SHV (47.16%, CTX-M-9 (35.84%, and CTX-M-10, (32.07% and the highest and lowest prevalent of genes were related to TEM and CTX-M10 in E.coli isolated from urinary tract infections respectively. Conclusion: According to the high prevalence of resistance to beta-lactam antibiotics, the current study showed that the noted genes play an important role in facilitating the spread of antimicrobial resistance in this region.

  17. Limitations of beta-lactam therapy for infections caused by susceptible Gram-positive bacteria.

    Science.gov (United States)

    English, B Keith

    2014-11-01

    Penicillin and related beta-lactam agents have been the most widely used and most important antimicrobials in medical history, and remain the recommended therapy for many infectious diseases 85 years after the discovery of penicillin by Alexander Fleming. Yet the efficacy of these agents has been undermined by two factors - the emergence of clinically significant resistance to the antimicrobial activity of these agents, and clinical situations in which these drugs may be suboptimal (even though the bacterial pathogens are not "resistant" to the drugs). Observations in experimental infection models in animals (group A streptococcal myositis, pneumococcal meningitis and pneumonia, group B streptococcal sepsis) and in some cases clinical studies suggest that monotherapy with beta-lactam antibiotics may be inferior to treatment with other types of antibiotics, alone or in combination with beta-lactams - even in situations where the bacterial pathogens remain fully "susceptible" to beta-lactams in vitro.

  18. A vacuolar membrane protein affects drastically the biosynthesis of the ACV tripeptide and the beta-lactam pathway of Penicillium chrysogenum.

    Science.gov (United States)

    Fernández-Aguado, Marta; Teijeira, Fernando; Martín, Juan F; Ullán, Ricardo V

    2013-01-01

    The knowledge about enzymes' compartmentalization and transport processes involved in the penicillin biosynthesis in Penicillium chrysogenum is very limited. The genome of this fungus contains multiple genes encoding transporter proteins, but very little is known about them. A bioinformatic search was made to find major facilitator supefamily (MFS) membrane proteins related to CefP transporter protein involved in the entry of isopenicillin N to the peroxisome in Acremonium chrysogenum. No strict homologue of CefP was observed in P. chrysogenum, but the penV gene was found to encode a membrane protein that contained 10 clear transmembrane spanners and two other motifs COG5594 and DUF221, typical of membrane proteins. RNAi-mediated silencing of penV gene provoked a drastic reduction of the production of the δ-(L-α-aminoadipyl-L-cysteinyl-D-valine) (ACV) and isopenicillin N intermediates and the final product of the pathway. RT-PCR and northern blot analyses confirmed a reduction in the expression levels of the pcbC and penDE biosynthetic genes, whereas that of the pcbAB gene increased. Localization studies by fluorescent laser scanning microscopy using Dsred and GFP fluorescent fusion proteins and the FM 4-64 fluorescent dye showed clearly that the protein was located in the vacuolar membrane. These results indicate that PenV participates in the first stage of the beta-lactam biosynthesis (i.e., the formation of the ACV tripeptide), probably taking part in the supply of amino acids from the vacuolar lumen to the vacuole-anchored ACV synthetase. This is in agreement with several reports on the localization of the ACV synthetase and provides increased evidence for a compartmentalized storage of precursor amino acids for non-ribosomal peptides. PenV is the first MFS transporter of P. chrysogenum linked to the beta-lactam biosynthesis that has been located in the vacuolar membrane.

  19. Ceftobiprole: a new beta-lactam antibiotic.

    Science.gov (United States)

    Stein, R A; Goetz, R M; Ganea, G M

    2009-06-01

    The increasing threat of antimicrobial resistance in general, and that of methicillin-resistant Staphylococcus aureus (MRSA) in particular, is raising significant medical, economical and public health challenges worldwide, both within hospitals and throughout the community. These considerations, along with the extensive time and costs associated with the development and approval of new therapeutic agents, represent some of the major reasons why understanding the advantages and limitations of new antibiotics, ensuring their judicious use and maximising their active shelf life should become global priorities. On March 18, 2008, the Food and Drug Administration issued an approvable letter for ceftobiprole, a broad-spectrum beta-lactam antibiotic active against MRSA and other clinically relevant Gram-positive and Gram-negative pathogens. Ceftobiprole is currently available only for parenteral administration, and besides its remarkable antimicrobial spectrum, this antibiotic possesses additional desirable characteristics, such as low propensity to select for resistance, efficacy in animal models of disease and good safety profile. Furthermore, in recently completed clinical trials, ceftobiprole demonstrated non-inferiority to comparator compounds such as vancomycin, and emerged as a promising clinical option of monotherapy for the treatment of complicated skin and skin structure infections and community-acquired pneumonia. Here, we discuss some of the most important clinically relevant findings on ceftobiprole obtained from in vitro studies, animal models of disease and recently completed phase III clinical trials.

  20. Energetic, Structural, and Antimicrobial Analyses of [beta]-Lactam Side Chain Recognition by [beta]-Lactamases

    Energy Technology Data Exchange (ETDEWEB)

    Caselli, E.; Powers, R.A.; Blaszczak, L.C.; Wu, C.Y.E.; Prati, F.; Shoichet, B.K. (NWU)

    2010-03-05

    Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these {beta}-lactams, most often through bacterial expression of {beta}-lactamases, threatens public health. To understand how {beta}-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because {beta}-lactams form covalent adducts with {beta}-lactamases. This has complicated functional analyses and inhibitor design. To investigate the contribution to interaction energy of the key amide (R1) side chain of {beta}-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well as four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine {beta}-lactamases. Therefore, binding energies can be calculated directly from K{sub i} values. The K{sub i} values measured span four orders of magnitude against the Group I {beta}-lactamase AmpC and three orders of magnitude against the Group II {beta}-lactamase TEM-1. The acylglycineboronic acids have K{sub i} values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of {beta}-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of {beta}-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to {beta}-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 {angstrom} and 1.75 {angstrom} resolution; these structures suggest interactions that are important to the affinity of the inhibitors. Acylglycineboronic acids allow us to begin to dissect interaction energies between {beta}-lactam side chains and {beta}-lactamases. Surprisingly

  1. Antimicrobial activity of beta-lactams against multiresistant micro-organisms from the family Enterobacteriaceae, and genus Pseudomonas.

    Science.gov (United States)

    Niebla, A; González, I; Vallín, C

    1994-01-01

    The antimicrobial activity of twenty beta-lactams was determined against multiresistant micro-organisms from the Enterobacteriaceae family (450) and the genus Pseudomonas (90). The antimicrobial susceptibility was assessed by the disk diffusion method. The most effective antibiotics were cephalosporins of the second and third generation, and non-classical beta-lactams (imipenem and moxalactam). A pronounced resistance was found to carbenicillin, ampicillin, cephalotin and cefazolin. These resistance patterns corresponded to a high consumption of these antibiotics.

  2. Lysine N[superscript zeta]-Decarboxylation Switch and Activation of the [beta]-Lactam Sensor Domain of BlaR1 Protein of Methicillin-resistant Staphylococcus aureus

    Energy Technology Data Exchange (ETDEWEB)

    Borbulevych, Oleg; Kumarasiri, Malika; Wilson, Brian; Llarrull1, Leticia I.; Lee, Mijoon; Hesek, Dusan; Shi, Qicun; Peng, Jeffrey; Baker, Brian M.; Mobashery, Shahriar (Notre)

    2012-10-29

    The integral membrane protein BlaR1 of methicillin-resistant Staphylococcus aureus senses the presence of {beta}-lactam antibiotics in the milieu and transduces the information to the cytoplasm, where the biochemical events that unleash induction of antibiotic resistance mechanisms take place. We report herein by two-dimensional and three-dimensional NMR experiments of the sensor domain of BlaR1 in solution and by determination of an x-ray structure for the apo protein that Lys-392 of the antibiotic-binding site is posttranslationally modified by N{sup {zeta}}-carboxylation. Additional crystallographic and NMR data reveal that on acylation of Ser-389 by antibiotics, Lys-392 experiences N{sup {zeta}}-decarboxylation. This unique process, termed the lysine N{sup {zeta}}-decarboxylation switch, arrests the sensor domain in the activated ('on') state, necessary for signal transduction and all the subsequent biochemical processes. We present structural information on how this receptor activation process takes place, imparting longevity to the antibiotic-receptor complex that is needed for the induction of the antibiotic-resistant phenotype in methicillin-resistant S. aureus.

  3. beta-Lactam and glycopeptide antibiotics: first and last line of defense?

    NARCIS (Netherlands)

    Jovetic, S.; Yang Zhu, Yang; Marcone, G.L.; Marinelli, F.; Tramper, J.

    2010-01-01

    Most infections are caused by bacteria, many of which are ever-evolving and resistant to nearly all available antibiotics beta-Lactams and glycopeptides are used to combat these infections by inhibiting bacterial cell-wall synthesis This mechanism remains an interesting target in the search for new

  4. [Emergence of beta-lactam-dependent Bacillus cereus associated with prolonged treatment with cefepime in a neutropenic patient].

    Science.gov (United States)

    Ko, Sun-Young; Chung, Hee-Jung; Sung, Heong-Sup; Kim, Mi-Na

    2007-06-01

    Antibiotic dependence in clinical isolates has been reported, albeit rarely, such as vancomycin-dependent enterococcus and beta-lactam-dependent Staphylococcus saprophyticus. We report herein a clinical isolate of beta-lactam-dependent Bacillus cereus. A 16-yr-old female was admitted on 8 September 2005 with neutropenic fever during chemotherapy following surgical removal of peripheral neuroectodermal tumor. She had had an indwelling chemoport since August 2004 and experienced B. cereus bacteremia three times during the recent 3-month period prior to the admission; the bacteremias were treated with cefepime-based chemotherapy. On hospital days 1 and 3, B. cereus was isolated from blood drawn through the chemoport. The isolates were resistant to penicillin, ceftriaxone, and erythromycin, and susceptible to vancomycin and ciprofloxacin. The isolate of hospital day 3 grew only nearby the beta-lactam disks including penicillin and ceftriaxone on disk diffusion testing. The beta-lactam-dependent isolate required a minimum of 0.064 microg/mL of penicillin or 0.023 microgram/mL of cefotaxime for growth, which was demonstrated by E test (AB Biodisk, Sweden). Light microscopy and transmission electron microscopy revealed a marked elongation of the dependent strain compared with the non-dependent strain. Prolonged therapy with beta-lactams in the patient with an indwelling intravenous catheter seemed to be a risk factor for the emergence of beta-lactam-dependence in B. cereus.

  5. Intravenous desensitization to beta-lactam antibiotics.

    Science.gov (United States)

    Borish, L; Tamir, R; Rosenwasser, L J

    1987-09-01

    Patients allergic to penicillin (PCN) often require treatment with beta-lactam antibiotics for life-threatening bacterial infections. In this article, we review our experience with rapid intravenous desensitization for patients who gave a history of PCN allergy and who had hypersensitivity demonstrated by skin tests. Skin testing was performed with both prick and intradermal techniques and with the recommended antibiotic as well as PCN G, penicilloyl polylysine, and a minor determinant mixture. Patients were transferred to the intensive care unit, and desensitization was performed with a buret technique that required minimal preparation and was easily applied to any antibiotic. Fifteen desensitizations in 12 patients were associated with no immediate reactions. One patient developed a delayed reaction consisting of a pruritic rash and angioedema. A second patient developed a more serious delayed serum sickness-like illness with fever, rash, eosinophilia, abnormal liver function tests, and urinary abnormalities. These reactions did not necessitate stopping the antibiotic, although the latter patient required corticosteroids to suppress his symptoms. Rapid intravenous desensitization is a rapid, safe, and effective technique for patients demonstrating hypersensitivity to beta-lactam antibiotics who require therapy with these medications.

  6. Abundances of tetracycline, sulphonamide and beta-lactam antibiotic resistance genes in conventional wastewater treatment plants (WWTPs) with different waste load

    DEFF Research Database (Denmark)

    Laht, Mailis; Karkman, Antti; Voolaid, Veiko;

    2014-01-01

    Antibiotics and antibiotic resistant bacteria enter wastewater treatment plants (WWTPs), an environment where resistance genes can potentially spread and exchange between microbes. Several antibiotic resistance genes (ARGs) were quantified using qPCR in three WWTPs of decreasing capacity located...... in the relative abundance of resistance genes, while the raw abundances fell by several orders of magnitude. Standard water quality variables (biological oxygen demand, total phosphorus and nitrogen, etc.) were weakly related or unrelated to the relative abundance of resistance genes. Based on our results we...... conclude that there is neither considerable enrichment nor purification of antibiotic resistance genes in studied conventional WWTPs....

  7. Clinical profile of ceftobiprole, a novel beta-lactam antibiotic.

    Science.gov (United States)

    Noel, G J

    2007-06-01

    Ceftobiprole, an investigational beta-lactam antibiotic, has been shown to have a broad spectrum of activity against Gram-positive and Gram-negative pathogens. Unlike currently available beta-lactams, ceftobiprole has been shown to be active against methicillin-resistant staphylococci because of its high affinity for penicillin-binding protein (PBP) 2' (2a). Ceftobiprole has undergone extensive evaluation in phase I studies to characterise dose, pharmacokinetics, and safety/tolerability. In an early phase II study, all 35 clinically evaluable patients (n = 40) with complicated skin and skin structure infections (cSSSIs) receiving intravenous ceftobiprole 750 mg twice-daily were cured, including four of four patients with methicillin-resistant Staphylococcus aureus (MRSA). Microbiological eradication was achieved in 91% (21/23) of evaluable patients. On the basis of these results, phase III studies of ceftobiprole for the treatment of cSSSIs were initiated. One study compared intravenous ceftobiprole (500 mg every 12 h) to intravenous vancomycin (1 g every 12 h) in patients with cSSSIs due to Gram-positive bacteria. Staphylococci were the predominant pathogens, and more than 25% of the microbiologically evaluable patients had infections caused by MRSA. In the clinically evaluable population, efficacy and adverse events were comparable between treatment arms. Additional clinical trials in cSSSI and pneumonia patients are underway to evaluate ceftobiprole for the treatment of infections due to both Gram-positive and Gram-negative bacteria. Ceftobiprole is the first cephalosporin to demonstrate clinical efficacy in patients with infections due to methicillin-resistant staphylococci and, if approved by regulatory authorities, is expected to be a useful addition to the armamentarium of agents for the treatment of complicated skin infections and pneumonia.

  8. How beta-lactam antibiotics enter bacteria: a dialogue with the porins.

    Directory of Open Access Journals (Sweden)

    Chloë E James

    Full Text Available BACKGROUND: Multi-drug resistant (MDR infections have become a major concern in hospitals worldwide. This study investigates membrane translocation, which is the first step required for drug action on internal bacterial targets. beta-lactams, a major antibiotic class, use porins to pass through the outer membrane barrier of Gram-negative bacteria. Clinical reports have linked the MDR phenotype to altered membrane permeability including porin modification and efflux pump expression. METHODOLOGY/PRINCIPAL FINDINGS: Here influx of beta-lactams through the major Enterobacter aerogenes porin Omp36 is characterized. Conductance measurements through a single Omp36 trimer reconstituted into a planar lipid bilayer allowed us to count the passage of single beta-lactam molecules. Statistical analysis of each transport event yielded the kinetic parameters of antibiotic travel through Omp36 and distinguishable translocation properties of beta-lactams were quantified for ertapenem and cefepime. Expression of Omp36 in an otherwise porin-null bacterial strain is shown to confer increases in the killing rate of these antibiotics and in the corresponding bacterial susceptibility. CONCLUSIONS/SIGNIFICANCE: We propose the idea of a molecular "passport" that allows rapid transport of substrates through porins. Deciphering antibiotic translocation provides new insights for the design of novel drugs that may be highly effective at passing through the porin constriction zone. Such data may hold the key for the next generation of antibiotics capable of rapid intracellular accumulation to circumvent the further development MDR infections.

  9. Unexpected inhibition of peptidoglycan LD-transpeptidase from Enterococcus faecium by the beta-lactam imipenem.

    Science.gov (United States)

    Mainardi, Jean-Luc; Hugonnet, Jean-Emmanuel; Rusconi, Filippo; Fourgeaud, Martine; Dubost, Lionel; Moumi, Angèle Nguekam; Delfosse, Vanessa; Mayer, Claudine; Gutmann, Laurent; Rice, Louis B; Arthur, Michel

    2007-10-19

    The beta-lactam antibiotics mimic the D-alanyl(4)-D-alanine(5) extremity of peptidoglycan precursors and act as "suicide" substrates of the DD-transpeptidases that catalyze the last cross-linking step of peptidoglycan synthesis. We have previously shown that bypass of the dd-transpeptidases by the LD-transpeptidase of Enterococcus faecium (Ldt(fm)) leads to high level resistance to ampicillin. Ldt(fm) is specific for the L-lysyl(3)-D-alanine(4) bond of peptidoglycan precursors containing a tetrapeptide stem lacking D-alanine(5). This specificity was proposed to account for resistance, because the substrate of Ldt(fm) does not mimic beta-lactams in contrast to the D-alanyl(4)-D-alanine(5) extremity of pentapeptide stems used by the DD-transpeptidases. Here, we unexpectedly show that imipenem, a beta-lactam of the carbapenem class, totally inhibited Ldt(fm) at a low drug concentration that was sufficient to inhibit growth of the bacteria. Peptidoglycan cross-linking was also inhibited, indicating that Ldt(fm) is the in vivo target of imipenem. Stoichiometric and covalent modification of Ldt(fm) by imipenem was detected by mass spectrometry. The modification was mapped into the trypsin fragment of Ldt(fm) containing the catalytic Cys residue, and the Cys to Ala substitution prevented imipenem binding. The mass increment matched the mass of imipenem, indicating that inactivation of Ldt(fm) is likely to involve rupture of the beta-lactam ring and acylation of the catalytic Cys residue. Thus, the spectrum of activity of beta-lactams is not restricted to transpeptidases of the DD-specificity, as previously thought. Combination therapy with imipenem and ampicillin could therefore be active against E. faecium strains having the dual capacity to manufacture peptidoglycan with transpeptidases of the LD- and DD-specificities.

  10. Soluble penicillin-binding protein 2a: beta-lactam binding and inhibition by non-beta-lactams using a 96-well format.

    Science.gov (United States)

    Toney, J H; Hammond, G G; Leiting, B; Pryor, K D; Wu, J K; Cuca, G C; Pompliano, D L

    1998-01-01

    High level methicillin resistance in Staphylococcus aureus is dependent upon the acquisition of the mecA gene encoding penicillin-binding protein 2a (PBP2a). PBP2a is a member of a family of peptidoglycan biosynthetic enzymes involved in assembly of the cell wall in bacteria and is poorly inactivated by beta-lactam antibiotics. We describe a 96-well-filter binding assay using recombinant, soluble PBP2a which allows for kinetic measurement of penicillin binding. The deacylation rate constant for the PBP2a-penicillin G covalent complex was found to be 5.7 +/- 1.0 x 10(-5) s-1 at 30 degrees C (half-life of approximately 200 min). For the PBP2a acylation reaction, the value of K(m) (penicillin G) = 0.5 +/- 0.1 mM and kcat = 1 x 10(-3) s-1, which yields a second-order rate constant (kcat/K(m)) for inactivation of 2.0 M-1 s-1. Using this assay, several non-beta-lactam inhibitors including Cibacron blue have been found which exhibit IC50 values between 10 and 30 microM. The binding affinities of several carbapenems and beta-lactams correlated well between the filter binding assay described in this report and an electrophoretic assay for PBP2a using membranes prepared form methicillin-resistant S. aureus.

  11. Chromosomal integration of a cephalosporinase gene from Acinetobacter baumannii into Oligella urethralis as a source of acquired resistance to beta-lactams.

    Science.gov (United States)

    Mammeri, Hedi; Poirel, Laurent; Mangeney, Nicole; Nordmann, Patrice

    2003-05-01

    Clinical Oligella urethralis isolate COH-1, which was uncommonly resistant to penicillins and narrow-spectrum cephalosporins, was recovered from a 55-year-old patient with a urinary tract infection. Shotgun cloning into Escherichia coli and expression experiments gave recombinant clones expressing either an AmpC beta-lactamase-type phenotype of resistance or a carbenicillin-hydrolyzing beta-lactamase-type phenotype of resistance. The AmpC beta-lactamase identified (ABA-1), which had a pI value of 8.2, had 98% amino acid identity with a chromosomally encoded cephalosporinase of Acinetobacter baumannii. A 820-bp insertion sequence element, ISOur1, belonging to the IS6 family of insertion sequence elements, was identified immediately upstream of bla(ABA-1), providing a -35 promoter sequence and likely giving rise to a hybrid promoter region. The carbenicillin-hydrolyzing beta-lactamase identified (CARB-8), which had a pI value of 6.4, differed from CARB-5 by two amino acid substitutions. Hybridization of CeuI fragment I-restricted DNA fragments of O. urethralis COH-1 with bla(ABA-1)-, bla(CARB-8)-, and 16S rRNA-specific probes indicated the chromosomal integration of the beta-lactamase genes. PCR and hybridization experiments failed to detect bla(CARB-8)- and bla(ABA-1)-like genes in three O. urethralis reference strains, indicating that the beta-lactamase genes identified were the source of acquired resistance in O. urethralis COH-1. This is one of the few examples of the interspecies transfer and the chromosomal integration of a gene encoding a naturally occurring beta-lactamase.

  12. Beta-lactam antibiotics prevent Salmonella-mediated bovine encephalopathy regardless of the β-lactam resistance status of the bacteria.

    Science.gov (United States)

    Xiong, Nalee; Brewer, Matt T; Anderson, Kristi L; Watrous, Gwyneth K; Weeks, Katherine E; Barnhill, Alison E; Day, Tim A; Kimber, Michael J; Carlson, Steve A

    2012-06-01

    This study assessed the capacity of β-lactam antibiotics to prevent salmonella-mediated encephalopathy in calves given the putative neuroprotective effects of these drugs of increasing glutamate export from the brain. Both ampicillin and ceftiofur prevented the development of encephalopathy despite resistance of the inoculated Salmonella enterica serovar Saint-Paul isolate to both drugs. A glutamate receptor antagonist also prevented this salmonella-mediated encephalopathy. Glutamate exporters were hyper-expressed in the presence of β-lactam antibiotics while a glutamate export inhibitor obviated the effects of these antibiotics, demonstrating a neuroprotective effect through glutamate export from the brain. The findings indicate that β-lactam antibiotics remain an important treatment option for this atypical form of bovine salmonellosis.

  13. Hydroxyl-radical-induced degradative oxidation of beta-lactam antibiotics in water: absolute rate constant measurements.

    Science.gov (United States)

    Dail, Michelle K; Mezyk, Stephen P

    2010-08-19

    The beta-lactam antibiotics are some of the most prevalent pharmaceutical contaminants currently being detected in aquatic environments. Because the presence of any trace level of antibiotic in water may adversely affect aquatic ecosystems and contribute to the production of antibiotic-resistant bacteria, active removal by additional water treatments, such as using advanced oxidation and reduction processes (AO/RPs), may be required. However, to ensure that any AOP treatment process occurs efficiently and quantitatively, a full understanding of the kinetics and mechanisms of all of the chemical reactions involved under the conditions of use is necessary. In this study, we report on our kinetic measurements for the hydroxyl-radical-induced oxidation of 11 beta-lactam antibiotics obtained using electron pulse radiolysis techniques. For the 5-member ring species, an average reaction rate constant of (7.9 +/- 0.8) x 10(9) M(-1) s(-1) was obtained, slightly faster than for the analogous 6-member ring containing antibiotics, (6.6 +/- 1.2) x 10(9) M(-1) s(-1). The consistency of these rate constants for each group infers a common reaction mechanism, consisting of the partitioning of the hydroxyl radical between addition to peripheral aromatic rings and reaction with the central double-ring core of these antibiotics.

  14. Noncovalent Interaction Energies in Covalent Complexes: TEM-1 beta-Lactamase and beta-Lactams

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaojun; Minasov, George; Shoichet, Brian K. (NWU)

    2010-03-08

    The class A {beta}-lactamase TEM-1 is a key bacterial resistance enzyme against {beta}-lactam antibiotics, but little is known about the energetic bases for complementarity between TEM-1 and its inhibitors. Most inhibitors form a covalent adduct with the catalytic Ser70, making the measurement of equilibriumconstants, and hence interaction energies, technically difficult. This study evaluates noncovalent interactions withincovalent complexes by examining the differential stability of TEM-1 and its inhibitor adducts. The thermal denaturation of TEM-1 follows a two-state, reversible model with a melting temperature (T{sub m}) of 51.6 C and a van't Hoff enthalpy of unfolding ({Delta}H{sub VH}) of 146.2 kcal/mol at pH 7.0. The stability of the enzyme changes on forming an inhibitor adduct. As expected, some inhibitors stabilize TEM-1; transition-state analogues increase the T{sub m} by up to 3.7 C(1.7 kcal/mol). Surprisingly, all {beta}-lactam covalent acyl-enzyme complexes tested destabilize TEM-1 significantly relative to the apoenzyme. For instance, the clinically used inhibitor clavulanic acid and the {beta}-lactamase-resistant {beta}-lactams moxalactam and imipenem destabilize TEM-1 by over 2.6 C (1.2 kcal/mol) in their covalent adducts. Based on the structure of the TEM-1/imipenem complex (Maveyraud et al., J Am Chem Soc 1998;120:9748-52), destabilization by moxalactam and imipenem is thought to be caused by a steric clash between the side-chain of Asn132 and the 6(7)-{alpha} group of these {beta}-lactams. To test this hypothesis, the mutant enzyme N132A was made. In contrast with wild-type, the covalent complexes between N132A and both imipenem and moxalactam stabilize the enzyme, consistent with the hypothesis. To investigate the structural bases of this dramatic change instability, the structure of N132A/imipenem was determined by X-ray crystallography. In the complex with N132A, imipenemadopts a very different conformation from that observed in the wild

  15. Diagnosis of allergy against beta-lactams in primary care : prevalence and diagnostic criteria

    NARCIS (Netherlands)

    Salden, Odette A E; Rockmann, Heike; Verheij, Theo J M; Broekhuizen, Berna D L

    2015-01-01

    BACKGROUND: Secondary care studies showed that a recorded allergy to beta-lactams could not be confirmed by valid allergy testing in >85% of cases. In daily practice, recorded beta-lactam allergies probably cause prescription of secondary choice antibiotics. This overrating of beta-lactam allergy ha

  16. Comparative in vitro activities of several new fluoroquinolones and beta-lactam antimicrobial agents against community isolates of Streptococcus pneumoniae.

    OpenAIRE

    Mazzulli, T.; Simor, A E; Jaeger, R.; Fuller, S; Low, D E

    1990-01-01

    The in vitro susceptibilities of 551 community isolates of Streptococcus pneumoniae from the Canadian province of Ontario to several new fluoroquinolones and beta-lactam antimicrobial agents were determined by a broth microdilution technique. Eight (1.5%) of these isolates were moderately susceptible (MICs, greater than or equal to 0.12 and less than or equal to 1.0 microgram/ml) to penicillin; none was resistant. Temafloxacin, ciprofloxacin, and ofloxacin (MICs for 90% of strains tested, bet...

  17. Continuous infusion of antibiotics in the critically ill: The new holy grail for beta-lactams and vancomycin?

    OpenAIRE

    Van Herendael, Bruno; Jeurissen, Axel; Tulkens, Paul M.; Vlieghe, Erika; Verbrugghe, Walter; Jorens, Philippe G.; Ieven, Margareta

    2012-01-01

    The alarming global rise of antimicrobial resistance combined with the lack of new antimicrobial agents has led to a renewed interest in optimization of our current antibiotics. Continuous infusion (CI) of time-dependent antibiotics has certain theoretical advantages toward efficacy based on pharmacokinetic/pharmacodynamic principles. We reviewed the available clinical studies concerning continuous infusion of beta-lactam antibiotics and vancomycin in critically ill patients. We conclude that...

  18. Is continuous infusion of beta-lactam antibiotics worthwhile?--efficacy and pharmacokinetic considerations

    OpenAIRE

    Mouton, Johan; Vinks, A A

    1996-01-01

    textabstractThe most important pharmacodynamic parameter for beta-lactam antibiotics has been shown to be the time above the MIC, which is used as an argument to administer beta-lactam antibiotics by continuous infusion. Studies in vitro and in laboratory animals comparing efficacy of continuous and intermittent infusion of beta-lactam antibiotics generally show continuous infusion to be more efficacious. While comparative trials in humans are scarce and a significant difference was only foun...

  19. Beta-lactam hypersensitivity and cross-reactivity.

    Science.gov (United States)

    Terico, Adrienne T; Gallagher, Jason C

    2014-12-01

    Penicillin is the most frequently reported cause of drug allergy, and cross-reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This review evaluates the available data on immunoglobulin E-mediated penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem, and monobactam antibiotics. A MEDLINE search was conducted from 1950 to October 2013, and selected references from review articles were also evaluated. There is a wide variety in reported incidences of cross-reactivity between penicillins and cephalosporins or carbapenems, with early retrospective studies suggesting up to 41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of monobactam antibiotics is frequently employed in the case of a penicillin allergy, as prescribers believe that there is no cross-reactivity between the 2 drug classes. More recent prospective studies suggest that the rates of cross-reactivity with cephalosporins and carbapenems are penicillin and cephalosporin side chains may play a role in cross-reactivity between these classes. Cross-reactivity with monobactams is essentially negligible; however, there are some clinical data to support an interaction between ceftazidime and aztreonam, due to the similarity of their side chains. The data reviewed suggest that avoidance of other beta-lactams in patients with type 1 hypersensitivity to penicillins should be reconsidered.

  20. Is continuous infusion of beta-lactam antibiotics worthwhile?--efficacy and pharmacokinetic considerations

    NARCIS (Netherlands)

    J.W. Mouton (Johan); A.A. Vinks

    1996-01-01

    textabstractThe most important pharmacodynamic parameter for beta-lactam antibiotics has been shown to be the time above the MIC, which is used as an argument to administer beta-lactam antibiotics by continuous infusion. Studies in vitro and in laboratory animals compar

  1. 78 FR 22887 - Guidance for Industry on Non-Penicillin Beta-Lactam Drugs: A Current Good Manufacturing Practices...

    Science.gov (United States)

    2013-04-17

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Non-Penicillin Beta-Lactam Drugs: A... announcing the availability of a guidance for industry entitled ``Non-Penicillin Beta- Lactam Drugs: A CGMP... announcing the availability of a guidance for industry entitled ``Non-Penicillin Beta-Lactam Drugs: A...

  2. [Spreading and mechanisms of antibiotic resistance of microorganisms, producing beta-lactamases. Molecular mechanisms of resistance to beta-lactams of Klebsiella spp. strains, isolated in cases of nosocomial infections].

    Science.gov (United States)

    Ivanov, D V; Egorov, A M

    2008-01-01

    Antibiotic sensivity of nosocomial Klebsiella spp. strains (n = 212), isolated from patients treated in 30 medical centers of 15 various regions of Russia was investigated. The Klebsiella genus was represented by the following species: Klebsiella pneumoniae ss. pneumoniae--182 (85.8%), Klebsiella pneumoniae ss. ozaenae--1 (0.5%), Klebsiella oxytoca--29 (13.7%) isolates. The most active antibacterial agents against the investigated strains were carbapenems (imipenem and meropenem). Among 3rd generation cephalosporine the lowest MICs were observed for ceftazidime/clavulanic acid (MIC50--0.25 microg/ml, MIC90--64 microg/ml) and cefoperazone/sulbactam (MIC50--16 microg/ml, MIC90--64 microg/ml). Beta-lactamase genes (TEM, SHV, CTX) were detected in 42 Klebsiella pneumoniae ss. pneumoniae strains by PCR. Alone or in various combinations TEM type beta-lactamases have been found in 16 (38.1%) isolates, SHV--in 29 (69%), and CTX--in 27 (64.3%). Combinations of 2 different determinants were detected in 23.8% of the isolates, 3--in 26.2%. There were not isolates producing MBL class B among resistant to carbapenems nosocomial Klebsiella spp. strains.

  3. Immunological aspects of nonimmediate reactions to beta-lactam antibiotics.

    Science.gov (United States)

    Rodilla, Esther Morena; González, Ignacio Dávila; Yges, Elena Laffond; Bellido, Francisco Javier Múñoz; Bara, María Teresa Gracia; Toledano, Félix Lorente

    2010-09-01

    beta-lactam antibiotics are the agents most frequently implied in immune drug adverse reactions. These can be classified as immediate or nonimmediate according to the time interval between the last drug administration and their onset. Mechanisms of immediate IgE-mediated reactions are widely studied and are therefore better understood. Nonimmediate reactions include a broad number of clinical entities like mild maculopapular exanthemas, the most common, and other less frequent but more severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute exanthematic pustulosis or cytopenias. These nonimmediate reactions are mainly mediated by T cells but the precise underlying mechanisms are not well elucidated. This fact complicates the allergological evaluation of patients with this type of reaction and available tests have demonstrated poor sensitivity and specificity.

  4. Beta-lactams interfering with PBP1 induce Panton-Valentine leukocidin expression by triggering sarA and rot global regulators of Staphylococcus aureus.

    Science.gov (United States)

    Dumitrescu, Oana; Choudhury, Priya; Boisset, Sandrine; Badiou, Cédric; Bes, Michele; Benito, Yvonne; Wolz, Christiane; Vandenesch, François; Etienne, Jerome; Cheung, Ambrose L; Bowden, Maria Gabriela; Lina, Gerard

    2011-07-01

    Previous articles reported that beta-lactam antibiotics increase the expression of Staphylococcus aureus Panton-Valentine leukocidin (PVL) by activating its transcription. We investigated the mechanisms underlying the inductor effect of beta-lactams on PVL expression by determining targets and regulatory pathways possibly implicated in this process. We measured PVL production in the presence of oxacillin (nonselective), imipenem (penicillin-binding protein 1 [PBP1] selective), cefotaxime (PBP2 selective), cefaclore (PBP3 selective), and cefoxitin (PBP4 selective). In vitro, we observed increased PVL production consistent with luk-PV mRNA levels that were 20 to 25 times higher for community-acquired methicillin-resistant S. aureus (CA-MRSA) cultures treated with PBP1-binding oxacillin and imipenem than for cultures treated with other beta-lactams or no antibiotic at all. This effect was also observed in vivo, with increased PVL mRNA levels in lung tissues from CA-MRSA-infected mice treated with imipenem but not cefoxitin. To confirm the involvement of PBP1 inhibition in this pathway, PBP1 depletion by use of an inducible pbp1 antisense RNA showed a dose-dependent relationship between the level of pbp1 antisense RNA and the luk-PV mRNA level. Upon imipenem treatment of exponential-phase cultures, we observed an increased sarA mRNA level after 30 min of incubation followed by a decreased rot mRNA level after 1 to 4 h of incubation. Unlike the agr and saeRS positive regulators, which were nonessential for PVL induction by beta-lactams, the sarA (positive) and rot (negative) PVL regulators were necessary for PVL induction by imipenem. Our results suggest that antibiotics binding to PBP1 increase PVL expression by modulating sarA and rot, which are essential mediators of the inductor effect of beta-lactams on PVL expression.

  5. Evaluation of the Osiris expert system for identification of beta-lactam phenotypes in isolates of Pseudomonas aeruginosa.

    Science.gov (United States)

    Bert, Frédéric; Ould-Hocine, Zahia; Juvin, Manette; Dubois, Véronique; Loncle-Provot, Véronique; Lefranc, Valérie; Quentin, Claudine; Lambert, Nicole; Arlet, Guillaume

    2003-08-01

    Osiris is a video zone size reader for disk diffusion tests featuring a built-in extended expert system (EES). The efficacy of the EES for the identification of the beta-lactam susceptibility phenotypes of Pseudomonas aeruginosa isolates was evaluated. Thirteen beta-lactams were tested in four laboratories by the disk diffusion test with 53 strains with well-characterized resistance mechanisms, including the production of 12 extended-spectrum beta-lactamases (ESBLs). The plates were read with the Osiris system and the results were interpreted with the ESS, and then the phenotype identified by the EES was compared to the resistance mechanism. The strains were also screened for the presence of ESBL production by a double-disk synergy test by placing the strains between an extended-spectrum cephalosporin-containing disk and a clavulanic acid-containing disk at distances of 30, 20, 15, and 10 mm from each other. Overall, the EES accurately identified the phenotypes of 88.2% of the strains and indicated an association with several mechanisms for 3.8% of the strains. No phenotype was identified in four strains with low levels of penicillinase production. Misidentifications were observed for two penicillinase-producing strains: one strain with partially derepressed cephalosporinase production and one strain overexpressing the MexA-MexB-OprM efflux system. The production of only four ESBLs was detected by the standard synergy test with a 30-mm distance between the disks. The production of five further ESBLs was identified by reducing the distance to 20 mm, and the production of the last three ESBLs was detected only at a distance of 15 or 10 mm. Our results indicate that the Osiris EES is an effective tool for the identification of P. aeruginosa beta-lactam phenotypes. A specific double-disk synergy test with reduced disk distances is necessary for the detection of ESBL production by this organism.

  6. [Activity of cefpodoxime and other oral beta-lactams against Haemophilus influenzae and Streptococcus pneumoniae with different susceptibilities to penicillin].

    Science.gov (United States)

    Fenoll, A; Robledo, O; Lerma, M; Giménez, M J; Cebrián, L; Casal, J; Aguilar, L; Gómez-Lus, M L

    2006-03-01

    This study explores the influence on the intrinsic activity of different oral beta-lactams of beta-lactamase production in Haemophilus influenzae and penicillin resistance in Streptococcus pneumoniae. Three substudies were performed: a) a general susceptibility study, analyzing 550 strains received by the Spanish Laboratorio de Referencia de Neumococos throughout February and March 2005; b) a study on the influence of penicillin resistance on the activity of beta-lactams, analyzing 251 penicillin-susceptible strains (MICor=2 mg/l) randomly chosen among those received by the Spanish Laboratorio de Referencia de Neumococos throughout 2005; and c) an H. influenzae susceptibility study analyzing 150 strains received by Instituto Valenciano de Microbiologia throughout 2005. A total of 71% of S. pneumoniae strains were susceptible to penicillin, 21% exhibited intermediate resistance and 8% strains presented full resistance. H. influenzae beta-lactamase production rate was 18.6%. Of the non-beta-lactamase-producing strains, 3% were not susceptible to ampicillin. Cefpodoxime and cefixime exhibited the highest intrinsic activity against H. influenzae, while amoxicillin and cefpodoxime were the most active compounds against S. pneumoniae. All H. influenzae strains were susceptible to oral cephalosporins and amoxicillin/clavulanic acid. The increase in penicillin resistance in S. pneumoniae influenced cefixime, cefaclor and cefuroxime to a higher degree than amoxicillin and cefpodoxime.

  7. Diastereoselective Synthesis of trans-beta-Lactams Using a Simple Multifunctional Catalyst.

    Science.gov (United States)

    Abraham, Ciby J; Paull, Daniel H; Dogo-Isonagie, Cajetan; Lectka, Thomas

    2009-01-01

    A catalytic, highly diastereoselective process for the synthesis of trans-beta-lactams is reported. This system is based on a phosphonium fluoride precatalyst that both activates the nucleophile and directs the reaction process for high yield and diastereoselectivity.

  8. Beta- lactam antibiotics stimulate biofilm formation in non-typeable haemophilus influenzae by up-regulating carbohydrate metabolism.

    Science.gov (United States)

    Wu, Siva; Li, Xiaojin; Gunawardana, Manjula; Maguire, Kathleen; Guerrero-Given, Debbie; Schaudinn, Christoph; Wang, Charles; Baum, Marc M; Webster, Paul

    2014-01-01

    Non-typeable Haemophilus influenzae (NTHi) is a common acute otitis media pathogen, with an incidence that is increased by previous antibiotic treatment. NTHi is also an emerging causative agent of other chronic infections in humans, some linked to morbidity, and all of which impose substantial treatment costs. In this study we explore the possibility that antibiotic exposure may stimulate biofilm formation by NTHi bacteria. We discovered that sub-inhibitory concentrations of beta-lactam antibiotic (i.e., amounts that partially inhibit bacterial growth) stimulated the biofilm-forming ability of NTHi strains, an effect that was strain and antibiotic dependent. When exposed to sub-inhibitory concentrations of beta-lactam antibiotics NTHi strains produced tightly packed biofilms with decreased numbers of culturable bacteria but increased biomass. The ratio of protein per unit weight of biofilm decreased as a result of antibiotic exposure. Antibiotic-stimulated biofilms had altered ultrastructure, and genes involved in glycogen production and transporter function were up regulated in response to antibiotic exposure. Down-regulated genes were linked to multiple metabolic processes but not those involved in stress response. Antibiotic-stimulated biofilm bacteria were more resistant to a lethal dose (10 µg/mL) of cefuroxime. Our results suggest that beta-lactam antibiotic exposure may act as a signaling molecule that promotes transformation into the biofilm phenotype. Loss of viable bacteria, increase in biofilm biomass and decreased protein production coupled with a concomitant up-regulation of genes involved with glycogen production might result in a biofilm of sessile, metabolically inactive bacteria sustained by stored glycogen. These biofilms may protect surviving bacteria from subsequent antibiotic challenges, and act as a reservoir of viable bacteria once antibiotic exposure has ended.

  9. Beta- lactam antibiotics stimulate biofilm formation in non-typeable haemophilus influenzae by up-regulating carbohydrate metabolism.

    Directory of Open Access Journals (Sweden)

    Siva Wu

    Full Text Available Non-typeable Haemophilus influenzae (NTHi is a common acute otitis media pathogen, with an incidence that is increased by previous antibiotic treatment. NTHi is also an emerging causative agent of other chronic infections in humans, some linked to morbidity, and all of which impose substantial treatment costs. In this study we explore the possibility that antibiotic exposure may stimulate biofilm formation by NTHi bacteria. We discovered that sub-inhibitory concentrations of beta-lactam antibiotic (i.e., amounts that partially inhibit bacterial growth stimulated the biofilm-forming ability of NTHi strains, an effect that was strain and antibiotic dependent. When exposed to sub-inhibitory concentrations of beta-lactam antibiotics NTHi strains produced tightly packed biofilms with decreased numbers of culturable bacteria but increased biomass. The ratio of protein per unit weight of biofilm decreased as a result of antibiotic exposure. Antibiotic-stimulated biofilms had altered ultrastructure, and genes involved in glycogen production and transporter function were up regulated in response to antibiotic exposure. Down-regulated genes were linked to multiple metabolic processes but not those involved in stress response. Antibiotic-stimulated biofilm bacteria were more resistant to a lethal dose (10 µg/mL of cefuroxime. Our results suggest that beta-lactam antibiotic exposure may act as a signaling molecule that promotes transformation into the biofilm phenotype. Loss of viable bacteria, increase in biofilm biomass and decreased protein production coupled with a concomitant up-regulation of genes involved with glycogen production might result in a biofilm of sessile, metabolically inactive bacteria sustained by stored glycogen. These biofilms may protect surviving bacteria from subsequent antibiotic challenges, and act as a reservoir of viable bacteria once antibiotic exposure has ended.

  10. Prevalencia y perfil de resistencia a betalactámicos en estafilococos de perros y gatos Prevalence and resistance profile to beta-lactam antibiotics in staphylococci from dogs and cats

    Directory of Open Access Journals (Sweden)

    G Denamiel

    2009-12-01

    Full Text Available El objetivo de este trabajo fue conocer la prevalencia de especies y perfil de resistencia a betalactámicos en estafilococos aislados de infecciones en caninos y felinos. En perros, de 207 aislamientos, el porcentaje de las especies identificadas fue: S. intermedius 29,5%, S. aureus y S. simulans 20,8%, S. saprophyticus 12,6%, S. chromogenes 10,6%, S. haemolyticus 3,9% y S. epidermidis 1,9%. De 63 aislamientos en gatos: S. simulans 33,3%, S. intermedius y S. aureus 15,4%, S. saprophyticus 11,1%, S. haemolyticus 6,34%, S. chromogenes y S. epidermidis 3,5%. En perros, el porcentaje de resistencia a penicilina fue: S. intermedius 47,5%, S. aureus 34,8% y S. saprophyticus 7,7%. Los aislamientos que expresaron meticilina resistencia correspondieron: S. intermedius 9,8% y S. saprophyticus 3,8%. En gatos los estafilococos resistentes a penicilina fueron S. saprophyticus 42,8%, S. aureus y S. intermedius 15,4% y S. simulans 9,5%. No se hallaron especies de estafilococos meticilino resistentes.The purpose of this study was to characterize the prevalence and resistance profile to betalactam antibiotics of staphylococci isolated from canine and feline infections. Staphylococci were isolated from 207 dog samples. The species frequency for identified staphylococci were: S. intermedius 29.5%, S. aureus and S. simulans 20.8%, S. saprophyticus 12.6%, S. chromogenes 10.6%, S. haemolyticus 3.9% and S. epidermidis 1.9%. Sixty three staphylococci isolates were from cats: S. simulans 33.3%, S. intermedius and S. aureus 15.4%, S. saprophyticus 11.1%, S. haemolyticus 6.34%, S. chromogenes and S. epidermidis 3.5%. Resistance to penicillin in samples from dogs were: S. intermedius 47.5%, S. aureus 34.8% and S. saprophyticus 7.7%. Methicillin-resistance was evidenced in S. intermedius 9.8% and S. saprophyticus 3.8%. In samples from cats, penicillin-resistant staphylococci were: S. saprophyticus 42.8%, S. aureus and S. intermedius 15.4% and S. simulans 9

  11. Salicylate decreases production of AmpC type beta-lactamases and increases susceptibility to beta-lactams in a Morganella morganii clinical isolate.

    Science.gov (United States)

    Tavío, María M; Perilli, Mariagrazia; Vila, Jordi; Becerro, Pino; Casañas, Lucía; Amicosante, Gianfranco; Jiménez de Anta, María Teresa

    2004-09-01

    The effect of salicylate, a marRAB inducer, on the resistance to beta-lactams was characterized in an AmpC beta-lactamase hyperproducer Morganella morganii clinical isolate (the M1 strain). Results were compared with those of the effect of salicylate in a wild-type M. morganii strain. Salicylate induced a decreased susceptibility to nalidixic acid, norfloxacin and tetracycline and simultaneously increased the susceptibility to beta-lactams apparently due to the repression of AmpC beta-lactamase synthesis in the M1 strain. Likewise, salicylate only repressed 46 kDa outer membrane protein expression in the wild-type strain, since the clinical isolate M1 did not express it.

  12. The beta-lactam-sensitive D,D-carboxypeptidase activity of Pbp4 controls the L,D and D,D transpeptidation pathways in Corynebacterium jeikeium.

    Science.gov (United States)

    Lavollay, Marie; Arthur, Michel; Fourgeaud, Martine; Dubost, Lionel; Marie, Arul; Riegel, Philippe; Gutmann, Laurent; Mainardi, Jean-Luc

    2009-11-01

    Corynebacterium jeikeium is an emerging nosocomial pathogen responsible for vascular catheters infections, prosthetic endocarditis and septicemia. The treatment of C. jeikeium infections is complicated by the multiresistance of clinical isolates to antibiotics, in particular to beta-lactams, the most broadly used class of antibiotics. To gain insight into the mechanism of beta-lactam resistance, we have determined the structure of the peptidoglycan and shown that C. jeikeium has the dual capacity to catalyse formation of cross-links generated by transpeptidases of the d,d and l,d specificities. Two ampicillin-insensitive cross-linking enzymes were identified, Ldt(Cjk1), a member of the active site cysteine l,d-transpeptidase family, and Pbp2c, a low-affinity class B penicillin-binding protein (PBP). In the absence of beta-lactam, the PBPs and the l,d-transpeptidase contributed to the formation of 62% and 38% of the cross-links respectively. Although Ldt(Cjk1) and Pbp2C were not inhibited by ampicillin, the participation of the l,d-transpeptidase to peptidoglycan cross-linking decreased in the presence of the drug. The specificity of Ldt(Cjk1) for acyl donors containing a tetrapeptide stem accounts for this effect of ampicillin since the essential substrate of Ldt(Cjk1) was produced by an ampicillin-sensitive d,d-carboxypeptidase (Pbp4(Cjk)). Acquisition and mutational alterations of pbp2C accounted for high-level beta-lactam resistance in C. jeikeium.

  13. Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics.

    Science.gov (United States)

    Mohd Hafiz, Abdul-Aziz; Staatz, C E; Kirkpatrick, C M J; Lipman, J; Roberts, J A

    2012-01-01

    Beta-lactam antibiotics display time-dependant pharmacodynamics whereby constant antibiotic concentrations rather than high peak concentrations are most likely to result in effective treatment of infections caused by susceptible bacteria. Continuous administration has been suggested as an alternative strategy, to conventional intermittent dosing, to optimise beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) properties. With the availability of emerging data, we elected to systematically investigate the published literature describing the comparative PK/PD and clinical outcomes of beta-lactam antibiotics administered by continuous or intermittent infusion. We found that the studies have been performed in various patient populations including critically ill, cancer and cystic fibrosis patients. Available in vitro PK/PD data conclusively support the administration of beta-lactams via continuous infusion for maximizing bacterial killing from consistent attainment of pharmacodynamic end-points. In addition, clinical outcome data supports equivalence, even with the use of a lower dose by continuous infusion. However, the present clinical data is limited with small sample sizes common with insufficient power to detect advantages in favour of either dosing strategy. With abundant positive pre-clinical data as well as document in vivo PK/PD advantages, large multi-centre trials are needed to describe whether continuous administration of beta-lactams is truly more effective than intermittent dosing.

  14. Detection and identification of beta-lactam residues in milk using a hybrid biosensor.

    Science.gov (United States)

    Ferrini, Anna Maria; Mannoni, Veruscka; Carpico, Graziella; Pellegrini, Guido Enrico

    2008-02-13

    A novel application of a hybrid biosensor is here employed as an analytical method for the detection and presumptive identification of beta-lactam residues in milk. The method is based on measurements of carbon dioxide (CO2), the production of which is related to the microbial growth of the test microorganism Bacillus stearothermophilus var. calidolactis. The presence of beta-lactams in milk inhibits microbial growth and, consequently, the CO2 production rate. The analysis is based on the variation of CO2 between a milk sample spiked with beta-lactams and a twin milk sample containing beta-lactams plus a broad spectrum beta-lactamase, using an electrochemical device of biosensor. A blank milk sample is included as control. The result is obtained starting from the first 120 min. Moreover, the ability to recognize all of the beta-lactams speeds the total time of analysis when chemical identification and quantification are required. The analytical method appears to be adequate for milk control for qualitative screening purposes, complying with the requirements stated in Decision 2002/657/EC.

  15. Mutations in Streptococcus pneumoniae penicillin-binding protein 2x: importance of the C-terminal penicillin-binding protein and serine/threonine kinase-associated domains for beta-lactam binding.

    Science.gov (United States)

    Maurer, Patrick; Todorova, Katya; Sauerbier, Julia; Hakenbeck, Regine

    2012-06-01

    Penicillin-binding protein 2x (PBP2x) mutations that occur during the selection with beta-lactams are located within the central penicillin-binding/transpeptidase (TP) domain, and are believed to mediate resistance by interfering with the formation of a covalent complex of the active site serine with the antibiotic. We now investigated the effect of two point mutations found in two independently obtained laboratory mutants that are located at the surface of the TP domain with their side chains facing outside (G422D respectively R426C). They have no significant effect on resistance to cefotaxime in vivo or on binding to Bocillin™FL to the active site in vitro using purified PBP2x derivatives, thus apparently do not affect the active site directly. In contrast, in silico modeling revealed that they affect van der Waal's interactions with the PASTA1 (PBP and serine/threonine kinase associated) domain of the C-terminal extension and a noncovalent cefuroxime molecule found in the X-ray structure of an acylated PBP2x, suggesting some effect of the mutations on the interaction of the TP domain with PASTA1 and/or with the antibiotic associated with PASTA1. The effect of the PASTA domains on covalent binding of PBP2x to Bocillin FL was then investigated using a series of soluble truncated PBP2x derivatives. Deletion of 127 C-terminal residues, that is, of both PASTA domains, decreased binding dramatically by ∼90%. Surprisingly, deletion of only 40 amino acids resulted in the same phenotype, whereas the absence of 30 amino acids affected binding marginally by 10%, documenting a crucial role of the C-terminal domain for beta-lactam binding.

  16. Revisiting Beta-lactams - PK/PD improves dosing of old antibiotics.

    Science.gov (United States)

    MacGowan, Alasdair

    2011-10-01

    Pre-clinical pharmacokinetic-pharmacodynamic assessments indicate Beta-lactam antibiotics have time-dependent killing, variable persistent antibiotic effects and that free drug T>MIC is the dominant pharmacodynamic index. Prolonged or continuous infusion therapy has improved microbiological responses in pathogens with MICs at or 2-4 fold higher than existing EUCAST clinical breakpoints in pre-clinical studies. Human population pharmacokinetic modelling combined with Monte Carlo Simulation indicates improved pharmacodynamic target attainment rates and hence predicts improved clinical responses for those pathogens with raised MICs. However, the majority of human clinical trials comparing prolonged or continuous infusion to intermittent injection have failed to show superior clinical cures and for the most part microbiological successes. The exception being in various subgroup analyses. Future clinical trials need to focus on defining the T>MIC sizes associated with clinical or microbiological cure in man, on those subgroups of patients where continuous, or prolonged infusion, is likely to be of greatest benefit, seek to reduce pharmacokinetic variability by the use of therapeutic drug monitoring and include measurement of the risks of emergence of resistance in target pathogens At present, the clinical evidence base for prolonged or continuous infusion therapy is insufficiently strong to support widespread use.

  17. Biosynthesis of the beta-lactam antibiotic, thienamycin, by Streptomyces cattleya.

    Science.gov (United States)

    Williamson, J M; Inamine, E; Wilson, K E; Douglas, A W; Liesch, J M; Albers-Schönberg, G

    1985-04-25

    Radioactive- and stable isotope-containing substrates were used to identify the biosynthetic precursors of the beta-lactam antibiotic, thienamycin, in Streptomyces cattleya. Acetate is utilized by the organism to form C(6) and C(7) of the beta-lactam ring. The two carbons of the hydroxyethyl group attached to C(6) are both derived from the methyl of methionine. The cysteaminyl side chain attached to C(2) is derived from cysteine. Selective inhibition of thienamycin and cephamycin C biosynthesis has been achieved either through the addition of metabolic inhibitors or through manipulation of the growth medium. These results suggest that the two beta-lactam antibiotics, thienamycin and cephamycin C, are formed by different biosynthetic pathways.

  18. Phage-Antibiotic Synergy (PAS): beta-lactam and quinolone antibiotics stimulate virulent phage growth.

    Science.gov (United States)

    Comeau, André M; Tétart, Françoise; Trojet, Sabrina N; Prère, Marie-Françoise; Krisch, H M

    2007-08-29

    Although the multiplication of bacteriophages (phages) has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage PhiMFP by more than 7-fold. We name this phenomenon Phage-Antibiotic Synergy (PAS). A related effect was observed in diverse host-phage systems, including the T4-like phages, with beta-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages.

  19. Phage-Antibiotic Synergy (PAS: beta-lactam and quinolone antibiotics stimulate virulent phage growth.

    Directory of Open Access Journals (Sweden)

    André M Comeau

    Full Text Available Although the multiplication of bacteriophages (phages has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage PhiMFP by more than 7-fold. We name this phenomenon Phage-Antibiotic Synergy (PAS. A related effect was observed in diverse host-phage systems, including the T4-like phages, with beta-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages.

  20. Determination of chromatographic and spectrophotometric dissociation constants of some beta lactam antibiotics.

    Science.gov (United States)

    Demiralay, Ebru Çubuk; Koç, Duygu; Daldal, Y Doğan; Cakır, Cansel

    2012-12-01

    In this work, dissociation constants values of seven beta lactam antibiotics in water and acetonitrile-water mixtures using spectrophotometric and reversed phase liquid chromatography methods were determined. The dissociation constant values of these compounds were calculated by NLREG and STAR programs. Aqueous pK(a) values of beta lactam antibiotics were calculated with extrapolation by means of the Yasuda-Shedlovsky and mole fraction equations. Finally, application of the different techniques was compared to the determination of aqueous pK(a) values of investigated compounds.

  1. High beta-Lactamase Levels Change the Pharmacodynamics of beta-Lactam Antibiotics in Pseudomonas aeruginosa Biofilms

    DEFF Research Database (Denmark)

    Wang, Hengzhuang; Ciofu, Oana; Yang, Liang

    2013-01-01

    Resistance to beta-lactam antibiotics is a frequent problem in Pseudomonas aeruginosa lung infection of cystic fibrosis (CF) patients. This resistance is mainly due to the hyperproduction of chromosomally encoded beta-lactamase and biofilm formation. The purpose of this study was to investigate...... the role of beta-lactamase in the pharmacokinetics (PK) and pharmacodynamics (PD) of ceftazidime and imipenem on P. aeruginosa biofilms. P. aeruginosa PAO1 and its corresponding beta-lactamase-overproducing mutant, PA Delta DDh2Dh3, were used in this study. Biofilms of these two strains in flow chambers...... activity of ceftazidime was observed for beta-lactamase-overproducing biofilms of P. aeruginosa in all three models. Ceftazidime showed time-dependent killing on planktonic PAO1 and PA Delta DDh2Dh3. This difference is probably due to the special distribution and accumulation in the biofilm matrix of beta...

  2. Properties of immobilised penicillin G Acylase in beta-lactam antibiotic synthesis

    NARCIS (Netherlands)

    Janssen, M.H.A.

    2006-01-01

    The beta-lactam antibiotics are the most important class of antibiotics used today. In the last decade the production routes of these antibiotics have shifted from chemical routes to more environmentally benign routes using the enzyme penicillin G acylase. For both practical and economical reasons t

  3. Biosynthetic concepts for the production of beta-lactam antibiotics in Penicillium chrysogenum

    NARCIS (Netherlands)

    Weber, Stefan S.; Bovenberg, Roel A. L.; Driessen, Arnold J. M.

    2012-01-01

    Industrial production of beta-lactam antibiotics by the filamentous fungus Penicillium chrysogenum is based on successive classical strain improvement cycles. This review summarizes our current knowledge on the results of this classical strain improvement process, and discusses avenues to improve be

  4. Continuous infusion of beta-lactam antibiotics in severe infections: a review of its role.

    Science.gov (United States)

    Roberts, Jason A; Paratz, Jennifer; Paratz, Elizabeth; Krueger, Wolfgang A; Lipman, Jeffrey

    2007-07-01

    Continuous infusion of beta-lactam antibiotics has been widely promoted to optimise their time-dependent activity. Increasing evidence is emerging suggesting potential benefits in patient populations with altered pathophysiology, such as seriously ill patients. From a pharmacokinetic viewpoint, much information supports higher trough concentrations of beta-lactam antibiotics when administered by continuous infusion. This advantage of continuous infusion translates into a superior ability to achieve pharmacodynamic targets, particularly when the minimum inhibitory concentration (MIC) of the pathogen is >or=4 mg/L. One drawback of continuous infusion may be limited physicochemical stability. This issue exists particularly for carbapenem antibiotics whereby prolonged infusions (i.e. >3h) can be used to improve the time above the MIC compared with conventional bolus dosing. Few studies have examined clinical outcomes of bolus and continuous dosing of beta-lactam antibiotics in seriously ill patients. No statistically significant differences have been shown for: mortality; time to normalisation of leukocytosis or pyrexia; or duration of mechanical ventilation, intensive care unit stay or hospital stay. Some evidence suggests improved clinical cure and resolution of illness with continuous infusion in seriously ill patients. Pharmacoeconomic advantages of continuous infusion of beta-lactam antibiotics are well characterised. Available data suggest that seriously ill patients with severe infections requiring significant antibiotic courses (>or=4 days) may be the subgroup that will achieve better outcomes with continuous infusion.

  5. Concentration-dependency of beta-lactam-induced filament formation in Gram-negative bacteria.

    NARCIS (Netherlands)

    Buijs, J.; Dofferhoff, A.S.M.; Mouton, J.W.; Wagenvoort, J.H.T.; Meer, J.W.M. van der

    2008-01-01

    Ceftazidime and cefotaxime are beta-lactam antibiotics with dose-related affinities for penicillin-binding protein (PBP)-3 and PBP-1. At low concentrations, these antibiotics inhibit PBP-3, leading to filament formation. Filaments are long strands of non-dividing bacteria that contain enhanced quant

  6. Physician approaches to beta-lactam use in patients with penicillin hypersensitivity.

    Science.gov (United States)

    Prematta, Tracy; Shah, Shenil; Ishmael, Faoud T

    2012-01-01

    Beta-lactam antibiotics are widely used, but hypersensitivity reactions are common and difficult to manage. This study was designed to identify lack of knowledge regarding the safe use of alternative beta-lactams in penicillin-allergic patients and assess management differences between allergists and nonallergists. An electronic physician survey was sent to 623 providers in allergy, internal medicine, pediatrics, and family medicine, querying beta-lactam use in patients with a history of penicillin allergy. A total of 110 (17.7%) surveys were completed. For patients with a prior maculopapular rash to penicillin, most providers were uncomfortable prescribing penicillins again, although they would use other beta-lactams. In patients with an exfoliative dermatitis to penicillin, 46% of responders would not prescribe any beta-lactam again. For patients with a positive skin test to penicillin, only 45.1% of nonallergists were comfortable prescribing monobactams versus 62.5% of allergists; 30.3% of all responders would give a carbapenem. In patients with urticaria to penicillin, pediatricians were the most comfortable prescribing third- or fourth-generation cephalosporins. Providers (both allergists and nonallergists) were unfamiliar with the safety of prescribing penicillin in patients with history of maculopapular rash, the safety of monobactams, and low cross-reactivity with carbapenems in penicillin-allergic individuals. Nonallergists were also unfamiliar with the usefulness of penicillin skin testing. Improved education is needed to address these areas. Additionally, we found variability in responses regarding exfoliative dermatitis and comfort prescribing cephalosporins in patients with suspected IgE-mediated drug allergy to penicillin, highlighting the need for additional research in these areas.

  7. Interaction of oxyimino beta-lactams with a class C beta-lactamase and a mutant with a spectrum extended to beta-lactams.

    OpenAIRE

    Nukaga, M; Tsukamoto, K; Yamaguchi, H; Sawai, T.

    1994-01-01

    The class C beta-lactamase of Citrobacter freundii GN346 is a typical cephalosporinase comprising 361 amino acids, and substitution of the glutamic acid at position 219 in the enzyme by lysine was previously shown to broaden its substrate spectrum to oxyimino beta-lactams (K. Tsukamoto, R. Ohno, and T. Sawai, J. Bacteriol. 172:4348-4351, 1990). To clarify this spectrum extension from the kinetic point of view, the interactions of cefuroxime, ceftazidime, and aztreonam with the wild-type and m...

  8. NADPH-dependent glutamate dehydrogenase in Penicillium chrysogenum is involved in regulation of beta-lactam production

    DEFF Research Database (Denmark)

    Thykær, Jette; Kildegaard, Kanchana Rueksomtawin; Noorman, H.

    2008-01-01

    The interactions between the ammonium assimilatory pathways and beta-lactam production were investigated by disruption of the NADPH-dependent glutamate dehydrogenase gene (gdhA) in two industrial beta-lactam-producing strains of Penicillium chrysogenum. The strains used were an adipoyl-7-ADCA......- and a penicillin-producing strain. The gdhA gene disruption caused a decrease in maximum specific growth rate of 26 % and 35 % for the adipoyl-7-ADCA-producing strain and the penicillin-producing strain, respectively, compared to the corresponding reference strains. Interestingly, no beta-lactam production...... was detected in either of the Delta gdhA strains. Supplementation with glutamate restored growth but no beta-lactam production was detected for the constructed strains. Cultures with high ammonium concentrations (repressing conditions) and with proline as nitrogen source (de-repressed conditions) showed...

  9. The beta-lactam antibiotic, ceftriaxone, inhibits the development of opioid-induced hyperalgesia in mice.

    Science.gov (United States)

    Chen, Zhijun; He, Ying; Wang, Zaijie Jim

    2012-02-16

    The glutamate transporter GLT-1 is primarily responsible for glutamate clearance in the spinal cord. beta-Lactam antibiotics have been shown to attenuate neuropathic pain behaviors by promoting GLT-1 expression and function in the CNS. The present study tested the hypothesis that ceftriaxone, a prototype beta-lactam antibiotic, can prevent the development of opioid-induced hyperalgesia (OIH) in mice. Repeated morphine administration produced mechanical allodynia and thermal hyperalgesia, signs of OIH, and reduced spinal GLT-1 expression in mice. Ceftriaxone (200mg/kg/d, i.p., for 7 d) inhibited OIH. Correlating with the behavioral effects, ceftriaxone reversed downregulation of GLT-1 expression that was induced by OIH. These results suggest that ceftriaxone inhibited the development of OIH by up-regulating spinal GLT-1 expression.

  10. Beta-lactam antibiotic-mediated changes in platelet reactivity and vascular endothelial functions.

    Science.gov (United States)

    Togna, G I; Togna, A R; Caprino, L

    2001-05-01

    To evaluate vascular and platelet compatibility of intravenous administration of beta-lactam antibiotics, we assessed the effects of therapeutic concentrations of ceftriaxone, aztreonam, and ceftazidime on platelet reactivity to different agonists (sodium arachidonate, collagen and adenosine diphosphate) and on selected vascular endothelial functions (adenosine diphosphatase activity, prostacyclin production and t-PA release). Ceftriaxone and, to a lesser degree, aztreonam, enhanced platelet reactivity, evaluated as onset of platelet aggregating response, and increased thromboxane production to subthreshold concentrations of arachidonate. There was no modification in platelet reactivity after ceftazidime treatment. Ceftriaxone and ceftazidime, but not aztreonam, inhibited endothelial adenosine diphosphatase activity. Prostacyclin production and t-PA release were inhibited only by ceftriaxone at high concentrations. While it is difficult to establish which marker (platelet or endothelial functions) has more clinical reference in human vascular compatibility, it seems feasible to consider aztreonam the most compatible of the beta-lactams studied.

  11. Properties of immobilised penicillin G Acylase in beta-lactam antibiotic synthesis

    OpenAIRE

    Janssen, M.H.A.

    2006-01-01

    The beta-lactam antibiotics are the most important class of antibiotics used today. In the last decade the production routes of these antibiotics have shifted from chemical routes to more environmentally benign routes using the enzyme penicillin G acylase. For both practical and economical reasons the enzyme is immobilised. As the kinetically controlled synthesis reaction is performed in aqueous medium with a hydrolytic enzyme, hydrolysis of the activated acyl donor, e.g. D-phenyl glycine ami...

  12. Continuous beta-lactam infusion in critically ill patients: the clinical evidence

    OpenAIRE

    Abdul-Aziz, Mohd H; Dulhunty, Joel M; Bellomo, Rinaldo; Lipman, Jeffrey; Roberts, Jason A

    2012-01-01

    There is controversy over whether traditional intermittent bolus dosing or continuous infusion of beta-lactam antibiotics is preferable in critically ill patients. No significant difference between these two dosing strategies in terms of patient outcomes has been shown yet. This is despite compelling in vitro and in vivo pharmacokinetic/pharmacodynamic (PK/PD) data. A lack of significance in clinical outcome studies may be due to several methodological flaws potentially masking the benefits o...

  13. 262 Hypersensitivity to Beta-Lactam Antibiotics Evaluation Using the European Network Drug Allergy (ENDA) Algorithm

    OpenAIRE

    Gonçalves, Tânia Maria; Martins, Emmanuel; Neto, Alfredo Alves; Delcourt, Nathalia; Rios, João; Arcanjo, Luiz; Rios, José Luiz

    2012-01-01

    Background Hypersensitivity to beta-lactam antibiotics are usually defined only by the history of suspected previous reaction to these medicines. This definition, however, can erroneously restrict the use of these important therapeutic resources if not assessed by the proper tests. The objective was to assess the presence of hypersensitivity to beta-lactams through adequate testing. Methods Thirty-three patients were referred to our allergic clinic for testing of penicillin hypersensitivity i...

  14. Staphylococcus pseudintermedius and Staphylococcus schleiferi Subspecies coagulans from Canine Pyoderma Cases in Grenada, West Indies, and Their Susceptibility to Beta-Lactam Drugs

    Directory of Open Access Journals (Sweden)

    Harry Hariharan

    2014-01-01

    Full Text Available Over a 2-year period 66 cases of canine pyoderma in Grenada, West Indies, were examined by aerobic culture in order to ascertain the bacteria involved and their antimicrobial resistance patterns. Of the 116 total bacterial isolates obtained, the majority belonged to Gram-positive species, and the most common organism identified through biochemical and molecular methods was Staphylococcus pseudintermedius. Additionally, identification of a Staphylococcus schleiferi subspecies coagulans isolate was confirmed by molecular methods. All isolates of staphylococci were susceptible to beta-lactam drugs: amoxicillin-clavulanic acid, cefovecin, cefoxitin, cefpodoxime, and cephalothin. They were also susceptible to chloramphenicol and enrofloxacin. Resistance was highest to tetracycline. Methicillin resistance was not detected in any isolate of S. pseudintermedius or in S. schleiferi. Among the Gram-negative bacteria, the most common species was Klebsiella pneumoniae, followed by Acinetobacter baumannii/calcoaceticus. The only drug to which all Gram-negative isolates were susceptible was enrofloxacin. This report is the first to confirm the presence of S. pseudintermedius and S. schleiferi subspecies coagulans, in dogs with pyoderma in Grenada, and the susceptibility of staphylococcal isolates to the majority of beta-lactam drugs used in veterinary practice.

  15. Ceftobiprole medocaril: a new generation beta-lactam.

    Science.gov (United States)

    Del Pozo, Jose L; Patel, Robin

    2008-11-01

    Ceftobiprole is a novel parenteral cephalosporin with high affinity for most penicillin-binding proteins, including the mecA product penicillin-binding protein (PBP) 2a, rendering it active against methicillin-resistant staphylococci. Its in vitro activity against staphylococci and multiresistant pneumococci, combined with its Gram-negative spectrum comparable to that of other extended-spectrum cephalosporins, its stability against a wide range of beta-lactamases and its pharmacokinetic and safety profile make ceftobiprole an attractive new antimicrobial agent. Because of its low water solubility, ceftobiprole is administered intravenously as a prodrug, ceftobiprole medocaril. Ceftobiprole medocaril is generally well tolerated (with the exception of a caramel-like taste disturbance). Ceftobiprole medocaril has been evaluated in two phase III clinical trials for the treatment of complicated skin infections and skin structure infections. Its broad spectrum of activity may allow ceftobiprole to be used as monotherapy for some infections where combination therapy would otherwise be required, especially regimens requiring coverage of methicillin-resistant Staphylococcus aureus (MRSA).

  16. The outpatient use of beta lactam antibiotics in Montenegro before the introduction of new reform strategy on drug market

    Directory of Open Access Journals (Sweden)

    Duborija-Kovačević Nataša

    2006-01-01

    Full Text Available Introduction: The study represents the first investigation of outpatient use of beta lactam antibiotics in Montenegro carried out in accordance with internationally approved methodology (DDD/ATC. Objective: The objective of our study was to establish both the scope and overall use of beta lactam antibiotics, and to assess their compatibility with current pharmacotherapeutic guidelines and their use in developed countries. Methods: The retrospective pharmaco-epidemiological study comprised a 100%-sample of beta lactams that were used in the period prior to introduction of new reform strategy on drug market. Results: Beta lactam antibiotics (J01C, J01D were the most frequently applied anti-infectives for systemic use (ATC group J in 2000 (11.3 DDD/1000 inh./day, 61%. Penicillins (J01C were the most utilized (8.0 DDD/1000 inh./day, 71%. Cephalosporin derivatives (cephalexin and cefaclor accounted for the remaining 29% (3.3 DDD/1000 inh./day. Aminopenicillins were prevailing among penicillins (85%. Beta lactamase sensitive penicillins were in the second place and approximately accounted for 14%. Conclusion: The results of our study showed that the use of beta lactam antibacterials could be estimated as partially satisfactory. There is a need to make additional efforts with a view of further rationalization.

  17. Exploring solid-phase approaches for the preparation of new beta-lactams from amino acids.

    Science.gov (United States)

    Gerona-Navarro, Guillermo; Royo, Miriam; García-López, Ma Teresa; Albericio, Fernando; González-Muñiz, Rosario

    2003-01-01

    Two solid-phase approaches, involving the base-assisted intramolecular alkylation of N-chloroacetyl-Phe derivatives anchored to appropriate solid supports, were investigated for the preparation of novel beta-lactams. When a BAL-type strategy was used, the resin-bound azetidinones were easily formed, as established by MAS-NMR, but final compounds could not be removed from the resin, unless a suitable two linkers system was used. In the second approach, in which the Phe residue is anchored to a Wang-type resin through the carboxylate group, the corresponding 1,4,4-trisubstituted 2-azetidinone was obtained in moderate to good yield and high purity.

  18. An international multicenter study of antimicrobial consumption and resistance in Staphylococcus aureus isolates from 15 hospitals in 14 countries

    DEFF Research Database (Denmark)

    Westh, Henrik Torkil; Zinn, Christina Scheel; Rosdahl, Vibeke Thamdrup

    2004-01-01

    of therapeutical subgroups of antimicrobials varied significantly between hospitals. A positive correlation was found between S. aureus resistance to methicillin (MRSA) and consumption of beta-lactam combinations, between resistance to quinolones and consumption of beta-lactam combinations and carbapenems...... and resistance to aminoglycosides and consumption of beta-lactam combinations. The consumption of beta-lactamase-sensitive antibiotics was negatively correlated to resistance to methicillin, quinolones, and aminoglycosides. Usage of the different antimicrobial therapeutical subgroups was also correlated...

  19. Beta-lactam type molecular scaffolds for antiproliferative activity: synthesis and cytotoxic effects in breast cancer cells.

    Science.gov (United States)

    Meegan, Mary J; Carr, Miriam; Knox, Andrew J S; Zisterer, Daniela M; Lloyd, David G

    2008-10-01

    A series of novel beta-lactam containing compounds are described as antiproliferative agents and potential selective modulators of the oestrogen receptor. The purpose of the study is to evaluate the antiproliferative effects of these compounds on human MCF-7 and MDA MB-231 breast cancer cells. The compounds are designed to contain three aryl ring substituents arranged on the heterocyclic azetidin-2-one (beta-lactam), thus providing conformationally restrained analogues of the triarylethylene arrangement exemplified in the tamoxifen type structure. The compounds demonstrated potency in antiproliferative assays against MCF-7 human breast cancer cell line at low micromolar to nanomolar concentrations with low cytotoxicity and moderate binding affinity to the oestrogen receptor. The effect of a number of aryl and amine functional group substitutions on the antiproliferative activity of the beta-lactam products was explored and a brief computational structure-activity relationship investigation with molecular simulation was investigated.

  20. Relationship between pharmacokinetics and pharmacodynamics of beta-lactams and outcome.

    Science.gov (United States)

    Sádaba, B; Azanza, J R; Campanero, M A; García-Quetglas, E

    2004-11-01

    The in-vitro susceptibility of an organism and the pharmacokinetics of an antimicrobial agent are two basic factors on which the choice of standardised treatment regimens is based. However, the inter-individual variability of these factors, which modifies the exposure of bacteria to an antibiotic in terms of time and quantity, is not usually taken into account. In 87 patients treated with beta-lactams (ceftriaxone, cefepime or piperacillin), the probability of failure was greater when the infectious process was located in tissues with barriers to the distribution of beta-lactams. Mean MICs of piperacillin and cefepime, but not ceftriaxone, were below the breakpoints in cases of both recovery and failure, but organisms isolated from patients with a poor outcome had higher MICs. Therefore, the use of breakpoints to determine the susceptibility of microorganisms was not satisfactory in predicting the outcome for a large number of patients. If MICs are determined and plasma concentrations are monitored, dosages can be adjusted according to these parameters, thereby allowing antibiotic treatment to be individualised.

  1. Affinity of ceftaroline and other beta-lactams for penicillin-binding proteins from Staphylococcus aureus and Streptococcus pneumoniae.

    Science.gov (United States)

    Kosowska-Shick, K; McGhee, P L; Appelbaum, P C

    2010-05-01

    We compared the affinities of ceftaroline for all penicillin-binding proteins (PBPs) with those of ceftriaxone and cefotaxime in 6 Staphylococcus aureus and 7 Streptococcus pneumoniae isolates with various resistance phenotypes. Ceftaroline MICs were pneumoniae. Ceftaroline affinities for penicillin-susceptible S. pneumoniae strains were in the order PBP2X and -3 > PBP1A, -1B, and -2A > PBP2B, and ceftaroline had >or=4-fold higher 50% inhibitory concentrations (IC(50)s) (0.1 to 4 microg/ml) for PBP2X, -2A, -2B, and -3 than those for the other cephalosporins tested. Among 3 penicillin-resistant S. pneumoniae strains, ceftaroline had a high affinity for PBP2X (IC(50), 0.1 to 1 microg/ml), a primary target for cephalosporin PBP binding activity, and high affinities for PBP2B (IC(50), 0.5 to 4 microg/ml) and PBP1A (IC(50), 0.125 to 0.25 microg/ml) as well, both of which are also known as major targets for PBP binding activity of cephalosporins. Ceftaroline PBP affinities in methicillin-susceptible S. aureus strains were greater than or equal to those of the 3 other beta-lactams tested. Ceftaroline bound to PBP2a in methicillin-resistant S. aureus (IC(50), 0.01 to 1 microg/ml) with up to 256-fold-higher affinity than those of other agents. Ceftaroline demonstrated very good PBP affinity against all S. aureus and S. pneumoniae strains tested, including resistant isolates.

  2. 76 FR 14024 - Draft Guidance for Industry on Non-Penicillin Beta-Lactam Risk Assessment: A CGMP Framework...

    Science.gov (United States)

    2011-03-15

    ... non- penicillin beta-lactam antibiotics. The draft guidance is intended to assist manufacturers in... Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to... Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 4370,...

  3. Pharmacokinetic optimisation of beta-lactams for the treatment of ventilator-associated pneumonia

    Directory of Open Access Journals (Sweden)

    G. L. Drusano

    2007-08-01

    Full Text Available Rational therapy of ventilator-associated pneumonia requires choosing the right drug at the right dose. The choice of dose depends on the microbiological goal, the range of minimum inhibitory concentrations (MICs for likely pathogens, the extent of the drug's protein binding and, in humans, pharmacokinetics. If protein binding and the distribution of pharmacokinetic parameters are known, as well as the likely pathogens and MICs in a given setting, Monte Carlo simulations can be used to calculate the likelihood that a given dose will attain an identified microbiological goal. For beta-lactams, the antibacterial effect depends on the percentage of time (%T during the dosing interval that the free (nonprotein bound antibiotic concentration remains above the MIC (%T >MIC; the required values are smaller for carbapenems than for penicillins or cephalosporins. Data show that infusion of an i.v. beta-lactam over an extended period may greatly increase %T >MIC, and hence efficacy, at a given dose. Alternatively, it may provide the same efficacy at a lower total dose, reducing cost and potential toxicity. In a real-life setting, a 4-h infusion of 3.375 g piperacillin-tazobactam q8 h (every 8 h; 3 times daily; proved more effective for severe Pseudomonas aeruginosa infections than a 30-min infusion of 3.375 g q6 h (every 6 h; 4 times daily or q4 h (every 4 h; 6 times daily. Data for doripenem, an investigational carbapenem, suggest that its stability following reconstitution may render it particularly suitable for extended infusion.

  4. Effect of clavulanic acid on activity of beta-lactam antibiotics in Serratia marcescens isolates producing both a TEM beta-lactamase and a chromosomal cephalosporinase.

    Science.gov (United States)

    Bush, K; Flamm, R K; Ohringer, S; Singer, S B; Summerill, R; Bonner, D P

    1991-01-01

    An isolate of Serratia marcescens that produced both an inducible chromosomal and a plasmid-mediated TEM-1 beta-lactamase was resistant to ampicillin and amoxicillin and also demonstrated decreased susceptibility to extended-spectrum beta-lactam antibiotics (ESBAs). Clavulanic acid did not lower the MICs of the ESBAs, but it decreased the MICs of the penicillins. The TEM-1-producing plasmid was transferred to a more susceptible S. marcescens strain that produced a well-characterized inducible chromosomal beta-lactamase. The MICs of the ESBAs remained at a low level for the transconjugant. Ampicillin and amoxicillin which were good substrates for the plasmid-mediated enzyme, were not well hydrolyzed by the chromosomal enzymes; the ESBAs were hydrolyzed slowly by all the enzymes. When each of the S. marcescens strains was grown with these beta-lactam antibiotics, at least modest increases in chromosomal beta-lactamase activity were observed. When organisms were grown in the presence of clavulanic acid and an ESBA, no enhanced induction was observed. The increases in the MICs of the ESBAs observed for the initial clinical isolate may have been due to a combination of low inducibility, slow hydrolysis, and differences in permeability between the S. marcescens isolates. When clavulanic acid and a penicillin were added to strains that produced both a plasmid-mediated TEM and a chromosomal beta-lactamase, much higher levels of chromosomal beta-lactamase activity were present than were observed in cultures induced by the penicillin alone. This was due to the higher levels of penicillin that were available for induction as a result of inhibition of the TEM enzyme by clavulanate. Images PMID:1803992

  5. [Cross allergy between penicillins and other beta lactam antibiotics--the risk is much less than previously thought].

    Science.gov (United States)

    Tängden, Thomas; Furebring, Mia; Löwdin, Elisabeth; Werner, Sonja

    2015-02-03

    Severe IgE-mediated allergic reactions to penicillins are rare but might be fatal. Because some studies demonstrated a high risk of cross-sensitivity to cephalosporins and carbapenems it has been recommended to avoid these antibiotics in patients with suspected hypersensitivity to penicillins. However, recent studies and analyses conclude that the risk of cross-reactivity was overestimated in the earlier studies and that it is in fact very low for parenteral cephalosporins and perhaps even negligible for carbapenems. The new knowledge has implications for the choice of therapy for bacterial infections in patients with a history of penicillin hypersensitivity, because alternative antibiotic regimens are often inferior to beta-lactam antibiotics. The aim of the present review is to present existing knowledge on cross-sensitivity between beta-lactams, as well as to discuss the management of patients with suspected allergic reactions to these antibiotics.

  6. [In vitro inhibition of granulopoiesis by beta-lactam antibiotics. Comparison of piperacillin, mezlocillin, ceftriaxone and ceftazidime].

    Science.gov (United States)

    Marie, J P; Thevenin, D; Zittoun, R

    1986-12-20

    The mechanism of neutropenia induced by beta-lactam antibiotics was explored by studying the action of these drugs on granulopoiesis in vitro. Normal bone marrows were cultivated in the presence of increasing concentrations of piperacillin (10 marrows), mezlocillin, ceftriaxone and ceftazidime (5 marrows each) in order to find out whether these antibiotics exhibited toxicity to granulocyte-monocyte precursors. A dose-dependent inhibition of granulopoiesis was found in all cases. When the doses used were equivalent to maximum plasma concentrations in vivo, inhibition was minimal with piperacillin and mezlocillin and much more pronounced with the cephalosporins. This dose-dependent inhibition suggests that toxicity is involved in the mechanism of neutropenia induced by beta-lactam antibiotics.

  7. Effect of clavulanic acid on susceptibility of Campylobacter jejuni and Campylobacter coli to eight beta-lactam antibiotics.

    Science.gov (United States)

    Gaudreau, C L; Lariviere, L A; Lauzer, J C; Turgeon, F F

    1987-01-01

    The effect of clavulanic acid on the susceptibility of 32 strains of Campylobacter jejuni and Campylobacter coli to eight beta-lactam agents was studied. Almost all strains tested became susceptible to amoxicillin and ticarcillin with 1 microgram of clavulanic acid per ml. This compound had little or no effect on susceptibility to penicillin G, cephalothin, cefamandole, and cefoxitin. Clavulanic acid had a marginal effect on cefotaxime and moxalactam susceptibility. PMID:3619428

  8. Effect of clavulanic acid on susceptibility of Campylobacter jejuni and Campylobacter coli to eight beta-lactam antibiotics.

    OpenAIRE

    Gaudreau, C L; Lariviere, L A; Lauzer, J C; Turgeon, F F

    1987-01-01

    The effect of clavulanic acid on the susceptibility of 32 strains of Campylobacter jejuni and Campylobacter coli to eight beta-lactam agents was studied. Almost all strains tested became susceptible to amoxicillin and ticarcillin with 1 microgram of clavulanic acid per ml. This compound had little or no effect on susceptibility to penicillin G, cephalothin, cefamandole, and cefoxitin. Clavulanic acid had a marginal effect on cefotaxime and moxalactam susceptibility.

  9. The complex clinical picture of beta-lactam hypersensitivity: penicillins, cephalosporins, monobactams, carbapenems, and clavams.

    Science.gov (United States)

    Torres, Maria J; Blanca, Miguel

    2010-07-01

    Beta-lactam antibiotics are the drugs most frequently involved in drug hypersensitivity reactions that are mediated by specific immunologic mechanisms. In addition to benzylpenicillin, several chemical structures belonging to 5 major subgroups can induce reactions. The most relevant structure is that of the amoxicillin molecule. Reactions belong to the 4 major mechanisms described by Coombs and Gell, whereby type IV reactions have recently been further subclassified. The most frequent reactions are type I, which are IgE mediated, and type IV, which are nonimmediate and T-cell dependent. IgE-specific antibodies may recognize the benzylpenicilloyl structure or another part of the molecule, such as the side chain, as antigenic determinants. Depending on specific recognition, subjects can be either cross-reactors or selective responders. A variety of entities exist in T-cell reactions, ranging from mild exanthema to life-threatening, severe reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis. Diagnostic tests for IgE-mediated reactions can be done in vivo by testing skin with different penicillin determinants or in vitro by quantitating specific IgE antibodies. For nonimmediate reactions, there are also in vitro and in vivo tests, with variable degrees of sensitivity and specificity. The natural history of IgE-mediated reactions indicates that the count of specific IgE antibodies decreases over time and that results of diagnostic tests can become negative.

  10. Enzymic analysis of NADPH metabolism in beta-lactam-producing Penicillium chrysogenum: presence of a mitochondrial NADPH dehydrogenase.

    Science.gov (United States)

    Harris, Diana M; Diderich, Jasper A; van der Krogt, Zita A; Luttik, Marijke A H; Raamsdonk, Léonie M; Bovenberg, Roel A L; van Gulik, Walter M; van Dijken, Johannes P; Pronk, Jack T

    2006-03-01

    Based on assumed reaction network structures, NADPH availability has been proposed to be a key constraint in beta-lactam production by Penicillium chrysogenum. In this study, NADPH metabolism was investigated in glucose-limited chemostat cultures of an industrial P. chrysogenum strain. Enzyme assays confirmed the NADP(+)-specificity of the dehydrogenases of the pentose-phosphate pathway and the presence of NADP(+)-dependent isocitrate dehydrogenase. Pyruvate decarboxylase/NADP(+)-linked acetaldehyde dehydrogenase and NADP(+)-linked glyceraldehyde-3-phosphate dehydrogenase were not detected. Although the NADPH requirement of penicillin-G-producing chemostat cultures was calculated to be 1.4-1.6-fold higher than that of non-producing cultures, in vitro measured activities of the major NADPH-providing enzymes were the same. Isolated mitochondria showed high rates of antimycin A-sensitive respiration of NADPH, thus indicating the presence of a mitochondrial NADPH dehydrogenase that oxidises cytosolic NADPH. The presence of this enzyme in P. chrysogenum might have important implications for stoichiometric modelling of central carbon metabolism and beta-lactam production and may provide an interesting target for metabolic engineering.

  11. Killing curve activity of ciprofloxacin is comparable to synergistic effect of beta-lactam-tobramycin combinations against Haemophilus species endocarditis strains

    DEFF Research Database (Denmark)

    Westh, H; Frimodt-Møller, N; Gutschik, E

    1992-01-01

    Nine Haemophilus species strains, all beta-lactamase negative, isolated from patients with endocarditis were tested in killing curve experiments. Antibiotics used were penicillin, amoxicillin, aztreonam alone and in combination with tobramycin, as well as ciprofloxacin alone. Synergism between beta......-lactams and tobramycin with reduction of colony counts to zero was seen after 24 h for H. influenzae, H. parainfluenzae and H. segnis strains. Ciprofloxacin was as effective as beta-lactam-tobramycin combinations. The H. aphrophilus strain was not killed as effectively as other strains by any of the antibiotics....

  12. 外膜孔道蛋白38缺失引起鲍曼不动杆菌对β-内酰胺类抗菌药物敏感性降低的实验研究%Decreased beta-lactam antibiotic susceptibility caused by outer membrane protein 38 deletion in Acinetobacter baumannii

    Institute of Scientific and Technical Information of China (English)

    王代荣; 李曦; 祝宏; 王爱华

    2016-01-01

    目的:探讨外膜孔道蛋白38(Omp38)在鲍曼不动杆菌对β-内酰胺类抗菌药物耐药中的作用。方法前期通过体外诱导试验获得1株鲍曼不动杆菌基因 Omp38缺失突变株,应用回补试验验证突变基因的作用;采用流式细胞术检测菌株细胞膜电位变化;通过测量菌株的相对生长率评估突变基因的适应性代价。结果 Omp38被证实涉及降低鲍曼不动杆菌对β-内酰胺类抗菌药物的敏感性;Omp38降低鲍曼不动杆菌膜电位并具有约3%的适应性代价(P<0.05)。结论 Omp38在鲍曼不动杆菌对β-内酰胺类抗菌药物耐药过程中发挥重要作用;Omp38微弱的适应性代价可能是鲍曼不动杆菌对β-内酰胺类抗菌药物耐药的重要原因。%Objective To investigate the influence of outer membrane protein 38(Omp38)on the susceptibility of beta-lactam antibiotic in Acinetobacter baumannii. Methods The isolate with Omp38 deletion was induced by in vitro experiment. The contribution of mutation to beta-lactam antibiotic susceptibility was validated by complementation experiment. The cell membrane potential change of isolates was determined by flow cytometry. The growth rates were determined in order to evaluate mutant gene fitness cost. Results The Omp38 was confirmed to be correlated with the decreased beta-lactam antibiotic susceptibility. The Omp38 decreased cell membrane potential,and the fitness cost of Omp38 was approximately 3% through measuring growth rates(P< 0.05). Conclusions Omp38 is deemed to play an important role in beta-lactam antibiotic resistance in Acinetobacter baumannii. The minor fitness cost of Omp38 may be a significant reason for the development of beta-lactam antibiotic resistance in Acinetobacter baumannii.

  13. A Designed Experiments Approach to Optimizing MALDI-TOF MS Spectrum Processing Parameters Enhances Detection of Antibiotic Resistance in Campylobacter jejuni

    Directory of Open Access Journals (Sweden)

    Christian ePenny

    2016-05-01

    categorization was created from the collection consisting of 31 strains resistant to beta-lactams and 141 strains sensitive to beta-lactams. Applying optimal preprocessing parameters, beta-lactam resistance detection was increased by 34 percent. These results suggest that spectrum processing parameters, which are rarely optimized or adjusted, affect the performance of MALDI-TOF MS-based detection of antibiotic resistance and can be fine-tuned to enhance screening performance.

  14. A Designed Experiments Approach to Optimizing MALDI-TOF MS Spectrum Processing Parameters Enhances Detection of Antibiotic Resistance in Campylobacter jejuni.

    Science.gov (United States)

    Penny, Christian; Grothendick, Beau; Zhang, Lin; Borror, Connie M; Barbano, Duane; Cornelius, Angela J; Gilpin, Brent J; Fagerquist, Clifton K; Zaragoza, William J; Jay-Russell, Michele T; Lastovica, Albert J; Ragimbeau, Catherine; Cauchie, Henry-Michel; Sandrin, Todd R

    2016-01-01

    collection consisting of 31 strains resistant to beta-lactams and 141 strains sensitive to beta-lactams. Applying optimal preprocessing parameters, beta-lactam resistance detection was increased by 34%. These results suggest that spectrum processing parameters, which are rarely optimized or adjusted, affect the performance of MALDI-TOF MS-based detection of antibiotic resistance and can be fine-tuned to enhance screening performance.

  15. Determination of Beta-Lactam residues in milk by high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Roseane Brandão de Brito

    2006-01-01

    Full Text Available A high performance liquid chromatographic method to assay beta-lactam residues in milk was developed and validated. Milk samples were spiked with standard solutions and deproteinated. The extract was cleaned-up on C18 SPE cartridge, the antibiotics eluted with acetonitrile:water (50:50 v/v and derivatized with acetic anhydride and 1-methyl-imidazole solution containing HgCl2. The chromatographic analysis was performed on C18 column using mobile phase consisting of acetonitrile and phosphate buffer (pH 6.5 in the presence of Na2S2O3 gradient and detection at 325 nm. The method was selective for ampicillin, penicillin G and penicillin V, the latter used as internal standard. Average recoveries for ampicillin and penicillin G ranged, respectively, from 60.0% to 104.9% and from 82.7% to 109.2%, with coefficients of variation from 11.1% to 24.6%, and from 2.1% to 25.2%, indicating accuracy and precision. Detection limit of 4.0 µg/L for ampicillin and 3.0 µg/L for penicillin G, and quantification limits of 4.0 µg/L for both were estimated.Um método para determinar resíduos de antibióticos beta-lactâmicos em leite por cromatografia líquida de alta eficiência (CLAE foi desenvolvido e validado. Amostras brancas foram adicionadas de padrão e desproteinizadas. O extrato foi purificado por extração em fase sólida C18, os antibióticos eluídos com acetonitrila:água (50:50 v/v e posteriormente derivatizados com anidrido acético e solução de 1-metil-imidazol contendo HgCl2. A análise cromatográfica foi realizada utilizando coluna C18, fase móvel composta por acetonitrila e tampão fosfato pH 6,5, na presença de Na2S2O3 em gradiente e detecção a 325 nm. O método foi seletivo para ampicilina, penicilina G e penicilina V, sendo este último utilizado como padrão interno. As médias de recuperação para ampicilina e penicilina G situaram-se, respectivamente, na faixa de 60,0% a 104,9% e de 82,7% a 109,2%, com coeficientes de varia

  16. A beta-lactam antibiotic dampens excitotoxic inflammatory CNS damage in a mouse model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Nico Melzer

    Full Text Available In multiple sclerosis (MS and its animal model experimental autoimmune encephalomyelitis (EAE, impairment of glial "Excitatory Amino Acid Transporters" (EAATs together with an excess glutamate-release by invading immune cells causes excitotoxic damage of the central nervous system (CNS. In order to identify pathways to dampen excitotoxic inflammatory CNS damage, we assessed the effects of a beta-lactam antibiotic, ceftriaxone, reported to enhance expression of glial EAAT2, in "Myelin Oligodendrocyte Glycoprotein" (MOG-induced EAE. Ceftriaxone profoundly ameliorated the clinical course of murine MOG-induced EAE both under preventive and therapeutic regimens. However, ceftriaxone had impact neither on EAAT2 protein expression levels in several brain areas, nor on the radioactive glutamate uptake capacity in a mixed primary glial cell-culture and the glutamate-induced uptake currents in a mammalian cell line mediated by EAAT2. Moreover, the clinical effect of ceftriaxone was preserved in the presence of the EAAT2-specific transport inhibitor, dihydrokainate, while dihydrokainate alone caused an aggravated EAE course. This demonstrates the need for sufficient glial glutamate uptake upon an excitotoxic autoimmune inflammatory challenge of the CNS and a molecular target of ceftriaxone other than the glutamate transporter. Ceftriaxone treatment indirectly hampered T cell proliferation and proinflammatory INFgamma and IL17 secretion through modulation of myelin-antigen presentation by antigen-presenting cells (APCs e.g. dendritic cells (DCs and reduced T cell migration into the CNS in vivo. Taken together, we demonstrate, that a beta-lactam antibiotic attenuates disease course and severity in a model of autoimmune CNS inflammation. The mechanisms are reduction of T cell activation by modulation of cellular antigen-presentation and impairment of antigen-specific T cell migration into the CNS rather than or modulation of central glutamate homeostasis.

  17. Crystal Structures of Covalent Complexes of [beta]-Lactam Antibiotics with Escherichia coli Penicillin-Binding Protein 5: Toward an Understanding of Antibiotic Specificity

    Energy Technology Data Exchange (ETDEWEB)

    Nicola, George; Tomberg, Joshua; Pratt, R.F.; Nicholas, Robert A.; Davies, Christopher (SC); (UNC); (Wesleyan)

    2010-12-07

    Penicillin-binding proteins (PBPs) are the molecular targets for the widely used {beta}-lactam class of antibiotics, but how these compounds act at the molecular level is not fully understood. We have determined crystal structures of Escherichia coli PBP 5 as covalent complexes with imipenem, cloxacillin, and cefoxitin. These antibiotics exhibit very different second-order rates of acylation for the enzyme. In all three structures, there is excellent electron density for the central portion of the {beta}-lactam, but weak or absent density for the R1 or R2 side chains. Areas of contact between the antibiotics and PBP 5 do not correlate with the rates of acylation. The same is true for conformational changes, because although a shift of a loop leading to an electrostatic interaction between Arg248 and the {beta}-lactam carboxylate, which occurs completely with cefoxitin and partially with imipenem and is absent with cloxacillin, is consistent with the different rates of acylation, mutagenesis of Arg248 decreased the level of cefoxitin acylation only 2-fold. Together, these data suggest that structures of postcovalent complexes of PBP 5 are unlikely to be useful vehicles for the design of new covalent inhibitors of PBPs. Finally, superimposition of the imipenem-acylated complex with PBP 5 in complex with a boronic acid peptidomimetic shows that the position corresponding to the hydrolytic water molecule is occluded by the ring nitrogen of the {beta}-lactam. Because the ring nitrogen occupies a similar position in all three complexes, this supports the hypothesis that deacylation is blocked by the continued presence of the leaving group after opening of the {beta}-lactam ring.

  18. Beta-Lactam Antibiotics as A Possible Novel Therapy for Managing Epilepsy and Autism, A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Ahmed GHANIZADEH*

    2015-01-01

    Full Text Available How to Cite This Article: Ghanizadeh A, Berk M. Beta-Lactam Antibiotics as A Possible Novel Therapy for Managing Epilepsy and Autism, A Case Report and Review of Literature. Iran J Child Neurol. 2015 Winter;9(1:99-102.AbstractAutism is a disorder of unknown etiology. There are few FDA approved medications for treating autism. Co-occurring autism and epilepsy is common, and glutamate antagonists improve some symptoms of autism. Ceftriaxone, a beta-lactam antibiotic, increases the expression of the glutamate transporter 1 which decreases extracellular glutamate levels. It is hypothesized that modulating astrocyte glutamate transporter expression by ceftriaxone or cefixime might improve some symptoms of autism. This case report of a child with autism and epilepsy suggests a decrease in seizures after taking cefixime.References Selassie AW, Wilson DA, Martz GU, Smith GG, Wagner JL, Wannamaker BB. Epilepsy beyond seizure: a population-based study of comorbidities. Epilepsy Res 2014;108(2: 305-315.Sansa G, Carlson C, Doyle W, Weiner HL, Bluvstein, Barr W, et al. Medically refractory epilepsy in autism. Epilepsia 2011; 52(6: 1071-1075.Ghanizadeh A. Increased glutamate and homocysteine and decreased glutamine levels in autism: a review and strategies for future studies of amino acids in autism. Dis Markers; 2013;35(5: 281-286.Yamada T, Kawahara K, Kosugi T, Tanaka M.Nitric oxide produced during sublethal ischemia is crucial for the preconditioning-induced down-regulation of glutamate transporter GLT-1 in neuron/astrocyte co-cultures. Neurochem Res 2006:31(1: 49-56.Zeng, LH, Ouyang Y, Gazit V, Cirrito JR, Jansen LA, Ess KC, et al. Abnormal glutamate homeostasis and impaired synaptic plasticity and learning in a mouse model of tuberous sclerosis complex. Neurobiol Dis 2007; 28(2: 184-196.Zeng LH, Bero AW, Zhang B, Holtzman D. M. , Wong M. Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of Tuberous Sclerosis Complex

  19. Development of a miniaturised microarray-based assay for the rapid identification of antimicrobial resistance genes in Gram-negative bacteria

    DEFF Research Database (Denmark)

    Batchelor, Miranda; Hopkins, Katie L; Liebana, Ernesto

    2008-01-01

    We describe the development of a miniaturised microarray for the detection of antimicrobial resistance genes in Gram-negative bacteria. Included on the array are genes encoding resistance to aminoglycosides, trimethoprim, sulphonamides, tetracyclines and beta-lactams, including extended-spectrum ......We describe the development of a miniaturised microarray for the detection of antimicrobial resistance genes in Gram-negative bacteria. Included on the array are genes encoding resistance to aminoglycosides, trimethoprim, sulphonamides, tetracyclines and beta-lactams, including extended...

  20. Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics.

    Directory of Open Access Journals (Sweden)

    David Sevillano

    Full Text Available BACKGROUND: Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae are bacteria present in the nasopharynx as part of normal flora. The ecological equilibrium in the nasopharynx can be disrupted by the presence of antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: A computerized two-compartment pharmacodynamic model was used to explore beta-lactam effects on the evolution over time of a bacterial load containing common pharyngeal isolates by simulating free serum concentrations obtained with amoxicillin (AMX 875 mg tid, amoxicillin/clavulanic acid (AMC 875/125 mg tid and cefditoren (CDN 400 mg bid regimens over 24 h. Strains and MICs (microg/ml of AMX, AMC and CDN were: S. pyogenes (0.03, 0.03 and 0.015, S. pneumoniae (2, 2 and 0.25, a beta-lactamase positive H. influenzae (BL(+; >16, 2 and 0.06 and a beta-lactamase positive AMC-resistant H. influenzae (BLPACR, >16, 8 and 0.06. Mixture of identical 1:1:1:1 volumes of each bacterial suspension were prepared yielding an inocula of approximately 4 x 10(6 cfu/ml. Antibiotic concentrations were measured both in bacterial and in bacteria-free antibiotic simulations. beta-lactamase production decreased AMX concentrations and fT(>MIC against S. pneumoniae (from 43.2% to 17.7% or S. pyogenes (from 99.9% to 24.9%, and eradication was precluded. The presence of clavulanic acid countered this effect of co-pathogenicity, and S. pyogenes (but not BL(+ and S. pneumoniae was eradicated. Resistance of CDN to TEM beta-lactamase avoided this co-pathogenicity effect, and CDN eradicated S. pyogenes and H. influenzae strains (fT(>MIC >58%, and reduced in 94% S. pneumoniae counts (fT(>MIC approximately 25%. CONCLUSIONS/SIGNIFICANCE: Co-pathogenicity seems to be gradual since clavulanic acid countered this effect for strains very susceptible to AMX as S. pyogenes but not for strains with AMX MIC values in the limit of susceptibility as S. pneumoniae. There is a potential therapeutic advantage for beta

  1. Quantification of beta-lactam antibiotics in veterinary drugs: amoxicillin and ampicillin determination by high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Gabriela Coelho Miguel

    2013-01-01

    Full Text Available This work focused on the development and validation of an RP-HPLC-UV method for quantification of beta-lactam antibiotics in three pharmaceutical samples. Active principles analyzed were amoxicillin and ampicillin, in 3 veterinary drugs. Mobile phase comprised 5 mmol L-1 phosphoric acid solution at pH 2.00, acetonitrile with gradient elution mode and detection wavelength at 220 nm. The method was validated according to the Brazilian National Health Surveillance regulation, where linear range and linearity, selectivity, precision, accuracy and ruggedness were evaluated. Inter day precision and accuracy for pharmaceutical samples 1, 2 and 3 were: 1.43 and 1.43%; 4.71 and 3.74%; 2.72 and 1.72%, respectively, while regression coefficients for analytical curves exceeded 0.99. The method had acceptable merit figure values, indicating reliable quantification. Analyzed samples had active principle concentrations varying from -12 to +21% compared to manufacturer label claims, rendering the medicine unsafe for administration to animals.

  2. Pseudomonas aeruginosa chromosomal beta-lactamase in patients with cystic fibrosis and chronic lung infection. Mechanism of antibiotic resistance and target of the humoral immune response

    DEFF Research Database (Denmark)

    Ciofu, Oana

    2003-01-01

    of this therapeutic strategy and our results showed the development of resistance of P. aeruginosa to several antibiotics during 25 years of intensive antibiotic treatment. Our studies have been concentrating on the development of resistance to beta-lactam antibiotics. We have shown an association between...... the development of resistance to beta-lactam antibiotics and the occurrence of high beta-lactamase producing strains and between the MIC of the beta-lactams and the levels of beta-lactamase expression. Partially derepressed mutants, characterized by high basal levels of beta-lactamase with the possibility...... of induction to even higher levels during treatment with beta-lactam antibiotics, were the most frequent phenotype found among resistant Danish P. aeruginosa CF isolates. We have also shown that the high alginate producing P. aeruginosa isolates, that characterize the chronic lung infection in CF patients...

  3. Beta Lactams Antibiotic Ceftriaxone Modulates Seizures, Oxidative Stress and Connexin 43 Expression in Hippocampus of Pentylenetetrazole Kindled Rats

    Science.gov (United States)

    Hussein, Abdelaziz M.; Ghalwash, Mohammed; Magdy, Khaled; Abulseoud, Osama A.

    2016-01-01

    Background and Purpose: This study aimed to investigate the effect of ceftriaxone on oxidative stress and gap junction protein (connexin 43, Cx-43) expression in pentylenetetrazole (PTZ) induced kindling model. Methods: Twenty four Sprague dawely rats were divided into 3 equal groups (a) normal group: normal rats. (b) PTZ kindled group: received PTZ at the dose of 50 mg/kg via intraperitoneal injection (i.p.) every other day for 2 weeks (c) ceftriaxone treated group: received ceftriaxone at the dose 200 mg\\kg/12 hrs via i.p. injection daily from the 6th dose of PTZ for 3 days. Racine score, latency before beginning the first myoclonic jerk and duration of the jerks used as parameters of behavioral assessment. Immunohistopathological study for Cx-43 expression in hippocampus and measurement of markers of oxidative stress (malondialdehyde [MDA], low reduced glutathione [GSH] and catalase [CAT]) in hippocampal neurons were done. Results: PTZ kindling was associated with behavioral changes (in the form high stage of Racine score, long seizure duration and short latency for the first jerk), enhanced oxidative stress state (as demonstrated by high MDA, low GSH and CAT) and up regulation of Cx43 in hippocampal regions. While, ceftriaxone treatment ameliorated, significantly, PTZ-induced convulsions and caused significant improvement in oxidative stress markers and Cx-43 expression in hippocamal regions (p < 0.05). Conclusions: These findings support the anticonvulsive effects of some beta-lactams antibiotics which could offer a possible contributor in the basic treatment of temporal lobe epilepsy. This effect might be due to reduction of oxidative stress and Cx43 expression. PMID:27390674

  4. Propenylamide and propenylsulfonamide cephalosporins as a novel class of anti-MRSA beta-lactams.

    Science.gov (United States)

    Pohlmann, Jens; Vasilevich, Natalya I; Glushkov, Andrei I; Kellenberger, Laurenz; Shapiro, Stuart; Caspers, Patrick; Page, Malcolm G P; Danel, Franck

    2010-08-01

    Novel C(3) propenylamide and propenylsulfonamide cephalosporins have been synthesized and tested for their ability to inhibit the penicillin-binding protein 2' (PBP2') from Staphylococcus epidermidis and the growth of a panel of clinically relevant bacterial species, including methicillin-resistant Staphylococcus aureus (MRSA). The most potent compounds inhibited the growth of MRSA strains with minimum inhibitory concentrations (MIC) as low as 1 microg/mL. The structure-activity relationship revealed the potential for further optimization of this new cephalosporin class.

  5. [Beta lactam antibiotics and the question of dose regimen for severe infection. Prolonged infusion theoretically appealing--yet no evidence of clinical benefit].

    Science.gov (United States)

    Leander, Gunilla; Eliasson, Erik; Hanberger, Håkan; Giske, Christian

    2015-03-24

    Patients with severe sepsis/septic shock have a high mortality. Beta-lactam antibiotics are normally first line treatment. This antimicrobial class has been associated with time-dependent efficacy. It is therefore plausible that administration as prolonged infusion will increase the therapeutic effect, as compared to short term bolus injections, which is the most common practice today. We have reviewed 14 randomized controlled studies to investigate whether prolonged infusion provides lower mortality and/or increased clinical cure. In summary, convincing advantages with prolonged infusion could not be found, however randomized studies are heterogeneous, and it cannot be excluded that some subgroups of critically ill patients could benefit from such treatment.

  6. Streptococcus pneumoniae R6 interspecies transformation: genetic analysis of penicillin resistance determinants and genome-wide recombination events.

    Science.gov (United States)

    Sauerbier, Julia; Maurer, Patrick; Rieger, Martin; Hakenbeck, Regine

    2012-11-01

    Interspecies gene transfer has been implicated as the major driving force for the evolution of penicillin resistance in Streptococcus pneumoniae. Genomic alterations of S. pneumoniae R6 introduced during four successive transformations with DNA of the high-level penicillin-resistant Streptococcus mitis B6 with beta-lactam selection have now been determined and the contribution of genes to high resistance levels was analysed genetically. Essential for high level resistance to penicillins of the transformant CCCB was the combination of murM(B) (6) and the 3' region of pbp2b(B) (6) . Sequences of both genes were detected in clinical isolates of S. pneumoniae, confirming the participation of S. mitis in the global gene pool of beta-lactam resistance determinants. The S. mitis PBP1b gene which contains an authentic stop codon within the transpeptidase domain is now shown to contribute only marginal to resistance, but it is possible that the presence of its transglycosylase domain is important in the context of cognate PBPs. The genome sequence of CCCB revealed 36 recombination events, including deletion and acquisition of genes and repeat elements. A total of 78 genes were affected representing 67 kb or 3.3% of the genome, documenting extensive alterations scattered throughout the genome.

  7. Antimicrobial resistance among pilgrims: a retrospective study from two hospitals in Makkah, Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Abdul Haseeb

    2016-06-01

    Conclusion: Overall, a high resistance was observed for beta-lactam antibiotics. In addition, a high resistance was noted for ceftazidime with A. baumannii species (n = 16, 77%. However, for quinolones, the highest resistance to ciprofloxacin was observed for E. coli, A. baumannii, methicillin-resistant Staphylococcus aureus, and K. pneumoniae.

  8. Successive emergence of Enterobacter aerogenes strains resistant to imipenem and colistin in a patient.

    Science.gov (United States)

    Thiolas, Aurélie; Bollet, Claude; La Scola, Bernard; Raoult, Didier; Pagès, Jean-Marie

    2005-04-01

    Enterobacter aerogenes is an agent of hospital-acquired infection that exhibits a remarkable resistance to beta-lactam antibiotics during therapy. Five successive isolates of E. aerogenes infecting a patient and exhibiting a multiresistance phenotype to beta-lactam antibiotics and fluoroquinolones were investigated. Among these clinical strains, four presented resistant phenotypes during successive imipenem and colistin treatments. The involved resistance mechanisms exhibited by the successive isolates were associated with alterations of the outer membrane that caused a porin decrease and lipopolysaccharide modifications.

  9. Useful dual Diels-Alder behavior of 2-azetidinone-tethered aryl imines as azadienophiles or azadienes: a beta-lactam-based stereocontrolled access to optically pure highly functionalized indolizidine systems.

    Science.gov (United States)

    Alcaide, Benito; Almendros, Pedro; Alonso, Jose M; Aly, Moustafa F

    2003-07-21

    Imines derived from 4-oxoazetidine-2-carbaldehydes have been found to be versatile Diels-Alder reagents in that they exhibit two reactivity patterns. 2-Azetidinone-tethered imines undergo diastereoselective reaction with Danishefsky's diene in the presence of different Lewis acids. The effect of the amount of catalyst on the conversion rate as well as on the product ratio has been studied. Under standard reaction conditions, indium(III) chloride and zinc(II) iodide provided the best yields, and indium(III) triflate the highest diastereoselectivity in the Lewis acid promoted aza-Diels-Alder cycloaddition. Treatment of the aforementioned imines with cyclopentadiene, 2,3-dimethyl-1,3-butadiene or 3,4-dihydro-2 H-pyran led to cycloadducts arising from inverse electron-demand condensation involving the beta-lactam-tethered aryl imine as the heterodiene component. In addition, the first methodology for preparing indolizidines from beta-lactams has been developed. This process involves amide bond cleavage of the beta-lactam ring in the aza-Diels-Alder cycloadducts with concomitant cyclization. Full chirality transfer occurs when the reaction is performed with an enantiomerically pure substrate.

  10. Meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance

    DEFF Research Database (Denmark)

    Petersen, Thomas Nordahl; Rasmussen, Simon; Hasman, Henrik

    2015-01-01

    for bacteria and antimicrobial resistance genes. An average of 106,839 (0.06%) reads were assigned to resistance genes with genes encoding resistance to tetracycline, macrolide and beta-lactam resistance genes as the most abundant in all samples. We found significantly higher abundance and diversity of genes...

  11. Reconceptualizing resistance: sociology and the affective dimension of resistance.

    Science.gov (United States)

    Hynes, Maria

    2013-12-01

    This paper re-examines the sociological study of resistance in light of growing interest in the concept of affect. Recent claims that we are witness to an 'affective turn' and calls for a 'new sociological empiricism' sensitive to affect indicate an emerging paradigm shift in sociology. Yet, mainstream sociological study of resistance tends to have been largely unaffected by this shift. To this end, this paper presents a case for the significance of affect as a lens by which to approach the study of resistance. My claim is not simply that the forms of actions we would normally recognize as resistance have an affective dimension. Rather, it is that the theory of affect broadens 'resistance' beyond the purview of the two dominant modes of analysis in sociology; namely, the study of macropolitical forms, on the one hand, and the micropolitics of everyday resistance on the other. This broadened perspective challenges the persistent assumption that ideological forms of power and resistance are the most pertinent to the contemporary world, suggesting that much power and resistance today is of a more affective nature. In making this argument, it is a Deleuzian reading of affect that is pursued, which opens up to a level of analysis beyond the common understanding of affect as emotion. I argue that an affective approach to resistance would pay attention to those barely perceptible transitions in power and mobilizations of bodily potential that operate below the conscious perceptions and subjective emotions of social actors. These affective transitions constitute a new site at which both power and resistance operate.

  12. Frequent emergence and limited geographic dispersal of methicillin-resistant Staphylococcus aureus

    DEFF Research Database (Denmark)

    Nübel, Ulrich; Roumagnac, Philippe; Feldkamp, Mirjam

    2008-01-01

    A small number of clonal lineages dominates the global population structure of methicillin-resistant Staphylococcus aureus (MRSA), resulting in the concept that MRSA has emerged on a few occasions after penicillinase-stable beta-lactam antibiotics were introduced to clinical practice, followed...

  13. Sublethal Ciprofloxacin Treatment Leads to Rapid Development of High-Level Ciprofloxacin Resistance during Long-Term Experimental Evolution of Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Jørgensen, Karin Meinike; Wassermann, Tina; Jensen, Peter Østrup

    2013-01-01

    lineages after 240 generations. The genetic basis of resistance was mutations in gyrA (C248T and G259T) and gyrB (C1397A). Cross-resistance to beta-lactam antibiotics was observed in the bacterial populations that evolved during exposure to sublethal concentrations of ciprofloxacin. Our study shows...

  14. The KPC type beta-lactamases: new enzymes that confer resistance to carbapenems in Gram-negative bacilli.

    Directory of Open Access Journals (Sweden)

    Piotr Wieczorek

    2010-05-01

    Full Text Available Antimicrobial resistance due to the continuous selective pressure from widespread use of antimicrobials in humans, animals and agriculture has been a growing problem for last decades. KPC beta-lactamases hydrolyzed beta-lactams of all classes. Especially, carbapenem antibiotics are hydrolyzed more efficiency than other beta-lactam antibiotics. The KPC enzymes are found most often in Enterobacteriaceae. Recently, these enzymes have been found in isolates of Pseudomonas aeruginosa and Acinetobacter spp. The observations of blaKPC genes isolated from different species in other countries indicate that these genes from common but unknown ancestor may have been mobilized in these areas or that blaKPC-carrying bacteria may have been passively by many vectors. The emergence of carbapenem resistance in Gram-negative bacteria is worrisome because the carbapenem resistance often may be associated with resistance to many beta-lactam and non-beta-lactam antibiotics. Treatment of infections caused by KPC-producing bacteria is extremely difficult because of their multidrug resistance, which results in high mortality rates. Therapeutic options to treat infections caused by multiresistant Gram-negative bacteria producing KPC-carbapenemases could be used polymyxin B or tigecycline.

  15. Antibiotic resistance determinants of a group of multidrug-resistant Acinetobacter baumannii in China.

    Science.gov (United States)

    Xiao-Min, Xu; You-Fen, Fan; Wei-Yun, Feng; Zu-Huang, Mi; Xing-Bei, Weng

    2014-06-01

    A group of Acinetobacter baumannii confers multidrug resistance, but the molecular epidemiology and multidrug resistance mechanisms are poorly understood. Nineteen isolates were identified, and the antimicrobial susceptibility profile was determined using the disc diffusion method. Then, PCR of 78 kinds of resistance-associated genes were performed. A novel variant of blaADC gene: blaADC-67 gene (Genbank accession No. JX169789) was prevalent in all 19 isolates. Moreover, ISAba1 could also provide strong promoter to upregulate the expression of blaADC67 to confer resistance to beta-lactam. This is the first report of emergence of blaADC-67 in A. baumannii worldwide, which might confer resistance to beta-lactam.

  16. Predictive Value of Prior Colonization and Antibiotic Use for Third-Generation Cephalosporin-Resistant Enterobacteriaceae Bacteremia in Patients With Sepsis

    NARCIS (Netherlands)

    Rottier, Wouter C.; Bamberg, Yara R. P.; Dorigo-Zetsma, J. Wendelien; van der Linden, Paul D.; Ammerlaan, Heidi S. M.; Bonten, Marc J. M.

    2015-01-01

    Background. To prevent inappropriate empiric antibiotic treatment in patients with bacteremia caused by third-generation cephalosporin (3GC)-resistant Enterobacteriaceae (3GC-R EB), Dutch guidelines recommend beta-lactam and aminoglycoside combination therapy or carbapenem monotherapy in patients wi

  17. Antibodies against beta-lactamase can improve ceftazidime treatment of lung infection with beta-lactam-resistant Pseudomonas aeruginosa in a rat model of chronic lung infection

    DEFF Research Database (Denmark)

    Ciofu, Oana; Bagge, Niels; Høiby, Niels

    2002-01-01

    To test the hypothesis that antibodies against the chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) might act as beta-lactamase inhibitors in patients with cystic fibrosis and chronic lung infection with P. aeruginosa, we compared in a rat model of chronic lung infection...... the efficacy of treatment with ceftazidime in beta-lactamase-immunized (group I) and non-immunized (group II) rats. Chronic lung infection was established with alginate-embedded P. aeruginosa producing high amounts of beta-lactamase in 133 Lewis rats. Prior to infection, group I (66 rats) was immunized three...... times at 2-week intervals with purified beta-lactamase in incomplete Freund's adjuvant (IFA) and group II (67 rats) received IFA. Ceftazidime treatment was initiated after challenge and continued for 10 days, after which the rats were sacrificed and the lung bacteriology and pathology were analysed. Rat...

  18. Prolonged weightlessness affects promyelocytic multidrug resistance.

    Science.gov (United States)

    Piepmeier, E H; Kalns, J E; McIntyre, K M; Lewis, M L

    1997-12-15

    An immortalized promyelocytic cell line was studied to detect how doxorubicin uptake is affected by microgravity. The purpose of this experiment was to identify the effect that microgravity may have on multidrug resistance in leukocytes. HL60 cells and HL60 cells resistant to anthracycline (HL60/AR) were grown in RPMI and 10% FBS. Upon reaching orbit in the Space Shuttle Endeavour, the cells were robotically mixed with doxorubicin. Three days after mixing, cells were fixed with paraformaldehyde/glutaraldehyde. Ground control experiments were conducted concurrently using a robot identical to the one used on the Shuttle. Fixed cells were analyzed within 2 weeks of launch. Confocal micrographs identified changes in cell structure (transmittance), drug distribution (fluorescence), and microtubule polymerization (fluorescence). Flight cells showed a lack of cytoskeletal polymerization resulting in an overall amorphic globular shape. Doxorubicin distribution in ground cells included a large numbers of vesicles relative to flight cells. There was a greater amount of doxorubicin present in flight cells (85% +/- 9.7) than in ground control cells (43% +/- 26) as determined by image analysis. Differences in microtubule formation between flight cells and ground cells could be partially responsible for the differences in drug distribution. Cytoskeletal interactions are critical to the function of P-glycoprotein as a drug efflux pump responsible for multidrug resistance.

  19. [Comparative susceptibility of Ochrobactrum anthropi, Agrobacterium tumefaciens, Alcaligenes faecalis, Alcaligenes denitrificans subsp. denitrificans, Alcaligenes denitrificans subsp. xylosidans and Bordetella bronchiseptica against 35 antibiotics including 17 beta-lactams].

    Science.gov (United States)

    Bizet, C; Bizet, J

    1995-04-01

    Ochrobactrum anthropi, formerly known as "Achromobacter sp." or CDC group Vd has been isolated from water, hospital environment (antiseptic solutions, dialysis fluids ... ). O. anthropi is a Gram negative, motile, strictly aerobic, oxydase positive and non-fermentative bacteria with a strong urease activity. The susceptibility of 13 strains of O. anthropi was determined by agar diffusion method and compared to those of type strains of Agrobacterium tumefaciens, Alcaligenes faecalis, Alcaligenes denitrificans subsp. denitrificans, Alcaligenes denitrificans subsp. xylosoxydans and Bordetella bronchiseptica. The MICs of 20 antimicrobial agents confirmed the distinct phenotype susceptibility of O. anthropi. All the strains of O. anthropi are sensitive to imipenem, amikacin, gentamicin, netilmicin, nalidixic acid, pefloxacin, ciprofloxacin, tetracyclin, colistin, sulphonamides and rifampicin and resistant to ampicillin, amoxycillin + clavulanic acid, ticarcillin, mezlocillin, cefuroxime, cefamandol, cefoxitin, cefotaxime, cefoperazon, ceftazidime, cefsulodin, aztreonam, streptomycin, kanamycin, pipemidic acid, chloramphenicol, erythromicin, pristinamycin, trimethoprim and fosfomycin. O. anthropi is implicated in nosocomial infections. O. anthropi was the species with the greatest resistance to beta-lactamins.

  20. Relatively high antibiotic resistance among heterotrophic bacteria from arctic fjord sediments than water - Evidence towards better selection pressure in the fjord sediments

    Science.gov (United States)

    Hatha, A. A. Mohamed; Neethu, C. S.; Nikhil, S. M.; Rahiman, K. M. Mujeeb; Krishnan, K. P.; Saramma, A. V.

    2015-12-01

    The objective of this study was to determine the prevalence of antibiotic resistance among aerobic heterotrophic bacteria and coliform bacteria from water and sediment of Kongsfjord. The study was based on the assumption that arctic fjord environments are relatively pristine and offer very little selection pressure for drug resistant mutants. In order to test the hypothesis, 200 isolates belonging to aerobic heterotrophic bacteria and 114 isolates belonging to coliforms were tested against 15 antibiotics belonging to 5 different classes such as beta lactams, aminoglycosides, quinolones, sulpha drugs and tetracyclines. Resistance to beta lactam and extended spectrum beta lactam (ESBL) antibiotics was considerably high and they found to vary significantly (p antibiotic resistance against ESBL's extent and diversity of antibiotic resistance (as revealed by multiple antibiotic resistance index and resistance patterns), was high in the aerobic heterotrophic bacteria. Most striking observation was that isolates from fjord sediments (both heterotrophic bacteria and coliforms) in general showed relatively high prevalence of antibiotic resistance against most of the antibiotics tested, indicating to better selection pressure for drug resistance mutants in the fjord sediments.

  1. The role of outer membrane in Serratia marcescens intrinsic resistance to antibiotics.

    Science.gov (United States)

    Sánchez, L; Ruiz, N; Leranoz, S; Viñas, M; Puig, M

    1997-09-01

    Three different porins from Serratia marcescens were described. They were named Omp1, Omp2 and Omp3 and their molecular weights were 42, 40 and 39 kDa respectively. Omp2 and Omp3 showed osmoregulation and thermoregulation in a similar way to OmpC and OmpF of Escherichia coli. Permeability coefficients of the outer membrane of this species were calculated following the Zimmermann and Rosselet method. P values were similar to those obtained in Escherichia coli, which suggests that the chromosomal beta-lactamase would play a major role in the resistance of Serratia marcescens to beta-lactam antibiotics. Both MIC values and permeabilities were modified by salycilates and acetylsalycilate. Synergism between the outer membrane and the beta-lactamase was also evaluated. When bacteria grew in the presence of a beta-lactam in the medium, the beta-lactamase accounted for most of the resistance.

  2. Alergia a beta-lactâmicos na clínica pediátrica: uma abordagem prática Allergy to beta-lactams in pediatrics: a practical approach

    Directory of Open Access Journals (Sweden)

    Nelson A. Rosário

    2006-11-01

    Full Text Available OBJETIVO: Apresentar uma abordagem prática ao diagnóstico e conduta na alergia a antibióticos beta-lactâmicos. FONTES DOS DADOS: Periódicos da área de alergia indexados nas bases MEDLINE e LILACS, além de estudos e textos clássicos que tratam do tema. SÍNTESE DOS DADOS: A alergia à penicilina é relatada com freqüência, em muitos casos resultando na exclusão desse medicamento do arsenal terapêutico. Cerca de 10% dos relatos de alergia a drogas são confirmados. As manifestações clínicas decorrentes da reação alérgica à penicilina são bastante amplas, destacando-se os quadros cutâneos. Os quatro mecanismos de hipersensibilidade de Gell & Coombs estão envolvidos nas reações alérgicas. A penicilina é degradada em determinante maior (95% dos produtos e em determinantes menores (5% dos produtos. As reações imediatas, mediadas por IgE, e que determinam quadros de anafilaxia, estão relacionadas aos determinantes menores em 95% dos casos. A hipersensibilidade a esses produtos pode ser avaliada através de testes cutâneos realizados com os determinantes maior e menores, permitindo, assim, evitar o choque anafilático em indivíduos alérgicos. O texto ressalta conhecimentos básicos sobre a alergia à penicilina, propiciando um diagnóstico mais adequado desse evento e a conduta em casos de suspeita de alergia a beta-lactâmicos. CONCLUSÃO: O diagnóstico de alergia à penicilina tem sido feito de forma inadequada, resultando em sua exclusão do arsenal terapêutico. O melhor reconhecimento dessas condições permitirá o uso da penicilina com diminuição dos riscos decorrentes da hipersensibilidade.OBJECTIVE: To present a practical approach to the diagnosis and management of allergy to beta-lactam antibiotics. SOURCES: Allergy journals indexed in MEDLINE and LILACS, as well as seminal studies and texts. SUMMARY OF THE FINDINGS: Allergy to penicillin is commonly reported. In many cases, this results in the decision not

  3. Type 1 Ig-E mediated allergy to human insulin, insulin analogues and beta-lactam antibiotics Hipersensibilidade imediata a insulina humana, análogos de insulina e a antibióticos beta-lactâmicos

    Directory of Open Access Journals (Sweden)

    Pedro Andrade

    2012-12-01

    Full Text Available Insulin, a crucial therapeutic agent for diabetes mellitus, has been rarely associated with hypersensitivity events. We present a 69-year-old type-2 diabetic patient with urticariform lesions on the sites of subcutaneous injection of insulin. The patient denied any known allergies, except for an unspecific cutaneous reaction after intramuscular penicillin administration in childhood. Prick tests revealed positive reactions to all tested human insulins and insulin analogues. Serum IgE levels were above normal range and RAST tests were positive for human, bovine and porcine insulins, as well as beta-lactams. Type 1 IgEmediated allergy to insulin analogues demands a prompt diagnosis and represents a significant therapeutic challenge in diabetic patients.A insulina é um agente indispensável para o controlo da diabetes mellitus. Os efeitos adversos da sua administração, em particular fenómenos de hipersensibilidade, são raros. Apresentamos um doente de 69 anos, diabético do tipo 2, com episódios recorrentes de lesões urticariformes nos locais de administração subcutânea de insulina. Negava alergias medicamentosas, à excepção de reacção não especificada na infância após penicilina intramuscular. Foram realizados testes cutâneos por puntura (prick tests com diversos tipos de insulina humana e análogos, todos com reacções positivas, associando elevação dos níveis de IgE sérica e provas RAST positivas para as insulinas humana, bovina e porcina e para os antibióticos beta-lactâmicos. A alergia a análogos de insulina exige um diagnóstico precoce, originando um desafio terapêutico importante no doente diabético.

  4. 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.

  5. Methicillin-resistant Staphylococcus saprophyticus in Sweden carries various types of staphylococcal cassette chromosome mec (SCCmec).

    Science.gov (United States)

    Söderquist, B; Berglund, C

    2009-12-01

    Staphylococcus saprophyticus is a common cause of uncomplicated urinary tract infections and is usually susceptible to the antimicrobial agents used for their treatment. However, S. saprophyticus resistant to beta-lactam antibiotics and carrying mecA has been reported. Eight Swedish isolates of mecA-positive S. saprophyticus with diverse origin carrying at least three different types of staphylococcal cassette chromosome mec (SCCmec) are described here.

  6. The selection of suitable columns for a reversed-phase liquid chromatographic separation of beta-lactam antibiotics and related substances via chromatographic column parameters.

    Science.gov (United States)

    Zhang, Wei-qing; Hu, Qiu-xin; Zhang, Xia; Li, Ya-ping; Wang, Ming-juan; Hu, Chang-qin

    2014-01-01

    The selection of RP-LC columns suitable for a particular analysis in official compendia is difficult as only a general description of the stationary phase in the description of a LC method is given. General methods to characterize RP-LC columns often assume that each of the column parameters is equally important. This can cause the user to select columns inappropriate for particular analyses. This paper focuses on the relationship between the critical peak pairs and the column parameters (H, S, A, B, and C) in the Snyder/Dolan column characterization methodology to find the key parameters influencing real separations. Some varieties of β-lactam antibiotics and their related compounds were used as test compounds. We found column parameter A to be the most important factor affecting their separation. Parameters B and C also played an important role in some separation processes. This indicated that the hydrogen bonding of column and solute can directly affect the separation of β-lactam antibiotics. Choosing columns for which column parameter A is near 0.1 can facilitate the ideal separations of impurities from β-lactam antibiotics. The most suitable column for any common pharmaceutical analysis could be selected easily if the key column parameters would be given in the description of the chromatographic method. For these reasons, key column parameters should be listed in the monographs of official compendia.

  7. Antibiotic resistance of Escherichia coli in leachates from municipal solid waste landfills: comparison between semi-aerobic and anaerobic operations.

    Science.gov (United States)

    Threedeach, Simanata; Chiemchaisri, Wilai; Watanabe, Toru; Chiemchaisri, Chart; Honda, Ryo; Yamamoto, Kazuo

    2012-06-01

    A bacterial susceptibility test to 31 antibiotics was conducted on the 80 isolated Escherichia coli from the leachates of the landfills in two different operations: semi-aerobic (SL) and anaerobic (AL) landfills. The average population of E. coli from SL and AL leachates were 2.2 × 10(4) and 9.4 × 10(3)CFU/100ml, respectively. Between 80.8% and 87.5% of the E. coli isolated from both leachates as resistant to the tested antibiotics and high resistances were found to doxycycline (53.8-68.8%), cephalothin (57.5-61.3%), tetracycline (51.3-67.5%) and minocycline (37.5-46.3%). The percentages of isolates resistant to most antibiotics were higher in the AL leachate. The exception was nitrofurantoin to which the isolates from the SL were highly resistant. E. coli from both sources showed similarly high susceptibilities (90-100%) to aminoglycosides, quinolones, chloramphenicol, sulfonamide and some new beta-lactams. The difference in available oxygen in landfills could affect E. coli susceptibility to antibiotics in leachates.

  8. Does natural variation in diversity affect biotic resistance?

    Science.gov (United States)

    Harrison, Susan; Cornell, Howard; Grace, James B.

    2015-01-01

    Theories linking diversity to ecosystem function have been challenged by the widespread observation of more exotic species in more diverse native communities. Few studies have addressed the key underlying process by dissecting how community diversity is shaped by the same environmental gradients that determine biotic and abiotic resistance to new invaders. In grasslands on highly heterogeneous soils, we used addition of a recent invader, competitor removal and structural equation modelling (SEM) to analyse soil influences on community diversity, biotic and abiotic resistance and invader success. Biotic resistance, measured by reduction in invader success in the presence of the resident community, was negatively correlated with species richness and functional diversity. However, in the multivariate SEM framework, biotic resistance was independent of all forms of diversity and was positively affected by soil fertility via community biomass. Abiotic resistance, measured by invader success in the absence of the resident community, peaked on infertile soils with low biomass and high community diversity. Net invader success was determined by biotic resistance, consistent with this invader's better performance on infertile soils in unmanipulated conditions. Seed predation added slightly to biotic resistance without qualitatively changing the results. Soil-related genotypic variation in the invader also did not affect the results. Synthesis. In natural systems, diversity may be correlated with invasibility and yet have no effect on either biotic or abiotic resistance to invasion. More generally, the environmental causes of variation in diversity should not be overlooked when considering the potential functional consequences of diversity.

  9. Spontaneous nisin-resistant Listeria monocytogenes mutants with increased expression of a putative penicillin-binding protein and their sensitivity to various antibiotics.

    Science.gov (United States)

    Gravesen, A; Sørensen, K; Aarestrup, F M; Knøchel, S

    2001-01-01

    A concern regarding the use of bacteriocins, as for example the lantibiotic nisin, for biopreservation of certain food products is the possibility of resistance development and potential cross-resistance to antibiotics in the target organism. The genetic basis for nisin resistance development is as yet unknown. We analyzed changes in gene expression following nisin resistance development in Listeria monocytogenes 412 by restriction fragment differential display. The mutant had increased expression of a protein with strong homology to the glycosyltransferase domain of high-molecular-weight penicillin-binding proteins (PBPs), a histidine protein kinase, a protein of unknown function, and ClpB (putative functions from homology). The three former proteins had increased expression in a total of six out of 10 independent mutants originating from five different wild-type strains, indicating a prevalent nisin resistance mechanism under the employed isolation conditions. Increased expression of the putative PBP may affect the cell wall composition and thereby alter the sensitivity to cell wall-targeting compounds. The mutants had an isolate-specific increase in sensitivity to different beta-lactams and a slight decrease in sensitivity to another lantibiotic, mersacidin. A model incorporating these observations is proposed based on current knowledge of nisin's mode of action.

  10. Occurrence, species distribution, antimicrobial resistance and clonality of methicillin- and erythromycin-resistant staphylococci in the nasal cavity of domestic animals

    DEFF Research Database (Denmark)

    Bagcigil, Funda A.; Moodley, Arshnee; Baptiste, Keith E.

    2007-01-01

    beta-Lactams and macrolides are important antibiotics for treatment of staphylococcal infections in both humans and animals. The aim of the study was to investigate the occurrence, species distribution and clonality of methicillin and erythromycin-resistant staphylococci in the nasal cavity of dogs...... = 2). mecA-mediated methicillin resistance in S. vitulinus was described for the first time. Methicillin-resistant S. aureus was not detected. PFGE analysis revealed the presence of specific MRCoNS clones in samples originating from the same veterinary hospital or equine farm. Erythromycin-resistant S...

  11. Expression, purification, crystallization, and preliminary X-ray crystallographic analysis of OXA-17, an extended-spectrum {beta}-lactamase conferring severe antibiotic resistance

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. H., E-mail: msgjhlee@mju.ac.kr; Sohn, S. G., E-mail: sgsohn@mju.ac.kr; Jung, H. I., E-mail: jhinumber1@hanmail.net; An, Y. J., E-mail: anyj0120@hanmail.net; Lee, S. H., E-mail: sangheelee@mju.ac.kr [Myongji University, Drug Resistance Proteomics Laboratory, Department of Biological Sciences (Korea, Republic of)

    2013-07-15

    OXA-17, an extended-spectrum {beta}-lactamase (ESBL) conferring severe antibiotic resistance, hydrolytically inactivates {beta}-lactam antibiotics, inducing a lack of eradication of pathogenic bacteria by oxyimino {beta}-lactams and not helping hospital infection control. Thus, the enzyme is a potential target for developing antimicrobial agents against pathogens producing ESBLs. OXA-17 was purified and crystallized at 298 K. X-ray diffraction data from OXA-17 crystal have been collected to 1.85 A resolution using synchrotron radiation. The crystal of OXA-17 belongs to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 48.37, b = 101.12, and c = 126.07 A. Analysis of the packing density shows that the asymmetric unit probably contains two molecules with a solvent content of 54.6%.

  12. Vancomycin use in a hospital with high prevalence of Methicillin-Resistant Staphylococcus aureus: comparison with Hospital Infection Control Practices Advisory Committe Guidelines (HICPAC

    Directory of Open Access Journals (Sweden)

    Daniela Oliveira de Melo

    2007-02-01

    Full Text Available This study evaluates vancomycin prescribing patterns in a tertiary-care hospital, with high prevalence of methicillin-resistant Staphylococcus aureus, comparing with the guidelines proposed by the Hospital Infection Control Practices Advisory Committee. The study was conducted in a 930-bed tertiary-care hospital, during 40 days (March 10 to April 30, 2003. Data were collected of all patients given vancomycin, using a standardized chart-extraction form designed. Inappropriate use was subdivided in five categories: empiric therapy without risk factors; continued empiric use for presumed infections in patients whose cultures were negative for beta-lactam-resistant Gram-positive microorganisms; treatment of infections caused by beta-lactam-sensitive Gram-positive microorganisms, without allergy history to beta-lactam antimicrobials; treatment in response to a single blood culture positive for coagulase-negative staphylococcus, if other blood cultures taken during the same time frame were negative; systemic or local prophylaxis for infection or colonization of indwelling central or peripheral intravascular catheters. Of 132 orders, 126 (95.4% were considered to have been appropriate. Of these 126 prescriptions, 31 (24.6% were administered for treatment of proven Gram-positive infections (78.1% of those were MRSA, 1 (0.8% for beta-lactam allergy and 95 (75.4% for empiric treatment of suspected Gram-positive infections. The majority of the patients (88.6% have used antimicrobial recently (3 months. The mean pre-treatment hospitalization period was 14±15 days. Of the 132 treatments, 105 (79.5% were nosocomial infections. In the institution analyzed, the vancomycin use was considered conscientious. Reduction in use of glycopeptide may be obtained by adaptations the CDC criteria, or by improvement of diagnostic criteria.

  13. Antibiotic-resistant soil bacteria in transgenic plant fields.

    Science.gov (United States)

    Demanèche, Sandrine; Sanguin, Hervé; Poté, John; Navarro, Elisabeth; Bernillon, Dominique; Mavingui, Patrick; Wildi, Walter; Vogel, Timothy M; Simonet, Pascal

    2008-03-11

    Understanding the prevalence and polymorphism of antibiotic resistance genes in soil bacteria and their potential to be transferred horizontally is required to evaluate the likelihood and ecological (and possibly clinical) consequences of the transfer of these genes from transgenic plants to soil bacteria. In this study, we combined culture-dependent and -independent approaches to study the prevalence and diversity of bla genes in soil bacteria and the potential impact that a 10-successive-year culture of the transgenic Bt176 corn, which has a blaTEM marker gene, could have had on the soil bacterial community. The bla gene encoding resistance to ampicillin belongs to the beta-lactam antibiotic family, which is widely used in medicine but is readily compromised by bacterial antibiotic resistance. Our results indicate that soil bacteria are naturally resistant to a broad spectrum of beta-lactam antibiotics, including the third cephalosporin generation, which has a slightly stronger discriminating effect on soil isolates than other cephalosporins. These high resistance levels for a wide range of antibiotics are partly due to the polymorphism of bla genes, which occur frequently among soil bacteria. The blaTEM116 gene of the transgenic corn Bt176 investigated here is among those frequently found, thus reducing any risk of introducing a new bacterial resistance trait from the transgenic material. In addition, no significant differences were observed in bacterial antibiotic-resistance levels between transgenic and nontransgenic corn fields, although the bacterial populations were different.

  14. [Analysis on the sensitivity to beta-lactam antibiotics of respiratory-infectious isolates on the second survey on the sensitivity of isolates conducted by the Japanese Society of Chemotherapy in 2007--concerning the aspect of PK/PD break points].

    Science.gov (United States)

    Niki, Yoshihito; Kohno, Shigeru; Watanabe, Akira; Aoki, Nobuki

    2009-06-01

    Sensitivity to beta-lactam antibiotics of isolates clinically obtained from respiratory infection sites in adults on the second survey on sensitivity of isolates conducted by the Japanese Society of Chemotherapy in 2007 was investigated according to the classification of the "Guideline for treatment for adult nosocomial pneumonia in 2008". Among the primary antibacterial drugs for mild (A) and moderate (B) nosocomial pneumonia in adults, beta-lactam antibiotics; ceftriaxone (CTRX), sulbactam/ampicillin (SBT/ABPC), panipenem/betamipron (PAPM/BP), tazobactam/piperacillin (TAZ/PIPC), imipenem/cilastatin (IPM/CS), meropenem (MEPM), doripenem (DRPM), biapenem (BIPM) were studied to evaluate their clinical efficacy. The covering rate was analyzed using the minimal inhibitory concentration (MIC) and break point of pharmacokinetics/pharmacodynamics (PK/PD). Consequently, the results with methicillin-susceptible Staphylococcus aureus (MSSA), Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Klebsiella pneumoniae revealed the MIC90 of all antibacterial drugs to be at low levels, while almost 100% of isolates were within the range of PK/PD break points except BIPM and SBT/ABPC to H. influenzae, and SBT/ABPC to K. pneumoniae. However, the analysis of P. aeruginosa didn't reach 100% for the covering rates of isolates, indicating that these drugs did not have a complete inhibitory action to restrict bacterial proliferation. The analysis of all 5 carbapenem drugs showed superiority to TAZ/PIPC in MIC90 while covering rates of isolates at PK/PD break points showed inferiority to TAZ/PIPC. This tendency was found to be more significant in covering the rates of isolates on the regular dose with maximal bactericidal action and on the maximum dose. This is because the maximum dose approved in Japan is as low as half that in IPM/CS and 1/3 that in MEPM in Western countries.

  15. Frequent emergence and limited geographic dispersal of methicillin-resistant Staphylococcus aureus

    DEFF Research Database (Denmark)

    Nubel, U.; Roumagnac, P.; Feldkamp, M.;

    2008-01-01

    A small number of clonal lineages dominates the global population structure of methicillin-resistant Staphylococcus aureus (MRSA), resulting in the concept that MRSA has emerged on a few occasions after penicillinase-stable beta-lactam antibiotics were introduced to clinical practice, followed...... of mutational steps that define geographically associated clades. These clades are not concordant with previously described groupings based on staphylococcal protein A gene (spa) typing. By mapping the number of independent imports of the staphylococcal cassette chromosome methicillin-resistance island, we also...

  16. Outcome of infections due to pandrug-resistant (PDR Gram-negative bacteria

    Directory of Open Access Journals (Sweden)

    Bliziotis Ioannis A

    2005-04-01

    Full Text Available Abstract Background The increasing problem of infections due to multidrug-resistant Gram-negative bacteria has led to re-use of polymyxins in several countries. However, there are already clinical isolates of Gram-negative bacteria that are resistant to all available antibiotics, including polymyxins. Methods We present a case series of patients with infections due to pathogens resistant to all antimicrobial agents tested, including polymyxins. An isolate was defined as pandrug-resistant (PDR if it exhibited resistance to all 7 anti-pseudomonal antimicrobial agents, i.e. antipseudomonal penicillins, cephalosporins, carbapenems, monobactams, quinolones, aminoglycosides, and polymyxins. Results Clinical cure of the infection due to pandrug-resistant (PDR Gram-negative bacteria, namely Pseudomonas aeruginosa or Klebsiella pneumoniae was observed in 4 out of 6 patients with combination of colistin and beta lactam antibiotics. Conclusion Colistin, in combination with beta lactam antibiotics, may be a useful agent for the management of pandrug-resistant Gram-negative bacterial infections. The re-use of polymyxins, an old class of antibiotics, should be done with caution in an attempt to delay the rate of development of pandrug-resistant Gram-negative bacterial infections.

  17. Heavy metals in liquid pig manure in light of bacterial antimicrobial resistance

    Energy Technology Data Exchange (ETDEWEB)

    Hoelzel, Christina S., E-mail: Christina.Hoelzel@wzw.tum.de [Chair of Animal Hygiene, Technische Universitaet Muenchen, Weihenstephaner Berg 3, 85354 Freising (Germany); Mueller, Christa [Institute for Agroecology, Organic Farming and Soil Protection, Bavarian State Research Center for Agriculture (LfL), Lange Point 12, 85354 Freising (Germany); Harms, Katrin S. [Chair of Animal Hygiene, Technische Universitaet Muenchen, Weihenstephaner Berg 3, 85354 Freising (Germany); Mikolajewski, Sabine [Department for Quality Assurance and Analytics, Bavarian State Research Center for Agriculture (LfL), Lange Point 4, 85354 Freising (Germany); Schaefer, Stefanie; Schwaiger, Karin; Bauer, Johann [Chair of Animal Hygiene, Technische Universitaet Muenchen, Weihenstephaner Berg 3, 85354 Freising (Germany)

    2012-02-15

    Heavy metals are regularly found in liquid pig manure, and might interact with bacterial antimicrobial resistance. Concentrations of heavy metals were determined by atomic spectroscopic methods in 305 pig manure samples and were connected to the phenotypic resistance of Escherichia coli (n=613) against 29 antimicrobial drugs. Concentrations of heavy metals (/kg dry matter) were 0.08-5.30 mg cadmium, 1.1-32.0 mg chrome, 22.4-3387.6 mg copper, <2.0-26.7 mg lead, <0.01-0.11 mg mercury, 3.1-97.3 mg nickel and 93.0-8239.0 mg zinc. Associated with the detection of copper and zinc, resistance rates against {beta}-lactams were significantly elevated. By contrast, the presence of mercury was significantly associated with low antimicrobial resistance rates of Escherichia coli against {beta}-lactams, aminoglycosides and other antibiotics. Effects of subinhibitory concentrations of mercury on bacterial resistance against penicillins, cephalosporins, aminoglycosides and doxycycline were also demonstrated in a laboratory trial. Antimicrobial resistance in the porcine microflora might be increased by copper and zinc. By contrast, the occurrence of mercury in the environment might, due to co-toxicity, act counter-selective against antimicrobial resistant strains.

  18. Development of antibiotic resistance in Pseudomonas aeruginosa during two decades of antipseudomonal treatment at the Danish CF Center

    DEFF Research Database (Denmark)

    Ciofu, O; Giwercman, B; Pedersen, S S

    1994-01-01

    was found between the MIC and the number of antipseudomonal courses of antibiotics. The proportion of resistant in vivo selected P. aeruginosa strains, presumed to be stably derepressed producers of chromosomal beta-lactamase, also increased significantly during the period studied. Our results confirm...... that the beta-lactamase production is an important mechanism of antibiotic resistance in P. aeruginosa.......At the Danish CF Center patients with chronic Pseudomonas aeruginosa lung infection were treated 3-4 times a year (from 1976) with a 2-week intravenous antipseudomonal course which included preferentially an aminoglycoside and a beta-lactam antibiotic. We investigated the development of antibiotic...

  19. Exposure to co-amoxiclav as a risk factor for co-amoxiclav-resistant Escherichia coli urinary tract infection.

    Science.gov (United States)

    Leflon-Guibout, Véronique; Ternat, Géraldine; Heym, Beate; Nicolas-Chanoine, Marie-Hélène

    2002-02-01

    The objective of the study was to define whether individual exposure to co-amoxiclav is a risk factor for selecting co-amoxiclav-resistant Escherichia coli in vivo. One hundred and eight patients were included in our study as soon as they were found to have a urinary tract infection (UTI) due to E. coli. Stool probes were also undertaken for some of these patients. Co-amoxiclav administration in the month before diagnosing the UTI, and any treatment to cure the current UTI were recorded for all patients. When co-amoxiclav-resistant E. coli was detected in the stools after diagnosis of E. coli UTI, isolates were compared with urinary E. coli isolates in terms of clonal relatedness, beta-lactam susceptibility and mechanisms of beta-lactam resistance. The patients who had taken co-amoxiclav in the month before the reported E. coli UTI had a significantly higher risk of being infected with co-amoxiclav-resistant E. coli. Those patients treated with amoxicillin for a current infection were at greater risk of intestinal carriage of co-amoxiclav-resistant E. coli; those treated with co-amoxiclav had a greater risk of intestinal carriage of co-amoxiclav-resistant Gram-negative bacilli than patients treated with third-generation cephalosporins or fluoroquinolones. Hence, individual exposure to co-amoxiclav is a risk factor for UTIs caused by co-amoxiclav-resistant E. coli or for carrying co-amoxiclav-resistant Gram-negative bacilli in the digestive tract.

  20. An important site in PBP2x of penicillin-resistant clinical isolates of Streptococcus pneumoniae: mutational analysis of Thr338.

    Science.gov (United States)

    Zerfass, Ilka; Hakenbeck, Regine; Denapaite, Dalia

    2009-03-01

    Penicillin-binding protein 2x (PBP2x) of Streptococcus pneumoniae represents a primary resistance determinant for beta-lactams, and low-affinity PBP2x variants can easily be selected with cefotaxime. Penicillin-resistant clinical isolates of S. pneumoniae frequently contain in their mosaic PBP2x the mutation T338A adjacent to the active site S337, and T338P as well as T338G substitutions are also known. Site-directed mutagenesis has now documented that a single point mutation at position T338 confers selectable levels of beta-lactam resistance preferentially to oxacillin. Despite the moderate impact on beta-lactam susceptibility, the function of the PBP2x mutants appears to be impaired, as can be documented in the absence of a functional CiaRH regulatory system, resulting in growth defects and morphological changes. The combination of low-affinity PBP2x and PBP1a encoded by mosaic genes is known to result in high cefotaxime resistance. In contrast, introduction of a mosaic pbp1a into the PBP2x(T338G) mutant did not lead to increased resistance. However, the mosaic PBP1a gene apparently complemented the PBP2x(T338G) defect, since Cia mutant derivatives grew normally. The data support the view that PBP2x and PBP1a interact with each other on some level and that alterations of both PBPs in resistant clinical isolates have evolved to ensure cooperation between both proteins.

  1. Redeploying β-Lactam Antibiotics as a Novel Antivirulence Strategy for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections

    Energy Technology Data Exchange (ETDEWEB)

    Waters, Elaine M.; Rudkin, Justine K.; Coughlan, Simone; Clair, Geremy C.; Adkins, Joshua N.; Gore, Suzanna; Xia, Guoqing; Black, Nikki S.; Downing, Tim; O' Neill, Eoghan; Kadioglu, Aras; O' Gara, James P.

    2016-11-14

    Innovative approaches to the use of existing antibiotics is an important strategy in efforts to address the escalating antimicrobial resistance crisis. Here, the beta-lactam antibiotic oxacillin was shown to significantly attenuate the virulence of MRSA despite the pathogen being resistant to this drug. Oxacillin-mediated repression of the Agr quorum-sensing system and altered cell wall architecture, was associated with reduced cytolytic activity and increased susceptibility to host killing. These findings support the inclusion of -lactam antibiotics as an adjunctive anti-virulence therapy in the treatment of MRSA infections, with the potential to significantly improve patient outcomes in a safe, cost effective manner.

  2. [High level of aminoglycoside resistance among Enterococcus faecalis and Enterococcus faecium strains].

    Science.gov (United States)

    Kozuszko, Sylwia; Białucha, Agata; Bogiel, Tomasz; Gospodarek, Eugenia

    2011-01-01

    Enterococcus sp. strains are believed as important reason of serious nosocomial infections currently. These infections are cured by using combination of beta-lactams and aminoglycosides for their treatment. Enterococcus sp. resistant to high-level doses of aminoglycosides, beta-lactams and vancomycin are responsible for therapeutic failure. The aim of our study was to evaluate the incidence of isolation and susceptibility to antibiotics of HLAR Enterococcus sp. strains isolated between 2007 and 2010 from the patients of University Hospital No. 1 of dr A. Jurasz Collegium Medicum of L. Rydygier in Bydgoszcz Nicolaus Copernicus University in Toruń. Amongst 6137 Enterococcus sp. strains 1124 (18,3%) presented HLAR phenotype; 53,1% of them was identified as E. faecalis and 46,9% as E. faecium. The highest percentage of all examined strains was isolated from the patients of different surgery clinics, Intensive Care Units, and Pediatrics, Hematology and Oncology Clinic. HLAR and HLSR phenotypes were noted in E. faecalis, for 45,7% and 27,5% strains, in E. faecium - 29,8% and 9,5%, respectively. HLGR phenotype was presented twice more often in E. faecium than E. faecalis. Highest percentages of E. faecium resistant to glycopeptides and rifampicin were observed when compared with E. faecalis. The highest percentages of strains intermediate, resistant to vancomycin and resistant to glycopeptides were noted for E. faecium strains with phenotypes HLAR, HLGR and HLSR.

  3. Does the context of reinforcement affect resistance to change?

    Science.gov (United States)

    Nevin, J A; Grace, R C

    1999-04-01

    Eight pigeons were trained on multiple schedules of reinforcement where pairs of components alternated in blocks on different keys to define 2 local contexts. On 1 key, components arranged 160 and 40 reinforcers/hr; on the other, components arranged 40 and 10 reinforcers/hr. Response rates in the 40/hr component were higher in the latter pair. Within pairs, resistance to prefeeding and resistance to extinction were generally greater in the richer component. The two 40/hr components did not differ in resistance to prefeeding, but the 40/hr component that alternated with 10/hr was more resistant to extinction. This discrepancy was interpreted by an algebraic model relating response strength to component reinforcer rate, including generalization decrement. According to this model, strength is independent of context, consistent with research on schedule preference.

  4. Glyphosate resistance does not affect Palmer amaranth seedbank longevity

    Science.gov (United States)

    A greater understanding of the factors that regulate weed seed return to and persistence in the soil seedbank is needed for the management of difficult to control herbicide resistant weeds. Studies were conducted in Tifton, GA to evaluate the longevity of buried Palmer amaranth seeds and estimate t...

  5. Clinical Management of an Increasing Threat: Outpatient Urinary Tract Infections Due to Multidrug-Resistant Uropathogens.

    Science.gov (United States)

    Walker, Emily; Lyman, Alessandra; Gupta, Kalpana; Mahoney, Monica V; Snyder, Graham M; Hirsch, Elizabeth B

    2016-10-01

    Urinary tract infections (UTIs) are among the most commonly treated bacterial infections. Over the past decade, antimicrobial resistance has become an increasingly common factor in the management of outpatient UTIs. As treatment options for multidrug-resistant (MDR) uropathogens are limited, clinicians need to be aware of specific clinical and epidemiological risk factors for these infections. Based on available literature, the activity of fosfomycin and nitrofurantoin remain high for most cases of MDR Escherichia coli UTIs. Trimethoprim-sulfamethoxazole retains clinical efficacy, but resistance rates are increasing internationally. Beta-lactam agents have the highest rates of resistance and lowest rates of clinical success. Fluoroquinolones have high resistance rates among MDR uropathogens and are being strongly discouraged as first-line agents for UTIs. In addition to accounting for local resistance rates, consideration of patient risk factors for resistance and pharmacological principles will help guide optimal empiric treatment of outpatient UTIs.

  6. Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

    Science.gov (United States)

    Lehtinen, Sonja; Blanquart, François; Croucher, Nicholas J.; Turner, Paul; Lipsitch, Marc; Fraser, Christophe

    2017-01-01

    Understanding how changes in antibiotic consumption affect the prevalence of antibiotic resistance in bacterial pathogens is important for public health. In a number of bacterial species, including Streptococcus pneumoniae, the prevalence of resistance has remained relatively stable despite prolonged selection pressure from antibiotics. The evolutionary processes allowing the robust coexistence of antibiotic sensitive and resistant strains are not fully understood. While allelic diversity can be maintained at a locus by direct balancing selection, there is no evidence for such selection acting in the case of resistance. In this work, we propose a mechanism for maintaining coexistence at the resistance locus: linkage to a second locus that is under balancing selection and that modulates the fitness effect of resistance. We show that duration of carriage plays such a role, with long duration of carriage increasing the fitness advantage gained from resistance. We therefore predict that resistance will be more common in strains with a long duration of carriage and that mechanisms maintaining diversity in duration of carriage will also maintain diversity in antibiotic resistance. We test these predictions in S. pneumoniae and find that the duration of carriage of a serotype is indeed positively correlated with the prevalence of resistance in that serotype. These findings suggest heterogeneity in duration of carriage is a partial explanation for the coexistence of sensitive and resistant strains and that factors determining bacterial duration of carriage will also affect the prevalence of resistance. PMID:28096340

  7. Multiple Breed Validation of Five QTL Affecting Mastitis Resistance

    DEFF Research Database (Denmark)

    Vilkki, Johanna; Dolezal, Marlies A; Sahana, Goutam

    the estimated effect: creating stop gain/loss, affecting splice site or RNA structure (RNAsnp), predicted disruptiveness (SIFT), occurring in miRNA or miRNA target site, or in UTR or ncSNP overlapping with a GERP element. Their effects on mastitis traits were estimated in new validation samples from Finnish...

  8. Multidrug resistance and ESBL-producing Salmonella spp. isolated from broiler processing plants.

    Science.gov (United States)

    Ziech, Rosangela Estel; Lampugnani, Camila; Perin, Ana Paula; Sereno, Mallu Jagnow; Sfaciotte, Ricardo Antônio Pilegi; Viana, Cibeli; Soares, Vanessa Mendonça; Pinto, José Paes de Almeida Nogueira; Bersot, Luciano dos Santos

    2016-01-01

    The aim of this study was to investigate the occurrence of multidrug-resistant, extended spectrum beta-lactamase (ESBL) producing Salmonella spp. isolated from conveyor belts of broiler cutting rooms in Brazilian broiler processing plants. Ninety-eight strains of Salmonella spp. were analyzed. Multidrug resistance was determined by the disk diffusion test and the susceptibility of the isolated bacteria was evaluated against 18 antimicrobials from seven different classes. The double disk diffusion test was used to evaluate ESBL production. Of the 98 strains tested, 84 were multidrug resistant. The highest rates of resistance were against nalidixic acid (95%), tetracycline (91%), and the beta-lactams: ampicillin and cefachlor (45%), followed by streptomycin and gentamicin with 19% and 15% of strain resistance, respectively. By contrast, 97% of the strains were sensitive to chloramphenicol. 45% of the strains were positive for the presence of ESBL activity. In this study, high rates of multidrug resistance and ESBL production were observed in Salmonella spp.

  9. Diverse and abundant multi-drug resistant E. coli in Matang mangrove estuaries, Malaysia.

    Science.gov (United States)

    Ghaderpour, Aziz; Ho, Wing Sze; Chew, Li-Lee; Bong, Chui Wei; Chong, Ving Ching; Thong, Kwai-Lin; Chai, Lay Ching

    2015-01-01

    E.coli, an important vector distributing antimicrobial resistance in the environment, was found to be multi-drug resistant, abundant, and genetically diverse in the Matang mangrove estuaries, Malaysia. One-third (34%) of the estuarine E. coli was multi-drug resistant. The highest antibiotic resistance prevalence was observed for aminoglycosides (83%) and beta-lactams (37%). Phylogenetic groups A and B1, being the most predominant E. coli, demonstrated the highest antibiotic resistant level and prevalence of integrons (integron I, 21%; integron II, 3%). Detection of phylogenetic group B23 downstream of fishing villages indicates human fecal contamination as a source of E. coli pollution. Enteroaggregative E. coli (1%) were also detected immediately downstream of the fishing village. The results indicated multi-drug resistance among E. coli circulating in Matang estuaries, which could be reflective of anthropogenic activities and aggravated by bacterial and antibiotic discharges from village lack of a sewerage system, aquaculture farms and upstream animal husbandry.

  10. Transfer of penicillin resistance from Streptococcus oralis to Streptococcus pneumoniae identifies murE as resistance determinant.

    Science.gov (United States)

    Todorova, Katya; Maurer, Patrick; Rieger, Martin; Becker, Tina; Bui, Nhat Khai; Gray, Joe; Vollmer, Waldemar; Hakenbeck, Regine

    2015-09-01

    Beta-lactam resistant clinical isolates of Streptococcus pneumoniae contain altered penicillin-binding protein (PBP) genes and occasionally an altered murM, presumably products of interspecies gene transfer. MurM and MurN are responsible for the synthesis of branched lipid II, substrate for the PBP catalyzed transpeptidation reaction. Here we used the high-level beta-lactam resistant S. oralis Uo5 as donor in transformation experiments with the sensitive laboratory strain S. pneumoniae R6 as recipient. Surprisingly, piperacillin-resistant transformants contained no alterations in PBP genes but carried murEUo5 encoding the UDP-N-acetylmuramyl tripeptide synthetase. Codons 83-183 of murEUo5 were sufficient to confer the resistance phenotype. Moreover, the promoter of murEUo5 , which drives a twofold higher expression compared to that of S. pneumoniae R6, could also confer increased resistance. Multiple independent transformations produced S. pneumoniae R6 derivatives containing murEUo5 , pbp2xUo5 , pbp1aUo5 and pbp2bUo5 , but not murMUo5 sequences; however, the resistance level of the donor strain could not be reached. S. oralis Uo5 harbors an unusual murM, and murN is absent. Accordingly, the peptidoglycan of S. oralis Uo5 contained interpeptide bridges with one L-Ala residue only. The data suggest that resistance in S. oralis Uo5 is based on a complex interplay of distinct PBPs and other enzymes involved in peptidoglycan biosynthesis.

  11. Glyphosate affects seed composition in glyphosate-resistant soybean.

    Science.gov (United States)

    Zobiole, Luiz H S; Oliveira, Rubem S; Visentainer, Jesui V; Kremer, Robert J; Bellaloui, Nacer; Yamada, Tsuioshi

    2010-04-14

    The cultivation of glyphosate-resistant (GR) soybeans has continuously increased worldwide in recent years mainly due to the importance of glyphosate in current weed management systems. However, not much has been done to understand eventual effects of glyphosate application on GR soybean physiology, especially those related to seed composition with potential effects on human health. Two experiments were conducted to evaluate the effects of glyphosate application on GR soybeans compared with its near-isogenic non-GR parental lines. Results of the first experiment showed that glyphosate application resulted in significant decreases in shoot nutrient concentrations, photosynthetic parameters, and biomass production. Similar trends were observed for the second experiment, although glyphosate application significantly altered seed nutrient concentrations and polyunsaturated fatty acid percentages. Glyphosate resulted in significant decreases in polyunsaturated linoleic acid (18:2n-6) (2.3% decrease) and linolenic acid (18:3n-3) (9.6% decrease) and a significant increase in monounsaturated fatty acids 17:1n-7 (30.3% increase) and 18:1n-7 (25% increase). The combined observations of decreased photosynthetic parameters and low nutrient availability in glyphosate-treated plants may explain potential adverse effects of glyphosate in GR soybeans.

  12. Molecular epidemiology and antimicrobial resistance of methicillin-resistant Staphylococcus aureus bloodstream isolates in Taiwan, 2010.

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    Chih-Jung Chen

    Full Text Available The information of molecular characteristics and antimicrobial susceptibility pattern of methicillin-resistant Staphylococcus aureus (MRSA is essential for control and treatment of diseases caused by this medically important pathogen. A total of 577 clinical MRSA bloodstream isolates from six major hospitals in Taiwan were determined for molecular types, carriage of Panton-Valentine leukocidin (PVL and sasX genes and susceptibilities to 9 non-beta-lactam antimicrobial agents. A total of 17 genotypes were identified in 577 strains by pulsotyping. Five major pulsotypes, which included type A (26.2%, belonging to sequence type (ST 239, carrying type III staphylococcal chromosomal cassette mec (SCCmec, type F (18.9%, ST5-SCCmecII, type C (18.5%, ST59-SCCmecIV, type B (12.0%, ST239-SCCmecIII and type D (10.9%, ST59-SCCmecVT/IV, prevailed in each of the six sampled hospitals. PVL and sasX genes were respectively carried by ST59-type D strains and ST239 strains with high frequencies (93.7% and 99.1%, respectively but rarely detected in strains of other genotypes. Isolates of different genotypes and from different hospitals exhibited distinct antibiograms. Multi-resistance to ≥3 non-beta-lactams was more common in ST239 isolates (100% than in ST5 isolates (97.2%, P = 0.0347 and ST59 isolates (8.2%, P<0.0001. Multivariate analysis further indicated that the genotype, but not the hospital, was an independent factor associated with muti-resistance of the MRSA strains. In conclusion, five common MRSA clones with distinct antibiograms prevailed in the major hospitals in Taiwan in 2010. The antimicrobial susceptibility pattern of invasive MRSA was mainly determined by the clonal distribution.

  13. Overview of the epidemiology and the threat of Klebsiella pneumoniae carbapenemases (KPC resistance

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    Chen LF

    2012-09-01

    Full Text Available Luke F Chen,1–4 Deverick J Anderson,1–4 David L Paterson51Duke Program for Infection Prevention and Healthcare Epidemiology, 2Duke Infection Control Outreach Network, 3Duke University Prevention Epicenter Program, 4Division of Infectious Diseases and International Health, Department of Medicine, Duke University Medical Center, Durham, NC, USA; 5University of Queensland Centre for Clinical Research (UQCCR, Royal Brisbane and Women's Hospital Campus, Brisbane, AustraliaAbstract: Klebsiella pneumoniae carbapenemases (KPCs confer resistance to nearly all ß-lactams. This broad-spectrum drug resistance mechanism has rapidly spread in the United States and is reportedly increasing elsewhere in the world. Thus, the emergence of KPC resistance is a major threat to global health. This article reviews the epidemiology and provides an overview of the dissemination of KPC-producing organisms.Keywords: beta-lactam resistance, carbapenemase, drug resistance, epidemiology, treatment failure

  14. Community-acquired methicillin-resistant Staphylococcus aureus in Central Australia.

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    Stevens, Claire L; Ralph, Anna; McLeod, James E T; McDonald, Malcolm I

    2006-01-01

    To date, there has been scant information about the burden of methicillin-resistant Staphylococcus aureus infections in Central Australia. Our aims were to determine the proportion of Staphylococcus aureus infections due to methicillin-resistant strains in Central Australia, to characterise resistance to non-beta lactam antibiotics and to correlate findings with available demographic information. We retrospectively reviewed S. aureus isolates identified by the Microbiology Laboratory of the Pathology Department, Alice Springs Hospital between September 2005 and February 2006. Multi-resistance was defined as resistance to three or more non-beta lactam antibiotics. We identified the recovery site and extended antibiotic resistance profile of each isolate. Demographic data included place of residence, discharge diagnosis and ethnicity. There were 524 S. aureus isolates: 417 (79.6%) methicillin-sensitive S. aureus, 104 (19.7%) non-multi-resistant MRSA (nmrMRSA) and 3 (0.7%) multi-resistant MRSA (mrMRSA). MRSA accounted for 7/22 (32%) invasive infections and 91/474 (19.2%) cases of staphylococcal skin infections. Aboriginal people comprised 89 per cent (93/104) of patients with nmrMRSA; 57 per cent lived in remote communities, 21 per cent in suburban Alice Springs, and 18 per cent in Alice Springs Town Camps. Six per cent (6/104) of nmrMRSA were hospital-acquired. Of the nmrMRSA isolates, 57 per cent (59/104) were resistant to erythromycin and 7 per cent (7/104) to fusidic acid. All MRSA isolates were susceptible to co-trimoxazole. In conclusion, Central Australia has high rates of community-acquired nmrMRSA and low rates of multi-resistant MRSA. Erythromycin resistance in S. aureus is also common. These findings should prompt the review of antimicrobial prescribing guidelines for the region, especially for treatment of skin and soft tissue infections.

  15. Impetigo update: new challenges in the era of methicillin resistance.

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    Geria, Aanand N; Schwartz, Robert A

    2010-02-01

    Impetigo is a bacterial infection of the superficial epidermis most commonly seen in infants and children. It is clinically characterized by crusted erosions or ulcers that may arise as a primary infection in which bacterial invasion occurs through minor breaks in the cutaneous surface or a secondary infection of a preexisting dermatosis or infestation. Impetigo occurs in 2 forms: bullous and nonbullous. Staphylococcus aureus currently is the most common overall cause of impetigo, but Streptococcus pyogenes remains an important cause in developing nations. Community-acquired methicillin-resistant S aureus (CA-MRSA) poses a challenge because of its enhanced virulence and increasing prevalence in children. For limited uncomplicated impetigo, either topical mupirocin or fusidic acid is as effective if not more effective than systemic antibiotics. For extensive or complicated impetigo, systemic antibiotics may be warranted, but beta-lactam antibiotics should be avoided if methicillin-resistant S aureus (MRSA) is suspected.

  16. Antimicrobial susceptibility and macrolide resistance genes in Streptococcus pyogenes collected in Austria and Hungary.

    Science.gov (United States)

    Gattringer, Rainer; Sauermann, Robert; Lagler, Heimo; Stich, Karin; Buxbaum, Astrid; Graninger, Wolfgang; Georgopoulos, Apostolos

    2004-09-01

    A total of 341 clinical isolates of Streptococcus pyogenes from Vienna, Austria and three Hungarian cities were tested for susceptibility to four macrolides and 12 other antibiotics. All isolates were fully susceptible to penicillin and the other beta-lactams tested. A high level of tetracycline resistance was found in Austria (26.7%) and in Hungary (30.5%). The rate of resistance to erythromycin, clarithromycin and azithromycin was 4.7% in Vienna and 3.7% in the Hungarian communities. In both countries, the MIC(90) values of erythromycin and clarithromycin were 0.12 mg/L and the MIC(90) of josamycin was 0.5mg/L. The M phenotype of resistance conferred by the mefA genes was predominant (n = 9) among the macrolide-resistant isolates (n = 14).

  17. Surveillance and Detection of Inhibitor-Resistant Beta-Lactamases in Clinical Isolates of Escherichia coli

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    Carl Urban

    2007-06-01

    Full Text Available In recent years, resistance to beta-lactam antibiotics, such as the widely-used cephalosporins and penicillins, has become a major challenge for disease therapy, particularly in common hospital-acquired infections. In the search for the mechanisms behind this increasingly prevalent form of resistance, microbiologists have identified a new type of beta-lactamase enzyme, called inhibitor-resistant TEMs (IRTs, which can withstand the effects of beta-lactamase inhibitor compounds, further reducing the arsenal of drugs available to physicians facing resistant bacteria. In this study, we examined the enzymatic and genetic basis of Escherichia coli isolates demonstrating such resistance to beta-lactam/beta-lactamase inhibitor combinations. Susceptibility trials played a major role in composing the experimental cohort for this project (n=50; each isolate was thoroughly tested to ensure that it was resistant to ampicillin-sulbactam, an inhibitor combination, but susceptible to the third-generation cephalosporin ceftazidime. Subsequently, a number of samples were subjected to assay by pulsed-field gel electrophoresis (n=18 and polymerase chain reaction (n=3 so that their genetic composition and relatedness might be known. In particular, the presence of genes coding for TEM-type beta-lactamases was investigated for each of the 3 isolates sequenced. Even though it was anticipated that the isolates would possess resistance to inhibitor combinations due to an IRT gene, this was not found to be the case. Instead, the mechanism of resistance turned out to be over-expression of a gene coding for a normal TEM enzyme. The results of these experiments have implications for ensuring successful therapy of bacterial infections and for preventing the spread of antimicrobial resistance.

  18. Autophagy deficiency promotes beta-lactam production in Penicillium chrysogenum.

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    Bartoszewska, Magdalena; Kiel, Jan A K W; Bovenberg, Roel A L; Veenhuis, Marten; van der Klei, Ida J

    2011-02-01

    We have investigated the significance of autophagy in the production of the β-lactam antibiotic penicillin (PEN) by the filamentous fungus Penicillium chrysogenum. In this fungus PEN production is compartmentalized in the cytosol and in peroxisomes. We demonstrate that under PEN-producing conditions significant amounts of cytosolic and peroxisomal proteins are degraded via autophagy. Morphological analysis, based on electron and fluorescence microscopy, revealed that this phenomenon might contribute to progressive deterioration of late subapical cells. We show that deletion of the P. chrysogenum ortholog of Saccharomyces cerevisiae serine-threonine kinase atg1 results in impairment of autophagy. In P. chrysogenum atg1 cells, a distinct delay in cell degeneration is observed relative to wild-type cells. This phenomenon is associated with an increase in the enzyme levels of the PEN biosynthetic pathway and enhanced production levels of this antibacterial compound.

  19. Selective spectrophotometric determination of phenolic beta-lactam antibiotics.

    Science.gov (United States)

    Salem, Hesham; Saleh, Gamal A

    2002-06-15

    Two simple and selective spectrophotometric methods were developed for the quantitative determination of cefoperazone sodium, cefadroxil monohydrate, cefprozil anhydrous and amoxicillin trihydrate in pure forms as well as in their pharmaceutical formulations. The methods are based on the selective oxidation of these drugs with either Ce (IV) or Fe (III) in acid medium to give an intense yellow coloured product (lambda(max)=397 nm). The reaction conditions were studied and optimized. Beer's plots were obeyed in a general concentration range of 5-30 microg ml(-1) with correlation coefficients not less than 0.9979 for the four drugs with the two reagents. The methods are successfully applied to the analysis of pharmaceutical formulations containing amoxicillin, either alone or in combination with potassium clavulanate, flucloxacillin or dicloxacillin. They were also applied to the analysis of the other three studied drugs in vials, capsules, tablets and suspensions with good recovery; percent ranged from 99.7 (+/-0.46) to 100.32 (+/-1.05) in the Ce (IV) method and 99.6 (+/-0.50) to 100.3 (+/-1.32) in the Fe (III) method. Interferences from other antibiotics and additives products were investigated.

  20. Process models for production of beta-lactam antibiotics.

    Science.gov (United States)

    Bellgardt, K H

    1998-01-01

    Great progress has been made in the modelling of biotechnical processes using filamentous microorganisms. This paper deals with cultivations of Penicillium chrysogenum for the production of Penicillin and of Acremonium chrysogenum for the production of Cephalosporin C. The properties of the processes and the existing models are reviewed. Models are presented for both processes that consider aspects which are important for industrial cultivation. The process model for Penicillin production is based on a detailed morphological description of growth of hyphal filaments and pellets. The model allows for simulation of the production process including the preculture and considering the inhomogenous pellet population. It opens new possibilities for understanding the complex kinetics of the process and improvement of its control. The structured segregated model for Cephalosporin C production considers soy oil as second carbon source besides sugar. The application of the model for dynamic optimization of feeding strategies by Iterative Dynamic Programming is demonstrated. As an alternative approach, modelling of the Cephalosporin production by an artificial neural network is discussed.

  1. Antibiotic Resistance Pattern of Extended-Spectrum Beta-Lactamases-Producing Klebsiella pneumoniae Clinical Isolates from Zahedan, Southeast Iran

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    Shahram Shahraki-Zahedani

    2016-10-01

    Full Text Available Background Resistance to various classes of antibiotics is common among extended-spectrum beta-lactamases (ESBLs-producing bacteria. Objectives To determine the antibiotic resistance pattern of ESBLs-producing K. pneumoniae clinical isolates from Zahedan. Methods In this sectional-descriptive study, susceptibility of 51 ESBLs-producing K. pneumoniae isolates to 18 antimicrobial agents was determined. Results All isolates were resistant to cefotaxime, cefpodoxime and amoxicillin as well as susceptible to colistin sulfate. Also, most isolates were resistant to trimethoprim/sulfamethoxazole and aztreonam. Conclusions Our findings demonstrated that the rate of resistance to beta-lactams, sulfonamides, tetracyclines, aminoglycosides and fluoroquinolones in ESBLs-producing K. pneumoniae isolates is high in Zahedan.

  2. The drinking water treatment process as a potential source of affecting the bacterial antibiotic resistance.

    Science.gov (United States)

    Bai, Xiaohui; Ma, Xiaolin; Xu, Fengming; Li, Jing; Zhang, Hang; Xiao, Xiang

    2015-11-15

    Two waterworks, with source water derived from the Huangpu or Yangtze River in Shanghai, were investigated, and the effluents were plate-screened for antibiotic-resistant bacteria (ARB) using five antibiotics: ampicillin (AMP), kanamycin (KAN), rifampicin (RFP), chloramphenicol (CM) and streptomycin (STR). The influence of water treatment procedures on the bacterial antibiotic resistance rate and the changes that bacteria underwent when exposed to the five antibiotics at concentration levels ranging from 1 to 100 μg/mL were studied. Multi-drug resistance was also analyzed using drug sensitivity tests. The results indicated that bacteria derived from water treatment plant effluent that used the Huangpu River rather than the Yangtze River as source water exhibited higher antibiotic resistance rates against AMP, STR, RFP and CM but lower antibiotic resistance rates against KAN. When the antibiotic concentration levels ranged from 1 to 10 μg/mL, the antibiotic resistance rates of the bacteria in the water increased as water treatment progressed. Biological activated carbon (BAC) filtration played a key role in increasing the antibiotic resistance rate of bacteria. Chloramine disinfection can enhance antibiotic resistance. Among the isolated ARB, 75% were resistant to multiple antibiotics. Ozone oxidation, BAC filtration and chloramine disinfection can greatly affect the relative abundance of bacteria in the community.

  3. A Cmv2 QTL on chromosome X affects MCMV resistance in New Zealand male mice.

    Science.gov (United States)

    Rodriguez, Marisela R; Lundgren, Alyssa; Sabastian, Pearl; Li, Qian; Churchill, Gary; Brown, Michael G

    2009-07-01

    NK cell-mediated resistance to viruses is subject to genetic control in humans and mice. Here we used classical and quantitative genetic strategies to examine NK-mediated murine cytomegalovirus (MCMV) control in genealogically related New Zealand white (NZW) and black (NZB) mice. NZW mice display NK cell-dependent MCMV resistance while NZB NK cells fail to limit viral replication after infection. Unlike Ly49H(+) NK resistance in C57BL/6 mice, NZW NK-mediated MCMV control was Ly49H-independent. Instead, MCMV resistance in NZW (Cmv2) involves multiple genetic factors. To establish the genetic basis of Cmv2 resistance, we further characterized a major chromosome X-linked resistance locus (DXMit216) responsible for innate MCMV control in NZW x NZB crosses. We found that the DXMit216 locus affects early MCMV control in New Zealand F(2) crosses and demonstrate that the NZB-derived DXMit216 allele enhances viral resistance in F(2) males. The evolutionary conservation of the DXMit216 region in mice and humans suggests that a Cmv2-related mechanism may affect human antiviral responses.

  4. Biofilm formation and antibiotic resistance in Salmonella Typhimurium are affected by different ribonucleases.

    Science.gov (United States)

    Saramago, Margarida; Domingues, Susana; Viegas, Sandra Cristina; Arraiano, Cecília Maria

    2014-01-01

    Biofilm formation and antibiotic resistance are important determinants for bacterial pathogenicity. Ribonucleases control RNA degradation and there is increasing evidence that they have an important role in virulence mechanisms. In this report, we show that ribonucleases affect susceptibility against ribosome-targeting antibiotics and biofilm formation in Salmonella.

  5. Diversity, Distribution and Quantification of Antibiotic Resistance Genes in Goat and Lamb Slaughterhouse Surfaces and Meat Products

    Science.gov (United States)

    Lavilla Lerma, Leyre; Benomar, Nabil; Knapp, Charles W.; Correa Galeote, David; Gálvez, Antonio; Abriouel, Hikmate

    2014-01-01

    The distribution and quantification of tetracycline, sulfonamide and beta-lactam resistance genes were assessed in slaughterhouse zones throughout meat chain production and the meat products; this study represents the first to report quantitatively monitor antibiotic resistance genes (ARG) in goat and lamb slaughterhouse using a culture independent approach, since most studies focused on individual bacterial species and their specific resistance types. Quantitative PCR (qPCR) revealed a high prevalence of tetracycline resistance genes tetA and tetB in almost all slaughterhouse zones. Sulfonamide resistance genes were largely distributed, while beta-lactam resistance genes were less predominant. Statistical analysis revealed that resistant bacteria, in most cases, were spread by the same route in almost all slaughterhouse zones, except for tetB, blaCTX and blaTEM genes, which occurred in few zones as isolated ‘hot spots.’ The sum of all analyzed ARG indicated that slaughterhouse surfaces and end products act as reservoirs of ARG, mainly tet genes, which were more prevalent in slaughtering room (SR), cutting room (CR) and commercial meat products (MP). Resistance gene patterns suggest they were disseminated throughout slaughterhouse zones being also detected in commercial meat products, with significant correlations between different sampling zones/end products and total resistance in SR, CR and white room (WR) zones, and also refrigerator 4 (F4) and MP were observed. Strategically controlling key zones in slaughterhouse (SR, CR and WR) by adequate disinfection methods could strategically reduce the risks of ARG transmission and minimize the issues of food safety and environment contamination. PMID:25479100

  6. Diversity, distribution and quantification of antibiotic resistance genes in goat and lamb slaughterhouse surfaces and meat products.

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    Leyre Lavilla Lerma

    Full Text Available The distribution and quantification of tetracycline, sulfonamide and beta-lactam resistance genes were assessed in slaughterhouse zones throughout meat chain production and the meat products; this study represents the first to report quantitatively monitor antibiotic resistance genes (ARG in goat and lamb slaughterhouse using a culture independent approach, since most studies focused on individual bacterial species and their specific resistance types. Quantitative PCR (qPCR revealed a high prevalence of tetracycline resistance genes tetA and tetB in almost all slaughterhouse zones. Sulfonamide resistance genes were largely distributed, while beta-lactam resistance genes were less predominant. Statistical analysis revealed that resistant bacteria, in most cases, were spread by the same route in almost all slaughterhouse zones, except for tetB, blaCTX and blaTEM genes, which occurred in few zones as isolated 'hot spots.' The sum of all analyzed ARG indicated that slaughterhouse surfaces and end products act as reservoirs of ARG, mainly tet genes, which were more prevalent in slaughtering room (SR, cutting room (CR and commercial meat products (MP. Resistance gene patterns suggest they were disseminated throughout slaughterhouse zones being also detected in commercial meat products, with significant correlations between different sampling zones/end products and total resistance in SR, CR and white room (WR zones, and also refrigerator 4 (F4 and MP were observed. Strategically controlling key zones in slaughterhouse (SR, CR and WR by adequate disinfection methods could strategically reduce the risks of ARG transmission and minimize the issues of food safety and environment contamination.

  7. The factors affecting improvement sensitivity, CDU, and resolution in EUV resist

    Science.gov (United States)

    Han, Joonhee; Lim, Hyun Soon; Kim, Jin Ho; Choi, Sumi; Shin, Jin Bong; Bae, Chang Wan; Yoo, In Young; Shin, Bong Ha; Lee, Eun Kyo; Joo, Hyun Sang; Seo, Dong Chul; Chun, Jun Sung

    2014-04-01

    The minimum target specificatons of EUV resist material are the resolution CDU CDU). Thus, we have studied that which factors such as acid diffusion, solvents, polymer platform and film density etc are affecting to improve CDU, sensitivity and resolution. Especially, CDU and sensitivity are the main issues among above these performances. With the results of these experiments, we could determine polymer blend PAG as polymer platform for EUV resist material. We have also researched polymer to improve the sensitivity and CDU with variation of molecular weight, poly dispersity and monomer feed ratio. Additionally, we have studied the effects of resist solvents and film density. And we have measured the outgas of our EUV resist. In this paper, we will discuss the results of these studies obtained by EUV tools of SEMATECH.

  8. Longitudinal nasopharyngeal carriage and antibiotic resistance of respiratory bacteria in indigenous Australian and Alaska native children with bronchiectasis.

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    Kim M Hare

    Full Text Available BACKGROUND: Indigenous children in Australia and Alaska have very high rates of chronic suppurative lung disease (CSLD/bronchiectasis. Antibiotics, including frequent or long-term azithromycin in Australia and short-term beta-lactam therapy in both countries, are often prescribed to treat these patients. In the Bronchiectasis Observational Study we examined over several years the nasopharyngeal carriage and antibiotic resistance of respiratory bacteria in these two PCV7-vaccinated populations. METHODS: Indigenous children aged 0.5-8.9 years with CSLD/bronchiectasis from remote Australia (n = 79 and Alaska (n = 41 were enrolled in a prospective cohort study during 2004-8. At scheduled study visits until 2010 antibiotic use in the preceding 2-weeks was recorded and nasopharyngeal swabs collected for culture and antimicrobial susceptibility testing. Analysis of respiratory bacterial carriage and antibiotic resistance was by baseline and final swabs, and total swabs by year. RESULTS: Streptococcus pneumoniae carriage changed little over time. In contrast, carriage of Haemophilus influenzae declined and Staphylococcus aureus increased (from 0% in 2005-6 to 23% in 2010 in Alaskan children; these changes were associated with increasing age. Moraxella catarrhalis carriage declined significantly in Australian, but not Alaskan, children (from 64% in 2004-6 to 11% in 2010. While beta-lactam antibiotic use was similar in the two cohorts, Australian children received more azithromycin. Macrolide resistance was significantly higher in Australian compared to Alaskan children, while H. influenzae beta-lactam resistance was higher in Alaskan children. Azithromycin use coincided significantly with reduced carriage of S. pneumoniae, H. influenzae and M. catarrhalis, but increased carriage of S. aureus and macrolide-resistant strains of S. pneumoniae and S. aureus (proportion of carriers and all swabs, in a 'cumulative dose-response' relationship

  9. Ketamine-induced affective switch in a patient with treatment-resistant depression

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    Girish Banwari

    2015-01-01

    Full Text Available There is growing evidence to support the rapid, albeit short-lived antidepressant effect of subanesthetic dose of ketamine, a noncompetitive glutamate N-methyl-D-aspartate receptor antagonist in treatment-resistant unipolar and bipolar depression. Ketamine is known to cause transient mood elevation or euphoria, psychotomimetic effects, and dissociative symptoms, but its use in unipolar or bipolar depression has not been reported to induce an affective switch amounting to persistent or prolonged hypomania/mania or manic-like syndrome. We report the case of a 52-year-old male with first episode, continuous, nonpsychotic, treatment-resistant, unipolar major depression of 10 years duration, who manifested a switch from depression to mania while being treated with subanesthetic dose of ketamine, given intramuscularly. This case suggests that polarity switch should be considered as a potential side effect while using ketamine for treatment-resistant depression.

  10. Analysis of the characteristics of slot design affecting resistance to sliding during active archwire configurations

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    Nucera, Riccardo; Giudice, Antonino Lo; Matarese, Giovanni; Artemisia, Alessandro; Bramanti, Ennio; Crupi, Paolo; Cordasco, Giancarlo

    2013-01-01

    Background During orthodontic treatment, a low resistance to slide (RS) is desirable when sliding mechanics are used. Many studies showed that several variables affect the RS at the bracket-wire interface; among these, the design of the bracket slot has not been deeply investigated yet. This study aimed to clarify the effect of different slot designs on the RS expressed by five types of low-friction brackets in vertical and horizontal active configurations of the wire. Methods Five low-fricti...

  11. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria.

    Science.gov (United States)

    Tängdén, Thomas

    2014-05-01

    Combination antibiotic therapy for Gram-negative sepsis is controversial. The present review provides a brief summary of the existing knowledge on combination therapy for severe infections with multidrug-resistant Pseudomonas spp., Acinetobacter spp., and Enterobacteriaceae. Empirical combination antibiotic therapy is recommended for severe sepsis and septic shock to reduce mortality related to inappropriate antibiotic treatment. Because definitive combination therapy has not been proven superior to monotherapy in meta-analyses, it is generally advised to de-escalate antibiotic therapy when the antibiotic susceptibility profile is known, although it cannot be excluded that some subgroups of patients might still benefit from continued combination therapy. Definitive combination therapy is recommended for carbapenemase-producing Enterobacteriaceae and should also be considered for severe infections with Pseudomonas and Acinetobacter spp. when beta-lactams cannot be used. Because resistance to broad-spectrum beta-lactams is increasing in Gram-negative bacteria and because no new antibiotics are expected to become available in the near future, the antibacterial potential of combination therapy should be further explored. In vitro data suggest that combinations can be effective even if the bacteria are resistant to the individual antibiotics, although existing evidence is insufficient to support the choice of combinations and explain the synergistic effects observed. In vitro models can be used to screen for effective combinations that can later be validated in animal or clinical studies. Further, in the absence of clinical evidence, in vitro data might be useful in supporting therapeutic decisions for severe infections with multidrug-resistant Gram-negative bacteria.

  12. Crystal Structures of Penicillin-Binding Protein 2 From Penicillin-Susceptible And -Resistant Strains of Neisseria Gonorrhoeae Reveal An Unexpectedly Subtle Mechanism for Antibiotic Resistance

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    Powell, A.J.; Tomberg, J.; Deacon, A.M.; Nicholas, R.A.; Davies, C.

    2009-05-21

    Penicillin-binding protein 2 (PBP2) from N. gonorrhoeae is the major molecular target for {beta}-lactam antibiotics used to treat gonococcal infections. PBP2 from penicillin-resistant strains of N. gonorrhoeae harbors an aspartate insertion after position 345 (Asp-345a) and 4-8 additional mutations, but how these alter the architecture of the protein is unknown. We have determined the crystal structure of PBP2 derived from the penicillin-susceptible strain FA19, which shows that the likely effect of Asp-345a is to alter a hydrogen-bonding network involving Asp-346 and the SXN triad at the active site. We have also solved the crystal structure of PBP2 derived from the penicillin-resistant strain FA6140 that contains four mutations near the C terminus of the protein. Although these mutations lower the second order rate of acylation for penicillin by 5-fold relative to wild type, comparison of the two structures shows only minor structural differences, with the positions of the conserved residues in the active site essentially the same in both. Kinetic analyses indicate that two mutations, P551S and F504L, are mainly responsible for the decrease in acylation rate. Melting curves show that the four mutations lower the thermal stability of the enzyme. Overall, these data suggest that the molecular mechanism underlying antibiotic resistance contributed by the four mutations is subtle and involves a small but measurable disordering of residues in the active site region that either restricts the binding of antibiotic or impedes conformational changes that are required for acylation by {beta}-lactam antibiotics.

  13. Evolutionary clade affects resistance of Clostridium difficile spores to Cold Atmospheric Plasma

    Science.gov (United States)

    Connor, Mairéad; Flynn, Padrig B.; Fairley, Derek J.; Marks, Nikki; Manesiotis, Panagiotis; Graham, William G.; Gilmore, Brendan F.; McGrath, John W.

    2017-02-01

    Clostridium difficile is a spore forming bacterium and the leading cause of colitis and antibiotic associated diarrhoea in the developed world. Spores produced by C. difficile are robust and can remain viable for months, leading to prolonged healthcare-associated outbreaks with high mortality. Exposure of C. difficile spores to a novel, non-thermal atmospheric pressure gas plasma was assessed. Factors affecting sporicidal efficacy, including percentage of oxygen in the helium carrier gas admixture, and the effect on spores from different strains representing the five evolutionary C. difficile clades was investigated. Strains from different clades displayed varying resistance to cold plasma. Strain R20291, representing the globally epidemic ribotype 027 type, was the most resistant. However all tested strains displayed a ~3 log reduction in viable spore counts after plasma treatment for 5 minutes. Inactivation of a ribotype 078 strain, the most prevalent clinical type seen in Northern Ireland, was further assessed with respect to surface decontamination, pH, and hydrogen peroxide concentration. Environmental factors affected plasma activity, with dry spores without the presence of organic matter being most susceptible. This study demonstrates that cold atmospheric plasma can effectively inactivate C. difficile spores, and highlights factors that can affect sporicidal activity.

  14. Inoculation of Transgenic Resistant Potato by Phytophthora infestans Affects Host Plant Choice of a Generalist Moth.

    Science.gov (United States)

    Abreha, Kibrom B; Alexandersson, Erik; Vossen, Jack H; Anderson, Peter; Andreasson, Erik

    2015-01-01

    Pathogen attack and the plant's response to this attack affect herbivore oviposition preference and larval performance. Introduction of major resistance genes against Phytophthora infestans (Rpi-genes), the cause of the devastating late blight disease, from wild Solanum species into potato changes the plant-pathogen interaction dynamics completely, but little is known about the effects on non-target organisms. Thus, we examined the effect of P. infestans itself and introduction of an Rpi-gene into the crop on host plant preference of the generalist insect herbivore, Spodoptera littoralis (Lepidoptera: Noctuidae). In two choice bioassays, S. littoralis preferred to oviposit on P. infestans-inoculated plants of both the susceptible potato (cv. Desiree) and an isogenic resistant clone (A01-22: cv. Desiree transformed with Rpi-blb1), when compared to uninoculated plants of the same genotype. Both cv. Desiree and clone A01-22 were equally preferred for oviposition by S. littoralis when uninoculated plants were used, while cv. Desiree received more eggs compared to the resistant clone when both were inoculated with the pathogen. No significant difference in larval and pupal weight was found between S. littoralis larvae reared on leaves of the susceptible potato plants inoculated or uninoculated with P. infestans. Thus, the herbivore's host plant preference in this system was not directly associated with larval performance. The results indicate that the Rpi-blb1 based resistance in itself does not influence insect behavior, but that herbivore oviposition preference is affected by a change in the plant-microbe interaction.

  15. Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance.

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    Alexander L Greninger

    Full Text Available Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA. These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described. Here we compare the genomes of 11 total parent-daughter strains of Staphylococcus aureus for which specific selection by serial passaging with ceftaroline or ceftobiprole was used to identify novel non-mecA mechanisms of resistance. All 5 ceftaroline-resistant strains, derived from 5 different parental strains, contained mutations directly upstream of the pbp4 gene (coding for the PBP4 protein, including four with the same thymidine insertion located 377 nucleotides upstream of the promoter site. In 4 of 5 independent ceftaroline-driven selections, we also isolated mutations to the same residue (Asn138 in PBP4. In addition, mutations in additional candidate genes such as ClpX endopeptidase, PP2C protein phosphatase and transcription terminator Rho, previously undescribed in the context of resistance to ceftaroline or ceftobiprole, were detected in multiple selections. These genomic findings suggest that non-mecA mechanisms, while yet to be encountered in the clinical setting, may also be important in mediating resistance to 5th-generation cephalosporins.

  16. Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance

    Science.gov (United States)

    Chan, Liana C.; Hamilton, Stephanie M.; Chambers, Henry F.; Chiu, Charles Y.

    2016-01-01

    Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA). These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described. Here we compare the genomes of 11 total parent-daughter strains of Staphylococcus aureus for which specific selection by serial passaging with ceftaroline or ceftobiprole was used to identify novel non-mecA mechanisms of resistance. All 5 ceftaroline-resistant strains, derived from 5 different parental strains, contained mutations directly upstream of the pbp4 gene (coding for the PBP4 protein), including four with the same thymidine insertion located 377 nucleotides upstream of the promoter site. In 4 of 5 independent ceftaroline-driven selections, we also isolated mutations to the same residue (Asn138) in PBP4. In addition, mutations in additional candidate genes such as ClpX endopeptidase, PP2C protein phosphatase and transcription terminator Rho, previously undescribed in the context of resistance to ceftaroline or ceftobiprole, were detected in multiple selections. These genomic findings suggest that non-mecA mechanisms, while yet to be encountered in the clinical setting, may also be important in mediating resistance to 5th-generation cephalosporins. PMID:26890675

  17. Methicillin-resistant Staphylococcus aureus containing mecC in Swedish dairy cows

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    Unnerstad Helle Ericsson

    2013-01-01

    Full Text Available Abstract Background Hitherto, methicillin-resistant Staphylococcus aureus (MRSA has not been detected in Swedish cattle. However, due to the report of mecC, a novel homologue to the mecA gene, there was reason to re-evaluate susceptibility results from strain collections of Staphylococcus aureus and test suspected isolates for the presence of mecC. Findings Bovine isolates of S. aureus with elevated minimum inhibitory concentrations of beta-lactams were retrospectively tested for presence of mecC. In four of the isolates mecC was detected. Conclusion In Sweden, this is the first finding of MRSA in cattle and the first detection of MRSA harbouring mecC of domestic animal origin. MRSA in animal populations has implications as a potential reservoir with risk for spread to humans. Occurrence of MRSA among Swedish cattle appears still very limited.

  18. [Resistance of hospital flora to imipenem. Experience in two intensive care units].

    Science.gov (United States)

    Hamon-Poupinel, V; Le Coutour, X; Vergnaud, M; Malbruny, B

    1991-10-19

    Imipenem is a beta-lactam antibiotic active against most Gram-negative bacilli. Between July 1, 1987 and September 30, 1989 (9 semesters), the activity of imipenem against 6 micro-organisms was tested in two intensive care units attached to the university hospital of Caen (Normandy). During the same period, the consumption of imipenem was evaluated from the number of vials drawn by each of these two units from the central pharmacy. Imipenem was found to be 100 percent effective against 5 of the 6 micro-organisms tested, but transient falls in sensitivity and an increase in imipenem consumption were observed when Pseudomonas aeruginosa was the pathogen. The most probable cause of these transient decreases of imipenem activity against Ps. aeruginosa was the existence of a resistant strain which showed a protein abnormality in its outer membrane by temporary selection pressure.

  19. Molecular basis for the role of Staphylococcus aureus penicillin binding protein 4 in antimicrobial resistance.

    Science.gov (United States)

    Navratna, Vikas; Nadig, Savitha; Sood, Varun; Prasad, K; Arakere, Gayathri; Gopal, B

    2010-01-01

    Penicillin binding proteins (PBPs) are membrane-associated proteins that catalyze the final step of murein biosynthesis. These proteins function as either transpeptidases or carboxypeptidases and in a few cases demonstrate transglycosylase activity. Both transpeptidase and carboxypeptidase activities of PBPs occur at the D-Ala-D-Ala terminus of a murein precursor containing a disaccharide pentapeptide comprising N-acetylglucosamine and N-acetyl-muramic acid-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala. Beta-lactam antibiotics inhibit these enzymes by competing with the pentapeptide precursor for binding to the active site of the enzyme. Here we describe the crystal structure, biochemical characteristics, and expression profile of PBP4, a low-molecular-mass PBP from Staphylococcus aureus strain COL. The crystal structures of PBP4-antibiotic complexes reported here were determined by molecular replacement, using the atomic coordinates deposited by the New York Structural Genomics Consortium. While the pbp4 gene is not essential for the viability of S. aureus, the knockout phenotype of this gene is characterized by a marked reduction in cross-linked muropeptide and increased vancomycin resistance. Unlike other PBPs, we note that expression of PBP4 was not substantially altered under different experimental conditions, nor did it change across representative hospital- or community-associated strains of S. aureus that were examined. In vitro data on purified recombinant S. aureus PBP4 suggest that it is a beta-lactamase and is not trapped as an acyl intermediate with beta-lactam antibiotics. Put together, the expression analysis and biochemical features of PBP4 provide a framework for understanding the function of this protein in S. aureus and its role in antimicrobial resistance.

  20. Prevalence of plasmid-mediated multidrug resistance determinants in fluoroquinolone-resistant bacteria isolated from sewage and surface water.

    Science.gov (United States)

    Osińska, Adriana; Harnisz, Monika; Korzeniewska, Ewa

    2016-06-01

    Fluoroquinolones (FQs) are fully synthetic broad-spectrum antibacterial agents that are becoming increasingly popular in the treatment of clinical and veterinary infections. Being excreted during treatment, mostly as active compounds, their biological action is not limited to the therapeutic site, but it is moved further as resistance selection pressure into the environment. Water environment is an ideal medium for the aggregation and dissemination of antibiotics, antibiotic-resistant bacteria (ARB), and antibiotic resistance genes (ARGs), which can pose a serious threat to human health. Because of this, the aim of this study was to determine the number of fluoroquinolone-resistant bacteria (FQRB) and their share in total heterotrophic plate counts (HPC) in treated wastewater (TWW), and upstream and downstream river water (URW, DRW) samples where TWW is discharged. The spread of plasmid-mediated quinolone resistance (PMQR) determinants and the presence/absence of resistance genes to other most popular antibiotic groups (against tetracyclines and beta-lactams) in selected 116 multiresistant isolates were investigated. The share of FQRB in total HPC in all samples was rather small and ranged from 0.7 % in URW samples to 7.5 % in TWW. Bacteria from Escherichia (25.0 %), Acinetobacter (25.0 %), and Aeromonas (6.9 %) genera were predominant in the FQRB group. Fluoroquinolone resistance was mostly caused by the presence of the gene aac(6')-1b-cr (91.4 %). More rarely reported was the occurrence of qnrS, qnrD, as well as oqxA, but qnrA, qnrB, qepA, and oqxB were extremely rarely or never noted in FQRB. The most prevalent bacterial genes connected with beta-lactams' resistance in FQRB were bla TEM, bla OXA, and bla CTX-M. The bla SHV was less common in the community of FQRB. The occurrence of bla genes was reported in almost 29.3 % of FQRB. The most abundant tet genes in FQRB were tet(A), tet(L), tet(K), and tet(S). The prevalence of tet genes was observed in 41.4

  1. Defective active silicon uptake affects some components of rice resistance to brown spot.

    Science.gov (United States)

    Dallagnol, Leandro J; Rodrigues, Fabrício A; Mielli, Mateus V B; Ma, Jian F; Datnoff, Lawrence E

    2009-01-01

    Rice is known to accumulate high amounts of silicon (Si) in plant tissue, which helps to decrease the intensity of many economically important rice diseases. Among these diseases, brown spot, caused by the fungus Bipolaris oryzae, is one of the most devastating because it negatively affects yield and grain quality. This study aimed to evaluate the importance of active root Si uptake in rice for controlling brown spot development. Some components of host resistance were evaluated in a rice mutant, low silicon 1 (lsi1), defective in active Si uptake, and its wild-type counterpart (cv. Oochikara). Plants were inoculated with B. oryzae after growing for 35 days in a hydroponic culture amended with 0 or 2 mMol Si. The components of host resistance evaluated were incubation period (IP), relative infection efficiency (RIE), area under brown spot progress curve (AUBSPC), final lesion size (FLS), rate of lesion expansion (r), and area under lesion expansion progress curve (AULEPC). Si content from both Oochikara and lsi1 in the +Si treatment increased in leaf tissue by 219 and 178%, respectively, over the nonamended controls. Plants from Oochikara had 112% more Si in leaf tissue than plants from lsi1. The IP of brown spot from Oochikara increased approximately 6 h in the presence of Si and the RIE, AUBSPC, FLS, r, and AULEPC were significantly reduced by 65, 75, 33, 36, and 35%, respectively. In the presence of Si, the IP increased 3 h for lsi1 but the RIE, AUBSPC, FLS, r, and AULEPC were reduced by only 40, 50, 12, 21, and 12%, respectively. The correlation between Si leaf content and IP was significantly positive but Si content was negatively correlated with RIE, AUBSPC, FLS, r, and AULEPC. Single degree-of-freedom contrasts showed that Oochikara and lsi1 supplied with Si were significantly different from those not supplied with Si for all components of resistance evaluated. This result showed that a reduced Si content in tissues of plants from lsi1 dramatically affected

  2. Characterization of multi-drug resistant ESBL producing nonfermenter bacteria isolated from patients blood samples using phenotypic methods in Shiraz (Iran

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    Maneli Amin Shahidi

    2015-10-01

    Full Text Available Background and Aim: The emergence of  nonfermenter bacteria that are resistant to multidrug resistant ESBL  are  nowadays a principal problem  for hospitalized patients. The present study aimed at surveying the emergence of nonfermenter bacteria resistant to multi-drug ESBL producing isolated from patients blood samples using BACTEC 9240 automatic system in Shiraz. Materials and Methods: In this cross-sectional study, 4825 blood specimens were collected from hospitalized patients in Shiraz (Iran, and positive samples were detected by means of  BACTEC 9240 automatic system. The isolates  containing nonfermenter bacteria were identified based on biochemical tests embedded in the API-20E system. Antibiotic sensitivity  test was performed  and identification of  ESBL producing strains were done  using phenotypic detection of extended spectrum beta-lactamase producing isolates(DDST according to CLSI(2013 guidelines.   Results: Out of 4825 blood samples, 1145 (24% specimen were gram-positive using BACTEC system. Among all isolated microorganisms, 206 isolates were non-fermenting gram- negative bacteria. The most common non-fermenter isolates were Pseudomonas spp. (48%, Acinetobacter spp. (41.7% ,and Stenotrophomonas spp. (8.2%. Seventy of them (81.4% were  Acinetobacter spp. which were ESBL positive. Among &beta-lactam antibiotics, Pseudomonas spp. showed  the best sensitivity to piperacillin-tazobactam (46.5%.  Conclusion: It was found that  &beta-lactam antibiotics are not effective against more than 40% of Pseudomonas spp. infections and 78% Acinetobacter infections. Emergence of multi-drug resistant strains that are resistant to most antibiotic classes is a major public health problem in Iran. To resolve this problem using of practical guidelines is critical.

  3. A genome scan for quantitative trait loci affecting resistance to Trichostrongylus colubriformis in sheep.

    Science.gov (United States)

    Beh, K J; Hulme, D J; Callaghan, M J; Leish, Z; Lenane, I; Windon, R G; Maddox, J F

    2002-04-01

    A genome linkage scan was carried out using a resource flock of 1029 sheep in six half-sib families. The families were offspring of sires derived by crossing divergent lines of sheep selected for response to challenge with the intestinal parasitic nematode Trichostrongylus colubriformis. All animals in the resource flock were phenotypically assessed for worm resistance soon after weaning using a vaccination/challenge regime. After correcting for fixed effects using a least squares linear model the faecal egg count data obtained following the first challenge and the faecal egg count data obtained after the second challenge were designated Trait 1 and Trait 2, respectively. A total of 472 lambs drawn from the phenotypic extremes of the Trait 2 faecal egg count distribution were genotyped with a panel of 133 microsatellite markers covering all 26 sheep autosomes. Detection of quantitative trait loci (QTL) for each of the faecal egg count traits was determined using interval analysis with the Animap program with recombination rates between markers derived from an existing marker map. No chromosomal regions attained genome-wide significance for QTL influencing either of the traits. However, one region attained chromosome-wide significance and five other regions attained point-wise significance for the presence of QTL affecting parasite resistance.

  4. Diclofop-methyl affects microbial rhizosphere community and induces systemic acquired resistance in rice.

    Science.gov (United States)

    Chen, Si; Li, Xingxing; Lavoie, Michel; Jin, Yujian; Xu, Jiahui; Fu, Zhengwei; Qian, Haifeng

    2017-01-01

    Diclofop-methyl (DM), a widely used herbicide in food crops, may partly contaminate the soil surface of natural ecosystems in agricultural area and exert toxic effects at low dose to nontarget plants. Even though rhizosphere microorganisms strongly interact with root cells, little is known regarding their potential modulating effect on herbicide toxicity in plants. Here we exposed rice seedlings (Xiushui 63) to 100μg/L DM for 2 to 8days and studied the effects of DM on rice rhizosphere microorganisms, rice systemic acquired resistance (SAR) and rice-microorganisms interactions. The results of metagenomic 16S rDNA Illumina tags show that DM increases bacterial biomass and affects their community structure in the rice rhizosphere. After DM treatment, the relative abundance of the bacterium genera Massilia and Anderseniella increased the most relative to the control. In parallel, malate and oxalate exudation by rice roots increased, potentially acting as a carbon source for several rhizosphere bacteria. Transcriptomic analyses suggest that DM induced SAR in rice seedlings through the salicylic acid (but not the jasmonic acid) signal pathway. This response to DM stress conferred resistance to infection by a pathogenic bacterium, but was not influenced by the presence of bacteria in the rhizosphere since SAR transcripts did not change significantly in xenic and axenic plant roots exposed to DM. The present study provides new insights on the response of rice and its associated microorganisms to DM stress.

  5. Resistin induces insulin resistance, but does not affect glucose output in rat-derived hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Feng LIU; Xiao-qing PAN; Mei GUO; Rong-hua CHEN; Xi-rong GUO; Tao YANG; Bin WANG; Min ZHANG; Nan GU; Jie QIU; Hong-qi FAN; Chun-mei ZHANG; Li FEI

    2008-01-01

    Aim: The aim of the present study was to observe the effects of resistin on insulin sensitivity and glucose output in rat-derived hepatocytes. Methods: The rat hepatoma cell line H4IIE was cultured and stimulated with resistin; supernant glucose and glycogen content were detected. The insulin receptor substrate (IRS)-1 and IRS-2, protein kinase B/Akt, glycogen synthase kinase-3β (GSK-3β), the suppressor of cytokine signaling 3 (SOCS-3) protein content, as well as the phosphorylation status were assessed by Western blotting. Specific antisense oligodeoxynucleotides directed against SOCS-3 were used to knockdown SOCS-3. Results: Resistin induced insulin resistance, but did not affect glucose output in rat hepatoma cell line H4IIE. Resistin attenuated multiple effects of insulin, including insulin-stimulated glycogen synthesis and phosphorylation of IRS, pro-tein kinase B/Akt, as well as GSK-3β. Resistin treatment markedly induced the gene and protein expression of SOCS-3, a known inhibitor of insulin signaling. Furthermore, a specific antisense oligodeoxynucleotide directed against SOCS-3 treatment prevented resistin from antagonizing insulin action. Conclusion: The major function of resistin on liver is to induce insulin resistance. SOCS-3 induc-tion may contribute to the resistin-mediated inhibition of insulin signaling in H4IIE hepatocytes.

  6. Prevalence and characteristics of methicillin-resistant coagulase-negative staphylococci from livestock, chicken carcasses, bulk tank milk, minced meat, and contact persons

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    Zweifel Claudio

    2011-01-01

    Full Text Available Abstract Background Methicillin-resistant coagulase-negative staphylococci (MR-CNS are of increasing importance to animal and public health. In veterinary medicine and along the meat and milk production line, only limited data were so far available on MR-CNS characteristics. The aim of the present study was to evaluate the prevalence of MR-CNS, to identify the detected staphylococci to species level, and to assess the antibiotic resistance profiles of isolated MR-CNS strains. Results After two-step enrichment and growth on chromogenic agar, MR-CNS were detected in 48.2% of samples from livestock and chicken carcasses, 46.4% of samples from bulk tank milk and minced meat, and 49.3% of human samples. Using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS, 414 selected MR-CNS strains belonged to seven different species (S. sciuri, 32.6%; S. fleurettii, 25.1%; S. haemolyticus, 17.4%; S. epidermidis, 14.5%, S. lentus, 9.2%; S. warneri, 0.7%; S. cohnii, 0.5%. S. sciuri and S. fleurettii thereby predominated in livestock, BTM and minced meat samples, whereas S. epidermidis and S. haemolyticus predominated in human samples. In addition to beta-lactam resistance, 33-49% of all 414 strains were resistant to certain non-beta-lactam antibiotics (ciproflaxacin, clindamycin, erythromycin, tetracycline. Conclusions A high prevalence of MR-CNS was found in livestock production. This is of concern in view of potential spread of mecA to S. aureus (MRSA. Multiresistant CNS strains might become an emerging problem for veterinary medicine. For species identification of MR-CNS isolated from different origins, MALDI-TOF MS proved to be a fast and reliable tool and is suitable for screening of large sample amounts.

  7. Mapping QTL affecting resistance to Marek's disease in an F6 advanced intercross population of commercial layer chickens

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    Wang Jing

    2009-01-01

    Full Text Available Abstract Background Marek's disease (MD is a T-cell lymphoma of chickens caused by the Marek's disease virus (MDV, an oncogenic avian herpesvirus. MD is a major cause of economic loss to the poultry industry and the most serious and persistent infectious disease concern. A full-sib intercross population, consisting of five independent families was generated by crossing and repeated intercrossing of two partially inbred commercial White Leghorn layer lines known to differ in genetic resistance to MD. At the F6 generation, a total of 1615 chicks were produced (98 to 248 per family and phenotyped for MD resistance measured as survival time in days after challenge with a very virulent plus (vv+ strain of MDV. Results QTL affecting MD resistance were identified by selective DNA pooling using a panel of 15 SNPs and 217 microsatellite markers. Since MHC blood type (BT is known to affect MD resistance, a total of 18 independent pool pairs were constructed according to family × BT combination, with some combinations represented twice for technical reasons. Twenty-one QTL regions (QTLR affecting post-challenge survival time were identified, distributed among 11 chromosomes (GGA1, 2, 3, 4, 5, 8, 9, 15, 18, 26 and Z, with about two-thirds of the MD resistance alleles derived from the more MD resistant parental line. Eight of the QTLR associated with MD resistance, were previously identified in a backcross (BC mapping study with the same parental lines. Of these, 7 originated from the more resistant line, and one from the less resistant line. Conclusion There was considerable evidence suggesting that MD resistance alleles tend to be recessive. The width of the QTLR for these QTL appeared to be reduced about two-fold in the F6 as compared to that found in the previous BC study. These results provide a firm basis for high-resolution linkage disequilibrium mapping and positional cloning of the resistance genes.

  8. Burden of methicillin-resistant Staphylococcus aureus pneumonia among hospitalized patients in Lebanon and Saudi Arabia

    Science.gov (United States)

    Althaqafi, Abdulhakeem O; Matar, Madonna J; Moghnieh, Rima; Alothman, Adel F; Alenazi, Thamer H; Farahat, Fayssal; Corman, Shelby; Solem, Caitlyn T; Raghubir, Nirvana; Macahilig, Cynthia; Haider, Seema; Stephens, Jennifer M

    2017-01-01

    Objectives The objective of this study is to describe the real-world treatment patterns and burden of suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in Saudi Arabia and Lebanon. Methods A retrospective chart review study evaluated 2011–2012 data from hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of MRSA pneumonia, which was culture proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients to capture demographics (eg, age and comorbidities), treatment patterns (eg, timing and use of antimicrobials), hospital resource utilization (eg, length of stay), and clinical outcomes (eg, clinical status at discharge and mortality). Descriptive results were reported using frequencies or proportions for categorical variables and mean and standard deviation for continuous variables. Results Chart-level data were collected for 93 patients with MRSA pneumonia, 50 in Saudi Arabia and 43 in Lebanon. The average age of the patients was 56 years, and 60% were male. The most common comorbidities were diabetes (39%), congestive heart failure (30%), coronary artery disease (29%), and chronic obstructive pulmonary disease (28%). Patients most frequently had positive cultures from pulmonary (87%) and blood (27%) samples. All isolates were sensitive to vancomycin, teicoplanin, and linezolid, and only one-third of the isolates tested were sensitive to ciprofloxacin. Beta-lactams (inactive therapy for MRSA) were prescribed 21% of the time across all lines of therapy, with 42% of patients receiving first-line beta-lactams. Fifteen percent of patients did not receive any antibiotics that were considered to be MRSA active. The mean hospital length of stay was 32 days, and in-hospital mortality was 30%. Conclusion The treatment for MRSA pneumonia in Saudi Arabia and Lebanon may be suboptimal with inactive therapy prescribed a substantial proportion

  9. Mapping of a quantitative trait locus for resistance against infectious salmon anaemia in Atlantic salmon (Salmo Salar: comparing survival analysis with analysis on affected/resistant data

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    Lien Sigbjørn

    2007-08-01

    Full Text Available Abstract Background Infectious Salmon Anaemia (ISA is a viral disease affecting farmed Atlantic salmon (Salmo salar worldwide. The identification of Quantitative Trait Loci (QTL affecting resistance to the disease could improve our understanding of the genetics underlying the trait and provide a means for Marker-Assisted Selection. We previously performed a genome scan on commercial Atlantic salmon families challenge tested for ISA resistance, identifying several putative QTL. In the present study, we set out to validate the strongest of these QTL in a larger family material coming from the same challenge test, and to determine the position of the QTL by interval mapping. We also wanted to explore different ways of performing QTL analysis within a survival analysis framework (i.e. using time-to-event data, and to compare results using survival analysis with results from analysis on the dichotomous trait 'affected/resistant'. Results The QTL, located on Atlantic salmon linkage group 8 (following SALMAP notation, was confirmed in the new data set. Its most likely position was at a marker cluster containing markers BHMS130, BHMS170 and BHMS553. Significant segregation distortion was observed in the same region, but was shown to be unrelated to the QTL. A maximum likelihood procedure for identifying QTL, based on the Cox proportional hazard model, was developed. QTL mapping was also done using the Haley-Knott method (affected/resistant data, and within a variance-component framework (affected/resistant data and time-to-event data. In all cases, analysis using affected/resistant data gave stronger evidence for a QTL than did analysis using time-to-event data. Conclusion A QTL for resistance to Infectious Salmon Anaemia in Atlantic salmon was validated in this study, and its more precise location on linkage group eight was determined. The QTL explained 6% of the phenotypic variation in resistance to the disease. The linkage group also displayed

  10. A genome scan for QTL affecting resistance to Haemonchus contortus in sheep.

    Science.gov (United States)

    Sallé, G; Jacquiet, P; Gruner, L; Cortet, J; Sauvé, C; Prévot, F; Grisez, C; Bergeaud, J P; Schibler, L; Tircazes, A; François, D; Pery, C; Bouvier, F; Thouly, J C; Brunel, J C; Legarra, A; Elsen, J M; Bouix, J; Rupp, R; Moreno, C R

    2012-12-01

    Gastrointestinal nematodes are one of the main health issues in sheep breeding. To identify loci affecting the resistance to Haemonchus contortus, a genome scan was carried out using 1,275 Romane × Martinik Black Belly backcross lambs. The entire population was challenged with Haemonchus contortus in 2 consecutive experimental infections, and fecal egg counts (FEC) and packed cell volumes were measured. A subgroup of 332 lambs with extreme FEC was necropsied to determine the total worm burden, length of female worms, sex ratio in the worm population, abomasal pH, and serum and mucosal G immunoglobulins (IgG) responses. Pepsinogen concentration was measured in another subset of 229 lambs. For QTL detection, 160 microsatellite markers were used as well as the Illumina OvineSNP50 BeadChip that provided 42,469 SNP markers after quality control. Linkage, association, and joint linkage and association analyses were performed with the QTLMAP software. Linkage disequilibrium (LD) was estimated within each pure breed, and association analyses were carried out either considering or not the breed origin of the haplotypes. Four QTL regions on sheep chromosomes (OAR)5, 12, 13, and 21 were identified as key players among many other QTL with small to moderate effects. A QTL on OAR21 affecting pepsinogen concentration exactly matched the pepsinogen (PGA5) locus. A 10-Mbp region affecting FEC after the 1st and 2nd infections was found on OAR12. The SNP markers outperformed microsatellites in the linkage analysis. Taking advantage of the LD helped to refine the locations of the QTL mapped on OAR5 and 13.

  11. Assessment of antibiotic resistance phenotype and integrons in Salmonella enterica serovar Typhimurium isolated from swine.

    Science.gov (United States)

    Rayamajhi, Nabin; Kang, Sang Gyun; Kang, Mi Lan; Lee, Hee Soo; Park, Kyung Yoon; Yoo, Han Sang

    2008-10-01

    Salmonella enterica serovar Typhimurium (S. Typhimurium) isolated and identified from swine were subjected for the analysis of antibiotic resistance pattern and clinically important class 1 and 2 integrons. In addition, S. Typhimurium isolates exhibiting ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, tetracycline and florfenicol (ACSSuTF) resistance pattern as described in most Salmonella enterica serotype Typhimurium definitive type 104 (DT104) were characterized by polymerase chain reaction. All the isolates were resistant to more than four antibiotics and showed the highest resistance to streptomycin (94.1%), followed by tetracycline (90.1%), ampicillin (64.7%), chloramphenicol (56.8%) and gentamicin (54.9%). MIC value for the ten isolates ranged between 0.125-2 mug/ml for ciprofloxacin. Among the beta-lactams used, only one of the isolate exhibited resistance to ceftiofur (MIC 8 microg/ml). Sixty eight percent of these multi drug resistance (MDR) S. Typhimurium isolates carried clinically important class 1 integron with 1kb (aadA) and/or 2kb (dhfrXII-orfF-aadA2) resistance gene cassettes. This study reports the increasing trend of multi drug resistance (MDR) S. Typhimurium with clinically important class 1 integron in pigs. In addition, emergence of the ACSSuTF-type resistance in S. Typhimurium PT other than DT104 may limit the use of resistance gene markers in its detection methods by PCR.

  12. Health risks associated with the presence of antibiotic resistant bacteria in greywater

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    Juan Moretton

    2012-04-01

    Full Text Available The removal and disposal of waste from domestic activities is a major health problem in densely populated urban areas. In many areas of Greater Buenos Aires, greywater is disposed in open ditches and risk potential of this has not been adequately quantified. The aim of this study was to evaluate the prevalence of antibiotic-resistant bacteria and its resistance profile present in raw greywater obtained from a channel located in the area of Ingeniero Budge Buenos Aires Province. Thus, the prevalence of heterotrophic bacteria, Gram-negative bacteria resistant to beta-lactam antibiotics and vancomycin-resistant enterococci in greywater, their typing, and resistance to other antibiotics were determined. The prevalence of resistant bacteria was determined by the agar dilution method. Of all the antibiotics tested, the highest prevalence of resistant heterotrophic bacteria was detected with cephalothin (19% and ampicillin (8%. With regard to Gram-negative bacteria, the highest prevalence of resistance was given by coliforms ampicillin (34% and cephalothin (17%. A total of 38% of enterococci with low level resistance to vancomycin was detected. The multiresistant isolates were identified as Escherichia coli, Alcaligenes faecalis y Stenotrophomonas maltophilia. These results indicate that greywater can be considered as a reservoir of bacteria resistant to antibiotics, thus increasing their health risk.

  13. Arabidopsis flower specific defense gene expression patterns affect resistance to pathogens

    KAUST Repository

    Ederli, Luisa

    2015-02-20

    We investigated whether the Arabidopsis flower evolved protective measures to increase reproductive success. Firstly, analyses of available transcriptome data show that the most highly expressed transcripts in the closed sepal (stage 12) are enriched in genes with roles in responses to chemical stimuli and cellular metabolic processes. At stage 15, there is enrichment in transcripts with a role in responses to biotic stimuli. Comparative analyses between the sepal and petal in the open flower mark an over-representation of transcripts with a role in responses to stress and catalytic activity. Secondly, the content of the biotic defense-associated phytohormone salicylic acid (SA) in sepals and petals is significantly higher than in leaves. To understand whether the high levels of stress responsive transcripts and the higher SA content affect defense, wild-type plants (Col-0) and transgenic plants defective in SA accumulation (nahG) were challenged with the biotrophic fungus Golovinomyces cichoracearum, the causal agent of powdery mildew, and the necrotrophic fungus Botrytis cinerea. NahG leaves were more sensitive than those of Col-0, suggesting that in leaves SA has a role in the defense against biotrophs. In contrast, sepals and petals of both genotypes were resistant to G. cichoracearum, indicating that in the flower, resistance to the biotrophic pathogen is not critically dependent on SA, but likely dependent on the up-regulation of stress-responsive genes. Since sepals and petals of both genotypes are equally susceptible to B. cinerea, we conclude that neither stress-response genes nor increased SA accumulation offers protection against the necrotrophic pathogen. These results are interpreted in the light of the distinctive role of the flower and we propose that in the early stages, the sepal may act as a chemical defense barrier of the developing reproductive structures against biotrophic pathogens.

  14. Does Culture Affect how People Receive and Resist Persuasive Messages? Research Proposals about Resistance to Persuasion in Cultural Groups

    Directory of Open Access Journals (Sweden)

    Renata Kolodziej-Smith

    2013-10-01

    Full Text Available Abstract Even though persuasion has been a widely researched topic in consumer behavior, the great majority of these studies have involved American consumers and focused on persuasion itself, with very few addressing resistance to persuasive attempts. None has addressed resistance to persuasion in a cross-cultural context. We aim to contribute to closing this gap in the literature with this paper. Specifically, we aim to expand knowledge of the persuasive process by applying the cultural dimensions of self-construal and face negotiation theories to Gopinath and Nyer’s (2009 work conducted on American consumers about the effect of public commitment on resistance to persuasion. Our research focus is on why people from different ethnic/cultural backgrounds will receive or resist persuasive messages differently. We anchor this notion in face negotiation theory (Ting-Toomey, 2005. This perspective addresses different types of facework behaviors that people choose in a multicultural environment, thus shedding light on processes underlying persuasion and resistance to persuasion mechanisms as influenced by culture. Understanding the effects of cultural differences on a person’s reception of, or resistance to, counter-attitudinal persuasion should be valuable to managers who make decisions about cultural adaptations and target audience changes.

  15. Antimicrobial resistance of Staphylococcus spp. from small ruminant mastitis in Brazil

    Directory of Open Access Journals (Sweden)

    Chirles A. França

    2012-08-01

    Full Text Available The study aimed to determine the antimicrobial resistance patterns and to identify molecular resistance markers in Staphylococcus spp. (n=210 isolated from small ruminant mastitis in Brazil. The antimicrobial resistance patterns were evaluated by the disk diffusion test and by detection of the presence of mecA, blaZ, ermA, ermB, ermC and msrA genes by PCR. The efflux pump test was performed using ethidium bromide and biofilm production was determined by Congo red agar test along with PCR for detection of the icaD gene. The isolates were most resistant to amoxicillin (50.0%, streptomycin (42.8%, tetracycline (40.4%, lincomycin (39.0% and erythromycin (33.8%. Pan-susceptibility to all tested drugs was observed in 71 (33.8% isolates and 41 Staphylococcus isolates were positive for the efflux pump. Although phenotypic resistance to oxacillin was observed in 12.8% of the isolates, none harbored the mecA gene. However, 45.7% of the isolates harbored blaZ indicating that beta-lactamase production was the main mechanism associated with staphylococci resistance to beta-lactams in the present study. The other determinants of resistance to antimicrobial agents ermA, ermB, ermC, and msrA were observed in 1.4%, 10.4%, 16.2%, and 0.9% of the isolates, respectively. In addition, the icaD gen was detected in 32.9% of the isolates. Seventy three isolates (54 from goats and 19 from sheep were negative for all resistance genes tested and 69 isolates presented two or more resistance genes. Association among blaZ, ermA, ermB, ermC and efflux pump were observed in 17 isolates, 14 of which originated from goats and three from sheep. The data obtained in this study show the resistance of the isolates to beta-lactamics, which may be associated with the use of antimicrobial drugs without veterinary control.

  16. Emergence of clonally related multidrug resistant Haemophilus influenzae with penicillin-binding protein 3-mediated resistance to extended-spectrum cephalosporins, Norway, 2006 to 2013.

    Science.gov (United States)

    Skaare, D; Anthonisen, I L; Kahlmeter, G; Matuschek, E; Natås, O B; Steinbakk, M; Sundsfjord, A; Kristiansen, B E

    2014-12-11

    Resistance to cephalosporins in Haemophilus influenzae is usually caused by characteristic alterations in penicillin-binding protein 3 (PBP3), encoded by the ftsI gene. Resistance to extended-spectrum cephalosporins is associated with high-level PBP3-mediated resistance (high-rPBP3), defined by the second stage S385T substitution in addition to a first stage substitution (R517H or N526K). The third stage L389F substitution is present in some high-rPBP3 strains. High-rPBP3 H. influenzae are considered rare outside Japan and Korea. In this study, 30 high-rPBP3 isolates from Norway, collected between 2006 and 2013, were examined by serotyping, multilocus sequence typing (MLST), ftsI sequencing, detection of beta-lactamase genes and minimum inhibitory concentration (MIC) determination. MICs were interpreted according to clinical breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Respiratory isolates predominated (proportion: 24/30). The 30 isolates included one serotype f isolate, while the remaining 29 lacked polysaccharide capsule genes. Resistance to extended-spectrum cephalosporins (cefixime, 29 isolates/30 isolates; cefepime, 28/30; cefotaxime, 26 /30; ceftaroline, 26/30; ceftriaxone, 14/30), beta-lactamase production (11/30) and co-resistance to non-beta-lactams (trimethoprim-sulfamethoxazole, 13/30; tetracycline, 4/30; chloramphenicol, 4/30; ciprofloxacin, 3/30) was frequent. The N526K substitution in PBP3 was present in 23 of 30 isolates; these included a blood isolate which represents the first invasive S385T + N526K isolate reported from Europe. The L389F substitution, present in 16 of 30 isolates, coincided with higher beta-lactam MICs. Non-susceptibility to meropenem was frequent in S385T + L389F + N526K isolates (8/12). All 11 beta-lactamase positive isolates were TEM-1. Five clonal groups of two to 10 isolates with identical MLST-ftsI allelic profiles were observed, including the first reported high-rPBP3

  17. Study on impact properties of creep-resistant steel thermally simulated heat affected zone

    Directory of Open Access Journals (Sweden)

    Mitrović Radivoje M.

    2012-01-01

    Full Text Available The steam pipe line (SPL and steam line material, along with its welded joints, subject to damage that accumulates during operation in coal power plants. As a result of thermal fatigue, dilatation of SPL at an operating temperature may lead to cracks initiation at the critical zones within heat affected zone (HAZ of steam pipe line welded joints. By registration of thermal cycle during welding and subsequent HAZ simulation is possible to obtain target microstructure. For the simulation is chosen heat resisting steel, 12H1MF (designation 13CrMo44 according to DIN standard. From the viewpoint of mechanical properties, special attention is on impact toughness mostly because very small number of available references. After simulation of single run and multi run welding test on instrumented Charpy pendulum. Metallographic and fractographic analysis is also performed, on simulated 12H1MF steel from service and new, unused steel. The results and correlation between microstructure and impact toughness is discussed, too.

  18. Antimicrobial resistances do not affect colonization parameters of intestinal E. coli in a small piglet group

    Directory of Open Access Journals (Sweden)

    Schierack Peter

    2009-10-01

    Full Text Available Abstract Background Although antimicrobial resistance and persistence of resistant bacteria in humans and animals are major health concerns worldwide, the impact of antimicrobial resistance on bacterial intestinal colonization in healthy domestic animals has only been rarely studied. We carried out a retrospective analysis of the antimicrobial susceptibility status and the presence of resistance genes in intestinal commensal E. coli clones from clinically healthy pigs from one production unit with particular focus on effects of pheno- and/or genotypic resistance on different nominal and numerical intestinal colonization parameters. In addition, we compared the occurrence of antimicrobial resistance phenotypes and genotypes with the occurrence of virulence associated genes typical for extraintestinal pathogenic E. coli. Results In general, up to 72.1% of all E. coli clones were resistant to ampicillin, chloramphenicol, kanamycin, streptomycin, sulfamethoxazole or tetracycline with a variety of different resistance genes involved. There was no significant correlation between one of the nominal or numerical colonization parameters and the absence or presence of antimicrobial resistance properties or resistance genes. However, there were several statistically significant associations between the occurrence of single resistance genes and single virulence associated genes. Conclusion The demonstrated resistance to the tested antibiotics might not play a dominant role for an intestinal colonization success in pigs in the absence of antimicrobial drugs, or cross-selection of other colonization factors e.g. virulence associated genes might compensate "the cost of antibiotic resistance". Nevertheless, resistant strains are not outcompeted by susceptible bacteria in the porcine intestine. Trial Registration The study was approved by the local animal welfare committee of the "Landesamt für Arbeitsschutz, Gesundheitsschutz und technische Sicherheit" Berlin

  19. Diversity and antibiotic resistance patterns of Sphingomonadaceae isolates from drinking water.

    Science.gov (United States)

    Vaz-Moreira, Ivone; Nunes, Olga C; Manaia, Célia M

    2011-08-15

    Sphingomonadaceae (n = 86) were isolated from a drinking water treatment plant (n = 6), tap water (n = 55), cup fillers for dental chairs (n = 21), and a water demineralization filter (n = 4). The bacterial isolates were identified based on analysis of the 16S rRNA gene sequence, and intraspecies variation was assessed on the basis of atpD gene sequence analysis. The isolates were identified as members of the genera Sphingomonas (n = 27), Sphingobium (n = 28), Novosphingobium (n = 12), Sphingopyxis (n = 7), and Blastomonas (n = 12). The patterns of susceptibility to five classes of antibiotics were analyzed and compared for the different sites of isolation and taxonomic groups. Colistin resistance was observed to be intrinsic (92%). The highest antibiotic resistance prevalence values were observed in members of the genera Sphingomonas and Sphingobium and for beta-lactams, ciprofloxacin, and cotrimoxazole. In tap water and in water from dental chairs, antibiotic resistance was more prevalent than in the other samples, mainly due to the predominance of isolates of the genera Sphingomonas and Sphingobium. These two genera presented distinct patterns of association with antibiotic resistance, suggesting different paths of resistance development. Antibiotic resistance patterns were often related to the species rather than to the site or strain, suggesting the importance of vertical resistance transmission in these bacteria. This is the first study demonstrating that members of the family Sphingomonadaceae are potential reservoirs of antibiotic resistance in drinking water.

  20. Prospective Study of Infection, Colonization and Carriage of Methicillin-Resistant Staphylococcus Aureus in an Outbreak Affecting 990 Patients

    NARCIS (Netherlands)

    R. Coello; J. Jimenez; M. Garcia (Melissa); P. Arroyo; D. Minguez; C. Fernandez; F. Cruzet; C. Gaspar

    1994-01-01

    textabstractIn the three years between November 1989 and October 1992, an outbreak of methicillin-resistantStaphylococcus aureus (MRSA) affected 990 patients at a university hospital. The distribution of patients with carriage, colonization or infection was investigated prospectively. Nosocomial acq

  1. A three-point time series study of antibiotic usage on an intensive care unit, following an antibiotic stewardship programme, after an outbreak of multi-resistant Acinetobacter baumannii.

    Science.gov (United States)

    Singh, S; Zhang, Y Z; Chalkley, S; Ananthan, K; Demertzi, E; Beach, M; Cohen, M; Grover, V; Chung, C; Tatlock, J; Soni, N; Azadian, B

    2015-09-01

    Antibiotic use in intensive care units (ICUs) can promote antimicrobial resistance. Outbreaks of multi-resistant bacteria significantly affect patient outcomes and delivery of care. Antibiotic stewardship programmes (ASPs), combining root-cause analyses and multi-faceted prevention strategies, are necessary, often at significant cost and time. Which elements of such strategies have the largest impact on antibiotic usage following an outbreak is unclear. The aim of this study was to investigate how antibiotic usage in a university hospital ICU changed with a non-protocolised ASP following a disruptive outbreak of multi-resistant Acinetobacter baumannii (MRAB). This was a three time-period observational cohort study. The primary endpoint was the change in overall antibiotic usage (daily defined dose, DDD, antibiotic-days, antibiotic-courses) for consecutive ICU patients staying >48 h, over three 6-month study time periods pre-MRAB (2008, n = 84) and post-MRAB (2010, n = 88; 2012, n = 122). Secondary endpoints were changes in antibiotic usage and patient demographics, in predefined admission categories (Medical Emergency, ME; Surgical Elective, SEL; and Surgical Emergency, SE). The mean age (54.6 ± 17.7, 58.1 ± 17.9, 62.8 ± 19.1 years*) and severity of illness (APACHE 14.8 ± 8.0, 16.7 ± 6.8, 18.3 ± 6.1*) increased, particularly medical admissions. There was a sustained reduction in DDD antibiotic usage [1895.1 (2008), 1224.2 (2010), 1236.6 (2012) per 1000 patient-days] but no overall change in antibiotic-days or antibiotic-courses. Antibiotic usage (antibiotic-days) fell significantly in surgical emergency admissions [20.2 ± 32.1, 4.6 ± 7.4*, 5.9 ± 7.3]. There was a sustained drop in beta-lactam, quinolone, glycopeptide and macrolide usage. Following an MRAB outbreak, and subsequent operational changes including enhanced ASPs (non-protocolised), there was a sustained overall fall in antibiotic usage in spite of

  2. Factors affecting the thermal shock resistance of several hafnia based composites containing graphite or tungsten. M.S. Thesis

    Science.gov (United States)

    Lineback, L. D.

    1974-01-01

    The thermal shock resistance of hafnia based composites containing graphite powder or tungsten fibers was investigated in terms of material properties which include thermal expansion, thermal conductivity, compressive fracture stress, modulus of elasticity, and phase stability in terms of the processing parameters of hot pressing pressure and/or density, degree of stabilization of the hafnia, and composition. All other parameters were held constant or assumed constant. The thermal shock resistance was directly proportional to the compressive fracture stress to modulus of elasticity ratio and was not affected appreciably by the small thermal expansion or thermal conductivity changes. This ratio was found to vary strongly with the composition and density such that the composites containing graphite had relatively poor thermal shock resistance, while the composites containing tungsten had superior thermal shock resistance.

  3. Disruption of the NADPH-dependent glutamate dehydrogenase affects the morphology of two industrial strains of Penicillium chrysogenum

    DEFF Research Database (Denmark)

    Thykær, Jette; Kildegaard, Kanchana Rueksomtawin; Noorman, H.

    2009-01-01

    New morphological aspects of Penicillium chrysogenum were found during physiological characterisation of two NADPH-dependent glutamate dehydrogenase mutant strains. A morphological characterisation of the previously constructed strains, together with the two beta-lactam producing industrial recip...

  4. Growing Menace of Antibacterial Resistance in Clinical Isolates of Pseudomonas aeruginosa in Nepal: An Insight of Beta-Lactamase Production

    Directory of Open Access Journals (Sweden)

    Shamshul Ansari

    2016-01-01

    Full Text Available Introduction. Pseudomonas aeruginosa is the most frequently isolated organism as it acts as the opportunistic pathogen and can cause infections in immunosuppressed patients. The production of different types of beta-lactamases renders this organism resistant to many commonly used antimicrobials. Therefore, the aim of this study was to document the antibiotic resistance rate in Pseudomonas aeruginosa isolated from different clinical specimens. Methods. Pseudomonas aeruginosa recovered was identified by standard microbiological methods. Antibiotic susceptibility testing was performed by modified Kirby-Bauer disc diffusion method following Clinical and Laboratory Standard Institute (CLSI guidelines and all the suspected isolates were tested for the production of ESBLs, MBLs, and AmpC. Results. Out of total (178 isolates, 83.1% were recovered from the inpatient department (IPD. Majority of the isolates mediated resistance towards the beta-lactam antibiotics, while nearly half of the isolates were resistant to ciprofloxacin. Most of the aminoglycosides used showed resistance rate up to 75% but amikacin proved to be better option. No resistance to polymyxin was observed. ESBLs, MBLs, and AmpC mediated resistance was seen in 33.1%, 30.9%, and 15.7% isolates, respectively. Conclusions. Antibiotic resistance rate and beta-lactamase mediated resistance were high. Thus, regular surveillance of drug resistance is of utmost importance.

  5. Antimicrobial resistance of Staphylococcus pseudintermedius isolates from healthy dogs and dogs affected with pyoderma in Japan.

    Science.gov (United States)

    Onuma, Kenta; Tanabe, Taishi; Sato, Hisaaki

    2012-02-01

    Staphylococcus pseudintermedius strains were isolated from healthy dogs and dogs with pyoderma in 2000-2002 and 2009. All the isolates from dogs with pyoderma in 1999-2000 and from healthy dogs in 2000-2002 and 2009 were susceptible to cefalexin and/or other cephalosporins and oxacillin. However, 7.1-12.5 and 11.4% of S. pseudintermedius isolates from dogs with pyoderma in 2009 were resistant to cephalosporins and oxacillin, respectively. All S. pseudintermedius isolates from dogs with pyoderma in 1999-2000 and those from healthy dogs in 2000-2002 were susceptible to fluoroquinolones; however, 50% of the S. pseudintermedius strains isolated from dogs with pyoderma in 2009 and 30% of the S. pseudintermedius strains isolated from healthy dogs in 2009 were resistant to fluoroquinolones. Of the 21 oxacillin-resistant S. pseudintermedius (MRSP) isolates, 11 carried SCCmec type V and 10 carried hybrid SCCmec types II-III. Staphylococcus pseudintermedius strains that were resistant to only one of three fluoroquinolones had a mutation in the quinolone resistance determination region of grlA, whereas S. pseudintermedius strains that were resistant to two or more fluoroquinolones had mutations in the quinolone resistance determination regions of both grlA and gyrA.

  6. Behavioral Avoidance - Will Physiological Insecticide Resistance Level of Insect Strains Affect Their Oviposition and Movement Responses?

    Science.gov (United States)

    Nansen, Christian; Baissac, Olivier; Nansen, Maria; Powis, Kevin; Baker, Greg

    2016-01-01

    Agricultural organisms, such as insect herbivores, provide unique opportunities for studies of adaptive evolutionary processes, including effects of insecticides on movement and oviposition behavior. In this study, Brassica leaves were treated with one of two non-systemic insecticides and exposed to two individual strains (referred to as single or double resistance) of diamondback moth (Plutella xylostella) (DBM) exhibiting physiological resistance. Behavioral responses by these two strains were compared as part of characterizing the relative effect of levels of physiological resistance on the likelihood of insects showing signs of behavioral avoidance. For each DBM strain, we used choice bioassays to quantify two possible types of behavioral avoidance: 1) females ovipositing predominantly on leaf surfaces without insecticides, and 2) larvae avoiding insecticide-treated leaf surfaces. In three-choice bioassays (leaves with no pesticide, 50% coverage with pesticide, or 100% coverage with pesticide), females from the single resistance DBM strain laid significantly more eggs on water treated leaves compared to leaves with 100% insecticide coverage (both gamma-cyhalothrin and spinetoram). Females from the double resistance DBM strain also laid significantly more eggs on water treated leaves compared to leaves with 100% gamma-cyhalothrin, while moths did not adjust their oviposition behavior in response to spinetoram. Larvae from the single resistance DBM strain showed a significant increase in mobility in response to both insecticides and avoided insecticide-treated portions of leaves when given a choice. On the other hand, DBM larvae from the double resistance strain showed a significant decrease in mobility in response to insecticides, and they did not avoid insecticide-treated portions of leaves when given a choice. Our results suggest that pest populations with physiological resistance may show behavioral avoidance, as resistant females avoided oviposition on

  7. Structures of ceftazidime and its transition-state analogue in complex with AmpC beta-lactamase: Implications for resistance mutations and inhibitor design

    Energy Technology Data Exchange (ETDEWEB)

    Powers, R.A.; Caselli, E.; Focia, P.J.; Prati, F.; Shoichet, B.K.

    2010-03-08

    Third-generation cephalosporins are widely used {beta}-lactam antibiotics that resist hydrolysis by {beta}-lactamases. Recently, mutant {beta}-lactamases that rapidly inactivate these drugs have emerged. To investigate why third-generation cephalosporins are relatively stable to wild-type class C {beta}-lactamases and how mutant enzymes might overcome this, the structures of the class C {beta}-lactamase AmpC in complex with the third-generation cephalosporin ceftazidime and with a transition-state analogue of ceftazidime were determined by X-ray crystallography to 2.0 and 2.3 {angstrom} resolution, respectively. Comparison of the acyl-enzyme structures of ceftazidime and loracarbef, a {beta}-lactam substrate, reveals that the conformation of ceftazidime in the active site differs from that of substrates. Comparison of the structures of the acyl-enzyme intermediate and the transition-state analogue suggests that ceftazidime blocks formation of the tetrahedral transition state, explaining why it is an inhibitor of AmpC. Ceftazidime cannot adopt a conformation competent for catalysis due to steric clashes that would occur with conserved residues Val211 and Tyr221. The X-ray crystal structure of the mutant {beta}-lactamase GC1, which has improved activity against third-generation cephalosporins, suggests that a tandem tripeptide insertion in the {Omega} loop, which contains Val211, has caused a shift of this residue and also of Tyr221 that would allow ceftazidime and other third-generation cephalosporins to adopt a more catalytically competent conformation. These structural differences may explain the extended spectrum activity of GC1 against this class of cephalosporins. In addition, the complexed structure of the transition-state analogue inhibitor (K{sub i} 20 nM) with AmpC reveals potential opportunities for further inhibitor design.

  8. Antimicrobial resistance in respiratory pathogens isolated in Brazil during 1999-2000

    Directory of Open Access Journals (Sweden)

    Critchley Ian A.

    2001-01-01

    Full Text Available The in vitro antimicrobial susceptibility of the respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis to commonly tested and prescribed agents was investigated during 1999-2000 and compared with results obtained during a previous 1997-1998 study. Of 448 isolates of S. pneumoniae collected and tested in 1999-2000, 77.2% were susceptible, 19.9% were intermediate, and 2.9% were resistant to penicillin, demonstrating that there were no major changes in susceptibility to penicillin from 1997-1998 (77.1% susceptible, 18.7% intermediate, 4.2% resistant. All S. pneumoniae isolates from 1999-2000 were susceptible to levofloxacin and vancomycin, and >90% were susceptible to the beta-lactams (amoxicillin-clavulanate, ceftriaxone, and cefuroxime and macrolides (azithromycin and clarithromycin, showing that susceptibility to these agents also remained unchanged since 1997-1998. The most notable increase in resistance between the two studies was demonstrated by trimethoprim-sulfamethoxazole, which increased from 23.4% to 38.6%. Penicillin resistance correlated with resistance to beta-lactams, macrolides, and trimethoprim-sulfamethoxazole in both studies. In H. influenzae, the prevalence of beta-lactamase-producing isolates remained unchanged (10.6% in 1999-2000; 11.0% in 1997-1998. All H. influenzae isolates were susceptible to levofloxacin, ceftriaxone, cefuroxime, and azithromycin, and showed no change between the two studies. Trimethoprim-sulfamethoxazole resistance was present in 40.1% of isolates in 1999-2000, and in 45.2% in 1997-1998. In M. catarrhalis, the prevalence of beta-lactamase-producing isolates was unchanged (97.9% in 1999-2000; 98.0% in 1997-1998. The most active agents against M. catarrhalis were azithromycin (MIC90, <0.03 mug/ml and levofloxacin (MIC90, 0.03 mug/ml. Overall, these results suggest that, in Brazil, between 1999-2000 and 1997-1998, there have been no significant changes in the

  9. Captures of MFO-resistant Cydia pomonella adults as affected by lure, crop management system and flight.

    Science.gov (United States)

    Bosch, D; Rodríguez, M A; Avilla, J

    2016-02-01

    The main resistance mechanism of codling moth (Cydia pomonella) in the tree fruit area of Lleida (NE Spain) is multifunction oxidases (MFO). We studied the frequency of MFO-resistant adults captured by different lures, with and without pear ester, and flights in orchards under different crop management systems. The factor year affected codling moth MFO-resistance level, particularly in the untreated orchards, highlighting the great influence of codling moth migration on the spread of resistance in field populations. Chemical treatments and adult flight were also very important but mating disruption technique showed no influence. The second adult flight showed the highest frequency, followed by the first flight and the third flight. In untreated orchards, there were no significant differences in the frequency of MFO-resistant individuals attracted by Combo and BioLure. Red septa lures baited with pear ester (DA) captured sufficient insects only in the first generation of 2010, obtaining a significantly lower proportion of MFO-resistant adults than Combo and BioLure. In the chemically treated orchards, in 2009 BioLure caught a significantly lower proportion of MFO-resistant adults than Combo during the first and third flight, and also than DA during the first flight. No significant differences were found between the lures or flights in 2010. These results cannot support the idea of a higher attractiveness of the pear ester for MFO-resistant adults in the field but do suggest a high influence of the response to the attractant depending on the management of the orchard, particularly with regard to the use of chemical insecticides.

  10. Epidemiology and resistance patterns in urinary pathogens from long-term care facilities and GP populations.

    LENUS (Irish Health Repository)

    Brabazon, E D

    2012-06-01

    Urinary tract infections (UTIs) are a major source of antimicrobial prescribing in the clinical setting and a potential reservoir for the emergence of resistant organisms. Although studies have been published on resistance rates for urinary pathogens from both hospital and general practitioner (GP) settings, there is little information from Long-Term Care Facilities (LTCFs) in Ireland. This study aimed to document the epidemiology and resistance rates in urinary isolates, in the LTCF and GP setting, from samples submitted to a typical microbiology laboratory. In 2010, there were 963 urinary isolates from LTCFs and 1,169 urinary isolates from GPs, identified from patients 65 years and over, with cytology suggestive of infection. E. coil was the most common causative organism identified. There were significantly higher levels of resistance to ampicillin, co-amoxiclav, ciprofloxacin, nitrofurantoin, trimethoprim, and piperacillin\\/tazobactam in the LTCF population compared to the GP population (e.g. for E. coli, 86%-v-69%; 30%-v- 21%; 58%-v-26%, 10%-v-3%, 68%-v-48%, 10%-v- 4% respectively). Isolates with resistance mechanisms to beta-lactams, were identified in both populations. Results presented in this paper demonstrate significant differences between resistance rates in LTCF and GP populations which suggest that there are implications for empiric antimicrobial prescribing for UTIs in the LTCF setting.

  11. Diversity of fecal coliforms and their antimicrobial resistance patterns in wastewater treatment model plant.

    Science.gov (United States)

    Luczkiewicz, A; Fudala-Ksiazek, S; Jankowska, K; Quant, B; Olańczuk-Neyman, K

    2010-01-01

    The occurrence of resistance patterns among wastewater fecal coliforms was determined in the study. Susceptibility of the isolates was tested against 19 antimicrobial agents: aminoglycosides, aztreonam, carbapenems, cephalosporines, beta-lactam/beta-lactamase inhibitors, penicillines, tetracycline, trimethoprim/sulfamethoxazole, and fluoroquinolones. Additionally the removal of resistant isolates was evaluated in the laboratory-scale wastewater treatment model plant (M-WWTP), continuously supplied with the wastewater obtained from the full-scale WWTP. Number of fecal coliforms in raw (after mechanical treatment) and treated wastewater, as well as in aerobic chamber effluent was determined using selective medium. The selected strains were identified and examined for antibiotic resistance using Phoenix Automated Microbiology System (BD Biosciences, USA). The strains were identified as Escherichia coli (n=222), Klebsiella pneumoniae ssp. ozaenae (n=9), and Pantoea agglomerans (n=1). The isolate of P. agglomerans as well as 48% of E. coli isolates were sensitive to all antimicrobials tested. The most frequent resistance patterns were found for ampicillin: 100% of K. pneumoniae ssp. ozaenae and 41% of E. coli isolates. Among E. coli isolates 12% was regarded as multiple antimicrobial resistant (MAR). In the studied M-WWTP, the applied activated sludge processes reduced considerably the number of fecal coliforms, but increased the ratio of antimicrobial-resistant E. coli isolates to sensitive ones, especially among strains with MAR patterns.

  12. Multidrug resistance and ESBL-producing Salmonella spp. isolated from broiler processing plants

    Directory of Open Access Journals (Sweden)

    Rosangela Estel Ziech

    2016-03-01

    Full Text Available Abstract The aim of this study was to investigate the occurrence of multidrug-resistant, extended spectrum beta-lactamase (ESBL producing Salmonella spp. isolated from conveyor belts of broiler cutting rooms in Brazilian broiler processing plants. Ninety-eight strains of Salmonella spp. were analyzed. Multidrug resistance was determined by the disk diffusion test and the susceptibility of the isolated bacteria was evaluated against 18 antimicrobials from seven different classes. The double disk diffusion test was used to evaluate ESBL production. Of the 98 strains tested, 84 were multidrug resistant. The highest rates of resistance were against nalidixic acid (95%, tetracycline (91%, and the beta-lactams: ampicillin and cefachlor (45%, followed by streptomycin and gentamicin with 19% and 15% of strain resistance, respectively. By contrast, 97% of the strains were sensitive to chloramphenicol. 45% of the strains were positive for the presence of ESBL activity. In this study, high rates of multidrug resistance and ESBL production were observed in Salmonella spp.

  13. Multidrug resistance and ESBL-producing Salmonella spp. isolated from broiler processing plants

    Science.gov (United States)

    Ziech, Rosangela Estel; Lampugnani, Camila; Perin, Ana Paula; Sereno, Mallu Jagnow; Sfaciotte, Ricardo Antônio Pilegi; Viana, Cibeli; Soares, Vanessa Mendonça; de Almeida Nogueira Pinto, José Paes; dos Santos Bersot, Luciano

    2016-01-01

    The aim of this study was to investigate the occurrence of multidrug-resistant, extended spectrum beta-lactamase (ESBL) producing Salmonella spp. isolated from conveyor belts of broiler cutting rooms in Brazilian broiler processing plants. Ninety-eight strains of Salmonella spp. were analyzed. Multidrug resistance was determined by the disk diffusion test and the susceptibility of the isolated bacteria was evaluated against 18 antimicrobials from seven different classes. The double disk diffusion test was used to evaluate ESBL production. Of the 98 strains tested, 84 were multidrug resistant. The highest rates of resistance were against nalidixic acid (95%), tetracycline (91%), and the beta-lactams: ampicillin and cefachlor (45%), followed by streptomycin and gentamicin with 19% and 15% of strain resistance, respectively. By contrast, 97% of the strains were sensitive to chloramphenicol. 45% of the strains were positive for the presence of ESBL activity. In this study, high rates of multidrug resistance and ESBL production were observed in Salmonella spp. PMID:26887244

  14. Development of ceftriaxone resistance affects the virulence properties of Salmonella enterica serotype Typhimurium strains.

    Science.gov (United States)

    Li, Liang; Yang, Yu-Rong; Liao, Xiao-Ping; Lei, Chun-Yin; Sun, Jian; Li, Lu-Lu; Liu, Bao-Tao; Yang, Shou-Shen; Liu, Ya-Hong

    2013-01-01

    Development of antibiotic resistance may alter the virulence properties of bacterial organisms. In this study, nine clinical ceftriaxone-susceptible Salmonella enterica serotype Typhimurium strains were subjected to stepwise selection with increasing concentrations of ceftriaxone in culture media. Mutations in virulence-associated genes and antibiotic efflux genes were analyzed by polymerase chain reaction (PCR) and DNA sequencing. The expression levels of virulence genes invA and stn as well as efflux pump genes tolC, arcA, and arcB before and after the selection were measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The stepwise selection resulted in the development of Salmonella strains that were highly resistant to ceftriaxone. Sequence analysis did not reveal any mutations or deletions in the examined virulence genes and regulatory gene, but a silent mutation (T423C) in acrR (encoding a repressor for the efflux pump) was detected in most of the ceftriaxone-resistant strains. The qRT-PCR revealed increased expression of the AcrAB-TolC efflux pump and decreased expression of invA and stn in the ceftriaxone-resistant strains. Moreover, decreased invasion into cultured epithelial cells and reduced growth rates were observed with the resistant strains. These results suggest that acquisition of ceftriaxone resistance is associated with the overexpression of the AcrAB-TolC efflux pump and leads to reduced virulence in Salmonella Typhimurium.

  15. Study of the Raveling Resistance of Porous Asphalt Pavements Used in Sustainable Drainage Systems Affected by Hydrocarbon Spills

    Directory of Open Access Journals (Sweden)

    Jorge Rodriguez-Hernandez

    2015-12-01

    Full Text Available Permeable pavements are one of the most commonly-used sustainable drainage systems (SuDS in urban areas for managing stormwater runoff problems. Porous asphalt is widely used in surface layers of permeable pavement systems, where it can suffer from accidental oil spills from vehicles. Oil spills affect bituminous mixes through the solvent action of the hydrocarbons on the bitumen, reducing the raveling resistance of asphalt pavements. In order to assess the raveling resistance in porous asphalt pavements, the Cantabro abrasion test was performed on 200 test samples after applying controlled oil spills. Three different types of binders were used: conventional bitumen, polymer-modified bitumen and special fuel-resistant bitumen. After analyzing the results, it was concluded that the most suitable bitumen to protect against oil leakages is the polymer-modified one, which is far better than the other two types of bitumen tested.

  16. Mutations in eukaryotic 18S ribosomal RNA affect translational fidelity and resistance to aminoglycoside antibiotics.

    Science.gov (United States)

    Chernoff, Y O; Vincent, A; Liebman, S W

    1994-02-15

    Mutations have been created in the Saccharomyces cerevisiae 18S rRNA gene that correspond to those known to be involved in the control of translational fidelity or antibiotic resistance in prokaryotes. Yeast strains, in which essentially all chromosomal rDNA repeats are deleted and all cellular rRNAs are encoded by plasmid, have been constructed that contain only mutant 18S rRNA. In Escherichia coli, a C-->U substitution at position 912 of the small subunit rRNA causes streptomycin resistance. Eukaryotes normally carry U at the corresponding position and are naturally resistant to streptomycin. We show that a U-->C transition (rdn-4) at this position of the yeast 18S rRNA gene decreases resistance to streptomycin. The rdn-4 mutation also increases resistance to paromomycin and G-418, and inhibits nonsense suppression induced by paromomycin. The same phenotypes, as well as a slow growth phenotype, are also associated with rdn-2, whose prokaryotic counterpart, 517 G-->A, manifests itself as a suppressor rather than an antisuppressor. Neither rdn-2- nor rdn-4-related phenotypes could be detected in the presence of the normal level of wild-type rDNA repeats. Our data demonstrate that eukaryotic rRNA is involved in the control of translational fidelity, and indicate that rRNA features important for interactions with aminoglycosides have been conserved throughout evolution.

  17. Analysis of the Factors Affecting Resistance to Changes in Management Accounting Systems

    Directory of Open Access Journals (Sweden)

    Rodrigo Angonese

    2014-12-01

    Full Text Available Despite changes in the environment and management accounting practices, studies indicate that management accounting systems do not change or change at a much slower rate than expected. The stability of the management accounting systems used by companies may relate to resistance to changing these systems. This study analyzes the factors that contribute to resistance to implementing an integrated management system from the perspective of institutional theory, grounded in the old institutional economics. Methodologically, this study provides a qualitative assessment of the problem and a descriptive analysis of the resistance factors through a case-study approach. The data were collected using semi-structured interviews and analyzed through content analysis. Two companies were selected for this study due to their differing characteristics. The following seven factors were analyzed for resistance to implementing integrated management systems: institutional power, ontological insecurity, trust, inertia, lack of knowledge, acceptance of routines and decoupling. However, there was no evidence to characterize hierarchical power. The research findings indicate that changing management accounting systems, through the implementation of an integrated management system, faces internal resistance in these organizations. Each factor varies in intensity but is permanently present in these companies, such as ontological insecurity, trust, inertia, lack of knowledge, acceptance of routines and decoupling. These factors are awakened when the change process begins and, if they gather enough force, can stop the change.

  18. Reduced expression of PBP-2A by neonatal mecA-positive coagulase-negative staphylococci (CoNS) blood isolates : beta-lactams are useful first-line agents for the treatment of neonatal CoNS sepsis, restricting the use of vancomycin

    NARCIS (Netherlands)

    Fleer, Andre; Hemels, Marieke A. C.; Paauw, Armand; Krediet, Tannette G.

    2012-01-01

    Vancomycin use for neonatal coagulase-negative staphylococci (CoNS) sepsis is based on a high CoNS carriage rate of mecA, encoding penicillin-binding protein (PBP)-2a, with low affinity for, and associated with resistance to, -lactam antibiotics. The relationship between mecA gene carriage, phenotyp

  19. Bacterial load of fresh vegetables and their resistance to the currently used antibiotics in Saudi Arabia.

    Science.gov (United States)

    Hassan, Sabry A; Altalhi, Abdullah D; Gherbawy, Youssuf A; El-Deeb, Bahig A

    2011-09-01

    This study was carried out to describe the bacterial load and the occurrence of some disease-causing enteric bacteria on raw vegetables sold in Saudi markets. The study further aimed to analyze antibiotic resistance rates, production of extended-spectrum beta lactamase, and plasmid carriage among bacterial population of raw vegetables. Results revealed that none of them contained Bacillus cereus, Salmonella, and Escherichia coli O157:H7. However, Staphylococcus aureus and Shigella were detected in 11.8% and 4.4% of the samples, respectively. The bacterial loads ranged from 3 to 8 log(10) CFUg(-1) for aerobic bacteria and 1 to 4 log(10) CFUg(-1) for coliforms as well as Enterobacteriaceae. The isolates exhibited resistance in decreasing order for ampicillin (76.5%), cephalothin (69.5%), trimethoprime-sulfamethoxazole (36.7%), aminoglycosides (21.9%), tetracycline (17.2%), fluoroquinolones (17.2%), amoxycillin-clavulanic acid (13.3%), and chloramphenicol (7.8%). Maximum resistance to extended-spectrum beta-lactam antibiotics occurred in 14.8% of isolates and the production of extended-spectrum beta-lactamase was achieved by 2.3% of isolates. Multiple resistances to four or more antimicrobial agents along with plasmid with varied sizes were documented. These investigations indicate the occurrence of antibiotic resistance and plasmid carriage among bacterial isolates populating raw vegetables.

  20. PREVALENCE AND ANTIMICROBIAL RESISTANCE PATTERN OF EXTENDED SPECTRUM BETA LACTAMASE PRODUCING KLEBSIEL LA SPP

    Directory of Open Access Journals (Sweden)

    Sunanda

    2013-03-01

    Full Text Available ABSTRACT: INTRODUCTION AND OBJECTIVES: Extended spectrum beta lactamase (ESBL producing Klebsiella spp have emerged as an important pathogen due to their high resistance against most of the antibiotics. Their detection an d antibiotic resistance pattern is required for proper management of cases. In this study we report th e prevalence and antibiotic resistance of such Klebsiella isolates. METHODS: A total of 100 clinical isolates of Klebsiella fro m different clinical samples were tested for ESBL production by d ouble disc approximation test and CLSI phenotypic method. Antibiotic susceptibility of all th e Klebsiella isolates were performed by Kirby-Bauer disc diffusion test. RESULTS: of 100 Klebsiella isolates 53 showed ESBL production. All ESBL producers were resistant to beta lactam antibiotics. Antibiotic resistance among ESBL producing strains was high as compared to non ESBL producing strains. INTERPRETATION & CONCLUSION: In the present study a large number of Klebsiella s pp. isolated were found to be ESBL producers. Continuing monitoring of ESBL production and antimicrobial susceptibility testing is essential to avoid treatment failure.

  1. Antibiotic resistance in coagulase negative staphylococci isolated from wastewater and drinking water.

    Science.gov (United States)

    Faria, Cátia; Vaz-Moreira, Ivone; Serapicos, Eduarda; Nunes, Olga C; Manaia, Célia M

    2009-06-01

    This study reports the antibiotic resistance patterns of coagulase negative staphylococci (CNS) isolated from a drinking water treatment plant (WTP), a drinking water distribution network, responsible for supplying water to the consumers (WDN), and a wastewater treatment plant (WWTP), responsible for receiving and treating domestic residual effluents. Genotyping and the 16S rRNA gene sequence analysis demonstrated a higher diversity of species both in the WTP (6 species/19 isolates) and WWTP (12 species/47 isolates) than in the WDN (6 species/172 isolates). Staphylococcus pasteuri and Staphylococcus epidermidis prevailed in the WTP and WDN and Staphylococcus saprophyticus in the WWTP. Staphylococci with reduced susceptibility (resistance or intermediary phenotype) to beta-lactams, tetracycline, clindamycin and erythromycin were observed in all types of water and belonged to the three major species groups. The highest resistance rate was found against erythromycin, presumably due to the presence of the efflux pump encoded by the determinant msrA, detected in the majority of the resistant isolates. This study demonstrates that antibiotic resistant CNS may colonize different types of water, namely drinking water fulfilling all the quality standards.

  2. Antibiotic resistance in lactic acid bacteria isolated from some pharmaceutical and dairy products

    Directory of Open Access Journals (Sweden)

    Gamal Fadl M. Gad

    2014-01-01

    Full Text Available A total of 244 lactic acid bacteria (LAB strains were isolated from 180 dairy and pharmaceutical products that were collected from different areas in Minia governorate, Egypt. LAB were identified phenotypically on basis of morphological, physiological and biochemical characteristics. Lactobacillus isolates were further confirmed using PCR-based assay. By combination of phenotypic with molecular identification Lactobacillus spp. were found to be the dominant genus (138, 76.7% followed by Streptococcus spp. (65, 36.1% and Lactococcus spp. (27, 15%. Some contaminant organisms such as (Staphylococcus spp., Escherichia coli, Salmonella spp., mould and yeast were isolated from the collected dairy samples but pharmaceutical products were free of such contaminants. Susceptibility of LAB isolates to antibiotics representing all major classes was tested by agar dilution method. Generally, LAB were highly susceptible to Beta-lactams except penicillin. Lactobacilli were resistant to vancomycin, however lactococci and streptococci proved to be very susceptible. Most strains were susceptible to tetracycline and showed a wide range of streptomycin MICs. The MICs of erythromycin and clindamycin for most of the LAB were within the normal range of susceptibility. Sixteen Lactobacillus,8 Lactococcus and 8 Streptococcus isolates including all tetracycline and/or erythromycin resistant strains were tested for the presence of tetracycline and/or erythromycin resistant genes [tet(M and/or erm(B]. PCR assays shows that some resistant strains harbor tet(M and/or erm(B resistance genes.

  3. Methuselah-like genes affect development, stress resistance, lifespan and reproduction in Tribolium castaneum.

    Science.gov (United States)

    Li, Chengjun; Zhang, Yi; Yun, Xiaopei; Wang, Yanyun; Sang, Ming; Liu, Xing; Hu, Xingxing; Li, Bin

    2014-10-01

    Methuselah (Mth) is associated with lifespan, stress resistance and reproduction in Drosophila melanogaster, but Mth is not present in nondrosophiline insects. A number of methuselah-likes (mthls) have been identified in nondrosophiline insects, but it is unknown whether the functions of mth are shared by mthls or are divergent from them. Five mthls have been identified in Tribolium castaneum. Although they have different developmental expression patterns, they all enhance resistance to starvation. Only mthl1 and mthl2 enhance resistance to high temperature, whereas mthl4 and mthl5 negatively regulate oxidative stress in T. castaneum. Unlike in the fly with mth mutation, knockdown of mthls, except mthl3, shortens the lifespan of T. castaneum. Moreover, mthl1 and mthl2 are critical for Tribolium development. mthl1 plays important roles in larval and pupal development and adult eclosion, while mthl2 is required for eclosion. Moreover, mthl1 and mthl2 silencing reduces the fertility of T. castaneum, and mthl1 and mthl4 are also essential for embryo development. In conclusion, mthls have a significant effect on insect development, lifespan, stress resistance and reproduction. These results provide experimental evidence for functional divergence among mthls/mth and clues for the signal transduction of Mthls.

  4. Characterization of Arabidopsis enhanced disease susceptibility mutants that are affected in systemically induced resistance

    NARCIS (Netherlands)

    Ton, J.; Vos, M. de; Robben, C.; Buchala, Anthony; Métraux, Jean-Pierre; Loon, L.C. van; Pieterse, C.M.J.

    2002-01-01

    In Arabidopsis, the rhizobacterial strain Pseudomonas fluorescens WCS417r triggers jasmonate (JA)- and ethylene (ET)-dependent induced systemic resistance (ISR) that is effective against different pathogens. Arabidopsis genotypes unable to express rhizobacteria-mediated ISR against the bacterial pat

  5. Glufosinate does not affect floral morphology and pollen viability in glufosinate-resistant cotton (Gossypium hirsutum)

    Science.gov (United States)

    Studies were conducted to determine whether glufosinate treatments to glufosinate-resistant cotton caused changes in floral morphology, pollen viability, and seed set. Four glufosinate treatments were included: (1) glufosinate applied postemergence over the top (POST) at the four-leaf stage, (2) glu...

  6. Selective pressure affects transfer and establishment of a Lactobacillus plantarum resistance plasmid in the gastrointestinal environment

    DEFF Research Database (Denmark)

    Feld, Louise; Schjorring, S.; Hammer, Karin;

    2008-01-01

    Objectives and methods: A Lactobacillus plantarum strain recently isolated from French raw-milk cheese was tested for its ability to transfer a small plasmid pLFE1 harbouring the erythromycin resistance gene erm(B) to Enterococcus faecalis. Mating was studied in vitro and in different...

  7. Rate of conditioned reinforcement affects observing rate but not resistance to change.

    Science.gov (United States)

    Shahan, Timothy A; Podlesnik, Christopher A

    2005-07-01

    The effects of rate of conditioned reinforcement on the resistance to change of operant behavior have not been examined. In addition, the effects of rate of conditioned reinforcement on the rate of observing have not been adequately examined. In two experiments, a multiple schedule of observing-response procedures was used to examine the effects of rate of conditioned reinforcement on observing rates and resistance to change. In a rich component, observing responses produced a higher frequency of stimuli correlated with alternating periods of random-interval schedule primary reinforcement or extinction. In a lean component, observing responses produced similar schedule-correlated stimuli but at a lower frequency. The rate of primary reinforcement in both components was the same. In Experiment 1, a 4:1 ratio of stimulus production was arranged by the rich and lean components. In Experiment 2, the ratio of stimulus production rates was increased to 6:1. In both experiments, observing rates were higher in the rich component than in the lean component. Disruptions in observing produced by presession feeding, extinction of observing responses, and response-independent food deliveries during intercomponent intervals usually were similar in the rich and lean components. When differences in resistance to change did occur, observing tended to be more resistant to change in the lean component. If resistance to change is accepted as a more appropriate measure of response strength than absolute response rates, then the present results provide no evidence that higher rates of stimuli generally considered to function as conditioned reinforcers engender greater response strength.

  8. Structural transformations and wear resistance of abrasive-affected amorphous Fe- and Co-based alloys

    Science.gov (United States)

    Korshunov, L. G.; Chernenko, N. L.

    2008-12-01

    The abrasive wear resistance of the Fe64Co30Si3B3, Fe82.6Nb5Cu3Si8B1.4, Co86.5Cr4Si7B2.5, and Fe81Si4B13C2 amorphous alloys (ribbon 30 μm thick) has been investigated upon sliding over fixed abrasives (corundum and silicon carbide). The character of fracture of the surface and structural transformations initiated in these materials by the abrasive action have been studied by the metallographic, X-ray diffraction, and electron-microscopic methods. It has been shown that the abrasive wear resistance of the amorphous alloys is smaller by a factor of 1.6-2.9 than that of the Kh12M and U8 tool steels possessing approximately the same level of hardness. A pronounced softening of the surface layer of the amorphous alloys in the process of wear, which is characterized by a decrease in their microhardness reaching 12.5%, has been found. It has been shown that in the surface layer of these amorphous alloys upon wear there arises a small amount (on the order of several volume percent) of the nanocrystalline structure, which does not exert a marked effect on the microhardness and wear resistance of the alloys. In the alloys under study, the main factor that is responsible for their comparatively low abrasive wear resistance is their local softening in the process of wear caused by specific features of deformation processes occurring heterogeneously under the action of high shear contact stresses.

  9. Soil penetration resistance in a rhodic eutrudox affected by machinery traffic and soil water content.

    OpenAIRE

    Moraes,Moacir T. de; Debiasi,Henrique; Julio C. Franchini; Silva,Vanderlei R. da

    2013-01-01

    Soil compaction caused by machinery traffic reduces crop yields. This study aimed to evaluate the effects of intensive traffic, and the soil water content, on the soil penetration resistance (PR) of a Rhodic Eutrudox (Distroferric Red Latosol, Brazilian Classification), managed under no-tillage (NT). The experiment consisted of six treatments: NT with recent chiseling, NT without additional compaction, and NT with additional compaction by 4, 8, 10 and 20 passes of a harvester with a weight of...

  10. FACTORS AFFECTING VARIABILITY OF RESISTANCE IN GAROLE SHEEP NATURALLY INFECTED WITH HAEMONCHUS CONTORTUS

    Directory of Open Access Journals (Sweden)

    Manoranjan Roy

    2013-06-01

    Full Text Available Resistance status against natural infection to Haemonchus contortus as well as influence of season, sex, body weight, and haemoglobin type on resistance levels were evaluated in 309 numbers of Garole sheep. In adult Garole sheep, egg per gram(EPG of faeces for Haemonchus contortus was varied from 300 to 1600, but overall EPG in Garole have been recorded as 829.96 ± 20.60. The effects of season, sex, and body weight and haemoglobin type on EPG were all found to be highly significant (P < 0.01. EPG count was highest during monsoon (986.27 ± 28.26, followed by summer (832.88 ± 28.26 and lowest during winter (670.74 ± 28.26 which indicated the existence of a seasonal variation of EPG. Rams had higher EPG (954.32 ± 57.93 than ewes (705.60 ± 45.79 which reflected that males appeared to be more susceptible to Haemonchus contortus infection compared to females. Animals with lower body weight (upto 10 kg showed higher EPG (1017.20 ± 54.82, then the infection level decreased as body weight increased (886.79 ± 56.23 for 10 kg to 12 kg and 737.18 ± 50.29 for 12 kg to 14 kg and lowest EPG was recorded in animals with above 14 kg body weight (678.68 ± 54.49. This study reveals Hb-BB type animals had higher EPG count (983.81 ± 18.22 in comparison to Hb-AB type animals (676.12 ± 33.96 indicating that Haemoglobin-A locus has some relation with resistance. From our study it can be concluded that resistant level of Garole sheep against Haemonchus contortus is influenced by some intrinsic factors like sex, body weight, and haemoglobin type of the sheep and also by extrinsic factor like season.

  11. Promoter strength of folic acid synthesis genes affects sulfa drug resistance in Saccharomyces cerevisiae.

    Science.gov (United States)

    Iliades, Peter; Berglez, Janette; Meshnick, Steven; Macreadie, Ian

    2003-01-01

    The enzyme dihydropteroate synthase (DHPS) is an important target for sulfa drugs in both prokaryotic and eukaryotic microbes. However, the understanding of DHPS function and the action of antifolates in eukaryotes has been limited due to technical difficulties and the complexity of DHPS being a part of a bifunctional or trifunctional protein that comprises the upstream enzymes involved in folic acid synthesis (FAS). Here, yeast strains have been constructed to study the effects of FOL1 expression on growth and sulfa drug resistance. A DHPS knockout yeast strain was complemented by yeast vectors expressing the FOL1 gene under the control of promoters of different strengths. An inverse relationship was observed between the growth rate of the strains and FOL1 expression levels. The use of stronger promoters to drive FOL1 expression led to increased sulfamethoxazole resistance when para-aminobenzoic acid (pABA) levels were elevated. However, high FOL1 expression levels resulted in increased susceptibility to sulfamethoxazole in pABA free media. These data suggest that up-regulation of FOL1 expression can lead to sulfa drug resistance in Saccharomyces cerevisiae.

  12. VARNISH LAYER HARDNESS, SCRATCH RESISTANCE, AND GLOSSINESS OF VARIOUS WOOD SPECIES AS AFFECTED BY HEAT TREATMENT

    Directory of Open Access Journals (Sweden)

    Nevzat Çakıcıer

    2011-03-01

    Full Text Available The aim of the study was to determine the effects of different heat treatment and varnish application combinations on hardness, scratch resistance, and glossiness of wood materials sampled from limba (Terminalia superba, iroko (Chlorophora excelsa, ash (Fraxinus excelsior L., and Anatolian chestnut (Castenea sativa Mill. species. The heat treatment was applied at two levels (150 and 180 oC for both 3 and 6 hour periods. After the heat treatment, four types of varnish (cellulose lacquer, synthetic varnish, polyurethane varnish, and water based varnish were applied, and hardness, scratch resistance, and glossiness of varnish film layers of the treated woods were measured. The effects of heat treatment and varnish combination applications on above mentioned variables were analyzed according to the study design (factorial design with 4 (species x 2 (heat x 2(duration x 4 (varnish = 64 experimental units with 10 samples for each combination of parameters. Glossiness increased on wood samples for all of the four wood species treated with cellulose lacquer and synthetic varnish and across all heating treatments. However, glossiness values were decreased for all the wood species depending on heating temperature and time. Values of hardness and scratch resistance were also decreased for all the four wood species across all the treatment combinations. The results were obtained from the upper surface of the application process and are thought to contribute to the national economy.

  13. Identifying quantitative trait loci affecting resistance to congenital hypothyroidism in 129/SvJcl strain mice.

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    Yayoi Hosoda

    Full Text Available Tyrosylprotein sulfotransferase 2 (TPST2 is one of the enzymes responsible for tyrosine O-sulfation and catalyzes the sulfation of the specific tyrosine residue of thyroid stimulating hormone receptor (TSHR. Since this modification is indispensable for the activation of TSH signaling, a non-functional TPST2 mutation (Tpst2(grt in DW/J-grt mice leads to congenital hypothyroidism (CH characterized by severe thyroid hypoplasia and dwarfism related to TSH hyporesponsiveness. Previous studies indicated that the genetic background of the 129(+Ter/SvJcl (129 mouse strain ameliorates Tpst2(grt-induced CH. To identify loci responsible for CH resistance in 129 mice, we performed quantitative trait locus (QTL analysis using backcross progenies from susceptible DW/J and resistant 129 mice. We used the first principal component calculated from body weights at 5, 8 and 10 weeks as an indicator of CH, and QTL analysis mapped a major QTL showing a highly significant linkage to the distal portion of chromosome (Chr 2; between D2Mit62 and D2Mit304, particularly close to D2Mit255. In addition, two male-specific QTLs showing statistically suggestive linkage were also detected on Chrs 4 and 18, respectively. All QTL alleles derived from the 129 strain increased resistance to growth retardation. There was also a positive correlation between recovery from thyroid hypoplasia and the presence of the 129 allele at D2Mit255 in male progenies. These results suggested that the major QTL on Chr 2 is involved in thyroid development. Moreover, since DW/J congenic strain mice carrying both a Tpst2(grt mutation and 129 alleles in the major QTL show resistance to dwarfism and thyroid hypoplasia, we confirmed the presence of the resistant gene in this region, and that it is involved in thyroid development. Further genetical analysis should lead to identification of genes for CH tolerance and, from a better understanding of thyroid organogenesis and function, the subsequent

  14. [Phenotypic and genotypic characterization of resistance to third-generation cephalosporins in Enterobacter spp].

    Science.gov (United States)

    Bertona, E; Radice, M; Rodríguez, C H; Barberis, C; Vay, C; Famiglietti, A; Gutkind, G

    2005-01-01

    Enterobacter spp. are becoming increasingly frequent nosocomial pathogens with multiple resistance mechanism to beta-lactam antibiotics. We carried out the phenotypic and genotypic characterization of beta-lactamases in 27 Enterobacter spp. (25 Enterobacter cloacae y 2 Enterobacter aerogenes), as well as the ability of different extended spectrum-lactamase (ESBL) screening methods. Resistance to third generation cephalosporins was observed in 15/27 (63%) isolates. Twelve resistant isolates produced high level chromosomal encoded AmpC beta-lactamase; 6 of them were also producers of PER-2. Resistance to third generation cephalosporins in the remaining 3 isolates was due to the presence of ESBLs, PER-2 in 2 cases, and CTX-M-2 in the other. Only CTX-M-2 production was detected with all tested cephalosporins using difusion synergy tests, while cefepime improved ESBLs detection in 7/8 PER-2 producers, 4/8 in the inhibitor approximation test and 7/8 with double disk test using cefepime containing disk with and without clavulanic acid. Dilution method, including cephalosporins with and without the inhibitor detected 1/9 ESBLs producers.

  15. Carbapenem Resistance among Enterobacter Species in a Tertiary Care Hospital in Central India

    Directory of Open Access Journals (Sweden)

    Atul Khajuria

    2014-01-01

    Full Text Available Objective. To detect genes encoding carbapenem resistance among Enterobacter species in a tertiary care hospital in central India. Methods. Bacterial identification of Enterobacter spp. isolates from various clinical specimens in patients admitted to intensive care units was performed by routine conventional microbial culture and biochemical tests using standard recommended techniques. Antibiotic sensitivity test was performed by standard Kirby Bauer disc diffusion technique. PCR amplification and automated sequencing was carried out. Transfer of resistance genes was determined by conjugation. Results. A total of 70/130 (53.84% isolates of Enterobacter spp. were found to exhibit reduced susceptibility to imipenem (diameter of zones of inhibition ≤13 mm by disc diffusion method. Among 70 isolates tested, 48 (68.57% isolates showed MIC values for imipenem and meropenem ranging from 32 to 64 mg/L as per CLSI breakpoints. All of these 70 isolates were found susceptible to colistin in vitro as per MIC breakpoints (<0.5 mg/L. PCR carried out on these 48 MBL (IP/IPI E-test positive isolates (12 Enterobacter aerogenes, 31 Enterobacter cloacae, and 05 Enterobacter cloacae complex was validated by sequencing for beta-lactam resistance genes and result was interpreted accordingly. Conclusion. The study showed MBL production as an important mechanism in carbapenem resistance in Enterobacter spp. and interspecies transfer of these genes through plasmids suggesting early detection by molecular methods.

  16. Protocol for the molecular detection of antibiotic resistance mechanisms in Neisseria gonorrhoeae.

    Science.gov (United States)

    Goire, Namraj; Sloots, Theo P; Nissen, Michael D; Whiley, David M

    2012-01-01

    Gonorrhoea is no longer an easily treatable ailment but rather is now a challenging disease in terms of antimicrobial resistance (AMR) with treatment options rapidly diminishing. The causative agent of gonorrhoea, Neisseria gonorrhoeae, has managed to develop resistance to almost every single drug used against it with the sole exception of extended spectrum cephalosporins. The situation is further exacerbated by the fact that not only are the rates of gonococcal infections on a steady rise globally, but tracking AMR is being undermined by the growing popularity of molecular methods at the expense of traditional bacterial culture in diagnostic laboratories. Recently, concerns have been raised over the emergence of a multi-resistant gonococci and the potential for untreatable gonorrhoea. Maintaining optimal epidemiological surveillance of gonococcal AMR remains an important aspect of gonorrhoea control. The development of molecular tools for tracking AMR in N. gonorrhoeae has the potential to further enhance such surveillance. In this chapter, we discuss nucleic acid amplification-based detection of AMR in gonorrhoea with a particular emphasis on chromosomal-mediated resistance to beta-lactam antibiotics.

  17. Dietary supplementation of probiotics affects growth, immune response and disease resistance of Cyprinus carpio fry.

    Science.gov (United States)

    Gupta, Akhil; Gupta, Paromita; Dhawan, Asha

    2014-12-01

    The effects of dietary Bacillus coagulans (MTCC 9872), Bacillus licheniformis (MTCC 6824) and Paenibacillus polymyxa (MTCC 122) supplementation on growth performance, non-specific immunity and protection against Aeromonas hydrophila infection were evaluated in common carp, Cyprinus carpio fry. Laboratory maintained B. coagulans, B. licheniformis and P. polymyxa were used to study antagonistic activity against fish pathogenic bacteria by agar well diffusion assay. Healthy fish fry were challenged by this bacterium for determination of its safety. Fish were fed for 80 days with control basal diet (B0) and experimental diets containing B. coagulans (B1), B. licheniformis (B2) and P. polymyxa (B3) at 10(9) CFU/g diet. Fish fry (mean weight 0.329 ± 0.01 g) were fed these diets and growth performance, various non-specific immune parameters and disease resistance study were conducted at 80 days post-feeding. The antagonism study showed inhibition zone against A. hydrophila and Vibrio harveyi. All the probiotic bacterial strains were harmless to fish fry as neither mortality nor morbidities were observed of the challenge. The growth-promoting influences of probiotic supplemented dietary treatments were observed with fish fry and the optimum survival, growth and feed utilization were obtained with P. polymyxa (B3) supplemented diet. Study of different non-specific innate immunological parameters viz. lysozyme activity, respiratory burst assay and myeloperoxidase content showed significant (p < 0.05) higher values in fish fry fed B3 diet at 10(9) CFU/g. The challenge test showed dietary supplementation of B. coagulans, B. licheniformis and P. polymyxa significantly (p < 0.05) enhanced the resistance of fish fry against bacterial challenge. These results collectively suggests that P. polymyxa is a potential probiotic species and can be used in aquaculture to improve growth, feed utilization, non-specific immune responses and disease resistance of fry common carp, C. carpio.

  18. Exposure of the grass shrimp, Palaemonetes pugio, to antimicrobial compounds affects associated Vibrio bacterial density and development of antibiotic resistance.

    Science.gov (United States)

    DeLorenzo, M E; Brooker, J; Chung, K W; Kelly, M; Martinez, J; Moore, J G; Thomas, M

    2016-04-01

    Antimicrobial compounds are widespread, emerging contaminants in the aquatic environment and may threaten ecosystem and human health. This study characterized effects of antimicrobial compounds common to human and veterinary medicine, aquaculture, and consumer personal care products [erythromycin (ERY), sulfamethoxazole (SMX), oxytetracycline (OTC), and triclosan (TCS)] in the grass shrimp Palaemonetes pugio. The effects of antimicrobial treatments on grass shrimp mortality and lipid peroxidation activity were measured. The effects of antimicrobial treatments on the bacterial community of the shrimp were then assessed by measuring Vibrio density and testing bacterial isolates for antibiotic resistance. TCS (0.33 mg/L) increased shrimp mortality by 37% and increased lipid peroxidation activity by 63%. A mixture of 0.33 mg/L TCS and 60 mg/L SMX caused a 47% increase in shrimp mortality and an 88% increase in lipid peroxidation activity. Exposure to SMX (30 mg/L or 60 mg/L) alone and to a mixture of SMX/ERY/OTC did not significantly affect shrimp survival or lipid peroxidation activity. Shrimp exposure to 0.33 mg/L TCS increased Vibrio density 350% as compared to the control whereas SMX, the SMX/TCS mixture, and the mixture of SMX/ERY/OTC decreased Vibrio density 78-94%. Increased Vibrio antibiotic resistance was observed for all shrimp antimicrobial treatments except for the mixture of SMX/ERY/OTC. Approximately 87% of grass shrimp Vibrio isolates displayed resistance to TCS in the control treatment suggesting a high level of TCS resistance in environmental Vibrio populations. The presence of TCS in coastal waters may preferentially increase the resistance and abundance of pathogenic bacteria. These results indicate the need for further study into the potential interactions between antimicrobials, aquatic organisms, and associated bacterial communities.

  19. Insulin Resistance and Obesity Affect Lipid Profile in the Salivary Glands

    Directory of Open Access Journals (Sweden)

    Jan Matczuk

    2016-01-01

    Full Text Available In today’s world wrong nutritional habits together with a low level of physical activity have given rise to the development of obesity and its comorbidity, insulin resistance. More specifically, many researches indicate that lipids are vitally involved in the onset of a peripheral tissue (e.g., skeletal muscle, heart, and liver insulin resistance. Moreover, it seems that diabetes can also induce changes in respect of lipid composition of both the salivary glands and saliva. However, judging by the number of research articles, the salivary glands lipid profile still has not been sufficiently explored. In the current study we aim to assess the changes in the main lipid fractions, namely, triacylglycerols, phospholipids, free fatty acids, and diacylglycerols, in the parotid and the submandibular salivary glands of rats exposed to a 5-week high fat diet regimen. We observed that the high caloric fat diet caused a significant change in the salivary glands lipid composition, especially with respect to PH and TG, but not DAG or FFAs, classes. The observed reduction in PH concentration is an interesting phenomenon frequently signifying the atrophy and malfunctions in the saliva secreting organs. On the other hand, the increased accumulation of TG in the glands may be an important clinical manifestation of metabolic syndrome and type 2 diabetes mellitus.

  20. Obesity and Prader-Willi Syndrome Affect Heart Rate Recovery from Dynamic Resistance Exercise in Youth

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    Diobel M. Castner

    2016-01-01

    Full Text Available Following exercise, heart rate decline is initially driven by parasympathetic reactivation and later by sympathetic withdrawal. Obesity delays endurance exercise heart rate recovery (HRR in both children and adults. Young people with Prader-Willi Syndrome (PWS, a congenital cause for obesity, have shown a slower 60-s endurance exercise HRR compared to lean and obese children, suggesting compromised regulation. This study further evaluated effects of obesity and PWS on resistance exercise HRR at 30 and 60 s in children. PWS (8–18 years and lean and obese controls (8–11 years completed a weighted step-up protocol (six sets x 10 reps per leg, separated by one-minute rest, standardized using participant stature and lean body mass. HRR was evaluated by calculated HRR value (HRRV = difference between HR at test termination and 30 (HRRV30 and 60 (HRRV60 s post-exercise. PWS and obese had a smaller HRRV30 than lean (p < 0.01 for both. Additionally, PWS had a smaller HRRV60 than lean and obese (p = 0.01 for both. Obesity appears to delay early parasympathetic reactivation, which occurs within 30 s following resistance exercise. However, the continued HRR delay at 60 s in PWS may be explained by either blunted parasympathetic nervous system reactivation, delayed sympathetic withdrawal and/or poor cardiovascular fitness.

  1. Resilience versus Resistance: Affectively Modulating Contemporary Diagrams of Social Resilience, Social Sustainability, and Social Innovation

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    Petra Hroch

    2013-11-01

    Full Text Available This article critically interrogates the twin notions of social sustainability and activities grouped under the term social innovation in order to argue that sustainability and innovation are schizoid modes of representing what Deleuze calls “the cliché” (the authority of the same as “the new” (difference that short-circuit any real possibility of social transformation. I argue that the kinds of solutions presented by social innovation to the problems of social sustainability in the context of a neoliberal governmentality are sustainable only in the sense that they are a model for a more collective mode of existence in an individualized realm that reciprocally supports a realm in which collective responsibility is individualized. In other words, this neo-liberal diagram catches and captures creative energies in service to the status quo. To illustrate these ideas I turn to Dutch filmmaker Bregtje van der Haak’s 2010 documentary, California Dreaming, in which she compares the popular response to the 2008 financial crisis by focusing on several families across the transatlantic transcontinental divide. She interviews Europeans who blame the state as the source of the economic problem, and thus expect the state to fix it. And she interviews Americans who, reflecting on the “American dream,” reveal their faith in meritocracy, blame themselves, and thus look to their own families and communities for solutions. Their respective stories tell us how different neo-liberal diagrams structure and modulate subjectivity and its relation to the social, as well as the emerging ways in which this relation is being framed. If, as Deleuze writes, “there is no diagram that does not also include, besides the points which it connects up, certain relatively free points, points of creativity, change and resistance,” how can analysis of these shifty subjective-social structures point us to points of resistance" (Foucault? And why is it crucial that

  2. High prevalence of antibiotic resistance in commensal Escherichia coli among children in rural Vietnam

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    Dyar Oliver

    2012-04-01

    Full Text Available Abstract Background Commensal bacteria represent an important reservoir of antibiotic resistance genes. Few community-based studies of antibiotic resistance in commensal bacteria have been conducted in Southeast Asia. We investigated the prevalence of resistance in commensal Escherichia coli in preschool children in rural Vietnam, and factors associated with carriage of resistant bacteria. Methods We tested isolates of E. coli from faecal samples of 818 children aged 6-60 months living in FilaBavi, a demographic surveillance site near Hanoi. Daily antibiotic use data was collected for participating children for three weeks prior to sampling and analysed with socioeconomic and demographic characteristics extracted from FilaBavi's re-census survey 2007. Descriptive statistics were generated, and a logistic regression model was used to identify contributions of the examined factors. Results High prevalences of resistance were found to tetracycline (74%, co-trimoxazole (68%, ampicillin (65%, chloramphenicol (40%, and nalidixic acid (27%. Two isolates were resistant to ciprofloxacin. Sixty percent of isolates were resistant to three or more antibiotics. Recent sulphonamide use was associated with co-trimoxazole resistance [OR 3.2, 95% CI 1.8-5.7], and beta-lactam use with ampicillin resistance [OR 1.8, 95% CI 1.3-2.4]. Isolates from children aged 6-23 months were more likely to be resistant to ampicillin [OR 1.8, 95% CI 1.3-2.4] and co-trimoxazole [OR 1.5, 95% CI 1.1-2.0]. Associations were identified between geographical areas and tetracycline and ampicillin resistance. Conclusions We present high prevalence of carriage of commensal E. coli resistant to commonly used antibiotics. The identified associations with recent antibiotic use, age, and geographical location might contribute to our understanding of carriage of antibiotic resistant commensal bacteria.

  3. Tribute and Resistance: Participation and affective engagement in Brazilian fangame makers and modders’ subscultures

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    Andre Boechat

    2014-03-01

    Full Text Available This paper proposes a discussion on particular aspects of production and circulation of Brazilian fangames and mods, in an effort to better comprehend those two growing phenomena as actual subcultures in the Brazilian context. Although not limited to the following characteristics, we assume that fangames are game productions that are not directly related to profit purposes; also, the production of these games is mainly based upon successful mainstream games. From this hypothesis, we observe that fangames and mods are essentially the result of today’s participatory culture, in which tribute and resistance – two concepts that will be properly treated along the paper – are two important engagement forms of the prosumer public.

  4. Resistant starch and arabinoxylan augment SCFA absorption, but affect postprandial glucose and insulin responses differently - CORRIGENDUM

    DEFF Research Database (Denmark)

    Ingerslev, Anne Krog; Theil, Peter Kappel; Hedemann, Mette Skou;

    2015-01-01

    adaptation to each diet. The pigs were fed a low DF western style control diet (WSD) and two high DF diets; an arabinoxylan (AXD) and a resistant starch (RSD) enriched diet. The NPF of insulin was lower (P = 0.04) in AXD fed pigs (4.6 nmol/h) compared to RSD fed pigs (10.5 nmol/h), despite the lowest NPF......The effects of increased colonic fermentation of dietary fibres (DF) on net portal flux (NPF) of carbohydrate-derived metabolites (glucose, SCFA and especially butyrate), hormones (insulin, C-peptide, GLP-1, GIP) and NEFA were studied in a healthy catheterised pig model. Six 59 ± 3.8 kg pigs were...... of glucose was observed in RSD fed pigs (203 mmol/h, P = 0.02). The NPF of total SCFA, acetate, propionate, and butyrate were high, intermediate, and low (P

  5. Surveillance of multidrug resistant suppurative infection causing bacteria in hospitalized patients in an Indian tertiary care hospital

    Institute of Scientific and Technical Information of China (English)

    Nabakishore Nayak; Rajesh K Lenka; Rabindra N Padhy

    2014-01-01

    Objective:To examine antibiograms of a cohort of suppurative bacteria isolated from wound-swabs from hospitalized patients of all economic groups of a typicalIndian teaching hospital. Methods:In surveillance, antibiotic resistance patterns of10 species of suppurative bacteria isolated from wound-swabs over a period of24 months were recorded.Those were subjected to antibiotic sensitivity test, using16 prescribed antibiotics of5 different groups(3 aminoglycosides, 4 beta-lactams,3 cephalosporins,4 fluoroquinolones, and2 stand-alone) in each6-month interval of the study period.Results:Of1156 samples collected,819 samples yielded pathogenic bacteria, of which,Staphylococcus aureus(S. aureus),Streptococcus pyogenes(S. pyogenes), Escherichia coli(E. coli),Pseudomonas aeruginosa(P. aeruginosa),Enterococcus faecalis(E. faecalis), Klebsiella pneumoniae(K. pneumoniae),Acinetobacter baumannii(A. baumannii),Enterobacter aerogenes(E. aerogenes),Proteus mirabilis(P. mirabilis) andProteus vulgaris(P. vulgaris) were isolated in the order of predominance.Isolated bacterial strains were floridly multidrug resistant.Strains ofE. faecalis andS. aureus were found resistant to vancomycin, one of the newly introduced antibiotics.Conclusions:Of theseS. aureus, particularly the methicillin resistant strain predominates, followed by strains ofS. pyogenes andP. aeruginosa that were in the higher proportions of multidrug resistance.

  6. Rapid experimental evolution of pesticide resistance in C. elegans entails no costs and affects the mating system.

    Science.gov (United States)

    Lopes, Patricia C; Sucena, Elio; Santos, M Emília; Magalhães, Sara

    2008-01-01

    Pesticide resistance is a major concern in natural populations and a model trait to study adaptation. Despite the importance of this trait, the dynamics of its evolution and of its ecological consequences remain largely unstudied. To fill this gap, we performed experimental evolution with replicated populations of Caenorhabditis elegans exposed to the pesticide Levamisole during 20 generations. Exposure to Levamisole resulted in decreased survival, fecundity and male frequency, which declined from 30% to zero. This was not due to differential susceptibility of males. Rather, the drug affected mobility, resulting in fewer encounters, probably leading to reduced outcrossing rates. Adaptation, i.e., increased survival and fecundity, occurred within 10 and 20 generations, respectively. Male frequency also increased by generation 20. Adaptation costs were undetected in the ancestral environment and in presence of Ivermectin, another widely-used pesticide with an opposite physiological effect. Our results demonstrate that pesticide resistance can evolve at an extremely rapid pace. Furthermore, we unravel the effects of behaviour on life-history traits and test the environmental dependence of adaptation costs. This study establishes experimental evolution as a powerful tool to tackle pesticide resistance, and paves the way to further investigations manipulating environmental and/or genetic factors underlying adaptation to pesticides.

  7. Environmental Conditions Influence Induction of Key ABC-Transporter Genes Affecting Glyphosate Resistance Mechanism in Conyza canadensis.

    Science.gov (United States)

    Tani, Eleni; Chachalis, Demosthenis; Travlos, Ilias S; Bilalis, Dimitrios

    2016-04-20

    Conyza canadensis has been reported to be the most frequent weed species that evolved resistance to glyphosate in various parts of the world. The objective of the present study was to investigate the effect of environmental conditions (temperature and light) on the expression levels of the EPSPS gene and two major ABC-transporter genes (M10 and M11) on glyphosate susceptible (GS) and glyphosate resistant (GR) horseweed populations, collected from several regions across Greece. Real-time PCR was conducted to determine the expression level of the aforementioned genes when glyphosate was applied at normal (1×; 533 g·a.e.·ha(-1)) and high rates (4×, 8×), measured at an early one day after treatment (DAT) and a later stage (four DAT) of expression. Plants were exposed to light or dark conditions, at three temperature regimes (8, 25, 35 °C). GR plants were made sensitive when exposed to 8 °C with light; those sensitized plants behaved biochemically (shikimate accumulation) and molecularly (expression of EPSPS and ABC-genes) like the GS plants. Results from the current study show the direct link between the environmental conditions and the induction level of the above key genes that likely affect the efficiency of the proposed mechanism of glyphosate resistance.

  8. Environmental Conditions Influence Induction of Key ABC-Transporter Genes Affecting Glyphosate Resistance Mechanism in Conyza canadensis

    Directory of Open Access Journals (Sweden)

    Eleni Tani

    2016-04-01

    Full Text Available Conyza canadensis has been reported to be the most frequent weed species that evolved resistance to glyphosate in various parts of the world. The objective of the present study was to investigate the effect of environmental conditions (temperature and light on the expression levels of the EPSPS gene and two major ABC-transporter genes (M10 and M11 on glyphosate susceptible (GS and glyphosate resistant (GR horseweed populations, collected from several regions across Greece. Real-time PCR was conducted to determine the expression level of the aforementioned genes when glyphosate was applied at normal (1×; 533 g·a.e.·ha−1 and high rates (4×, 8×, measured at an early one day after treatment (DAT and a later stage (four DAT of expression. Plants were exposed to light or dark conditions, at three temperature regimes (8, 25, 35 °C. GR plants were made sensitive when exposed to 8 °C with light; those sensitized plants behaved biochemically (shikimate accumulation and molecularly (expression of EPSPS and ABC-genes like the GS plants. Results from the current study show the direct link between the environmental conditions and the induction level of the above key genes that likely affect the efficiency of the proposed mechanism of glyphosate resistance.

  9. Rapid experimental evolution of pesticide resistance in C. elegans entails no costs and affects the mating system.

    Directory of Open Access Journals (Sweden)

    Patricia C Lopes

    Full Text Available Pesticide resistance is a major concern in natural populations and a model trait to study adaptation. Despite the importance of this trait, the dynamics of its evolution and of its ecological consequences remain largely unstudied. To fill this gap, we performed experimental evolution with replicated populations of Caenorhabditis elegans exposed to the pesticide Levamisole during 20 generations. Exposure to Levamisole resulted in decreased survival, fecundity and male frequency, which declined from 30% to zero. This was not due to differential susceptibility of males. Rather, the drug affected mobility, resulting in fewer encounters, probably leading to reduced outcrossing rates. Adaptation, i.e., increased survival and fecundity, occurred within 10 and 20 generations, respectively. Male frequency also increased by generation 20. Adaptation costs were undetected in the ancestral environment and in presence of Ivermectin, another widely-used pesticide with an opposite physiological effect. Our results demonstrate that pesticide resistance can evolve at an extremely rapid pace. Furthermore, we unravel the effects of behaviour on life-history traits and test the environmental dependence of adaptation costs. This study establishes experimental evolution as a powerful tool to tackle pesticide resistance, and paves the way to further investigations manipulating environmental and/or genetic factors underlying adaptation to pesticides.

  10. A genome-screen experiment to detect quantitative trait loci affecting resistance to facial eczema disease in sheep.

    Science.gov (United States)

    Phua, S H; Dodds, K G; Morris, C A; Henry, H M; Beattie, A E; Garmonsway, H G; Towers, N R; Crawford, A M

    2009-02-01

    Facial eczema (FE) is a secondary photosensitization disease arising from liver cirrhosis caused by the mycotoxin sporidesmin. The disease affects sheep, cattle, deer and goats, and costs the New Zealand sheep industry alone an estimated NZ$63M annually. A long-term sustainable solution to this century-old FE problem is to breed for disease-resistant animals by marker-assisted selection. As a step towards finding a diagnostic DNA test for FE sensitivity, we have conducted a genome-scan experiment to screen for quantitative trait loci (QTL) affecting this trait in Romney sheep. Four F(1) sires, obtained from reciprocal matings of FE resistant and susceptible selection-line animals, were used to generate four outcross families. The resulting half-sib progeny were artificially challenged with sporidesmin to phenotype their FE traits measured in terms of their serum levels of liver-specific enzymes, namely gamma-glutamyl transferase and glutamate dehydrogenase. In a primary screen using selective genotyping on extreme progeny of each family, a total of 244 DNA markers uniformly distributed over all 26 ovine autosomes (with an autosomal genome coverage of 79-91%) were tested for linkage to the FE traits. Data were analysed using Haley-Knott regression. The primary screen detected one significant and one suggestive QTL on chromosomes 3 and 8 respectively. Both the significant and suggestive QTL were followed up in a secondary screen where all progeny were genotyped and analysed; the QTL on chromosome 3 was significant in this analysis.

  11. Atividade antimicrobiana in vitro da cefpiroma em comparação com outros beta-lactâmicos de amplo espectro contra 804 amostras clínicas de nove hospitais brasileiros Antimicrobial activity of Cefpirome compared to other broad-spectrum Beta-Lactam drugs against 804 clinical isolates from 9 Brazilian hospitals

    Directory of Open Access Journals (Sweden)

    H.S. Sader

    1998-12-01

    Full Text Available OBJETIVO: Avaliar a atividade in vitro da cefalosporina de quarta geração, cefpiroma em comparação com ceftazidima, ceftriaxona, cefotaxima e imipenem em um estudo multicêntrico envolvendo nove hospitais de seis cidades em quatro estados. MATERIAL E MÉTODOS: Foram estudadas 804 amostras clínicas isoladas em pacientes internados em unidades de terapia intensiva ou unidades de oncohematologia. As amostras foram coletadas no período de junho a novembro de 1995, isto é, antes da cefpiroma estar disponível comercialmente no Brasil, e testadas através do método de microdiluição em placas conforme descrito pelo National Committee for Clinical Laboratory Standards (NCCLS. Todas as amostras resistentes à cefpiroma foram retestadas utilizando-se o E-test. RESULTADOS: Contra as amostras de enterobactérias (n= 344, a cefpiroma apresentou atividade de 2 a 32 vezes superior àquela apresentada pelas cefalosporinas de terceira geração (CTGs e semelhante àquela apresentada pelo imipenem. As porcentagens de enterobactérias sensíveis foram: 88% para a cefpiroma, 69% para as CTGs e 96% para o imipenem. O espectro de ação da cefpiroma foi maior ou igual ao do imipenem contra as espécies Citrobacter freundii, E. aerogenes, Morganella morganii e Serratia marcescens. Contra Acinetobacter sp. (n=77, a cefpiroma foi ligeiramente mais ativa que a ceftazidima, porém as porcentagens de resistência foram muito altas para esses compostos (84% e 88% respectivamente. As atividades da cefpiroma, ceftazidima e imipenem foram semelhantes contra Pseudomonas aeruginosa (n=128, com MIC50/porcentagem de sensibilidade de 8/59%, 8/62% e 4/62% respectivamente. Contra bactérias aeróbias gram-positivas, a cefpiroma foi de 4 a 16 vezes mais ativa que as CTGs. Contra S. epidermidis e outras espécies de estafilococos coagulase-negativos a cefpiroma foi ligeiramente superior ao imipenem, porém, contra as outras espécies de bactérias gram-positivas avaliadas, o

  12. Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (II

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    Rongshi Li

    2013-08-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA continues to be a major problem, causing severe and intractable infections worldwide. MRSA is resistant to all beta-lactam antibiotics, and alternative treatments are limited. A very limited number of new antibiotics have been discovered over the last half-century, novel agents for the treatment of MRSA infections are urgently needed. Marinopyrrole A was reported to show antibiotic activity against MRSA in 2008. After we reported the first total synthesis of (±-marinopyrrole A, we designed and synthesized a series of marinopyrrole derivatives. Our structure activity relationship (SAR studies of these novel derivatives against a panel of Gram-positive pathogens in antibacterial assays have revealed that a para-trifluoromethyl analog (33 of marinopyrrole A is ≥63-, 8-, and 4-fold more potent than vancomycin against methicillin-resistant Staphylococcus epidermidis (MRSE, methicillin-susceptible Staphylococcus aureus (MSSA and MRSA, respectively. The results provide valuable information in the search for new-generation antibiotics.

  13. Amoxicillin functionalized gold nanoparticles reverts MRSA resistance

    Energy Technology Data Exchange (ETDEWEB)

    Kalita, Sanjeeb; Kandimalla, Raghuram; Sharma, Kaustav Kalyan [Drug Discovery Lab, Life Science Division, Institute of Advanced Study in Science and Technology (IASST), Paschim Boragaon, Garchuk, Guwahati 781035, Assam (India); Kataki, Amal Chandra [Dr. B. Borooah Cancer Institute, Guwahati, Assam (India); Department of Applied Sciences, Gopinath Bordoloi Nagar, Jalukbari, Gauhati University, Guwahati 781014, Assam (India); Deka, Manab [Department of Applied Sciences, Gopinath Bordoloi Nagar, Jalukbari, Gauhati University, Guwahati 781014, Assam (India); Kotoky, Jibon, E-mail: jkotoky@gmail.com [Drug Discovery Lab, Life Science Division, Institute of Advanced Study in Science and Technology (IASST), Paschim Boragaon, Garchuk, Guwahati 781035, Assam (India)

    2016-04-01

    In this study, we have described the biosynthesis of biocompatible gold nanoparticles (GNPs) from aqueous extract of the aerial parts of a pteridophyte, “Adiantum philippense” by microwave irradiation and its surface functionalization with broad spectrum beta lactam antibiotic, amoxicillin (Amox). The functionalization of amoxicillin on GNPs (GNP-Amox) was carried out via electrostatic interaction of protonated amino group and thioether moiety mediated attractive forces. The synthesized GNPs and GNP-Amox were physicochemically characterized. UV–Vis spectroscopy, Zeta potential, XRD, FTIR and SERS (surface enhanced raman spectra) results confirmed the loading of Amox into GNPs. Loading of Amox to GNPs reduce amoxicillin cytotoxicity, whereas GNPs were found to be nontoxic to mouse fibroblast cell line (L929) as evident from MTT and acridine orange/ethidium bromide (AO/EtBr) live/dead cell assays. The GNP-Amox conjugates demonstrated enhanced broad-spectrum bactericidal activity against both Gram-positive and Gram-negative bacteria. Furthermore, in-vitro and in-vivo assays of GNP-Amox revealed potent anti-MRSA activity and improved the survival rate. This indicates the subversion of antibiotic resistance mechanism by overcoming the effect of high levels of β-lactamase produced by methicillin resistant Staphylococcus aureus (MRSA). Taken together, this study demonstrates the positive attributes from GNP-Amox conjugates as a promising antibacterial therapeutic agent against MRSA as well as other pathogens. - Highlights: • Aqueous extract of A. phillippens was used as a reducing and capping agent for synthesis of microwave irradiated gold nanoparticles. • GNPs were loaded with amoxicillin for restoration in antibacterial activity of amoxicillin against MRSA strains. • Gold nanoparticles and GNP-Amox were found biocompitable as tested on L929 cell line. • The nanoparticle antibiotic conjugates exhibited restoration of amoxicillin activity against MRSA in

  14. Does wheat genetically modified for disease resistance affect root-colonizing pseudomonads and arbuscular mycorrhizal fungi?

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    Joana Beatrice Meyer

    Full Text Available This study aimed to evaluate the impact of genetically modified (GM wheat with introduced pm3b mildew resistance transgene, on two types of root-colonizing microorganisms, namely pseudomonads and arbuscular mycorrhizal fungi (AMF. Our investigations were carried out in field trials over three field seasons and at two locations. Serial dilution in selective King's B medium and microscopy were used to assess the abundance of cultivable pseudomonads and AMF, respectively. We developed a denaturing gradient gel electrophoresis (DGGE method to characterize the diversity of the pqqC gene, which is involved in Pseudomonas phosphate solubilization. A major result was that in the first field season Pseudomonas abundances and diversity on roots of GM pm3b lines, but also on non-GM sister lines were different from those of the parental lines and conventional wheat cultivars. This indicates a strong effect of the procedures by which these plants were created, as GM and sister lines were generated via tissue cultures and propagated in the greenhouse. Moreover, Pseudomonas population sizes and DGGE profiles varied considerably between individual GM lines with different genomic locations of the pm3b transgene. At individual time points, differences in Pseudomonas and AMF accumulation between GM and control lines were detected, but they were not consistent and much less pronounced than differences detected between young and old plants, different conventional wheat cultivars or at different locations and field seasons. Thus, we conclude that impacts of GM wheat on plant-beneficial root-colonizing microorganisms are minor and not of ecological importance. The cultivation-independent pqqC-DGGE approach proved to be a useful tool for monitoring the dynamics of Pseudomonas populations in a wheat field and even sensitive enough for detecting population responses to altered plant physiology.

  15. A narrow quantitative trait locus in C. elegans coordinately affects longevity, thermotolerance, and resistance to paraquat

    Directory of Open Access Journals (Sweden)

    Anthony eVertino

    2011-09-01

    Full Text Available By linkage mapping of quantitative trait loci, we previously identified at least 11 natural genetic variants that significantly modulate C. elegans lifespan, many of which would have eluded discovery by knockdown or mutation screens. A region on chromosome IV between markers stP13 and stP35 had striking effects on longevity in three interstrain crosses (each P < 1E–9. In order to define the limits of that interval, we have now constructed two independent lines by marker-based selection during 20 backcross generations, isolating the stP13–stP35 interval from strain Bergerac-BO in a CL2a background. These congenic lines differed significantly from CL2a in lifespan, assayed in two environments (each P<0.001. We then screened for exchange of flanking markers to isolate recombinants that partition this region, because fine mapping the boundaries for overlapping heteroallelic spans can greatly narrow the implicated interval. Recombinants carrying the CL2a allele at stP35 were consistently long-lived compared to those retaining the Bergerac-BO allele (P<0.001, and more resistant to temperature elevation and paraquat (each ~1.7-fold, P<0.0001, but gained little protection from ultraviolet or peroxide stresses. Two rounds of recombinant screening, followed by fine-mapping of break-points and survival testing, narrowed the interval to 0.18 Mb (13.35–13.53 Mb containing 26 putative genes and 6 small-nuclear RNAs – a manageable number of targets for functional assessment.

  16. Exposure to ertapenem is possibly associated with Pseudomonas aeruginosa antibiotic resistance.

    Science.gov (United States)

    Cohen, M J; Block, C S; Moses, A E; Nir-Paz, R

    2014-03-01

    The role of antibiotic exposure in the evolution and emergence of resistance is challenging to assess. We used carbapenem-resistant Pseudomonas aeruginosa (PA) phenotypes to assess possible factors that are associated with the occurrence and prognosis of such a phenotype and to examine the possible contribution of antibiotic exposure to the evolution of antimicrobial resistance. We conducted a nested case-control study. Cases were defined as patients from whom carbapenem-resistant ureidopenicillin-sensitive PA (CRUS-PA) was isolated; matched controls were PA patients who did not have isolation of CRUS-PA. We analysed potential predictors of CRUS-PA isolation and assessed their clinical significance (mortality and eventual isolation of pan-resistant PA), taking into account antibiotic exposures. We matched 800 case-control pairs. Case patients were more likely to have been exposed to anti-PA carbapenems (OR = 6.9; 95% CI, 2.5-18.6). This finding did not apply to the administration of other antibiotics. The mortality among CRUS-PA patients was similar to that of the controls (HR, 0.8 95%; CI, 0.6-1.1). Subsequent isolation of pan-resistant PA was more frequent among case patients compared with non-pan-resistant controls (p-value resistant PA isolation was increased in ertapenem recipients, only after and not prior to the index specimen date (HR, 1.9, 95%; CI, 1.01-3.4). Therefore we suggest that the CRUS-PA phenotype may represent pan beta-lactam resistance and that antibiotic exposure is associated with evolution of PA resistance phenotypes. We demonstrate a novel association of ertapenem with sequentially appearing PA resistance patterns.

  17. Occurrence of Ambler Class B Metallo-β-Lactamase Gene in Imipenem-Resistant Pseudomonas Aeruginosa Strains Isolated from Clinical Samples

    Directory of Open Access Journals (Sweden)

    Zeynab Golshani

    2014-02-01

    Full Text Available Background: 5TMetallo-β-lactamase (MBLs can hydrolyze a broad spectrum of beta-lactams, including penicillins, cephalosporins, and carbapenems. Genes encoding these enzymes are located on the plasmid that can easily be transferred to other bacteria. The aim of this study was to isolate and identify the Pseudomonas aeruginosa strains encoding VIM1 gene, in clinical samples, using the PCR technique. Materials and Methods: During a 4 month period, 100 strains of Pseudomonas aeruginosa from clinical specimens were collected. Standard tests were performed to identify strains of Pseudomonas aeruginosa. Resistance to antibiotics was examined and then the PCR was used to detect VIM1gene. Results:In this study, the highest rates of resistance to antibiotics, amikacin and cefotaxime was observed (65% and 62%, the lowest resistance to antibiotics piperacillin (48% and imipenem and cefepime with 55% resistance was reported. DDST method was performed for 37 strains for the MBl detection. Among the 37 isolate, 30 strains were MBL-producing with imipenem-EDTA method. Twelve strains (18% were carriers of VIM1 gene using the PCR method. Conclusion: In the present study, the prevalence of strains producing MBL genes in strains of hospitals is a growing trend; correct prescription of medications can prevent the spread of resistant pathogens. It is suggested that molecular methods for rapid detection of resistance genes can be used to prevent the spread of this genes.

  18. Heat-Affected Zone Liquation Cracking Resistance of Friction Stir Processed Aluminum-Copper Alloy AA 2219

    Science.gov (United States)

    Karthik, G. M.; Janaki Ram, G. D.; Kottada, Ravi Sankar

    2016-12-01

    In the current work, the effect of friction stir processing on heat-affected zone (HAZ) liquation cracking resistance of aluminum-copper alloy AA 2219 was evaluated. In Gleeble hot-ductility tests and longitudinal Varestraint tests, the FSPed material, despite its very fine dynamically recrystallized equiaxed grain structure, showed considerably higher susceptibility to HAZ liquation cracking when compared to the base material. Detailed microstructural studies showed that the increased cracking susceptibility of the FSPed material is due to (i) increase in the amount of liquating θ phase (equilibrium Al2Cu) and (ii) increase in the population of grain boundary θ particles. An important learning from the current work is that, in certain materials like alloy 2219, the use of FSP as a pretreatment to fusion welding can be counterproductive.

  19. Modified expression of alternative oxidase in transgenic tomato and petunia affects the level of tomato spotted wilt virus resistance

    Directory of Open Access Journals (Sweden)

    Ma Hao

    2011-10-01

    Full Text Available Abstract Background Tomato spotted wilt virus (TSWV has a very wide host range, and is transmitted in a persistent manner by several species of thrips. These characteristics make this virus difficult to control. We show here that the over-expression of the mitochondrial alternative oxidase (AOX in tomato and petunia is related to TSWV resistance. Results The open reading frame and full-length sequence of the tomato AOX gene LeAox1au were cloned and introduced into tomato 'Healani' and petunia 'Sheer Madness' using Agrobacterium-mediated transformation. Highly expressed AOX transgenic tomato and petunia plants were selfed and transgenic R1 seedlings from 10 tomato lines and 12 petunia lines were used for bioassay. For each assayed line, 22 to 32 tomato R1 progeny in three replications and 39 to 128 petunia progeny in 13 replications were challenged with TSWV. Enzyme-Linked Immunosorbent Assays showed that the TSWV levels in transgenic tomato line FKT4-1 was significantly lower than that of wild-type controls after challenge with TSWV. In addition, transgenic petunia line FKP10 showed significantly less lesion number and smaller lesion size than non-transgenic controls after inoculation by TSWV. Conclusion In all assayed transgenic tomato lines, a higher percentage of transgenic progeny had lower TSWV levels than non-transgenic plants after challenge with TSWV, and the significantly increased resistant levels of tomato and petunia lines identified in this study indicate that altered expression levels of AOX in tomato and petunia can affect the levels of TSWV resistance.

  20. Fatigue Crack Growth Rate and Fracture Resistance of Heat Affected Zone of Stainless Steel Narrow Gap Welds

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ho Jung; Kim, Min U; Jang, Chang Heui [KAIST, Daejeon (Korea, Republic of); Cho, Sun Young [Korea Laboratory Engineering System, Daejeon (Korea, Republic of); Yang, Jun Seog [KEPCO, Daejeon (Korea, Republic of)

    2011-05-15

    In nuclear power plants, the automated narrow gap welding (NGW) technique has been widely used in joining stainless steel pipes in primary coolant system. As the primary system pipes are subjected to various transients during plant operation, cracks could initiate and propagate that would cause accidents. To prevent the cracking from developing into sudden failure in the primary system, leak-before-break (LBB) design concept has been developed and applied to many nuclear power plants. Meanwhile, to apply the LBB design, mechanical properties of the structural materials of piping systems should be evaluated, especially at weld zone and heat affected zone (HAZ), because mechanical properties within those regions show considerable scatter and spatial differences. In this study, fatigue crack grow rate (FCGR) and fracture resistance of base metal, weld zone, and HAZ of type 316L stainless steel narrow gap welds were performed at plant operating temperature (315 .deg. C) and room temperature. In particular, FCGR and fracture resistance of HAZ were evaluated in detail and compared to those of base metal

  1. Frequency of Aminoglycoside-Resistance Genes in Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates from Hospitalized Patients

    Science.gov (United States)

    Mahdiyoun, Seyed Mohsen; Kazemian, Hossein; Ahanjan, Mohammad; Houri, Hamidreza; Goudarzi, Mehdi

    2016-01-01

    Background Staphylococcus aureus is one of the most important causative agents in community- and hospital-acquired infections. Aminoglycosides are powerful bactericidal drugs that are often used in combination with beta-lactams or glycopeptides to treat staphylococcal infections. Objectives The main objective of the present study was to determine the prevalence of aminoglycoside resistance among methicillin-resistant Staphylococcus aureus (MRSA) isolates in hospitalized patients in Sari and Tehran, Iran. Methods In this study, 174 MRSA strains isolated from different clinical samples, such as blood, sputum, tracheal exudates, bronchus, pleura, urine, wounds, and catheters, were collected from hospitalized patients in Tehran and Sari during 2014. Antibiotic susceptibility testing was performed against nine antibiotics with the Kirby-Bauer disk diffusion method according to CLSI guidelines. The MRSA strains were examined with oxacillin and cefoxitin disks. MRSA was then validated by detection of the mecA gene. PCR was used to evaluate the prevalence of the aminoglycoside-resistance genes aac (6’)-Ie/aph (2”), aph (3’)-IIIa, and ant (4’) among the MRSA isolates. Results The results of drug susceptibility testing showed that the highest rate of resistance was against erythromycin in Tehran (84.4%) and gentamicin (71.7%) in Sari. All isolates were sensitive to vancomycin, and all strains harbored the mecA gene. The aac (6’)-Ie/aph (2”), aph (3’)-IIIa, and ant (4’)-Ia genes were detected among 134 (77%), 119 (68.4%), and 122 (70.1%) of the isolates, respectively. Conclusions The present study showed a high prevalence of aminoglycoside-resistance genes among MRSA isolates in two cities in Iran.

  2. Características de la resistencia antimicrobiana de una colección clínica de Strptococcus pyogenes Antimicrobial resistance of Streptococcus pyogenes clinical strains

    Directory of Open Access Journals (Sweden)

    Romeo S. Rodríguez

    2000-06-01

    Full Text Available OBJETIVO: Determinar la susceptibilidad antimicrobiana de Streptococcus pyogenes con el fin de estimar la prevalencia de los fenotipos de resistencia a los macrólidos. MATERIAL Y MÉTODOS: Se realizó un estudio de tipo transversal, en 1999, en el que se evaluaron 100 cepas de S. pyogenes, aislados en el Hospital Infantil de México Federico Gómez, en el lapso comprendido entre 1992 y 1998, procedentes de niños con faringoamigdalitis, conservadas en congelación en el laboratorio de bacteriología hasta su procesamiento. Se determinó la susceptibilidad antimicrobiana a algunos beta-lactámicos, macrólidos y clindamicina. La resistencia a eritromicina se probó por medio de la prueba de difusión de doble disco. Se calcularon medidas de tendencia central. RESULTADOS: Todas las cepas fueron sensibles a los beta-lactámicos y clindamicina; 16% fueron resistentes a los macrólidos, y todas correspondieron al fenotipo M. CONCLUSIONES: Es conveniente realizar periódicamente pruebas de escrutinio para conocer los posibles cambios en los patrones de sensibilidad estreptocócica.OBJECTIVE: To determine the antibiotic susceptibility of recent isolates of Streptococcus pyogenes and to evaluate the prevalence of macrolide-resistant phenotypes. MATERIAL AND METHODS: In 1999, we conducted a cross-sectional study at Mexico Children's Hospital "Federico Gomez", to analyze one hundred strains of S. pyogenes isolated from 1992 to 1998, in children with uncomplicated pharyngotonsillitis. Strains were frozen at the bacteriology lab until they were analyzed. Strains were tested for susceptibility against some beta-lactams, macrolides and clindamycin. Double-disk testing was carried out to evaluate erythromycin-resistant phenotypes. Data are presented using central tendency measures. RESULTS: All tested strains were not resistant to beta-lactams and clindamycin; 16% of the strains were resistant to macrolides and all of them belonged to phenotype M. CONCLUSIONS

  3. Different Levels of Eccentric Resistance during Eight Weeks of Training Affect Muscle Strength and Lean Tissue Mass

    Science.gov (United States)

    English, K. L.; Loehr, J. A.; Lee, S. M. C.; Laughlin, M. S.; Hagan, R. D.

    2008-01-01

    .3%) groups. All groups significantly increased HR strength pre- to posttraining (33%: 7.5 +/- 6.1%; 66%: 6.6 +/- 3.7%; 100%: 12.2 +/- 1.8%; 138%: 11.0 +/- 6.4%) except for the 0% (4.9 +/- 9.1%) group. There were no differences between groups. LLM increased significantly pre- to post-training in only the 138% group; there were no differences between groups. CONCLUSIONS: Eight wks of lower body resistive exercise training with eccentric overload resulted in greater increases in LP strength than training with eccentric loads of 66% or less. Post-training HR strength was not affected by eccentric training load, perhaps because of the predominance of Type I fibers typical in the gastrocnemius. Only 138% eccentric training significantly increased LLM. PRACTICAL APPLICATIONS: For athletes or others desiring to maximize muscle strength and hypertrophy gains, training with eccentric loads greater than 100% of concentric resistance will provide greater increases in muscle strength and lean tissue mass in some muscle groups. In a rehabilitation or geriatric exercise setting that places primary emphasis on program adherence and moderate strength gains, training with an eccentric underload may provide strength increases comparable to those of traditional 1:1 training but with less muscle soreness and physiologic insult to the patient, but this has yet to be proven.

  4. Seasonal variations in antibiotic resistance gene transport in the almendares river, havana, cuba.

    Science.gov (United States)

    Knapp, Charles W; Lima, Lazaro; Olivares-Rieumont, Susana; Bowen, Emma; Werner, David; Graham, David W

    2012-01-01

    Numerous studies have quantified antibiotic resistance genes (ARG) in rivers and streams around the world, and significant relationships have been shown that relate different pollutant outputs and increased local ARG levels. However, most studies have not considered ambient flow conditions, which can vary dramatically especially in tropical countries. Here, ARG were quantified in water column and sediment samples during the dry- and wet-seasons to assess how seasonal and other factors influence ARG transport down the Almendares River (Havana, Cuba). Eight locations were sampled and stream flow estimated during both seasons; qPCR was used to quantify four tetracycline, two erythromycin, and three beta-lactam resistance genes. ARG concentrations were higher in wet-season versus dry-season samples, which combined with higher flows, indicated much greater ARG transport downstream during the wet-season. However, water column ARG levels were more spatially variable in the dry-season than the wet-season, with the proximity of waste outfalls strongly influencing local ARG levels. Results confirm that dry-season sampling provides a useful picture of the impact of individual waste inputs on local stream ARG levels, whereas the majority of ARGs in this tropical river were transported downstream during the wet-season, possibly due to re-entrainment of ARG from sediments.

  5. Seasonal variations in antibiotic resistance gene transport in the Almendares River, Havana, Cuba

    Directory of Open Access Journals (Sweden)

    Charles W Knapp

    2012-11-01

    Full Text Available Numerous studies have quantified antibiotic resistance genes (ARG in rivers and streams around the world, and significant relationships have been shown that relate different pollutant outputs and increased local ARG levels. However, most studies have not considered ambient flow conditions, which can vary dramatically especially in tropical countries. Here, ARG were quantified in water-column and sediment samples during the dry-and wet-seasons to assess how seasonal and other factors influence ARG transport down the Almendares River (Havana, Cuba. Eight locations were sampled and stream flow estimated during both seasons; qPCR was used to quantify four tetracycline, two erythromycin, and three beta-lactam resistance genes. ARG concentrations were higher in wet-season versus dry-season samples, which combined with higher flows, indicated greater ARG transport downstream during the wet season. Water-column ARG levels were more spatially variable in the dry-season than the wet-season, with the proximity of waste outfalls strongly influencing local ARG levels. Results confirm that dry-season sampling provides a useful picture of the impact of individual waste inputs on local stream ARG levels, whereas, the majority of ARGs in this tropical river were transported downstream during the wet season, possibly due to re-entrainment of ARG from sediments.

  6. Research advances in carbapenem-resistant Acinetobacter baumannii%耐碳青霉烯鲍曼不动杆菌研究进展

    Institute of Scientific and Technical Information of China (English)

    何翠娥; 胡志东

    2012-01-01

    With the extensive use of antibiotics,Acinetobacter baumannii has appeared resistant to aminoglycosides,fluoroquinolones,beta-lactams and other drugs.Carbapenem antibiotics is considered to be one of the most effecfive drugs in clinical treatment of Acinetobacter baumannii,but carbapenem-resistant Acinetobacter baumannii is increasing gradually in recent years.This review is mainly about the resistant status,resistant mechanisms and treatment of carbapenem-resistant Acinetobacter baumanuii.%随着抗菌药物的广泛应用,鲍曼不动杆菌已出现对氨基糖苷类、氟喹诺酮类、β-内酰胺类等药物耐药,碳青霉烯类抗生素被认为是目前临床治疗鲍曼不动杆菌最有效的药物之一,但近年来耐碳青霉烯类抗生素鲍曼不动杆菌比例逐年增长.此文将对耐碳青霉烯鲍曼不动杆菌的耐药现状、耐药机制及治疗进行综述.

  7. Characterization of Multidrug Resistant Extended-Spectrum Beta-Lactamase-Producing Escherichia coli among Uropathogens of Pediatrics in North of Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Sadegh Rezai

    2015-01-01

    Full Text Available Escherichia coli remains as one of the most important bacteria causing infections in pediatrics and producing extended-spectrum beta-lactamases (ESBLs making them resistant to beta-lactam antibiotics. In this study we aimed to genotype ESBL-producing E. coli isolates from pediatric patients for ESBL genes and determine their association with antimicrobial resistance. One hundred of the E. coli isolates were initially considered ESBL producing based on their MIC results. These isolates were then tested by polymerase chain reaction (PCR for the presence or absence of CTX, TEM, SHV, GES, and VEB beta-lactamase genes. About 30.5% of isolated E. coli was ESBL-producing strain. The TEM gene was the most prevalent (49% followed by SHV (44%, CTX (28%, VEB (8%, and GES (0% genes. The ESBL-producing E. coli isolates were susceptible to carbapenems (66% and amikacin (58% and showed high resistance to cefixime (99%, colistin (82%, and ciprofloxacin (76%. In conclusion, carbapenems were the most effective antibiotics against ESBl-producing E. coli in urinary tract infection in North of Iran. The most prevalent gene is the TEM-type, but the other resistant genes and their antimicrobial resistance are on the rise.

  8. Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

    OpenAIRE

    Valeria Contreras; Sebastián Sepúlveda; Ana Heredia

    2016-01-01

    En pacientes con cáncer que se presentan con neutropenia febril existe controversia sobre si es mejor utilizar una combinación de antibióticos betalactámicos y aminoglicósidos o si bastaría la monoterapia con betalactámicos de amplio espectro como tratamiento empírico inicial. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen 14 estudios aleatorizados pertinentes a esta p...

  9. Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

    Directory of Open Access Journals (Sweden)

    Valeria Contreras

    2016-03-01

    Full Text Available En pacientes con cáncer que se presentan con neutropenia febril existe controversia sobre si es mejor utilizar una combinación de antibióticos betalactámicos y aminoglicósidos o si bastaría la monoterapia con betalactámicos de amplio espectro como tratamiento empírico inicial. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos tres revisiones sistemáticas que en conjunto incluyen 14 estudios aleatorizados pertinentes a esta pregunta. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que adicionar aminoglicósidos a los betalactámicos en el tratamiento de la neutropenia febril en pacientes con cáncer aumenta la nefrotoxicidad y podría aumentar la mortalidad en comparación con la monoterapia con betalactámicos.

  10. Synthesis and biological activity of some heterocyclic compounds containing benzimidazole and beta-lactam moiety

    Indian Academy of Sciences (India)

    K F Ansari; C Lal

    2009-11-01

    A number of 1-substituted-2-methyl benzimidazole derivatives have been synthesized and tested for their antibacterial activities. The chemical structures of the newly synthesized compounds were verified on the basis of spectral and elemental methods of analyses. Investigation of antimicrobial activity of the compounds was done by disc diffusion method using Gram-positive (S. aureus, S. mutans and B. subtilis), Gram-negative (E. coli, S. typhi and P. aeruginosa) bacteria and fungi (C. albicans, A. flavus and A. niger). Among the compounds tested 5a, 5b, 5d, 5i, 5j and 5k exhibited good antibacterial activities against Gram positive bacteria, while 5d and 5i also showed notable antifungal activity. Specially compounds 5a and 5b exhibited appreciable activity against S. aureus and B. subtilis comparable to reference drugs.

  11. Enzyme-catalyzed ring-opening polymerization of unsubstituted beta-lactam

    NARCIS (Netherlands)

    Schwab, Leendert W.; Kroon, Renee; Schouten, Arend Jan; Loos, Katja

    2008-01-01

    The synthesis of poly(beta-alanine) by Candida antarctica lipase B immobilized as novozyme 435 catalyzed ring-opening of 2-azetidinone is reported. After removal of cyclic side products and low molecular weight species pure linear poly(beta-alanine) is obtained. The formation of the polymer is confi

  12. Atomistic Model for the Polyamide Formation from beta-Lactam Catalyzed by Candida antarctica Lipase B

    NARCIS (Netherlands)

    Baum, Iris; Elsaesser, Brigitta; Schwab, Leendert W.; Loos, Katja; Fels, Gregor; Elsässer, Brigitta

    2011-01-01

    Candida antarctica lipase B (CALB) is an established biocatalyst for a variety of transesterification, amidation, and polymerization. reactions. In contrast to polyesters, poly amides are not yet generally accessible via enzymatic polymerization. In this regard, an enzyme-catalyzed ring-opening poly

  13. [Evaluation and characterization of 125 patients with a history of reaction to beta-lactams].

    Science.gov (United States)

    Beltrán-Sierra, Kaddy Juliana; Sánchez, Jorge; Cardona, Ricardo

    2016-01-01

    Antecedentes: Las reacciones a betalactámicos son frecuentes y es difícil establecer la relación entre el medicamento y los síntomas. Objetivo: Describir las características clínicas y explorar los mecanismos inmunológicos de pacientes con sospecha de reacción adversa a betalactámicos. Métodos: Estudio retrospectivo de pacientes con antecedentes de reacción a betalactámicos y pruebas para reacción con medicamentos. Resultados: De 125 pacientes, 71 eran mujeres (56.8%); 73 tenían historia de reacción inmediata y 52 de reacción tardía; Se realizaron 590 pruebas de alergia: medición de IgE específica, pruebas intradérmicas, de parche y de provocación. Los medicamentos más relacionados fueron amoxicilina, en 62 pacientes (49.6%), penicilina cristalina en 17 (13.6%), penicilina benzatínica en 15 (12%) y cefalexina en 13 (10.4%). La severidad de la reacción fue leve en la mayoría (82%). 7.7% tuvo antecedente de anafilaxia y 10.8% consultaba por una prueba cutánea con penicilina positiva, sin antecedente de reacción. Solo 6.7% resultó con una prueba positiva. Más de 62% inició los estudios dos años después de la reacción por la que consultó. Conclusiones: La historia clínica es insuficiente para determinar la alergia a betalactámicos. En nuestra muestra, pocos pacientes con antecedente de reacción a betalactámicos tuvo evidencia de reacciones inmunológicamente mediadas.

  14. Study of antimicrobial resistance due to extended spectrum beta-lactamase-producing Escherichia coli in healthy broilers of Jabalpur

    Science.gov (United States)

    Shrivastav, Arpita; Sharma, R. K.; Sahni, Y. P.; Shrivastav, Neeraj; Gautam, Vidhi; Jain, Sachin

    2016-01-01

    Aim: To study the prevalence of antimicrobial resistance due to extended spectrum beta-lactamase (ESBL)-producing Escherichia coli in samples collected from the ceca of healthy broilers of poultry sale outlets (PSOs) Jabalpur. Materials and Methods: A total of 400 cecal swab samples were taken randomly from freshly slaughtered poultry of 39 PSOs located at four different zones or areas of Jabalpur and were screened for the presence of ESBL-producing E. coli using standard methods. Further they were characterized phenotypically by standard methods. Results: All the 400 samples were screened for E. coli producing ESBL enzyme. Among the samples positive for E. coli 135 were positive for ESBL E. coli giving an overall prevalence of 33.5%. Conclusion: This study related to the prevalence of ESBL-producing E. coli in healthy broilers in Jabalpur is indicative of antibiotic resistance prevalent in the healthy birds which are used for human consumption as well. It also signifies resistance prevalent against beta-lactam antibiotics including third and fourth generations of cephalosporins. PMID:27956778

  15. Longer resistance of some DNA traits from BT176 maize to gastric juice from gastrointestinal affected patients.

    Science.gov (United States)

    Ferrini, A M; Mannoni, V; Pontieri, E; Pourshaban, M

    2007-01-01

    The presence of antibiotic resistance marker genes in genetically engineered plants is one of the most controversial issues related to Genetically Modified Organism (GMO)-containing food, raising concern about the possibility that these markers could increase the pool of antibiotic resistance genes. This study investigates the in vitro survival of genes bla and cryIA(b) of maize Bt176 in human gastric juice samples. Five samples of gastric juice were collected from patients affected by gastro-esophageal reflux or celiac disease and three additional samples were obtained by pH modification with NaHCO3. DNA was extracted from maize Bt176 and incubated with samples of gastric juices at different times. The survival of the target traits (bla gene, whole 1914 bp gene cry1A(b), and its 211 bp fragment) was determined using PCR. The stability of the target genes was an inverse function of their lengths in all the samples. Survival in samples from untreated subjects was below the normal physiological time of gastric digestion. On the contrary, survival time in samples from patients under anti-acid drug treatment or in samples whose pH was modified, resulted strongly increased. Our data indicate the possibility that in particular cases the survival time could be so delayed that, as a consequence, some traits of DNA could reach the intestine. In general, this aspect must be considered for vulnerable consumers (people suffering from gastrointestinal diseases related to altered digestive functionality, physiological problems or drug side-effects) in the risk analysis usually referred to healthy subjects.

  16. Heavy metal ions affecting the removal of polycyclic aromatic hydrocarbons by fungi with heavy-metal resistance.

    Science.gov (United States)

    Ma, Xiao-Kui; Ling Wu, Ling; Fam, Hala

    2014-12-01

    The co-occurrence of polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) is very common in contaminated environments. It is of paramount importance and great challenge to exploit a bioremediation to remove PAHs in these environments with combined pollution. We approached this question by probing the influence of HMs coexisting with PAHs on the removal of PAHs by Acremonium sp. P0997 possessing metal resistance. A removal capability for naphthalene, fluorene, phenanthrene, anthracene, and fluoranthenepresentalone (98.6, 99.3, 89.9, 60.4, and 70 %, respectively) and in a mixture (96.9, 71.8, 67.0, 85.0, and 87.9 %, respectively) was achieved in mineral culture inoculated with Acremonium sp. P0997, and this strain also displayed high resistance to the individual HMs (Mn(2+), Fe(2+), Zn(2+), Cu(2+), Al(3+), and Pb(2+)). The removal of individual PAHs existing in a mixture was differently affected by the separately tested HMs. Cu(2+)enhanced the partition process of anthracene to dead or alive mycelia and the contribution of the biosorption by this strain but imposed a little negative influence on the contribution of biodegradation to the total removal of anthracene individually in a culture. However, Mn(2+) had an inhibitory effect on the partition process of anthracene to dead or alive mycelia and decreased the contributions of both biosorption and biodegradation to the total anthracene removal. This work showcased the value of fungi in bioremediation for the environments with combined pollution, and the findings have major implications for the bioremediation of organic pollutants in metal-organic mixed contaminated sites.

  17. Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin Resistance: The Air Pollution and Cardiometabolic Disease Study.

    Science.gov (United States)

    Brook, Robert D; Sun, Zhichao; Brook, Jeffrey R; Zhao, Xiaoyi; Ruan, Yanping; Yan, Jianhua; Mukherjee, Bhramar; Rao, Xiaoquan; Duan, Fengkui; Sun, Lixian; Liang, Ruijuan; Lian, Hui; Zhang, Shuyang; Fang, Quan; Gu, Dongfeng; Sun, Qinghua; Fan, Zhongjie; Rajagopalan, Sanjay

    2016-01-01

    Mounting evidence supports that fine particulate matter adversely affects cardiometabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia are not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of 4 repeated visits across 4 seasons since 2012. Daily ambient fine particulate matter and personal black carbon levels ranged from 9.0 to 552.5 µg/m(3) and 0.2 to 24.5 µg/m(3), respectively, with extreme levels observed during January 2013. Cumulative fine particulate matter exposure windows across the prior 1 to 7 days were significantly associated with systolic blood pressure elevations ranging from 2.0 (95% confidence interval, 0.3-3.7) to 2.7 (0.6-4.8) mm Hg per SD increase (67.2 µg/m(3)), whereas cumulative black carbon exposure during the previous 2 to 5 days were significantly associated with ranges in elevations in diastolic blood pressure from 1.3 (0.0-2.5) to 1.7 (0.3-3.2) mm Hg per SD increase (3.6 µg/m(3)). Both black carbon and fine particulate matter were significantly associated with worsening insulin resistance (0.18 [0.01-0.36] and 0.22 [0.04-0.39] unit increase per SD increase of personal-level black carbon and 0.18 [0.02-0.34] and 0.22 [0.08-0.36] unit increase per SD increase of ambient fine particulate matter on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardiometabolic health even at the extremely high concentrations faced by billions of people in the developing world today.

  18. Few genetic and environmental correlations between life history and stress resistance traits affect adaptation to fluctuating thermal regimes.

    Science.gov (United States)

    Manenti, T; Sørensen, J G; Moghadam, N N; Loeschcke, V

    2016-09-01

    Laboratory selection in thermal regimes that differed in the amplitude and the predictability of daily fluctuations had a marked effect on stress resistance and life history traits in Drosophila simulans. The observed evolutionary changes are expected to be the result of both direct and correlated responses to selection. Thus, a given trait might not evolve independently from other traits because of genetic correlations among these traits. Moreover, different test environments can induce novel genetic correlations because of the activation of environmentally dependent genes. To test whether and how genetic correlations among stress resistance and life history traits constrain evolutionary adaptation, we used three populations of D. simulans selected for 20 generations in constant, predictable and unpredictable daily fluctuating thermal regimes and tested each of these selected populations in the same three thermal regimes. We explored the relationship between genetic correlations between traits and the evolutionary potential of D. simulans by comparing genetic correlation matrices in flies selected and tested in different thermal test regimes. We observed genetic correlations mainly between productivity, body size, starvation and desiccation tolerance, suggesting that adaptation to the three thermal regimes was affected by correlations between these traits. We also found that the correlations between some traits such as body size and productivity or starvation tolerance and productivity were determined by test regime rather than selection regime that is expected to limit genetic adaptation to thermal regimes in these traits. The results of this study suggest that several traits and several environments are needed to explore adaptive responses, as genetic and environmentally induced correlations between traits as results obtained in one environment cannot be used to predict the response of the same population in another environment.

  19. Phenotypic and Genotypic Detection of Metallo-beta-lactamases among Imipenem-Resistant Gram Negative Isolates

    Directory of Open Access Journals (Sweden)

    Mohammad Mohammadzadeh

    2016-08-01

    Full Text Available Background:   Imipenem-resistant gram negative bacteria, resulting from metallo-beta-lactamase (MBLs-producing strains have been reported to be among the important causes of nosocomial infections and of serious therapeutic problem worldwide. Because of their broad range, potent carbapenemase activity and resistance to inhibitors, these enzymes can confer resistance to almost all beta-lactams. The prevalence of metallo-beta-lactamase among imipenem-resistant Acinetobacter spp., Pseudomonas spp. and Enerobacteriaceae isolates is determined.Methods:   In this descriptive study 864 clinical isolates of Acinetobacter spp., Pseudomonas spp. and Enterobacteriaceae, were initially tested for imipenem susceptibility. The metallo-beta-lactamase production was detected using combined disk diffusion, double disk synergy test, and Hodge test. Then all imipenem resistant isolates were tested by PCR for imp, vim and ndm genes. Results:   Among 864 isolates, 62 (7.17 % were imipenem-resistant. Positive phonetypic test for metallo-beta-lactamase was 40 (64.5%, of which 24 (17.1% and 16 (9.2% isolates were Acinetobacter spp. and Pseudomonas spp., respectively. By PCR method 30 (48.4% of imipenem resistant Acinetobacter, and Pseudomonas isolates were positive for MBL-producing genes. None of the Enterobacteriaceae isolates were positive for metallo-beta-lactamase activity. Conclusion:   The results of this study are indicative of the growing number of nosocomial infections associated with multidrug-resistant gram negative bacteria in this region leading to difficulties in antibiotic therapy. Thereby, using of phenotypic methods can be helpful for management of this problem.

  20. Quantitative resistance affects the speed of frequency increase but not the diversity of the virulence alleles overcoming a major resistance gene to Leptosphaeria maculans in oilseed rape.

    Science.gov (United States)

    Delourme, R; Bousset, L; Ermel, M; Duffé, P; Besnard, A L; Marquer, B; Fudal, I; Linglin, J; Chadœuf, J; Brun, H

    2014-10-01

    Quantitative resistance mediated by multiple genetic factors has been shown to increase the potential for durability of major resistance genes. This was demonstrated in the Leptosphaeria maculans/Brassica napus pathosystem in a 5year recurrent selection field experiment on lines harboring the qualitative resistance gene Rlm6 combined or not with quantitative resistance. The quantitative resistance limited the size of the virulent isolate population. In this study we continued this recurrent selection experiment in the same way to examine whether the pathogen population could adapt and render the major gene ineffective in the longer term. The cultivars Eurol, with a susceptible background, and Darmor, with quantitative resistance, were used. We confirmed that the combination of qualitative and quantitative resistance is an effective approach for controlling the pathogen epidemics over time. This combination did not prevent isolates virulent against the major gene from amplifying in the long term but the quantitative resistance significantly delayed for 5years the loss of effectiveness of the qualitative resistance and disease severity was maintained at a low level on the genotype with both types of resistance after the fungus population had adapted to the major gene. We also showed that diversity of AvrLm6 virulence alleles was comparable in isolates recovered after the recurrent selection on lines carrying either the major gene alone or in combination with quantitative resistance: a single repeat-induced point mutation and deletion events were observed in both situations. Breeding varieties which combine qualitative and quantitative resistance can effectively contribute to disease control by increasing the potential for durability of major resistance genes.

  1. Detection of Extended Spectrum Beta-Lactamases Resistance Genes among Bacteria Isolated from Selected Drinking Water Distribution Channels in Southwestern Nigeria

    Science.gov (United States)

    Ogunjobi, Adeniyi A.

    2016-01-01

    Extended Spectrum Beta-Lactamases (ESBL) provide high level resistance to beta-lactam antibiotics among bacteria. In this study, previously described multidrug resistant bacteria from raw, treated, and municipal taps of DWDS from selected dams in southwestern Nigeria were assessed for the presence of ESBL resistance genes which include blaTEM, blaSHV, and blaCTX by PCR amplification. A total of 164 bacteria spread across treated (33), raw (66), and municipal taps (68), belonging to α-Proteobacteria, β-Proteobacteria, γ-Proteobacteria, Flavobacteriia, Bacilli, and Actinobacteria group, were selected for this study. Among these bacteria, the most commonly observed resistance was for ampicillin and amoxicillin/clavulanic acid (61 isolates). Sixty-one isolates carried at least one of the targeted ESBL genes with blaTEM being the most abundant (50/61) and blaCTX being detected least (3/61). Klebsiella was the most frequently identified genus (18.03%) to harbour ESBL gene followed by Proteus (14.75%). Moreover, combinations of two ESBL genes, blaSHV + blaTEM or blaCTX + blaTEM, were observed in 11 and 1 isolate, respectively. In conclusion, classic blaTEM ESBL gene was present in multiple bacterial strains that were isolated from DWDS sources in Nigeria. These environments may serve as foci exchange of genetic traits in a diversity of Gram-negative bacteria. PMID:27563674

  2. Phenotypes and gene expression profiles of Saccharopolyspora erythraea rifampicin-resistant (rif mutants affected in erythromycin production

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    Bicciato Silvio

    2009-03-01

    Full Text Available Abstract Background There is evidence from previous works that bacterial secondary metabolism may be stimulated by genetic manipulation of RNA polymerase (RNAP. In this study we have used rifampicin selection as a strategy to genetically improve the erythromycin producer Saccharopolyspora erythraea. Results Spontaneous rifampicin-resistant (rif mutants were isolated from the parental strain NRRL2338 and two rif mutations mapping within rpoB, S444F and Q426R, were characterized. With respect to the parental strain, S444F mutants exhibited higher respiratory performance and up to four-fold higher final erythromycin yields; in contrast, Q426R mutants were slow-growing, developmental-defective and severely impaired in erythromycin production. DNA microarray analysis demonstrated that these rif mutations deeply changed the transcriptional profile of S. erythraea. The expression of genes coding for key enzymes of carbon (and energy and nitrogen central metabolism was dramatically altered in turn affecting the flux of metabolites through erythromycin feeder pathways. In particular, the valine catabolic pathway that supplies propionyl-CoA for biosynthesis of the erythromycin precursor 6-deoxyerythronolide B was strongly up-regulated in the S444F mutants, while the expression of the biosynthetic gene cluster of erythromycin (ery was not significantly affected. In contrast, the ery cluster was down-regulated ( Conclusion Rifampicin selection is a simple and reliable tool to investigate novel links between primary and secondary metabolism and morphological differentiation in S. erythraea and to improve erythromycin production. At the same time genome-wide analysis of expression profiles using DNA microarrays allowed information to be gained about the mechanisms underlying the stimulatory/inhibitory effects of the rif mutations on erythromycin production.

  3.     Developmental acclimation affects clinal variation in stress resistance traits in Drosophila buzzatii

    DEFF Research Database (Denmark)

    Sarup, Pernille Merete; Loeschcke, Volker

    2010-01-01

    -down resistance after development at either constant or fluctuating temperatures in nine Drosophila buzzatii populations collected along an altitudinal gradient in Tenerife, Spain. Flies that developed at fluctuating temperatures had higher stress resistance despite experiencing a slightly lower average...

  4. Prevalence of multi-drug resistant uropathogenic Escherichia coli in Potohar region of Pakistan

    Institute of Scientific and Technical Information of China (English)

    Ihsan Ali; Zara Rafaque; Safia Ahmed; Sajid Malik; Javid Iqbal Dasti

    2016-01-01

    Objective: To scrutinize patterns of multi-drug-resistant uropathogenic Escherichia coli (UPEC) strains and particularly of fluoroquinolone-resistance this is an alternative choice for the treatment of urinary tract infections. Methods: Bacterial samples (n = 250) were collected from out-patients from August 2012 to August 2014 Islamabad. Antibiotic susceptibility profiling and determination of mini-mum inhibitory concentrations (MICs) and minimum bactericidal concentrations were performed according to the guidelines of Clinical and Laboratory Standards Institute (CLSI, 2012). Genes, qnrA, qnrB and qnrS were identified by DNA amplification and sequencing. Results: The highest percentage of UPEC isolates were resistant to co-trimoxazole (82%) followed by cephalothin (80%), 2nd Gen, 3rd Gen and 4th Gen cephalosporins, respectively. Resistance against gentamicin, amikacin remained 29% and 4%. For other drugs including nitrofurantoin, tetracycline, carbapenem and beta-lactam inhibitors remained below 10%. Altogether, 59% of the isolates were resistant to at least three antibiotics including one fluoroquinolone. Overall, MICs for ciprofloxacin remained (MIC≥256 mg/mL) and for levofloxacin (MIC≥16 mg/mL and 32 mg/mL). No significant differences were observed regarding MIC values of extended spectrum b-lactamase (ESBL) and non-ESBL producers. For qnrS and qnrB positive isolates MICs remained above 32 mg/mL. Prevalence of UPEC was significantly higher among females and 40% of the isolates were ESBL producers. Conclusions: Higher percentages of ESBL producing UPEC were associated with uri-nary tract infections. Moreover, the majority of these isolates were multi-drug resistant and fluoroquinolone-resistant.

  5. Prevalence of multi-drug resistant uropathogenic Escherichia coli in Potohar region of Pakistan

    Institute of Scientific and Technical Information of China (English)

    Ihsan Ali; Zara Rafaque; Safia Ahmed; Sajid Malik; Javid Iqbal Dasti

    2016-01-01

    Objective:To scrutinize patterns of multi-drug-resistant uropathogenic Escherichia coli(UPEC) strains and particularly of fluoroquinolone-resistance this is an alternative choice for the treatment of urinary tract infections.Methods:Bacterial samples(n = 250) were collected from out-patients from August 2012 to August 2014 Islamabad.Antibiotic susceptibility profiling and determination of minimum inhibitory concentrations(MICs) and minimum bactericidal concentrations were performed according to the guidelines of Clinical and Laboratory Standards Institute(CLSI,2012).Genes,qnrA,qnrB and qnrS were identified by DNA amplification and sequencing.Results:The highest percentage of UPEC isolates were resistant to co-trimoxazole(82%) followed by cephalothin(80%),2nd Gen,3rd Gen and 4th Gen cephalosporins,respectively.Resistance against gentamicin,amikacin remained 29% and 4%.For other drugs including nitrofurantoin,tetracycline,carbapenem and beta-lactam inhibitors remained below 10%.Altogether,59% of the isolates were resistant to at least three antibiotics including one fluoroquinolone.Overall,MICs for ciprofloxacin remained(MIC≥256 μg/mL) and for levofloxacin(MIC≥16 μg/mL and 32 μg/mL).No significant differences were observed regarding MIC values of extended spectrumβ-lactamase(ESBL) and non-ESBL producers.For qnrS and qnrB positive isolates MICs remained above 32 μg/mL.Prevalence of UPEC was significantly higher among females and 40% of the isolates were ESBL producers.Conclusions:Higher percentages of ESBL producing UPEC were associated with urinary tract infections.Moreover,the majority of these isolates were multi-drug resistant and fluoroquinolone-resistant.

  6. A fitness cost associated with the antibiotic resistance enzyme SME-1 beta-lactamase.

    Science.gov (United States)

    Marciano, David C; Karkouti, Omid Y; Palzkill, Timothy

    2007-08-01

    The bla(TEM-1) beta-lactamase gene has become widespread due to the selective pressure of beta-lactam use and its stable maintenance on transferable DNA elements. In contrast, bla(SME-1) is rarely isolated and is confined to the chromosome of carbapenem-resistant Serratia marcescens strains. Dissemination of bla(SME-1) via transfer to a mobile DNA element could hinder the use of carbapenems. In this study, bla(SME-1) was determined to impart a fitness cost upon Escherichia coli in multiple genetic contexts and assays. Genetic screens and designed SME-1 mutants were utilized to identify the source of this fitness cost. These experiments established that the SME-1 protein was required for the fitness cost but also that the enzyme activity of SME-1 was not associated with the fitness cost. The genetic screens suggested that the SME-1 signal sequence was involved in the fitness cost. Consistent with these findings, exchange of the SME-1 signal sequence for the TEM-1 signal sequence alleviated the fitness cost while replacing the TEM-1 signal sequence with the SME-1 signal sequence imparted a fitness cost to TEM-1 beta-lactamase. Taken together, these results suggest that fitness costs associated with some beta-lactamases may limit their dissemination.

  7. A review of community-acquired methicillin-resistant Staphylococcus aureus for primary care physicians

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    Huda A Bukharie

    2010-01-01

    Full Text Available Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA infections among young people without healthcare-associated risk factors have emerged during the past decade. Reported prevalence rates of CA-MRSA vary widely among studies, largely because of the different definitions employed and different settings in which the studies have been performed. Although the majority of CA-MRSA infections are mild skin and soft tissue infections, severe life-threatening cases have been reported. CA-MRSA infections have mostly been associated with staphylococcal strains bearing the staphylococcal cassette chromosome mec type IV element and Panton-Valentine leukocidin genes. These strains are more frequently susceptible to a variety of non-beta-lactam antibiotics. Clinicians must be aware of the wide spectrum of disease caused by CA-MRSA. Continued emergence of MRSA in the community is a public health problem, and therefore warrants increased vigilance in the diagnosis and management of suspected and confirmed staphylococcal infections.

  8. Antimicrobial resistance of abnormal vaginal discharges microorganisms in Ouagadougou, Burkina Faso

    Institute of Scientific and Technical Information of China (English)

    Simplice D Karou; Virginio Pietra; Salvatore Pignatelli; Jacques Simpore; Florencia Djigma; Tani Sagna; Christelle Nadembega; Moctar Zeba; Aboudoulaye Kabre; Kokou Anani; Djeneba Ouermi; Charlemagne Gnoula

    2012-01-01

    Objective: To assess the prevalence of bacterial strains and fungal strains infecting the vaginal tract and test their sensitivity to antibiotics in women attending Saint Camille Medical Centre in Ouagadougou. Methods: From January 2008 to December 2009, a total of 2000 vaginal swabs were cultivated for bacterial and fungal identification and isolation. Furthermore, bacterial strains were tested for their susceptibility to several antibiotics used in routine in the centre.Results:1536/2000 sample, a positivity rate of 76.80%. Candida albicans (48.76%), followed by Escherichiacoli The results revealed that microbial isolation and identification was attempted for (16.67%), Streptococcus agalactiae (8.14%) and Staphylococcus aureus (7.55%) were the major agents of genital tract infections in patients. Mycoplasma hominis and Ureaplasma urealyticum combined accounted for less than 7%. Trichomonas vaginalis was identified in 1.04% cases. The antimicrobial tests revealed that the microorganisms developed resistance to several antibiotics including beta lactams. However, antibiotics such as cefamenzol, ciprofloxacin and norfloxacin were still active on these bacteria. Conclusions: The results reveal that many sexually active women are infected by one or more microbial pathogens, probably because of the lack of hygiene or the adoption of some risky behaviors, such as not using condoms or having multiple sexual partners. Efforts should be made to address these points in the country.

  9. Factors that affect transfer of the IncI1 β-lactam resistance plasmid pESBL-283 between E. coli strains.

    Science.gov (United States)

    Händel, Nadine; Otte, Sarah; Jonker, Martijs; Brul, Stanley; ter Kuile, Benno H

    2015-01-01

    The spread of antibiotic resistant bacteria worldwide presents a major health threat to human health care that results in therapy failure and increasing costs. The transfer of resistance conferring plasmids by conjugation is a major route by which resistance genes disseminate at the intra- and interspecies level. High similarities between resistance genes identified in foodborne and hospital-acquired pathogens suggest transmission of resistance conferring and transferrable mobile elements through the food chain, either as part of intact strains, or through transfer of plasmids from foodborne to human strains. To study the factors that affect the rate of plasmid transfer, the transmission of an extended-spectrum β-lactamase (ESBL) plasmid from a foodborne Escherichia coli strain to the β-lactam sensitive E. coli MG1655 strain was documented as a function of simulated environmental factors. The foodborne E. coli isolate used as donor carried a CTX-M-1 harboring IncI1 plasmid that confers resistance to β-lactam antibiotics. Cell density, energy availability and growth rate were identified as factors that affect plasmid transfer efficiency. Transfer rates were highest in the absence of the antibiotic, with almost every acceptor cell picking up the plasmid. Raising the antibiotic concentrations above the minimum inhibitory concentration (MIC) resulted in reduced transfer rates, but also selected for the plasmid carrying donor and recombinant strains. Based on the mutational pattern of transconjugant cells, a common mechanism is proposed which compensates for fitness costs due to plasmid carriage by reducing other cell functions. Reducing potential fitness costs due to maintenance and expression of the plasmid could contribute to persistence of resistance genes in the environment even without antibiotic pressure. Taken together, the results identify factors that drive the spread and persistence of resistance conferring plasmids in natural isolates and shows how these

  10. Factors that affect transfer of the IncI1 β-lactam resistance plasmid pESBL-283 between E. coli strains.

    Directory of Open Access Journals (Sweden)

    Nadine Händel

    Full Text Available The spread of antibiotic resistant bacteria worldwide presents a major health threat to human health care that results in therapy failure and increasing costs. The transfer of resistance conferring plasmids by conjugation is a major route by which resistance genes disseminate at the intra- and interspecies level. High similarities between resistance genes identified in foodborne and hospital-acquired pathogens suggest transmission of resistance conferring and transferrable mobile elements through the food chain, either as part of intact strains, or through transfer of plasmids from foodborne to human strains. To study the factors that affect the rate of plasmid transfer, the transmission of an extended-spectrum β-lactamase (ESBL plasmid from a foodborne Escherichia coli strain to the β-lactam sensitive E. coli MG1655 strain was documented as a function of simulated environmental factors. The foodborne E. coli isolate used as donor carried a CTX-M-1 harboring IncI1 plasmid that confers resistance to β-lactam antibiotics. Cell density, energy availability and growth rate were identified as factors that affect plasmid transfer efficiency. Transfer rates were highest in the absence of the antibiotic, with almost every acceptor cell picking up the plasmid. Raising the antibiotic concentrations above the minimum inhibitory concentration (MIC resulted in reduced transfer rates, but also selected for the plasmid carrying donor and recombinant strains. Based on the mutational pattern of transconjugant cells, a common mechanism is proposed which compensates for fitness costs due to plasmid carriage by reducing other cell functions. Reducing potential fitness costs due to maintenance and expression of the plasmid could contribute to persistence of resistance genes in the environment even without antibiotic pressure. Taken together, the results identify factors that drive the spread and persistence of resistance conferring plasmids in natural isolates

  11. Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Ito, T; Katayama, Y; Asada, K; Mori, N; Tsutsumimoto, K; Tiensasitorn, C; Hiramatsu, K

    2001-05-01

    The beta-lactam resistance gene mecA of Staphylococcus aureus is carried by a novel mobile genetic element, designated staphylococcal cassette chromosome mec (SCCmec), identified in the chromosome of a Japanese methicillin-resistant S. aureus (MRSA) strain. We now report identification of two additional types of mecA-carrying genetic elements found in the MRSA strains isolated in other countries of the world. There were substantial differences in the size and nucleotide sequences between the elements and the SCCmec. However, new elements shared the chromosomal integration site with the SCCmec. Structural analysis of the new elements revealed that they possessed all of the salient features of the SCCmec: conserved terminal inverted repeats and direct repeats at the integration junction points, conserved genetic organization around the mecA gene, and the presence of cassette chromosome recombinase (ccr) genes responsible for the movements of SCCmec. The elements, therefore, were considered to comprise the SCCmec family of staphylococcal mobile genetic elements together with the previously identified SCCmec. Among 38 epidemic MRSA strains isolated in 20 countries, 34 were shown to possess one of the three typical SCCmec elements on the chromosome. Our findings indicated that there are at least three distinct MRSA clones in the world with different types of SCCmec in their chromosome.

  12. Physiological characterisation of the efflux pump system of antibiotic-susceptible and multidrug-resistant Enterobacter aerogenes.

    Science.gov (United States)

    Martins, A; Spengler, G; Martins, M; Rodrigues, L; Viveiros, M; Davin-Regli, A; Chevalier, J; Couto, I; Pagès, J M; Amaral, L

    2010-10-01

    Enterobacter aerogenes predominates amongst Enterobacteriaceae species that are increasingly reported as producers of extended-spectrum beta-lactamases. Although this mechanism of resistance to beta-lactams is important, other mechanisms bestowing a multidrug-resistant (MDR) phenotype in this species are now well documented. Amongst these mechanisms is the overexpression of efflux pumps that extrude structurally unrelated antibiotics prior to their reaching their targets. Interestingly, although knowledge of the genetic background behind efflux pumps is rapidly advancing, few studies assess the physiological nature of the overall efflux pump system of this, or for that matter any other, bacterium. The study reported here evaluates physiologically the efflux pump system of an E. aerogenes ATCC reference as well as two strains whose MDR phenotypes are mediated by overexpressed efflux pumps. The activities of the efflux pumps in these strains are modulated by pH and glucose, although the effects of the latter are essentially restricted to pH 8, suggesting the presence of two general efflux pump systems, i.e. proton-motive force-dependent and ABC transporter types, respectively.

  13. Garenoxacin activity against isolates form patients hospitalized with community-acquired pneumonia and multidrug-resistant Streptococcus pneumoniae.

    Science.gov (United States)

    Jones, Ronald N; Sader, Helio S; Stilwell, Matthew G; Fritsche, Thomas R

    2007-05-01

    Community-acquired pneumonia (CAP) continues to cause significant morbidity worldwide, and the principal bacterial pathogens (Streptococcus pneumoniae and Haemophilus influenzae) have acquired numerous resistance mechanisms over the last few decades. CAP treatment guidelines have suggested the use of broader spectrum agents, such as antipneumococcal fluoroquinolones as the therapy for at-risk patient population. In this report, we studied 3087 CAP isolates from the SENTRY Antimicrobial Surveillance Program (1999-2005) worldwide and all respiratory tract infection (RTI) isolate population of pneumococci (14665 strains) grouped by antibiogram patterns against a new des-F(6)-quinolone, garenoxacin. Results indicated that garenoxacin was highly active against CAP isolates of S. pneumoniae (MIC(90), 0.06 microg/mL) and H. influenzae (MIC(90), 99.9% of strains were inhibited at pneumoniae strains to penicillin or erythromycin; however, coresistances were high among the beta-lactams (penicillins and cephalosporins), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. Analysis of S. pneumoniae isolates with various antimicrobial resistance patterns to 6 drug classes demonstrated that garenoxacin was active against >99.9% (MIC, pneumoniae that have created therapeutic dilemmas for all RTI presentations. Garenoxacin appears to be a welcome addition to the CAP treatment options, particularly for the emerging MDR pneumococci strains.

  14. In vitro efficacy of the combination of ciprofloxacin and cefotaxime against nalidixic acid-resistant Salmonella enterica serotype Typhi.

    Science.gov (United States)

    Kim, Dong-Min; Neupane, Ganesh Prasad; Jang, Sook Jin; Kim, Sung Hun; Lee, Bok Kwon

    2010-08-01

    Typhoid fever is a systemic intracellular infection caused by Salmonellaenterica serotype Typhi. The emergence and spread of nalidixic acid-resistant S. Typhi (NARST) is challenging for clinicians in many countries owing to the lack of suitable treatment options. The aim of this study was to identify in vitro synergistic combinations of antibiotics against S. Typhi. In vitro time-kill studies were performed on three clinical NARST isolates and one type strain of nalidixic acid-susceptible S. Typhi (NASST) ATCC 9992 with ciprofloxacin, cefotaxime and azithromycin in various combinations. The combination of ciprofloxacin (0.012-0.375 microg/mL) and cefotaxime (0.063-0.125 microg/mL) against all three NARST strains and the NASST strain was significantly more effective in vitro in reducing bacterial counts by >or=3log(10) colony-forming units at 24h and showed synergistic effects. Combination therapy with ciprofloxacin and cefotaxime might be the treatment of choice for patients with typhoid fever. The combination of a fluoroquinolone and a beta-lactam, which are directed against different targets, may improve efficacy compared with a fluoroquinolone alone and may reduce the chance of fluoroquinolone-resistant mutants emerging in patients with severe typhoid fever.

  15. Apramycin treatment affects selection and spread of a multidrug-resistant Escherichia coli strain able to colonize the human gut in the intestinal microbiota of pigs

    DEFF Research Database (Denmark)

    Herrero-Fresno, Ana; Zachariasen, Camilla; Hansen, Monica Hegstad;

    2016-01-01

    The effect of apramycin treatment on transfer and selection of an Escherichia coli strain (E. coli 912) in the intestine of pigs was analyzed through an in vivo experiment. The strain was sequenced and assigned to the sequence type ST101 and serotype O11. It carried resistance genes to apramycin...... of treatment, and apramycin treatment resulted in significantly higher counts compared to the non-treated group. This represents the first demonstration of how antimicrobial treatment affects spread of resistant bacteria in pig production. The use of apramycin may lead to enhanced spread of gentamicin-resistant......-treated (pen 3), along with a non-inoculated control group (pen 1). Two pigs of pen 2 and 3 were inoculated intragastrically with a rifampicin resistant variant of the strain. Apramycin treatment in pen 2 was initiated immediately after inoculation. Strain colonization was assessed in the feces from all pigs...

  16. [Evaluation of penicillin-binding protein genotypes in penicillin susceptible and resistant Streptococcus pneumoniae isolates].

    Science.gov (United States)

    Aslan, Gönül; Tezcan, Seda; Delialioğlu, Nuran; Aydın, Fatma Esin; Kuyucu, Necdet; Emekdaş, Gürol

    2012-04-01

    Penicillin-binding proteins (PBPs) are the natural targets of beta-lactam antibiotics and mutations in pbp1a, pbp2b, and pbp2x genes, which encode PBPs, are responsible for resistance to beta-lactams in Streptococcus pneumoniae. In the present study, we intended to determine how often the common mutation patterns occurred within the pbp1a, pbp2b, and pbp2x PBP gene regions and evaluate the PBP genotype mutations which were associated with penicillin resistance in several penicillin-susceptible and - resistant S.pneumoniae isolates in Mersin, Turkey. A total of 62 S.pneumoniae strains isolated from different clinical specimens (32 nasopharyngeal swab, 16 sputum, 3 blood, 3 wound, 2 cerebrospinal fluids and one of each urine, abscess, bronchoalveolar lavage, conjunctival swab, tracheal aspirate, middle ear effusion) were included in the study. Penicillin susceptibilities of the isolates were searched by disc diffusion and E-test methods, and 23 of them were identified as susceptible, 31 were intermediate susceptible, and eight were resistant to penicillin. A rapid DNA extraction procedure was performed for the isolation of nucleic acids from the strains. Distribution of PBP gene mutations in pbp1a, pbp2b, and pbp2x gene regions related to penicillin resistance was determined by using a wild-type specific polymerase chain reaction (PCR) based technique. PBP gene alterations of those isolates were also evaluated in relation to penicillin susceptibility and resistance patterns. Twenty two (95.7%) of 23 penicillin-susceptible S.pneumoniae isolates exhibited no mutation in the three PBP genes (pbp1a, pbp2x, and pbp 2b), while 1 (4.3%) of these harbored mutations in all of the three PBP genes. The penicillin-intermediate susceptible S.pneumoniae isolates exhibited various combinations of mutations. One (3.2%) of 31 penicillin-intermediate susceptible isolates exhibited no mutation in the three PBP genes, while 22 (71%) of them yielded mutations in all of the three PBP

  17. Mechanisms of antibiotic resistance of Enterobacteriaceae family representatives

    Directory of Open Access Journals (Sweden)

    K. R. Kotsyuba

    2014-04-01

    Full Text Available The paper deals with the basic medical scheme of antibiotics use for treatment of lesions caused by enterobacteria and mechanisms of resistance of Enterobacteriaceae to different classes of antibiotics. It is known that the main mechanisms of resistance to antibiotics are enzymatic inactivation, modification of the target, efflux, violation of conduct through the membrane and formation of metabolic shunt. The most common cases of resistance to beta-lactams among Enterobacteriaceae relate to production of plasmid and chromosomal beta-lactamases, violation of the permeability of the outer membrane, and modification of target penicillin binding proteins. Active release of antibiotics from the cell, or efflux, in Enterobacteriaceae is used for maintaining resistance to tetracyclines, macrolides, carbapenems. Genes of efflux system are localized on plasmids and contribute to rapid spreading among Enterobacteriaceae. Mutations are the basis of resistance to novobiocinum and rifampicinum. Enzymatic inactivation by modifying is typical for resistance to aminoglycosides. Three groups of enzymes are engaged in the process, by adding the molecule of acetic acid, phosphate or adenine. Joining of these groups is irreversible and leads to complete loss of biological activity of the antibiotic. Resistance to aminoglycosides appears also due to inhibition of drug penetration, that is associated with genetically determined mechanisms of electron transport through the membrane. Resistance to quinolones and fluoroquinolones is associated with the modification of topoisomerase II and IV which are targets of these groups of antibiotics. Resistance is possible as a result of changes in the structure of the target, breaching of penetration into the cell, and active release from the cell. The highest level of resistance is develope in the case of two- or three-stage mutations in one or the other, or both, subunits in different genes. At the same time, for breaching of

  18. Antimicrobial susceptibility of methicillin-resistant Staphylococcus pseudintermedius isolated from veterinary clinical cases in the UK.

    Science.gov (United States)

    Maluping, R P; Paul, N C; Moodley, A

    2014-01-01

    Staphylococcus pseudintermedius is a leading aetiologic agent of pyoderma and other body tissue infections in dogs and cats. In recent years, an increased prevalence of methicillin-resistant S. pseudintermedius (MRSP) has been reported. Isolation of MRSP in serious infections poses a major therapeutic challenge as strains are often resistant to all forms of systemic antibiotic used to treat S. pseudintermedius -related infections. This study investigates the occurrence of MRSP from a total of 7183 clinical samples submitted to the authors' laboratories over a 15-month period. Identification was based on standard microbiological identification methods, and by S. pseudintermedius-specific nuc polymerase chain reaction (PCR). Methicillin resistance was confirmed by PBP2a latex agglutination and mecA PCR. Susceptibility against non-beta-lactam antibiotics was carried out using a disc-diffusion method according to Clinical and Laboratory Standards Institute (CLSI) guidelines. In addition, susceptibility to pradofloxacin--a new veterinary fluoroquinolone--was also investigated. SCCmec types were determined by multiplex PCR. Staphylococcus pseudintermedius was isolated from 391 (5%) samples and 20 were confirmed as MRSP from cases of pyoderma, otitis, wound infections, urinary tract infection and mastitis in dogs only. All 20 isolates were resistant to clindamycin and sulphamethoxazole/trimethoprim. Nineteen were resistant to chloramphenicol, enrofloxacin, gentamicin, marbofloxacin and pradofloxacin; additionally, seven isolates were resistant to tetracycline. Fifteen isolates carried SCCmec type II-III, four isolates had type V and one harboured type IV. To date, only a few scientific papers on clinical MRSP strains isolated from the UK have been published, thus the results from this study would provide additional baseline data for further investigations.

  19. Chemokine-like receptor 1 deficiency does not affect the development of insulin resistance and nonalcoholic fatty liver disease in mice.

    Directory of Open Access Journals (Sweden)

    Nanda Gruben

    Full Text Available The adipokine chemerin and its receptor, chemokine-like receptor 1 (Cmklr1, are associated with insulin resistance and nonalcoholic fatty liver disease (NAFLD, which covers a broad spectrum of liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH. It is possible that chemerin and/or Cmklr1 exert their effects on these disorders through inflammation, but so far the data have been controversial. To gain further insight into this matter, we studied the effect of whole-body Cmklr1 deficiency on insulin resistance and NAFLD. In view of the primary role of macrophages in hepatic inflammation, we also transplanted bone marrow from Cmklr1 knock-out (Cmklr1-/- mice and wild type (WT mice into low-density lipoprotein receptor knock-out (Ldlr-/- mice, a mouse model for NASH. All mice were fed a high fat, high cholesterol diet containing 21% fat from milk butter and 0.2% cholesterol for 12 weeks. Insulin resistance was assessed by an oral glucose tolerance test, an insulin tolerance test, and by measurement of plasma glucose and insulin levels. Liver pathology was determined by measuring hepatic inflammation, fibrosis, lipid accumulation and the NAFLD activity score (NAS. Whole-body Cmklr1 deficiency did not affect body weight gain or food intake. In addition, we observed no differences between WT and Cmklr1-/- mice for hepatic inflammatory and fibrotic gene expression, immune cell infiltration, lipid accumulation or NAS. In line with this, we detected no differences in insulin resistance. In concordance with whole-body Cmklr1 deficiency, the absence of Cmklr1 in bone marrow-derived cells in Ldlr-/- mice did not affect their insulin resistance or liver pathology. Our results indicate that Cmklr1 is not involved in the pathogenesis of insulin resistance or NAFLD. Thus, we recommend that the associations reported between Cmklr1 and insulin resistance or NAFLD should be interpreted with caution.

  20. Occurrence and persistence of antibiotic resistance genes in river biofilms after wastewater inputs in small rivers.

    Science.gov (United States)

    Proia, Lorenzo; von Schiller, Daniel; Sànchez-Melsió, Alexandre; Sabater, Sergi; Borrego, Carles M; Rodríguez-Mozaz, Sara; Balcázar, José Luis

    2016-03-01

    The extensive use of antibiotics in human and veterinary medicine and their subsequent release into the environment may have direct consequences for autochthonous bacterial communities, especially in freshwater ecosystems. In small streams and rivers, local inputs of wastewater treatment plants (WWTPs) may become important sources of organic matter, nutrients and emerging pollutants, such as antibiotic resistance genes (ARGs). In this study, we evaluated the effect of WWTP effluents as a source of ARGs in river biofilms. The prevalence of genes conferring resistance to main antibiotic families, such as beta-lactams (blaCTX-M), fluoroquinolones (qnrS), sulfonamides (sul I), and macrolides (ermB), was determined using quantitative PCR (qPCR) in biofilm samples collected upstream and downstream WWTPs discharge points in four low-order streams. Our results showed that the WWTP effluents strongly modified the hydrology, physico-chemistry and biological characteristics of the receiving streams and favoured the persistence and spread of antibiotic resistance in microbial benthic communities. It was also shown that the magnitude of effects depended on the relative contribution of each WWTP to the receiving system. Specifically, low concentrations of ARGs were detected at sites located upstream of the WWTPs, while a significant increase of their concentrations was observed in biofilms collected downstream of the WWTP discharge points (particularly ermB and sul I genes). These findings suggest that WWTP discharges may favour the increase and spread of antibiotic resistance among streambed biofilms. The present study also showed that the presence of ARGs in biofilms was noticeable far downstream of the WWTP discharge (up to 1 km). It is therefore reasonable to assume that biofilms may represent an ideal setting for the acquisition and spread of antibiotic resistance determinants and thus be considered suitable biological indicators of anthropogenic pollution by active

  1. Risk factors affecting nasal colonization of methicillin-resistant Staphylococcus aureus when admitted in intensive care unit

    Institute of Scientific and Technical Information of China (English)

    Li Qiang; Zhuang Taifeng; Lin Ying; Xi Jingjing; Yao Gaiqi

    2014-01-01

    Background Colonization with methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for subsequent invasive MRSA infection,particularly in patients admitted for critical care.The purpose of this study was to investigate the risk factors affecting nasal colonization of MRSA in patients admitted to intensive care units (ICU).Methods Between August 1,2011 and June 30,2012,we screened for MRSA nasal colonization in 350 patients by Real-time PCR within 24 hours of admission by means of swab samples taken from the anterior nares.According to the results of PCR,the patients were divided into 2 groups:the positive group with nasal MRSA colonization and the negative group without nasal MRSA colonization.The 31 (8.86%) patients were MRSA positive.The risk factors evaluated included thirteen variables,which were analyzed by t test for continuous variables and X2 test for discrete variables.The variables with significance (P <0.05) were analyzed with stepwise Logistic regression.Results There were differences (P <0.05) in four variables between two groups.The duration of stay in hospital prior to ICU admission in the positive group was (35.7±16.1) days,vs.(4.5±3.1) days in the negative group.The average blood albumin level was (28.4±2.9) g/L in the positive group,vs.(30.5±4.3) g/L in the negative group.Of 31 patients in the positive group,seven had been treated with antibiotics longer than seven days vs.34 of 319 patients in the negative group.In the positive group,four of 31 patients received treatment with more than two classes of antibiotics prior to admission in ICU,contrasted to 13 of 319 patients in the negative group.Furthermore,stepwise Logistic regression analysis for these four variables indicates that the duration of stay in hospital prior to ICU admission may be an independent risk factor.Conclusions MRSA colonization in ICU admission may be related to many factors.The duration of stay in hospital prior to ICU admission is an independent risk

  2. Evolution toward small molecule inhibitor resistance affects native enzyme function and stability, generating acarbose-insensitive cyclodextrin glucanotransferase variants

    NARCIS (Netherlands)

    Kelly, Ronan M.; Leemhuis, Hans; Gatjen, Linda; Dijkhuizen, Lubbert; Gätjen, Linda

    2008-01-01

    Small molecule inhibitors play an essential role in the selective inhibition of enzymes associated with human infection and metabolic disorders. Targeted enzymes may evolve toward inhibitor resistance through selective incorporation of mutations. Acquisition of insensitivity may, however, result in

  3. Development of a Geo-Referenced Database for Weed Mapping and Analysis of Agronomic Factors Affecting Herbicide Resistance in Apera spica-venti L. Beauv. (Silky Windgrass

    Directory of Open Access Journals (Sweden)

    Dario Massa

    2013-01-01

    Full Text Available In this work, we evaluate the role of agronomic factors in the selection for herbicide resistance in Apera spica-venti L. Beauv. (silky windgrass. During a period of three years, populations were collected in more than 250 conventional fields across Europe and tested for resistance in the greenhouse. After recording the field history of locations, a geo-referenced database has been developed to map the distribution of herbicide-resistant A. spica-venti populations in Europe. A Logistic Regression Model was used to assess whether and to what extent agricultural and biological factors (crop rotation, soil tillage, sowing date, soil texture and weed density affect the probability of resistance selection apart from the selection pressure due to herbicide application. Our results revealed that rotation management and soil tillage are the factors that have the greatest influence on the model. In addition, first order interactions between these two variables were highly significant. Under conventional tillage, a percentage of winter crops in the rotation exceeding 75% resulted in a 1280-times higher risk of resistance selection compared to rotations with less than 50% of winter crops. Under conservation tillage, the adoption of >75% of winter crops increased the risk of resistance 13-times compared to rotations with less than 50% of winter crops. Finally, early sowing and high weed density significantly increased the risk of resistance compared to the reference categories (later sowing and low weed density, respectively. Soil texture had no significant influence. The developed model can find application in management programs aimed at preventing the evolution and spread of herbicide resistance in weed populations.

  4. The beta2 adrenergic receptor Gln27Glu polymorphism affects insulin resistance in patients with heart failure: possible modulation by choice of beta blocker.

    Science.gov (United States)

    Vardeny, Orly; Detry, Michelle A; Moran, John J M; Johnson, Maryl R; Sweitzer, Nancy K

    2008-12-01

    Insulin resistance is prevalent in heart failure (HF) patients, and beta2 adrenergic receptors (beta2-AR) are involved in glucose homeostasis. We hypothesized that beta2-AR Gln27Glu and Arg16Gly polymorphisms affect insulin resistance in HF patients, and we explored if effects of beta2-AR polymorphisms on glucose handling are modified by choice of beta blocker. We studied 30 nondiabetic adults with HF and a history of systolic dysfunction; 15 were receiving metoprolol succinate, and 15 were receiving carvedilol. We measured fasting glucose, insulin, and insulin resistance, and we determined beta2-AR genotypes at codons 27 and 16. The cohort was insulin resistant with a mean HOMA-IR score of 3.4 (95% CI, 2.3 to 4.5; normal value, 1.0). Patients with the Glu27Glu genotype exhibited higher insulin and HOMA-IR compared to individuals carrying a Gln allele (P = 0.019). Patients taking carvedilol demonstrated lower insulin resistance if also carrying a wild-type allele at codon 27 (fasting insulin, 9.8 +/- 10.5 versus 20.5 +/- 2.1 for variant, P = 0.072; HOMA-IR, 2.4 +/- 2.7 versus 5.1 +/- 0.6, P = 0.074); those on metoprolol succinate had high insulin resistance irrespective of genotype. The beta2-AR Glu27Glu genotype may be associated with higher insulin concentrations and insulin resistance in patients with HF. Future studies are needed to confirm whether treatment with carvedilol may be associated with decreased insulin and insulin resistance in beta2-AR codon 27 Gln carriers.

  5. Methicillin-resistant Staphylococcus saprophyticus isolates carrying staphylococcal cassette chromosome mec have emerged in urogenital tract infections.

    Science.gov (United States)

    Higashide, Masato; Kuroda, Makoto; Omura, Carlos Takashi Neves; Kumano, Miyuki; Ohkawa, Saburo; Ichimura, Sadahiro; Ohta, Toshiko

    2008-06-01

    Staphylococcus saprophyticus is a uropathogenic bacterium that causes acute uncomplicated urinary tract infections, particularly in female outpatients. We investigated the dissemination and antimicrobial susceptibilities of 101 S. saprophyticus isolates from the genitourinary tracts of patients in Japan. Eight of these isolates were mecA positive and showed beta-lactam resistance. Pulsed-field gel electrophoresis showed that only some isolates were isogenic, indicating that the mecA gene was apparently acquired independently by mecA-positive isolates through staphylococcal cassette chromosome mec (SCCmec). Type determination of SCCmec by multiplex PCR showed a nontypeable element in the eight mecA-positive isolates. Sequence analysis of the entire SCCmec element from a prototype S. saprophyticus strain revealed that it was nontypeable with the current SCCmec classification due to the novel composition of the class A mec gene complex (IS431-mecA-mecR1-mecI genes) and the ccrA1/ccrB3 gene complex. Intriguingly, the attachment sites of SCCmec are similar to those of type I SCCmec in S. aureus NCTC 10442. Furthermore, the genes around the mec gene complex are similar to those of type II/III SCCmec in S. aureus, while those around the ccr gene complex are similar to those of SCC15305RM found in S. saprophyticus ATCC 15305. In comparison with known SCCmec elements, this S. saprophyticus SCCmec is a novel type.

  6. Nutrients, heavy metals and microbial communities co-driven distribution of antibiotic resistance genes in adjacent environment of mariculture.

    Science.gov (United States)

    Zhao, Zelong; Wang, Jing; Han, Ying; Chen, Jingwen; Liu, Guangfei; Lu, Hong; Yan, Bin; Chen, Shiaoshing

    2017-01-01

    With the rapid development of aquaculture, the large amounts of pollutants were discharged into the aquatic environment, where the detected antibiotic resistance genes (ARGs) have drawn increasing attention due to their potential threats to ecological environment and human health. Thus, the impact of mariculture on ARGs was assessed and the underlying mechanism of their propagation was explained. Sediments from eight sampling sites were collected along a mariculture drainage ditch, and the sediment in Yellow River Delta National Park was used as a non-mariculture control. Microbial ARGs qPCR array and illumina sequencing of 16S rRNA gene were applied to examine the changing patterns of ARGs and bacterial communities. Results showed that 18 ARGs (3 fluoroquinolone, 1 aminoglycoside, 3 macrolide-lincosamide-streptogramin B, 2 tetracycline, and 9 beta-lactam resistance genes) were influenced by mariculture, and ARGs abundance and diversity were significantly increased in mariculture sediments (p < 0.05). A remarkable shift in bacterial community structure and composition was also observed. The abundance of most of ARGs were significantly decreased in the estuary samples, implying that seawater had a significant dilution effect on the ARGs emission from the mariculture sites. Partial redundancy analysis showed that nutrients, heavy metals, and bacteria communities might directly and indirectly contribute to ARGs propagation, suggesting that the profile and dissemination of ARGs were driven by the combined effects of multiple factors in mariculture-impacted sites.

  7. An uncommon presentation for a severe invasive infection due to methicillin-resistant Staphylococcus aureus clone USA300 in Italy: a case report

    Directory of Open Access Journals (Sweden)

    Tronci Mirella

    2008-04-01

    Full Text Available Abstract Background Methicillin resistant Staphylococcus aureus (MRSA has been considered for many years a typical nosocomial pathogen. Recently MRSA has emerged as a frequent cause of infections in the community. More commonly, community-acquired (CA-MRSA is a cause of infections of the skin and soft-tissues, but life-threatening infections such as necrotizing pneumonia and sepsis can occasionally occur. Case presentation This report describes an uncommon presentation of invasive CA-MRSA infection in an adolescent without known risk factors. The presentation was typical for bacterial meningitis, but the clinical findings also revealed necrotizing pneumonia. Following the development of deep venous thrombosis, the presence of an inherited trombophilic defect (factor V Leiden was detected. The patient was successfully treated with an antibiotic combination including linezolid and with anticoagulant therapy. CA-MRSA was isolated from both cerebrospinal fluid and blood. The isolates were resistant to oxacillin and other beta-lactam antibiotics and susceptible to the other antibiotics tested including erythromycin. Molecular typing revealed that the strains contained the Panton-Valentine leukocidin genes and type IV SCCmec, and were ST8, spa type t008, and agr type 1. This genetic background is identical to that of the USA300 clone. Conclusion This report highlights that meningitis can be a new serious presentation of CA-MRSA infection. CA-MRSA strains with the genetic background of the USA300 clone are circulating in Italy and are able to cause severe infections.

  8. Activities of ceftobiprole and other cephalosporins against extracellular and intracellular (THP-1 macrophages and keratinocytes) forms of methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Lemaire, Sandrine; Glupczynski, Youri; Duval, Valérie; Joris, Bernard; Tulkens, Paul M; Van Bambeke, Françoise

    2009-06-01

    Staphylococcus aureus is an opportunistic intracellular organism. Although they poorly accumulate in eukaryotic cells, beta-lactams show activity against intracellular methicillin (methicillin)-susceptible S. aureus (MSSA) if the exposure times and the drug concentrations are sufficient. Intraphagocytic methicillin-resistant S. aureus (MRSA) strains are susceptible to penicillins and carbapenems because the acidic pH favors the acylation of PBP 2a by these beta-lactams through pH-induced conformational changes. The intracellular activity (THP-1 macrophages and keratinocytes) of ceftobiprole, which shows almost similar in vitro activities against MRSA and MSSA in broth, was examined against a panel of hospital-acquired and community-acquired MRSA strains (MICs, 0.5 to 2.0 mg/liter at pH 7.4 and 0.25 to 1.0 mg/liter at pH 5.5) and was compared with its activity against MSSA isolates. The key pharmacological descriptors {relative maximal efficacy (E(max)), relative potency (the concentration causing a reduction of the inoculum halfway between E(0) and E(max) [EC(50)]), and static concentration (C(s))} were measured. All strains showed sigmoidal dose-responses, with E(max) being about a 1 log(10) CFU decrease from the postphagocytosis inoculum, and EC(50) and C(s) being 0.2 to 0.3x and 0.6 to 0.9x the MIC, respectively. Ceftobiprole effectively competed with Bocillin FL (a fluorescent derivative of penicillin V) for binding to PBP 2a at both pH 5.5 and pH 7.4. In contrast, cephalexin, cefuroxime, cefoxitin, or ceftriaxone (i) were less potent in PBP 2a competitive binding assays, (ii) showed only partial restoration of the activity against MRSA in broth at acidic pH, and (iii) were collectively less effective against MRSA in THP-1 macrophages and were ineffective in keratinocytes. The improved activity of ceftobiprole toward intracellular MRSA compared with the activities of conventional cephalosporins can be explained, at least in part, by its greater ability to bind

  9. Antimicrobial resistance profile of Staphylococcus aureus isolates obtained from skin and soft tissue infections of outpatients from a university hospital in Recife - PE, Brazil*

    Science.gov (United States)

    Caraciolo, Fabiana Beserra; Maciel, Maria Amélia Vieira; dos Santos, Josemir Belo; Rabelo, Marcelle Aquino; Magalhães, Vera

    2012-01-01

    BACKGROUND Staphylococcus aureus has a notable ability to acquire resistance to antibiotics, and methicillin resistance represents a growing public health problem. Methicillin-resistant S. aureus (MRSA) has also become important outside the hospital environment, particularly in the United States. In Brazil, since 2005, cases of community skin infections caused by MRSA have been reported, but resistance studies involving outpatients are scarce. OBJECTIVE To know the resistance profile of S. aureus involved in skin and soft tissue infections of patients seen at the Dermatology outpatient clinic of a university hospital in Recife, Pernambuco State, northeastern Brazil. METHODS Prospective study involving 30 patients with skin and soft tissue infections, seen at the Dermatology outpatient clinic from May until November 2011. To evaluate the susceptibility of S. aureus to antibiotics, the disk diffusion method and oxacillin screening agar were used. RESULTS From a total of 30 samples of skin lesions, 19 (63%) had positive culture for S. aureus. The following resistance patterns of S. aureus were observed: penicillin, 95%; tetracycline, 32%; erythromycin, 21%; gentamicin, 16%; cefoxitin, 11%; oxacillin, 11%; trimethoprim-sulfamethoxazole, 11%; chloramphenicol, 11%; clindamycin, 5% ; and ciprofloxacin, 0%. One of the identified MRSA was obtained from a patient without risk factors for its acquisition, and was resistant, beyond to the beta-lactams, only to tetracycline. CONCLUSIONS With regard to the resistance patterns of S. aureus, resistances to tetracycline, erythromycin and gentamicin were the highest. It was documented, for the first time in Pernambuco, a case of skin infection caused by community-associated MRSA. PMID:23197204

  10. Chronic resistance training does not affect post-exercise blood pressure in normotensive older women: a randomized controlled trial.

    Science.gov (United States)

    Gerage, Aline Mendes; Ritti-Dias, Raphael Mendes; do Nascimento, Matheus Amarante; Pina, Fábio Luiz Cheche; Gonçalves, Cássio Gustavo Santana; Sardinha, Luís B; Cyrino, Edilson Serpeloni

    2015-06-01

    Resistance training has been recommended for maintenance or improvement of the functional health of older adults, but its effect on acute cardiovascular responses remains unclear. Thus, the purpose of this study was to analyze the effect of 12 weeks of resistance training on post-exercise blood pressure (BP) in normotensive older women. Twenty-eight normotensive and physically inactive women (≥ 60 years) were randomly assigned to a training group (TG) or a control group (CG). The TG underwent a resistance training program (12 weeks, 8 exercises, 2 sets, 10-15 repetitions, 3 days/week), while the CG performed stretching exercises (12 weeks, 2 sets, 20 s each, 2 days/week). At baseline and after the intervention, participants were randomly submitted to two experimental sessions: a resistance exercise session (7 exercises, 2 sets, 10-15 repetitions) and a control session. BP was obtained pre- and post-sessions (90 min), through auscultation. Post-exercise hypotension was observed for systolic, diastolic, and mean BP in the TG (-6.1, -3.4, and -4.3 mmHg, respectively; P post-exercise BP and 12 weeks of resistance training program do not change the occurrence or magnitude of this hypotension. (ClinicalTrial.gov: NCT02346981).

  11. Characterization and comparative analysis of antibiotic resistance plasmids isolated from a wastewater treatment plant.

    Directory of Open Access Journals (Sweden)

    Teddie O Rahube

    2014-10-01

    Full Text Available A wastewater treatment plant (WWTP is an environment high in nutrient concentration with diverse bacterial populations and can provide an ideal environment for the proliferation of mobile elements such as plasmids. WWTPs have also been identified as reservoirs for antibiotic resistance genes that are associated with human pathogens. The objectives of this study were to isolate and characterize self-transmissible or mobilizable resistance plasmids associated with effluent from wastewater treatment plant. An enrichment culture approach designed to capture plasmids conferring resistance to high concentrations of erythromycin was used to capture plasmids from an urban wastewater treatment plant servicing a population of ca. 210,000. DNA sequencing of the plasmids revealed diversity of plasmids represented by incompatibility groups IncU, col-E, IncFII and IncP-1β. Genes coding resistance to clinically relevant antibiotics (macrolide, tetracycline, beta-lactam, trimethoprim, chloramphenicol, sulphonamide, quaternary ammonium compounds and heavy metals were co-located on these plasmids, often within transposable and integrative mobile elements. Several of the plasmids were self-transmissible or mobilizable and could be maintained in the absence of antibiotic selection. The IncFII plasmid pEFC36a showed the highest degree of sequence identity to plasmid R1 which has been isolated in England more than fifty years ago from a patient suffering from a Salmonella infection. Functional conservation of key regulatory features of this F-like conjugation module were demonstrated by the finding that the conjugation frequency of pEFC36a could be stimulated by the positive regulator of plasmid R1 DNA transfer genes, TraJ.

  12. Characterization and comparative analysis of antibiotic resistance plasmids isolated from a wastewater treatment plant.

    Science.gov (United States)

    Rahube, Teddie O; Viana, Laia S; Koraimann, Günther; Yost, Christopher K

    2014-01-01

    A wastewater treatment plant (WWTP) is an environment high in nutrient concentration with diverse bacterial populations and can provide an ideal environment for the proliferation of mobile elements such as plasmids. WWTPs have also been identified as reservoirs for antibiotic resistance genes that are associated with human pathogens. The objectives of this study were to isolate and characterize self-transmissible or mobilizable resistance plasmids associated with effluent from WWTP. An enrichment culture approach designed to capture plasmids conferring resistance to high concentrations of erythromycin was used to capture plasmids from an urban WWTP servicing a population of ca. 210,000. DNA sequencing of the plasmids revealed diversity of plasmids represented by incompatibility groups IncU, col-E, IncFII and IncP-1β. Genes coding resistance to clinically relevant antibiotics (macrolide, tetracycline, beta-lactam, trimethoprim, chloramphenicol, sulphonamide), quaternary ammonium compounds and heavy metals were co-located on these plasmids, often within transposable and integrative mobile elements. Several of the plasmids were self-transmissible or mobilizable and could be maintained in the absence of antibiotic selection. The IncFII plasmid pEFC36a showed the highest degree of sequence identity to plasmid R1 which has been isolated in England more than 50 years ago from a patient suffering from a Salmonella infection. Functional conservation of key regulatory features of this F-like conjugation module were demonstrated by the finding that the conjugation frequency of pEFC36a could be stimulated by the positive regulator of plasmid R1 DNA transfer genes, TraJ.

  13. Modeling of the bacterial mechanism of methicillin-resistance by a systems biology approach.

    Directory of Open Access Journals (Sweden)

    Ida Autiero

    Full Text Available BACKGROUND: A microorganism is a complex biological system able to preserve its functional features against external perturbations and the ability of the living systems to oppose to these external perturbations is defined "robustness". The antibiotic resistance, developed by different bacteria strains, is a clear example of robustness and of ability of the bacterial system to acquire a particular functional behaviour in response to environmental changes. In this work we have modeled the whole mechanism essential to the methicillin-resistance through a systems biology approach. The methicillin is a beta-lactamic antibiotic that act by inhibiting the penicillin-binding proteins (PBPs. These PBPs are involved in the synthesis of peptidoglycans, essential mesh-like polymers that surround cellular enzymes and are crucial for the bacterium survival. METHODOLOGY: The network of genes, mRNA, proteins and metabolites was created using CellDesigner program and the data of molecular interactions are stored in Systems Biology Markup Language (SBML. To simulate the dynamic behaviour of this biochemical network, the kinetic equations were associated with each reaction. CONCLUSIONS: Our model simulates the mechanism of the inactivation of the PBP by methicillin, as well as the expression of PBP2a isoform, the regulation of the SCCmec elements (SCC: staphylococcal cassette chromosome and the synthesis of peptidoglycan by PBP2a. The obtained results by our integrated approach show that the model describes correctly the whole phenomenon of the methicillin resistance and is able to respond to the external perturbations in the same way of the real cell. Therefore, this model can be useful to develop new therapeutic approaches for the methicillin control and to understand the general mechanism regarding the cellular resistance to some antibiotics.

  14. Metagenomic Evidence of the Prevalence and Distribution Patterns of Antimicrobial Resistance Genes in Dairy Agroecosystems.

    Science.gov (United States)

    Pitta, Dipti W; Dou, Zhengxia; Kumar, Sanjay; Indugu, Nagaraju; Toth, John Daniel; Vecchiarelli, Bonnie; Bhukya, Bhima

    2016-06-01

    Antimicrobial resistance (AR) is a global problem with serious implications for public health. AR genes are frequently detected on animal farms, but little is known about their origin and distribution patterns. We hypothesized that AR genes can transfer from animal feces to the environment through manure, and to this end, we characterized and compared the resistomes (collections of AR genes) of animal feces, manure, and soil samples collected from five dairy farms using a metagenomics approach. Resistomes constituted only up to 1% of the total gene content, but were variable by sector and also farm. Broadly, the identified AR genes were associated with 18 antibiotic resistances classes across all samples; however, the most abundant genes were classified under multidrug transporters (44.75%), followed by resistance to vancomycin (12.48%), tetracycline (10.52%), bacitracin (10.43%), beta-lactam resistance (7.12%), and MLS efflux pump (6.86%) antimicrobials. The AR gene profiles were variable between farms. Farm 09 was categorized as a high risk farm, as a greater proportion of AR genes were common to at least three sectors, suggesting possible horizontal transfer of AR genes. Taxonomic characterization of AR genes revealed that a majority of AR genes were associated with the phylum Proteobacteria. Nonetheless, there were several members of Bacteroidetes, particularly Bacteroides genus and several lineages from Firmicutes that carried similar AR genes in different sectors, suggesting a strong potential for horizontal transfer of AR genes between unrelated bacterial hosts in different sectors of the farms. Further studies are required to affirm the horizontal gene transfer mechanisms between microbiomes of different sectors in animal agroecosystems.

  15. Automated image analysis for quantification of filamentous bacteria

    DEFF Research Database (Denmark)

    Fredborg, M.; Rosenvinge, F. S.; Spillum, E.

    2015-01-01

    Background: Antibiotics of the beta-lactam group are able to alter the shape of the bacterial cell wall, e.g. filamentation or a spheroplast formation. Early determination of antimicrobial susceptibility may be complicated by filamentation of bacteria as this can be falsely interpreted as growth...... displaying different resistant profiles and differences in filamentation kinetics were used to study a novel image analysis algorithm to quantify length of bacteria and bacterial filamentation. A total of 12 beta-lactam antibiotics or beta-lactam-beta-lactamase inhibitor combinations were analyzed...

  16. Extended spectrum beta-lactamase-producing Escherichia coli forms filaments as an initial response to cefotaxime treatment

    DEFF Research Database (Denmark)

    Kjeldsen, Thea S. B.; Sommer, Morten Otto Alexander; Olsen, John E.

    2015-01-01

    Background: beta-lactams target the peptidoglycan layer in the bacterial cell wall and most beta-lactam antibiotics cause filamentation in susceptible Gram-negative bacteria at low concentrations. The objective was to determine the initial morphological response of cephalosporin resistant CTX-M-1......-17 hours in cultures of the resistant strains. Filaments were also observed in sensitive control strains with sub-inhibitory concentrations of cefotaxime. Conclusions: We showed that E. coli resistant to beta-lactams by an extended-spectrum beta-lactamase, bla(CTX-M-1), produced filaments when exposed...... to cefotaxime. The filament formation was restricted to early growth phases and the time the cells grew as filaments was antibiotic concentration dependent. This indicates that antibiotic resistant E. coli undergo the same morphological changes as sensitive bacteria in the presence of beta-lactam antibiotic...

  17. Paromomycin affects translation and vesicle-mediated trafficking as revealed by proteomics of paromomycin -susceptible -resistant Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Bhavna Chawla

    Full Text Available Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis (VL and is responsible for significant mortality and morbidity. Increasing resistance towards antimonial drugs poses a great challenge in chemotherapy of VL. Paromomycin is an aminoglycosidic antibiotic and is one of the drugs currently being used in the chemotherapy of cutaneous and visceral leishmaniasis. To understand the mode of action of this antibiotic at the molecular level, we have investigated the global proteome differences between the wild type AG83 strain and a paromomycin resistant (PRr strain of L. donovani. Stable isotope labeling of amino acids in cell culture (SILAC followed by quantitative mass spectrometry of the wild type AG83 strain and the paromomycin resistant (PRr strain identified a total of 226 proteins at ≥ 95% confidence. Data analysis revealed upregulation of 29 proteins and down-regulation of 21 proteins in the PRr strain. Comparative proteomic analysis of the wild type and the paromomycin resistant strains showed upregulation of the ribosomal proteins in the resistant strain indicating role in translation. Elevated levels of glycolytic enzymes and stress proteins were also observed in the PRr strain. Most importantly, we observed upregulation of proteins that may have a role in intracellular survival and vesicular trafficking in the PRr strain. Furthermore, ultra-structural analysis by electron microscopy demonstrated increased number of vesicular vacuoles in PRr strain when compared to the wild-type strain. Drug affinity pull-down assay followed by mass spectrometery identified proteins in L. donovani wild type strain that were specifically and covalently bound to paromomycin. These results provide the first comprehensive insight into the mode of action and underlying mechanism of resistance to paromomycin in Leishmania donovani.

  18. Chronic resistance training does not affect post-exercise blood pressure in normotensive older women: a randomized controlled trial

    OpenAIRE

    Gerage,Aline Mendes; Ritti-Dias, Raphael Mendes; do Nascimento, Matheus Amarante; Pina,Fábio Luiz Cheche; Gonçalves,Cássio Gustavo Santana; Sardinha, Luís B; Edilson Serpeloni CYRINO

    2015-01-01

    Resistance training has been recommended for maintenance or improvement of the functional health of older adults, but its effect on acute cardiovascular responses remains unclear. Thus, the purpose of this study was to analyze the effect of 12 weeks of resistance training on post-exercise blood pressure (BP) in normotensive older women. Twenty-eight normotensive and physically inactive women (≥60 years) were randomly assigned to a training group (TG) or a control group (CG). The TG underwent ...

  19. Endurance and Resistance Training Affect High Fat Diet-Induced Increase of Ceramides, Inflammasome Expression, and Systemic Inflammation in Mice.

    Science.gov (United States)

    Mardare, Cornelia; Krüger, Karsten; Liebisch, Gerhard; Seimetz, Michael; Couturier, Aline; Ringseis, Robert; Wilhelm, Jochen; Weissmann, Norbert; Eder, Klaus; Mooren, Frank-Christoph

    2016-01-01

    The study aimed to investigate the effects of differentiated exercise regimes on high fat-induced metabolic and inflammatory pathways. Mice were fed a standard diet (ST) or a high fat diet (HFD) and subjected to regular endurance training (ET) or resistance training (RT). After 10 weeks body weight, glucose tolerance, fatty acids (FAs), circulating ceramides, cytokines, and immunological mediators were determined. The HFD induced a significant increase in body weight and a disturbed glucose tolerance (p resistance training decreased body weight (p induced complications possibly through a reduction of ceramides, the reduction of inflammasome activation in adipose tissues, and a systemic downregulation of inflammatory cytokines.

  20. The breast cancer resistance protein (BCRP/ABCG2) affects pharmacokinetics, hepatobiliary excretion, and milk secretion of the antibiotic nitrofurantoin

    NARCIS (Netherlands)

    Merino, G; Jonker, JW; Wagenaar, E; van Herwaarden, AE; Schinkel, AH

    2005-01-01

    Nitrofurantoin is a commonly used urinary tract antibiotic prescribed to lactating woman. It is actively transported into human and rat milk by an unknown mechanism. Our group has demonstrated an important role of the breast cancer resistance protein (BCRP/ABCG2) in the secretion of xenotoxins into

  1. First identification of class A carbapenemase-producing Klebsiella pneumoniae in the Republic of Ireland.

    LENUS (Irish Health Repository)

    Roche, C

    2009-04-02

    The Klebsiella pneumoniae carbapenemase (KPC) was detected in a carbapenem-resistant respiratory isolate of Klebsiella pneumoniae in an Irish hospital. This is the first report of a KPC-producing isolate in the Republic of Ireland. The isolate was resistant to all beta-lactams. Furthermore, it had reduced susceptibility to three other classes of non-beta-lactam antibiotics. The isolate was not associated with travel abroad. Detection of KPC-producing bacteria has important infection control and public health implications.

  2. Evolution of linked avirulence effectors in Leptosphaeria maculans is affected by genomic environment and exposure to resistance genes in host plants.

    Directory of Open Access Journals (Sweden)

    Angela P Van de Wouw

    Full Text Available Brassica napus (canola cultivars and isolates of the blackleg fungus, Leptosphaeria maculans interact in a 'gene for gene' manner whereby plant resistance (R genes are complementary to pathogen avirulence (Avr genes. Avirulence genes encode proteins that belong to a class of pathogen molecules known as effectors, which includes small secreted proteins that play a role in disease. In Australia in 2003 canola cultivars with the Rlm1 resistance gene suffered a breakdown of disease resistance, resulting in severe yield losses. This was associated with a large increase in the frequency of virulence alleles of the complementary avirulence gene, AvrLm1, in fungal populations. Surprisingly, the frequency of virulence alleles of AvrLm6 (complementary to Rlm6 also increased dramatically, even though the cultivars did not contain Rlm6. In the L. maculans genome, AvrLm1 and AvrLm6 are linked along with five other genes in a region interspersed with transposable elements that have been degenerated by Repeat-Induced Point (RIP mutations. Analyses of 295 Australian isolates showed deletions, RIP mutations and/or non-RIP derived amino acid substitutions in the predicted proteins encoded by these seven genes. The degree of RIP mutations within single copy sequences in this region was proportional to their proximity to the degenerated transposable elements. The RIP alleles were monophyletic and were present only in isolates collected after resistance conferred by Rlm1 broke down, whereas deletion alleles belonged to several polyphyletic lineages and were present before and after the resistance breakdown. Thus, genomic environment and exposure to resistance genes in B. napus has affected the evolution of these linked avirulence genes in L. maculans.

  3. High-throughput profiling of antibiotic resistance genes in drinking water treatment plants and distribution systems.

    Science.gov (United States)

    Xu, Like; Ouyang, Weiying; Qian, Yanyun; Su, Chao; Su, Jianqiang; Chen, Hong

    2016-06-01

    Antibiotic resistance genes (ARGs) are present in surface water and often cannot be completely eliminated by drinking water treatment plants (DWTPs). Improper elimination of the ARG-harboring microorganisms contaminates the water supply and would lead to animal and human disease. Therefore, it is of utmost importance to determine the most effective ways by which DWTPs can eliminate ARGs. Here, we tested water samples from two DWTPs and distribution systems and detected the presence of 285 ARGs, 8 transposases, and intI-1 by utilizing high-throughput qPCR. The prevalence of ARGs differed in the two DWTPs, one of which employed conventional water treatments while the other had advanced treatment processes. The relative abundance of ARGs increased significantly after the treatment with biological activated carbon (BAC), raising the number of detected ARGs from 76 to 150. Furthermore, the final chlorination step enhanced the relative abundance of ARGs in the finished water generated from both DWTPs. The total enrichment of ARGs varied from 6.4-to 109.2-fold in tap water compared to finished water, among which beta-lactam resistance genes displayed the highest enrichment. Six transposase genes were detected in tap water samples, with the transposase gene TnpA-04 showing the greatest enrichment (up to 124.9-fold). We observed significant positive correlations between ARGs and mobile genetic elements (MGEs) during the distribution systems, indicating that transposases and intI-1 may contribute to antibiotic resistance in drinking water. To our knowledge, this is the first study to investigate the diversity and abundance of ARGs in drinking water treatment systems utilizing high-throughput qPCR techniques in China.

  4. Resistance and the management of complicated skin and skin structure infections: the role of ceftobiprole.

    Science.gov (United States)

    Barbour, April; Derendorf, Hartmut

    2010-10-05

    Antimicrobial resistant bacteria are an increasing concern due to the resulting increase in morbidity, mortality, and health-care costs associated with the administration of inadequate or delayed antimicrobial therapy. The implications of inadequate antimicrobial therapy in complicated skin and skin structure infections (cSSSIs) have gained more attention recently, most likely due to the recent emergence of community-acquired methicillin resistant Staphylococcus aureus (MRSA) and the already high prevalence of MRSA in the nosocomial setting. Due to the continuous threat of resistance arising and the limitations of currently available agents for the treatment of cSSSIs, it is necessary to develop new antimicrobials for this indication. Ceftobiprole medocaril, the prodrug of ceftobiprole, is a parental investigational cephalosporin for the treatment of cSSSIs displaying a wide-spectrum of activity against both Gram-positive and Gram-negative species, including MRSA. Ceftobiprole displays noncomplex linear pharmacokinetics, is eliminated primarily by glomerular filtration, and distributes to extracellular fluid. Additionally, it has been shown that the extent of distribution to the site of action with regard to cSSSIs, ie, the extracellular space fluid of subcutaneous adipose tissue and skeletal muscle, is expected to be efficacious, as free concentrations meet efficacy targets for most pathogens. Similar to other beta-lactams, it displays an excellent safety and tolerability profile with the primary adverse events being dysgeusia in healthy volunteers, resulting from the conversion of the prodrug to the active, and nausea in patients. Ceftobiprole has demonstrated noninferiority in two large-scale pivotal studies comparing it to vancomycin, clinical cure rates 93.3% vs 93.5%, respectively, or vancomycin plus ceftazidime, clinical cure rates 90.5% vs 90.2%, respectively. Given the pharmacokinetic and pharmacodynamic properties, ceftobiprole is a promising new agent

  5. Eight Weeks of Phosphatidic Acid Supplementation in Conjunction with Resistance Training Does Not Differentially Affect Body Composition and Muscle Strength in Resistance-Trained Men

    Directory of Open Access Journals (Sweden)

    Thomas L. Andre, Joshua J. Gann, Sarah K. McKinley-Barnard, Joon J. Song, Darryn S. Willoughby

    2016-09-01

    Full Text Available This study attempted to determine the effects of eight weeks of resistance training (RT combined with phosphatidic acid (PA supplementation at a dose of either 250 mg or 375 mg on body composition and muscle size and strength. Twenty-eight resistance-trained men were randomly assigned to ingest 375 mg [PA375 (n = 9] or 250 mg [PA250 (n = 9] of PA or 375 mg of placebo [PLC (n = 10] daily for eight weeks with RT. Supplements were ingested 60 minutes prior to RT and in the morning on non-RT days. Participants’ body composition, muscle size, and lower-body muscle strength were determined before and after training/supplementation. Separate group x time ANOVAs for each criterion variable were used employing an alpha level of ≤ 0.05. Magnitude- based inferences were utilized to determine the likely or unlikely impact of PA on each criterion variable. A significant main effect for time was observed for improvements in total body mass (p = 0.003, lean mass (p = 0.008, rectus femoris cross-sectional area [RF CSA (p = 0.011], and lower-body strength (p 0.05. Collectively, magnitude-based inferences determined both doses of PA to have a likely impact of increasing body mass (74.2%, lean mass (71.3%, RF CSA (92.2%, and very likely impact on increasing lower-body strength (98.1% beneficial. When combined with RT, it appears that PA has a more than likely impact on improving lower-body strength, whereas a likely impact exists for increasing muscle size and lean mass.

  6. Eight Weeks of Phosphatidic Acid Supplementation in Conjunction with Resistance Training Does Not Differentially Affect Body Composition and Muscle Strength in Resistance-Trained Men.

    Science.gov (United States)

    Andre, Thomas L; Gann, Joshua J; McKinley-Barnard, Sarah K; Song, Joon J; Willoughby, Darryn S

    2016-09-01

    This study attempted to determine the effects of eight weeks of resistance training (RT) combined with phosphatidic acid (PA) supplementation at a dose of either 250 mg or 375 mg on body composition and muscle size and strength. Twenty-eight resistance-trained men were randomly assigned to ingest 375 mg [PA375 (n = 9)] or 250 mg [PA250 (n = 9)] of PA or 375 mg of placebo [PLC (n = 10)] daily for eight weeks with RT. Supplements were ingested 60 minutes prior to RT and in the morning on non-RT days. Participants' body composition, muscle size, and lower-body muscle strength were determined before and after training/supplementation. Separate group x time ANOVAs for each criterion variable were used employing an alpha level of ≤ 0.05. Magnitude- based inferences were utilized to determine the likely or unlikely impact of PA on each criterion variable. A significant main effect for time was observed for improvements in total body mass (p = 0.003), lean mass (p = 0.008), rectus femoris cross-sectional area [RF CSA (p = 0.011)], and lower-body strength (p 0.05). Collectively, magnitude-based inferences determined both doses of PA to have a likely impact of increasing body mass (74.2%), lean mass (71.3%), RF CSA (92.2%), and very likely impact on increasing lower-body strength (98.1% beneficial). When combined with RT, it appears that PA has a more than likely impact on improving lower-body strength, whereas a likely impact exists for increasing muscle size and lean mass.

  7. Management Options and Factors Affecting Control of a Common Waterhemp (Amaranthus rudis Biotype Resistant to Protoporphyrinogen Oxidase-Inhibiting Herbicides

    Directory of Open Access Journals (Sweden)

    Dana B. Harder

    2012-01-01

    Full Text Available Repeated use of protox-inhibiting herbicides has resulted in a common waterhemp (Amaranthus rudis Sauer biotype that survived lactofen applied up to 10 times the labeled rate. Field and greenhouse research evaluated control options for this biotype of common waterhemp. In the field, PRE applications of flumioxazin at 72 g ai ha−1, sulfentrazone at 240 g ai ha−1, and isoxaflutole at 70 g ai ha−1 controlled common waterhemp >90% up to 6 weeks after treatment. POST applications of fomesafen at 330 g ai ha−1, lactofen at 220 g ai ha−1, and acifluorfen at 420 g ai ha−1 resulted in <60% visual control of common waterhemp, but differences were detected among herbicides. In the greenhouse, glyphosate was the only herbicide that controlled protox resistant waterhemp. The majority of herbicide activity from POST flumioxazin, fomesafen, acifluorfen, and lactofen was from foliar placement, but control was less than 40% regardless of placement. Control of common waterhemp seeded at weekly intervals after herbicide treatment with flumioxazin, fomesafen, sulfentrazone, atrazine, and isoxaflutole exceeded 85% at 0 weeks after herbicide application (WAHA, while control with isoxaflutole was greater than 60% 6 WAHA. PRE and POST options for protox-resistant common waterhemp are available to manage herbicide resistance.

  8. Cabozantinib inhibits growth of androgen-sensitive and castration-resistant prostate cancer and affects bone remodeling.

    Directory of Open Access Journals (Sweden)

    Holly M Nguyen

    Full Text Available Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa, cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease.

  9. Efficient dsRNA-mediated transgenic resistance to Beet necrotic yellow vein virus in sugar beets is not affected by other soilborne and aphid-transmitted viruses.

    Science.gov (United States)

    Lennefors, Britt-Louise; van Roggen, Petra M; Yndgaard, Flemming; Savenkov, Eugene I; Valkonen, Jari P T

    2008-04-01

    Rhizomania caused by Beet necrotic yellow vein virus (BNYVV) is one of the most devastating sugar beet diseases. Sugar beet plants engineered to express a 0.4 kb inverted repeat construct based on the BNYVV replicase gene accumulated the transgene mRNA to similar levels in leaves and roots, whereas accumulation of the transgene-homologous siRNA was more pronounced in roots. The roots expressed high levels of resistance to BNYVV transmitted by the vector, Polymyxa betae. Resistance to BNYVV was not decreased following co-infection of the plants with Beet soil borne virus and Beet virus Q that share the same vector with BNYVV. Similarly, co-infection with the aphid-transmitted Beet mild yellowing virus, Beet yellows virus (BYV), or with all of the aforementioned viruses did not affect the resistance to BNYVV, while they accumulated in roots. These viruses are common in most of the sugar beet growing areas in Europe and world wide. However, there was a competitive interaction between BYV and BMYV in sugar beet leaves, as infection with BYV decreased the titres of BMYV. Other interactions between the viruses studied were not observed. The results suggest that the engineered resistance to BNYVV expressed in the sugar beets of this study is efficient in roots and not readily compromised following infection of the plants with heterologous viruses.

  10. Supplementation with a proprietary blend of ancient peat and apple extract may improve body composition without affecting hematology in resistance-trained men.

    Science.gov (United States)

    Joy, Jordan M; Falcone, Paul H; Vogel, Roxanne M; Mosman, Matt M; Kim, Michael P; Moon, Jordan R

    2015-11-01

    Adenosine-5'-triphosphate (ATP) is primarily known as a cellular source of energy. Increased ATP levels may have the potential to enhance body composition. A novel, proprietary blend of ancient peat and apple extracts has been reported to increase ATP levels, potentially by enhancing mitochondrial ATP production. Therefore, the purpose of this investigation was to determine the supplement's effects on body composition when consumed during 12 weeks of resistance training. Twenty-five healthy, resistance-trained, male subjects (age, 27.7 ± 4.8 years; height, 176.0 ± 6.5 cm; body mass, 83.2 ± 12.1 kg) completed this study. Subjects supplemented once daily with either 1 serving (150 mg) of a proprietary blend of ancient peat and apple extracts (TRT) or placebo (PLA). Supervised resistance training consisted of 8 weeks of daily undulating periodized training followed by a 2-week overreach and a 2-week taper phase. Body composition was assessed using dual-energy X-ray absorptiometry and ultrasound at weeks 0, 4, 8, 10, and 12. Vital signs and blood markers were assessed at weeks 0, 8, and 12. Significant group × time (p ancient peat and apple extracts may enhance resistance training-induced skeletal muscle hypertrophy without affecting fat mass or blood chemistry in healthy males.

  11. The Staphylococcus aureus Chaperone PrsA Is a New Auxiliary Factor of Oxacillin Resistance Affecting Penicillin-Binding Protein 2A.

    Science.gov (United States)

    Jousselin, Ambre; Manzano, Caroline; Biette, Alexandra; Reed, Patricia; Pinho, Mariana G; Rosato, Adriana E; Kelley, William L; Renzoni, Adriana

    2015-12-28

    Expression of the methicillin-resistant S. aureus (MRSA) phenotype results from the expression of the extra penicillin-binding protein 2A (PBP2A), which is encoded by mecA and acquired horizontally on part of the SCCmec cassette. PBP2A can catalyze dd-transpeptidation of peptidoglycan (PG) because of its low affinity for β-lactam antibiotics and can functionally cooperate with the PBP2 transglycosylase in the biosynthesis of PG. Here, we focus upon the role of the membrane-bound PrsA foldase protein as a regulator of β-lactam resistance expression. Deletion of prsA altered oxacillin resistance in three different SCCmec backgrounds and, more importantly, caused a decrease in PBP2A membrane amounts without affecting mecA mRNA levels. The N- and C-terminal domains of PrsA were found to be critical features for PBP2A protein membrane levels and oxacillin resistance. We propose that PrsA has a role in posttranscriptional maturation of PBP2A, possibly in the export and/or folding of newly synthesized PBP2A. This additional level of control in the expression of the mecA-dependent MRSA phenotype constitutes an opportunity to expand the strategies to design anti-infective agents.

  12. The Prevalence Of Nosocomial Infections Caused By Enterobacter Cloacae And Antibiotic Resistant Patterns In Samples Isolated From Patients In Two Hospitals In Tehran

    Directory of Open Access Journals (Sweden)

    S Soleymanzadeh

    2012-06-01

    Full Text Available Background: The increasing use of β-lactam antibiotics in clinics for the treatment of different bacterial infections since early 1980s has led to increased rates of resistant bacteria isolated from patients. One of the problems in the treatment of nosocomial infections is related to resistant bacteria such as Enterobacter cloacae due to cross resistance through extended-spectrum beta-lactamase production. The aim of this study was to determine the prevalence of extended-spectrum beta-lactamase producing E. cloacae from different clinical specimens collected from hospitalized patients. Methods: In the present study, 101 E. cloacae confirmed by standard specific microbiologic tests were collected from different specimens in Milad and Motahri hospitals in Tehran, Iran during February 2010 and September 2011. Antibiotic susceptibility tests were conducted according to the process recommended by the Clinical and Laboratory Standards Institute for 13 antibiotics of choice. Extended-spectrum beta-lactamase producing strains were screened for by combined disk method as a phenotypic diagnostic test. Results: From a total of 101 E. cloacae, 33 (33% were shown to produce extended-spectrum beta-lactamase by phenotypic tests; 5% of the bacteria were resistant to imipenem too. Conclusion: This study clearly showed the high prevalence of resistance to broad-spectrum beta-lactam antibiotics in the isolated E. cloacae among which 5% were multi drug resistant. All the isolated E. cloacae were susceptible to Colistin. These results can be alarming for physicians treating resistant E. cloacae infections, especially extended-spectrum beta-lactamase producing species.

  13. A surveillance study of antimicrobial resistance of gram-negative bacteria isolated from intensive care units in eight hospitals in Turkey.

    Science.gov (United States)

    Günseren, F; Mamikoğlu, L; Oztürk, S; Yücesoy, M; Biberoğlu, K; Yuluğ, N; Doğanay, M; Sümerkan, B; Kocagöz, S; Unal, S; Cetin, S; Calangu, S; Köksal, I; Leblebicioğlu, H; Günaydin, M

    1999-03-01

    This study was carried out with the participation of eight hospitals in Turkey to determine the frequency of gram-negative bacteria isolated in intensive care units (ICU) and to compare their resistance rates to selected antibiotics. Aerobic gram-negative bacteria isolated from ICUs during 1996 were studied. Antibiotic susceptibilities to imipenem, ceftazidime, ceftazidime-clavulanate, ceftriaxone, cefotaxime, cefepime, cefodizime, cefuroxime, piperacillin/tazobactam, amoxycillin-clavulanate, gentamicin, amikacin and ciprofloxacin were determined by Etest. A total of 748 isolates were obtained from 547 patients. The majority of organisms were isolated from the respiratory (38.8%) and urinary tracts (30.9%). Pseudomonas spp. were the most frequently isolated gram-negative species (26.8%), followed by Klebsiella spp. (26.2%). Escherichia coli, Acinetobacter spp. and Enterobacter spp. were the other commonly isolated organisms. High resistance rates were observed for all antibiotics studied. Imipenem appeared to be the most active agent against the majority of isolates. Although resistance rates exceeded 50%, ciprofloxacin, cefepime and amikacin were found to be relatively effective. Extended-spectrum beta-lactamase (ESBL) production appeared to be a major mechanism of resistance to beta-lactam antibiotics. In contrast to ceftazidime-clavulanate, piperacillin/tazobactam showed poor activity against organisms thought to produce ESBL, suggesting the presence of an enzyme resistant to tazobactam action. This study has yielded high rates of resistance in aerobic gram-negative isolates from ICUs in Turkey. High resistance rates to all the other antibacterials studied leave imipenem as the only reliable agent for the empirical treatment of ICU infections in Turkey.

  14. Endurance and Resistance Training Affect High Fat Diet-Induced Increase of Ceramides, Inflammasome Expression, and Systemic Inflammation in Mice

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    Cornelia Mardare

    2016-01-01

    Full Text Available The study aimed to investigate the effects of differentiated exercise regimes on high fat-induced metabolic and inflammatory pathways. Mice were fed a standard diet (ST or a high fat diet (HFD and subjected to regular endurance training (ET or resistance training (RT. After 10 weeks body weight, glucose tolerance, fatty acids (FAs, circulating ceramides, cytokines, and immunological mediators were determined. The HFD induced a significant increase in body weight and a disturbed glucose tolerance (p<0.05. An increase of plasma FA, ceramides, and inflammatory mediators in adipose tissue and serum was found (p<0.05. Both endurance and resistance training decreased body weight (p<0.05 and reduced serum ceramides (p<0.005. While RT attenuated the increase of NLRP-3 (RT expression in adipose tissue, ET was effective in reducing TNF-α and IL-18 expression. Furthermore, ET reduced levels of MIP-1γ, while RT decreased levels of IL-18, MIP-1γ, Timp-1, and CD40 in serum (p<0.001, respectively. Although both exercise regimes improved glucose tolerance (p<0.001, ET was more effective than RT. These results suggest that exercise improves HFD-induced complications possibly through a reduction of ceramides, the reduction of inflammasome activation in adipose tissues, and a systemic downregulation of inflammatory cytokines.

  15. Virulence characterisation of Salmonella enterica isolates of differing antimicrobial resistance recovered from UK livestock and imported meat samples.

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    Roderick eCard

    2016-05-01

    Full Text Available Salmonella enterica is a foodborne zoonotic pathogen of significant public health concern. We have characterised the virulence and antimicrobial resistance gene content of 95 Salmonella isolates from 11 serovars by DNA microarray recovered from UK livestock or imported meat. Genes encoding resistance to sulphonamides (sul1, sul2, tetracycline (tet(A, tet(B, streptomycin (strA, strB, aminoglycoside (aadA1, aadA2, beta-lactam (blaTEM, and trimethoprim (dfrA17 were common. Virulence gene content differed between serovars; S. Typhimurium formed two subclades based on virulence plasmid presence. Thirteen isolates were selected by their virulence profile for pathotyping using the Galleria mellonella pathogenesis model. Infection with a chicken invasive S. Enteritidis or S. Gallinarum isolate, a multidrug resistant S. Kentucky, or a S. Typhimurium DT104 isolate resulted in high mortality of the larvae; notably presence of the virulence plasmid in S. Typhimurium was not associated with increased larvae mortality. Histopathological examination showed that infection caused severe damage to the Galleria gut structure. Enumeration of intracellular bacteria in the larvae 24 hours post-infection showed increases of up to 7 log above the initial inoculum and transmission electron microscopy (TEM showed bacterial replication in the haemolymph. TEM also revealed the presence of vacuoles containing bacteria in the haemocytes, similar to Salmonella containing vacuoles observed in mammalian macrophages; although there was no evidence from our work of bacterial replication within vacuoles. This work shows that microarrays can be used for rapid virulence genotyping of S. enterica and that the Galleria animal model replicates some aspects of Salmonella infection in mammals. These procedures can be used to help inform on the pathogenicity of isolates that may be antibiotic resistant and have scope to aid the assessment of their potential public and animal health risk.

  16. Analysis of plasmid-mediated multidrug resistance in Escherichia coli and Klebsiella oxytoca isolates from clinical specimens in Japan.

    Science.gov (United States)

    Ode, Takashi; Saito, Ryoichi; Kumita, Wakako; Sato, Kenya; Okugawa, Shu; Moriya, Kyoji; Koike, Kazuhiko; Okamura, Noboru

    2009-10-01

    This study investigated the relationship of plasmid-mediated quinolone resistance (PMQR) and aminoglycoside resistance among oxyimino-cephalosporin-resistant Escherichia coli (n=46) and Klebsiella oxytoca (n=28) clinical isolates in Japan. Seventy-three isolates appeared to produce an extended-spectrum beta-lactamase (ESBL) and one K. oxytoca isolate produced IMP-1 metallo-beta-lactamase (MBL). Polymerase chain reaction (PCR) and sequencing confirmed that eight CTX-M-9/SHV-12-producing isolates, one IMP-1-producing K. oxytoca isolate, and six ESBL-positive E. coli isolates respectively possessed PMQR genes qnrA1, qnrB6, and aac(6')-Ib-cr. All qnr-positive isolates also carried either aac(6')-Ib or aac(6')-IIc aminoglycoside acetyltransferase genes. Resistance determinants to beta-lactams, quinolones and aminoglycosides were co-transferred with a plasmid of ca. 140 kb. The qnrA1 gene was located downstream of insertion sequence ISCR1 in complex class 1 integrons. A novel qnrA1-carrying class 1 integron with the cassette arrangement aac(6')-IIc-aadA2 as well as a unique class 1 integron with bla(IMP-1)-aac(6')-IIc cassettes on the plasmid carrying qnrB6 were found in K. oxytoca isolates. We describe the identification of qnrB6 and aac(6')-Ib-cr and the close association of qnr with aac(6')-Ib and aac(6')-IIc for the first time in clinical isolates producing ESBL or MBL in Japan.

  17. Emergence and Spread of A Plasmid-Mediated Polymyxin Resistance Mechanism, MCR-1: Are Bacteria Winning?

    Directory of Open Access Journals (Sweden)

    Chao Yang

    2015-12-01

    Full Text Available The report of the emergence of mcr-1, the first plasmid-mediated polymyxin resistance mechanism, in Enterobacteriaceae in November 2015 challenged our last psychological line of defense. However, we still trusted that this resistance factor had not spread globally. One month later, in December 2015, the detection of mcr-1 in an Escherichia coliisolate from a septicemic patient in Denmark and in five E. coli isolates from imported chicken meat really defeated us. The worst news was that one of the chicken meat isolates belonged to ST131, a spreading epidemic sequence type. In China, 15%-21% of E. coli strains isolated from raw meat and animals carried mcr-1, and about 1% of patient isolates carried this gene, indicating that E. coli carrying this plasmid is not a rare phenomenon. This gene is transferable by conjugation and can be maintained in Klebsiella pneumonia and Pseudomonas aeruginosa, suggesting the risk of transfer between different bacterial genera. The good news is that the strains carrying mcr-1 do not contain genes for pan-resistance profiles, although some Danish strains contain 15 different resistance genes, including genes for extended-spectrum beta-lactam antibiotics, and gene mutations leading to high-level fluoroquinolone resistance. If the mcr-1-bearing strains acquire multidrug resistance, extensive drug resistance, or pandrug resistance, no antibiotic drugs will be available with which clinicians can treat infected patients. Therefore, the use of antibiotics in both hospitals and the animal breeding industry must be strictly regulated. The origin of mcr-1 may be associated with the wide use of colistin in agriculture. There is no evidence that the Danish mcr-1 gene spread from China. Therefore, it is likely that mcr-1 genes originated in multiple sites simultaneously under the pressure of colistin use, because India and Denmark are the world’ s greatest users of this antibiotic. More surveys must be conducted in different

  18. Linkage mapping and identification of QTL affecting deoxynivalenol (DON) content (Fusarium resistance) in oats (Avena sativa L.).

    Science.gov (United States)

    He, Xinyao; Skinnes, Helge; Oliver, Rebekah E; Jackson, Eric W; Bjørnstad, Asmund

    2013-10-01

    Mycotoxins caused by Fusarium spp. is a major concern on food and feed safety in oats, although Fusarium head blight (FHB) is often less apparent than in other small grain cereals. Breeding resistant cultivars is an economic and environment-friendly way to reduce toxin content, either by the identification of resistance QTL or phenotypic evaluation. Both are little explored in oats. A recombinant-inbred line population, Hurdal × Z595-7 (HZ595, with 184 lines), was used for QTL mapping and was phenotyped for 3 years. Spawn inoculation was applied and deoxynivalenol (DON) content, FHB severity, days to heading and maturity (DH and DM), and plant height (PH) were measured. The population was genotyped with DArTs, AFLPs, SSRs and selected SNPs, and a linkage map of 1,132 cM was constructed, covering all 21 oat chromosomes. A QTL for DON on chromosome 17A/7C, tentatively designated as Qdon.umb-17A/7C, was detected in all experiments using composite interval mapping, with phenotypic effects of 12.2–26.6 %. In addition, QTL for DON were also found on chromosomes 5C, 9D, 13A, 14D and unknown_3, while a QTL for FHB was found on 11A. Several of the DON/FHB QTL coincided with those for DH, DM and/or PH. A half-sib population of HZ595, Hurdal × Z615-4 (HZ615, with 91 lines), was phenotyped in 2011 for validation of QTL found in HZ595, and Qdon.umb-17A/7C was again localized with a phenotypic effect of 12.4 %. Three SNPs closely linked to Qdon.umb-17A/7C were identified in both populations, and one each for QTL on 5C, 11A and 13A were identified in HZ595. These SNPs, together with those yet to be identified, could be useful in marker-assisted selection to pyramiding resistance QTL.

  19. Lipid induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling

    DEFF Research Database (Denmark)

    Høeg, Louise D; Sjøberg, Kim Anker; Jeppesen, Jacob

    2011-01-01

    AbstractObjective: We have previously shown that overnight fasted women have higher insulin stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism...... than men. We therefore hypothesized that women would be less prone to lipid induced insulin resistance. Research and design methods: Insulin sensitivity of whole body and leg glucose disposal was studied in 16 young well matched healthy men and women infused with intralipid or saline for 7h. Muscle...... biopsies were obtained before and during a euglycemic hyperinsulinemic (1.42 mU·kg(-1)·min(-1)) clamp. Results: Intralipid infusion reduced whole body glucose infusion rate 26% in women and 38% in men (pmen...

  20. Multi-drugs resistant acne rosacea in a child affected by Ataxia-Telangiectasia: successful treatment with Isotretinoin.

    Science.gov (United States)

    Cantarutti, Nicoletta; Claps, Alessia; Angelino, Giulia; Chessa, Luciana; Callea, Francesco; El Hachem, May; Diociaiuti, Andrea; Finocchi, Andrea

    2015-03-28

    Ataxia-Telangiectasia is a rare multisystem autosomal recessive disorder [OMIM 208900], caused by mutations in Ataxia-Telangiectasia Mutated gene. It is characterized by neurological, immunological and cutaneous involvement. Granulomas have been previously reported in Ataxia-Telangiectasia patients, even if acne rosacea has not been described.We report a case of a young Ataxia-Telangiectasia patient with a severe immunological and neurological involvement, who developed granulomatous skin lesions diagnosed by skin biopsy as acne rosacea. Considering the severe clinical picture and the lack of improvement to multiple topic and systemic therapies, treatment with Isotretinoin was started and the skin lesions disappeared after five months. However the therapy was stopped due to drug-hepatotoxicity.Systemic treatment with Isotretinoin should be carefully considered in patient with Ataxia-Telangiectasia for the treatment of multi-drug resistant acne rosacea, however its toxicity may limit long-term use and the risk/benefit ratio of the treatment should be evaluated.

  1. Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in yeast

    Directory of Open Access Journals (Sweden)

    Srinivas eAyyadevara

    2014-08-01

    Full Text Available A quantitative trait locus (QTL in the nematode C. elegans, lsq4, was recently implicated by mapping longevity genes. QTLs for lifespan and 3 stress-resistance traits coincided within a span of <300 kbp, later narrowed to <200 kbp. A single gene in this interval is now shown to modulate all lsq4-associated traits. Full-genome analysis of transcript levels indicates that lsq4 contains a dimorphic gene governing expression of sperm-specific genes, suggesting effects on spermatogenesis. Quantitation of allele-specific transcripts encoded within the lsq4 interval revealed significant, 2- to 15-fold expression differences for 10 of 33 genes. Fourteen genes, implicated by both position and expression, were tested for RNA-interference effects on QTL-linked traits. In a strain carrying the shorter-lived allele, knockdown of rec-8 (encoding a meiotic cohesin reduced its transcripts 4-fold, to a level similar to the longer-lived strain, and extended lifespan 25–26% whether begun before fertilization or at maturity. The short-lived lsq4 allele also conferred sensitivity to oxidative and thermal stresses, and lower male frequency, traits reversed uniquely by rec-8 knockdown. A strain bearing the longer-lived lsq4 allele, differing from the short-lived strain at <0.3% of its genome, derived no lifespan or stress-survival benefit from rec-8 knockdown. We consider two possible explanations: high rec-8 expression may include increased leaky expression in mitotic cells, leading to deleterious destabilization of somatic genomes; or REC-8 may act entirely in germ-line meiotic cells to reduce aberrations such as nondisjunction, thereby blunting a stress-resistance response mediated by innate immunity. Replicative lifespan was extended 20% in haploid S. cerevisiae (BY4741 by deletion of REC8, orthologous to nematode rec-8, implying that REC8 disruption of mitotic-cell survival is widespread, reflecting antagonistic pleiotropy and/or balancing selection.

  2. Carbapenemases in Enterobacteriaceae: types and molecular epidemiology.

    Science.gov (United States)

    Martínez-Martínez, Luis; González-López, Juan José

    2014-12-01

    The most important mechanism of carbapenem resistance in Enterobacteriaceae is the production of carbapenemases, although resistance can also result from the synergistic activity between AmpC-type or (to a lesser extent) extended-spectrum beta-lactamases combined with decreased outer membrane permeability. Three major molecular classes of carbapenemases are recognized: A, B and D. Classes A and D are serine-beta-lactamases, whereas class B are metallo-beta-lactamases (their hydrolytic activity depends on the presence of zinc). In addition to carbapenems, carbapenemases also hydrolyze other beta-lactams, but the concrete substrate profile depends on the enzyme type. In general terms, class A enzymes are to some extent inhibited by clavulanic acid, and class B enzymes do not affect monobactams and are inhibited by zinc chelators. Given Enterobacteriaceae producing carbapenemases usually also contain gene coding for other mechanisms of resistance to beta-lactams, it is not unusual for the organisms to present complex beta-lactam resistance phenotypes. Additionally, these organisms frequently contain other genes that confer resistance to quinolones, aminoglycosides, tetracyclines, sulphonamides and other families of antimicrobial agents, which cause multiresistance or even panresistance. Currently, the most important type of class A carbapenemases are KPC enzymes, whereas VIM, IMP and (particularly) NDM in class B and OXA-48 (and related) in class D are the more relevant enzymes. Whereas some enzymes are encoded by chromosomal genes, most carbapenemases are plasmid-mediated (with genes frequently located in integrons), which favors the dissemination of the enzymes. Detailed information of the genetic platforms and the context of the genes coding for the most relevant enzymes will be presented in this review.

  3. Treatment-time regimen of hypertension medications significantly affects ambulatory blood pressure and clinical characteristics of patients with resistant hypertension.

    Science.gov (United States)

    Hermida, Ramón C; Ríos, María T; Crespo, Juan J; Moyá, Ana; Domínguez-Sardiña, Manuel; Otero, Alfonso; Sánchez, Juan J; Mojón, Artemio; Fernández, José R; Ayala, Diana E

    2013-03-01

    Patients with resistant hypertension (RH) are at greater risk for stroke, renal insufficiency, and cardiovascular disease (CVD) events than are those for whom blood pressure (BP) is responsive to and well controlled by therapeutic interventions. Although all chronotherapy trials have compared the effects on BP regulation of full daily doses of medications when ingested in the morning versus at bedtime, prescription of the same medications in divided doses twice daily (BID) is frequent. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and laboratory medicine parameters of RH patients evaluated by 48-h ambulatory BP monitoring (ABPM). This cross-sectional study evaluated 2899 such patients (1701 men/1198 women), 64.2 ± 11.8 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 1084 were ingesting all hypertension medications upon awakening (upon-awakening regimen), 1436 patients were ingesting the full daily dose of ≥1 of them at bedtime (bedtime regimen), and 379 were ingesting split doses of ≥1 medications BID upon awakening and at bedtime (BID regimen). Patients of the bedtime regimen compared with the other two treatment-time regimens had lower likelihood of microalbuminuria and chronic kidney disease; significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; plus higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. The bedtime regimen was also significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than the upon-awakening and BID regimens. The sleep-time relative SBP and DBP decline was significantly attenuated by the upon-awakening and BID regimens (p treatment-time regimen groups (80.5% and 77.3%, respectively) than in the bedtime regimen (54.4%; p treatment regimens, compared with the

  4. Potato powders prepared by successive cooking-process depending on resistant starch content affect the intestinal fermentation in rats.

    Science.gov (United States)

    Kawakami, Sakura; Han, Kyu-Ho; Araki, Takahiro; Ohba, Kiyoshi; Wakabayashi, Tatsuya; Shimada, Kenichiro; Fukushima, Michihiro

    2017-02-01

    The effects of resistant starch (RS) in dry potato powders prepared by various processes on intestinal fermentation in rats were assessed. Rats were fed raw potato powder (RP), blanched potato powder (BP), steamed potato powder (SP), or drum-dried potato powder (DP) for 4 weeks. The cecal RS content was significantly higher in the RP group than in the control diet (CN) group and other dry potato powder groups. Cecum pH was significantly lower in the RP group compared to the CN group, and was also significantly lower than that in the SP, BP, and DP groups. Lactic acid bacteria levels in the RP group were significantly higher than those in the CN group, and levels in the SP group also increased relative to the control group. Lactobacillus levels in the RP group were higher than in the CN and other dry potato powder groups. Cecal short-chain fatty acid (SCFA) concentrations in the RP group followed by the SP group exhibited significantly higher levels relative to the control levels. Dry potato powders containing RS produced during the cooking process may represent a useful food material that increases intestinal concentrations of SCFA and enhances the growth of certain lactic acid bacteria.

  5. The WRKY57 Transcription Factor Affects the Expression of Jasmonate ZIM-Domain Genes Transcriptionally to Compromise Botrytis cinerea Resistance.

    Science.gov (United States)

    Jiang, Yanjuan; Yu, Diqiu

    2016-08-01

    Although necrotrophic pathogens cause many devastating plant diseases, our understanding of the plant defense response to them is limited. Here, we found that loss of function of WRKY57 enhanced the resistance of Arabidopsis (Arabidopsis thaliana) against Botrytis cinerea infection. Further investigation suggested that the negative regulation of WRKY57 against B cinerea depends on the jasmonic acid (JA) signaling pathway. Chromatin immunoprecipitation experiments revealed that WRKY57 directly binds to the promoters of JASMONATE ZIM-DOMAIN1 (JAZ1) and JAZ5, encoding two important repressors of the JA signaling pathway, and activates their transcription. In vivo and in vitro experiments demonstrated that WRKY57 interacts with nuclear-encoded SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2. Further experiments display that the same domain, the VQ motif, of SIB1 and SIB2 interact with WRKY33 and WRKY57. Moreover, transient transcriptional activity assays confirmed that WRKY57 and WRKY33 competitively regulate JAZ1 and JAZ5, SIB1 and SIB2 further enhance these competitions of WRKY57 to WRKY33. Therefore, coordinated regulation of Arabidopsis against B cinerea by transcription activators and repressors would benefit plants by allowing fine regulation of defense.

  6. Mutation of the rice XA21 predicted nuclear localization sequence does not affect resistance to Xanthomonas oryzae pv. oryzae

    Science.gov (United States)

    Ho, Yuen Ting

    2016-01-01

    Background The rice receptor kinase XA21 confers robust resistance to the bacterial pathogen Xanthomonas oryzaepv. oryzae(Xoo). We previously reported that XA21 is cleaved in transgenic plants overexpressing XA21 with a GFP tag (Ubi-XA21-GFP) and that the released C-terminal domain is localized to the nucleus. XA21 carries a predicted nuclear localization sequence (NLS) that directs the C-terminal domain to the nucleus in transient assays, whereas alanine substitutions in the NLS disrupt the nuclear localization. Methods To determine if the predicted NLS is required for XA21-mediated immunity in planta, we generated transgenic plants overexpressing an XA21 variant carrying the NLS with the same alanine substitutions (Ubi-XA21nls-GFP). Results Ubi-XA21nls-GFP plants displayed slightly longer lesion lengths, higher Xoobacterial populations after inoculation and lower levels of reactive oxygen species production compared with the Ubi-XA21-GFP control plants. However, the Ubi-XA21nls-GFP plants express lower levels of protein than that observed in Ubi-XA21-GFP. Discussion These results demonstrate that the predicted NLS is not required for XA21-mediated immunity.

  7. TRENDS IN ANTIMICROBIAL RESISTANCE AMONG UROPATHOGENS WITH SPECIAL REFERENCE TO ESCHERICHIA COLI IN COMMUNITY ACQUIRED PEDIATRIC URINARY TRACT INFECTIONS FROM KERALA

    Directory of Open Access Journals (Sweden)

    Nisha

    2015-07-01

    Full Text Available CONTEXT: Resistance of uropathogens to commonly used antibiotics is increasingly reported from India in adults. There is little data on resistance patterns in childhood community acquired urinary tract infections (UTI. AIMS: To study antibiotic resistanc e trends of uropathogens isolated in community acquired UTI in children from a geographic area. SETTINGS AND DESIGN: Prospective study conducted in a northern Kerala tertiary pediatric centre between November 2012 and October 2014. METHODS : Urine samples were obtained by clean catch midstream, bladder catheterization or supra - pubic aspiration. Bacterial growth, when significant were identified by standard biochemical reactions with antibiogram by Kirby Bauers disc diffusion method. STATISTICAL ANALYSIS : P roportions were calculated and statistical significance obtained by Chi - square. RESULTS : Of the 1387 cultures with suspected community acquired UTI, 274 (19.75% were positive. Mean age of study group was 28.52 months and 64.6% were boys. Escherichia coli (E.coli was the predominant pathogen [189(69%] followed by Klebsiella 50(18.2%. Citrobacter, Enterococcus, Proteus and Pseudomonas constituted less than 6%. All urinary isolates showed high combined resistance to most commonly used antimicrobials inclu ding beta - lactam antibiotics (84.3% to cefotaxime, 83.2% to cefixime, 74.5% to ampicillin, quinolones (54.2% to ciprofloxacin, 46.4% to norfloxacin, 32.8% to levofloxacin, 52.9% to co - trimoxazole, 30.2% to gentamicin, 24.1% to nitrofurantoin and 14.2% to netilmicin. E.coli was highly resistant tocephalosporins and ampicillin (>80%. CONCLUSIONS: There is increasing resistance amongst E.coli coli and Klebsiella to third generation cephalosporins in pediatric age group. It is important to generate regional data on antibiogram pattern to guide therapy.

  8. Relationships between antimicrobial resistance, distribution of virulence factor genes and the origin of Trueperella pyogenes isolated from domestic animals and European bison (Bison bonasus).

    Science.gov (United States)

    Rzewuska, Magdalena; Czopowicz, Michał; Gawryś, Marta; Markowska-Daniel, Iwona; Bielecki, Wojciech

    2016-07-01

    Trueperella pyogenes is an opportunistic pathogen causing suppurative infections in livestock and wild animals. Although this bacterium is known for a long time, our knowledge about its pathogenicity is still insufficient. In this study the relationships between antimicrobial resistance profiles, distribution of virulence factor genes and the origin of T. pyogenes isolates were investigated. Isolates (n = 97) from various infections in domestic animals and European bison were studied. Minimal inhibitory concentrations of 12 antimicrobials were determined by a strip diffusion method, and PCR was used for detection of genes encoding seven putative virulence factors. All strains were susceptible to tested beta-lactams, and a statistically significant correlation between the resistance to enrofloxacin, tetracycline, macrolides, clindamycin, and a strain origin was found. The isolates from European bison were more susceptible than those from livestock, however the resistance to tetracycline and fluoroquinolones was observed. The plo and fimA genes were detected in all strains. There was no statistically significant association between the distribution of particular virulence factor genes and the type of infection, but the nanH, nanP and fimG genes were less frequently found in the isolates from European bison. The presence of three genes, nanP, nanH and cbpA, was found to be related to the resistance to tetracycline and ciprofloxacin. In conclusion, the resistance patterns of T. pyogenes were correlated with an isolate origin, but our findings did not allow to indicate which of the putative virulence factors may play a crucial role in the pathogenesis of particular types of T. pyogenes infection.

  9. TEM-1 AND ROB-1 PRESENCE AND ANTIMICROBIAL RESISTANCE IN HAEMOPHILUS INFLUENZAE STRAINS, ISTANBUL, TURKEY.

    Science.gov (United States)

    Kuvat, Nuray; Nazik, Hasan; Berkiten, Rahmiye; Öngen, Betigül

    2015-03-01

    Resistance of 235 Haemophilus influenzae clinical isolates from Istanbul Medical Faculty Hospital, Turkey were determined against 19 antibiotics by disc diffusion method, and minimum inhibitory concentrations (MICs) of those found resistant to ampicillin, cefuroxim, chloramphenicol and meropenem were measured using E-test. Ampicillin-resistant isolates producing beta-lactamase as demonstrated by a nitrocefin assay were analyzed for the presence of TEM-1 and ROB-1 genes by PCR. Eleven percent of the isolates were resistant to ampicillin (10 µg/ml), of which 73% were beta-lactamase positive and carried TEM-1 gene, but none were positive for ROB-1 gene. All isolates susceptible to amoxicillin-clavulanate (20/10 µg/ml), azithromycin (15 µg/ml), aztreonam (30 µg/ml), cefotaxime (30 µg/ml), ceftriaxone (30 µg/ml), ciprofloxacin (5 µg/ml), levofloxacin (5 µg/ml), and telithromycin (15 µg/ml) but 24%, 15%, 4%, 4%, 2%, 1%, 1%, 0.5%, 0.5% and 0.5% were resistant to trimethoprim-sulfamethoxazole (1.25/23.75 µg/ml), tetracycline (30 µg/ml), cefaclor (30 µg/ml), clarithromycin (15 µg/ml), cefuroxime (30 µg/ml), meropenem (10 µg/ml), chloramphenicol (30 µg/ml), ampicillin-sulbactam (10/10 µg/ml), nalidixic acid (30 µg/ml), and fosfomycin (30 µg/ml), respectively. MIC values of three cefuroxime-resistant isolates was 24, 48 and > 256 µg/ml, respectively; of two meropenem-resistant strains > 256 µg/ml; and of two chloramphenicol-susceptible isolates (by disc diffusion method) 6 µg/ml (considered as intermediate susceptible). Multiple- antibiotics resistance was detected in 15% of the strains, with resistance to 2, 3, 4, 5 and 6 antibiotics in 8.5%, 4%, 2%, 0.5% and 0.5% of the isolates, respectively. By identifying beta-lactamase-negative ampicillin-resistant H. influenzae, empirical therapy with beta-lactam/beta-lactamase inhibitor combinations and second generation cephalosporins would be inappropriate for such patients (approximately 3%). Our findings will

  10. Study on Cultural Technologies and Salt-resistance of Nitraria sibirica in Coastal Areas with Serious Salt-affected Soil

    Institute of Scientific and Technical Information of China (English)

    ZHANGJianfeng; XINGShangjun; SUNQixiang; XIJinbiao; SONGYumin

    2004-01-01

    In this research, five Nitraria sibirica provenances such as Dayilu were selected to do experiment of salt-resistance, combining fixed plots test with typical plot investigation, measuring survival rate and growth as main indicators. The experiments of main cultural technology were done on Nitraria sibirica in 4 types of site preparation, 3 types of planting, 3 designs for planting density. The Nitraria sibirica experiments for the effects of curbing salt and improving soil were done by testing soil nutrients, salt content, soil physical properties as focal points in typical site of 3-4 years woods. The experiment results showed that the Nitraria sibirica could survive well with soil salt content of 0.6%, and that survival rate declined distinctively as soil salt content exceeded 0.8%. However, high soil salt content did not influence growth in the year of planting. There were obvious differences in salt-tolerance among Nitraria sibirica provenances; Dayilu was the best on salt-tolerance, the other 4 provenances had no differences, and obviously inferior to Dayilu. The different types of site preparation clearly influenced planting survival rate, conserving rate and growth. The method of two-ploughing-two-harrowing was the best among all 4 types of site preparation. Seed forestation was largely limited, bared-rooted seedling forestation may be popularised when soil salt content was less than 1% and soil moisture content was better in spring. Forestation with container seedling was suited to coastal saline soil in rainy season. The optimum planting density of Nitraria sibirica was 2 505/ha in the Yellow River Delta area in view of coverage rate, yield of fruits and cost of planting. Generally speaking,Nitraria sibirica could effectively refrain soil from accumulation of salt in the surface soil, decrease salt content and increase soil nutrient, and heighten soil capillary pore rate.

  11. Selenium Supplementation Affects Insulin Resistance and Serum hs-CRP in Patients with Type 2 Diabetes and Coronary Heart Disease.

    Science.gov (United States)

    Farrokhian, A; Bahmani, F; Taghizadeh, M; Mirhashemi, S M; Aarabi, M H; Raygan, F; Aghadavod, E; Asemi, Z

    2016-04-01

    To our knowledge, this study is the first indicating the effects of selenium supplementation on metabolic status of patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). This study was conducted to evaluate the effects of selenium supplementation on metabolic profiles, biomarkers of inflammation, and oxidative stress of patients with T2DM and CHD. This randomized, double-blind, placebo-controlled trial was performed among 60 patients with T2DM and CHD aged 40-85 years. Participants were randomly divided into 2 groups. Group A received 200 μg selenium supplements (n=30) and group B received placebo per day (n=30) for 8 weeks. Fasting blood samples were taken at the beginning of the study and after 8-week intervention to quantify metabolic profiles. After 8 weeks, compared with the placebo, selenium supplementation resulted in a significant decrease in serum insulin levels (- 2.2±4.6 vs. + 3.6±8.4 μIU/ml, p=0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (- 0.7±1.3 vs. + 0.9±2.4, p=0.004), homeostatic model assessment-beta cell function (HOMA-B) (- 7.5±17.2 vs. + 15.1±34.5, p=0.002) and a significant increase in quantitative insulin sensitivity check index (QUICKI) (+0.01±0.03 vs. - 0.01±0.03, p=0.02). In addition, patients who received selenium supplements had a significant reduction in serum high-sensitivity C-reactive protein (hs-CRP) (- 1 372.3±2 318.8 vs. - 99.8±1 453.6 ng/ml, p=0.01) and a significant rise in plasma total antioxidant capacity (TAC) concentrations (+ 301.3±400.6 vs. - 127.2±428.0 mmol/l, phs-CRP, and a significant increase in QUICKI score and TAC concentrations.

  12. Does vancomycin prescribing intervention affect vancomycin-resistant enterococcus infection and colonization in hospitals? A systematic review

    Directory of Open Access Journals (Sweden)

    Riley Lee W

    2007-04-01

    Full Text Available Abstract Background Vancomycin resistant enterococcus (VRE is a major cause of nosocomial infections in the United States and may be associated with greater morbidity, mortality, and healthcare costs than vancomycin-susceptible enterococcus. Current guidelines for the control of VRE include prudent use of vancomycin. While vancomycin exposure appears to be a risk factor for VRE acquisition in individual patients, the effect of vancomycin usage at the population level is not known. We conducted a systematic review to determine the impact of reducing vancomycin use through prescribing interventions on the prevalence and incidence of VRE colonization and infection in hospitals within the United States. Methods To identify relevant studies, we searched three electronic databases, and hand searched selected journals. Thirteen studies from 12 articles met our inclusion criteria. Data were extracted and summarized for study setting, design, patient characteristics, types of intervention(s, and outcome measures. The relative risk, 95% confidence interval, and p-value associated with change in VRE acquisition pre- and post-vancomycin prescription interventions were calculated and compared. Heterogeneity in study results was formally explored by stratified analysis. Results No randomized clinical trials on this topic were found. Each of the 13 included studies used a quasi-experimental design of low hierarchy. Seven of the 13 studies reported statistically significant reductions in VRE acquisition following interventions, three studies reported no significant change, and three studies reported increases in VRE acquisition, one of which reported statistical significance. Results ranged from a reduction of 82.5% to an increase of 475%. Studies of specific wards, which included sicker patients, were more likely to report positive results than studies of an entire hospital including general inpatients (Fisher's exact test 0.029. The type of intervention

  13. On conditions of negativity of friction resistance for nonstationary modes of blood flow and possible mechanism of affecting of environmental factors on energy effectiveness of cardiovascular system function

    Directory of Open Access Journals (Sweden)

    Sergey G. Chefranov

    2013-05-01

    Full Text Available It is shown that initiated by action of molecular viscosity impulse flow, directed usually from the moving fluid to limiting it solid surface, can, under certain conditions, turn to zero and get negative values in the case of non-stationary flow caused by alternating in time longitudinal (along the pipe axis pressure gradient. It is noted that this non-equilibrium mechanism of negative friction resistance in the similar case of pulsating blood flow in the blood vessels, in addition to the stable to turbulent disturbances swirled blood flow structure providing, can also constitute hydro-mechanical basis of the observed but not explained yet paradoxically high energy effectiveness of the normal functioning of the cardiovascular system (CVS. We consider respective mechanism of affecting on the stability of the normal work of CVS by environmental variable factors using shifting of hydro-dynamic mode with negative resistance realization range boundaries and variation of linear hydrodynamic instability leading to the structurally stable swirled blood flow organization.

  14. Streptococcus pneumoniae: low frequency of penicillin resistance and high resistance to trimethoprim-sulfamethoxazole in nasopharyngeal isolates from children in a rural area in Mexico.

    Science.gov (United States)

    Miranda Novales, M G; Solorzano Santos, F; Guiscafre Gallardo, H; Leaños Miranda, B; Echaniz Aviles, G; Carnalla Barajas, M N; Palafox Torres, M; Muñoz Hernandez, O

    1997-01-01

    Due to the changes in the frequency of penicillin-resistant strains of S. pneumoniae, it is necessary to perform surveillance studies of bacterial resistance. Isolates from the upper respiratory tract of asymptomatic children have been useful. There is no information about the difference between isolates from children with and without upper respiratory tract infection (URTI). The objective of the authors in this paper is to establish the prevalence of carrier-state, serotype and antimicrobial resistance of S. pneumoniae isolates from children with and without acute upper respiratory tract infection (URTI) in a rural area in Mexico. A cross-sectional comparative study was performed in Tlaxcala, Mexico. Children from one month 5 years of age were included. Nasopharyngeal swabs were obtained. Identification was done by international microbiology standards. Serotyping was done by the capsular Quellung test. The susceptibility testing was performed by the agar dilution method. Four-hundred and fifty patients were included. S. pneumoniae was isolated in 134 children (29.7%). Frequency of carriers was greater in patients with URTI (107/323) than without URTI (27/127) (33.1% vs. 21.1% p = 0.012, OR 1.84, IC 95% 1.1-3.08). The six most frequent serotypes were: 6B (16.4%); 19F (11.9%); 19A (6.7%); 14, 23F, and 35 (5.2% each), with no difference among the groups. Only 3% of the strains had high level resistance to penicillin, and 12.6% had intermediate resistance, and for ampicillin 4%, amoxicillin 4%, amoxicillin-clavulanate 4%, ceftriaxone 3%, cefotaxime 1.5%, erythromycin 6%, miocamycin 3%, chloramphenicol 4%, and vancomycin 0%. Trimethoprim-sulfamethoxazole resistance was very high (42%). In conclusion, colonization is higher in children with URTI. Five of the most frequent serotypes identified in this study were the same as those identified in patients with S. pneumoniae invasive diseases in Mexico City. In Tlaxcala, Mexico, beta-lactams could be the drug of choice for

  15. Emergence of co-production of plasmid-mediated AmpC beta-lactamase and ESBL in cefoxitin-resistant uropathogenic Escherichia coli.

    Science.gov (United States)

    Ghosh, B; Mukherjee, M

    2016-09-01

    Plasmid-mediated AmpC (pAmpC) and ESBL co-production was detected in Escherichia coli a major etiologic agent of urinary tract infection. Isolates resistant to cefoxitin by CLSI methodology were tested for pAmpC beta-lactamase using phenylboronic acid and ESBLs by combined disk diffusion method. pAmpC/ESBL genes were characterized by PCR and sequencing. Transconjugation experiments were done to study the transfer of pAmpC and ESBL production from clinical isolates as donor to E. coli J53 AziR as recipient. Incompatibility groups of transmissible plasmids were classified by PCR-based replicon typing (PBRT). Among 148 urine culture positive isolates, E. coli was reported in 39.86 % (59/148), with 93.22 % (55/59) of cefoxitin resistance. pAmpC production was detected in 25, with varied distribution of blaCMY-2 and blaDHA-1type genes alone (n = 13 and 7 respectively) or in combination (n = 5). ESBL co-production was observed in 88 % (22/25) of pAmpC producing isolates with predominance of blaTEM (n = 20). Twenty-three transconjugants showed transmission of pAmpC-and ESBL-resistant genes with co-carriage of blaCMY-2 and blaTEM (n = 15) in plasmids of IncF type (n = 9) being predominant, followed by IncI1 (n = 4) and IncH1 (n = 2) in combination. All clinical isolates were clonally diverse. Resistance against different beta-lactams in uropathogenic E. coli has been an emerging concern in resource- poor countries such as India. Knowledge on the occurrence of AmpC beta-lactamases and ESBL amongst this pathogen and its transmission dynamics may aid in hospital infection control.

  16. Crystallographic Studies of Two Bacterial AntibioticResistance Enzymes: Aminoglycoside Phosphotransferase (2')-Ic and GES-1\\beta-lactamase

    Energy Technology Data Exchange (ETDEWEB)

    Brynes, Laura; /Rensselaer Poly.

    2007-10-31

    Guiana Extended-Spectrum-1 (GES-1) and Aminoglycoside phosphotransferase (2')-Ic (APH(2')-Ic) are two bacteria-produced enzymes that essentially perform the same task: they provide resistance to an array of antibiotics. Both enzymes are part of a growing resistance problem in the medical world. In order to overcome the ever-growing arsenal of antibiotic-resistance enzymes, it is necessary to understand the molecular basis of their action. Accurate structures of these proteins have become an invaluable tool to do this. Using protein crystallography techniques and X-ray diffraction, the protein structure of GES-1 bound to imipenem (an inhibitor) has been solved. Also, APH(2')-Ic has been successfully crystallized, but its structure was unable to be solved using molecular replacement using APH(2')-Ib as a search model. The structure of GES-1, with bound imipenem was solved to a resolution of 1.89A, and though the inhibitor is bound with only moderate occupancy, the structure shows crucial interactions inside the active site that render the enzyme unable to complete the hydrolysis of the {beta}-lactam ring. The APH(2')-Ic dataset could not be matched to the model, APH(2')-Ib, with which it shares 25% sequence identity. The structural information gained from GES-1, and future studies using isomorphous replacement to solve the APH(2')-Ic structure can aid directly to the creation of novel drugs to combat both of these classes of resistance enzymes.

  17. [The first metronidazole-resistant Bacteroides species isolated at Marmara University Hospital: Bacteroides thetaiotaomicron].

    Science.gov (United States)

    Toprak Ülger, Nurver; Sayın, Elvan; Soyad, Ad; Dane, Faysal; Söyletir, Güner

    2013-10-01

    Bacteroides species, the predominant constituents of the human intestinal microbiota can cause serious intraabdominal and postoperative wound infections and bacteremia. Moreover, these bacteria are more resistant to antimicrobial agents than the other anaerobes. The limited number of the antimicrobials, such as carbapenems, beta-lactam/beta-lactamase inhibitors and nitroimidazoles are highly effective in eliminating Bacteroides. However, a few metronidazole-resistant isolates have been reported from several countries recently. The nim genes (nim A-G) are suggested to be responsible for the majority of the metronidazole resistance. Here, we describe a metronidazole-resistant Bacteroides thetaiotaomicron isolated from a blood culture. A gram-negative obligate anaerobic rod was isolated from the postoperative 5th day blood culture of a 62-year-old male patient with adenocarcinoma of the pancreas head. The strain was identified as B.thetaiotaomicron by using a combination of conventional tests and commercially available biochemical kits. Antimicrobial susceptibility testing was performed by agar dilution method. The resistance genes were investigated by means of PCR using specific primer pairs for nim gene. The purified PCR product was sequenced and analyzed by comparison of the consensus sequences with GenBank sequences. The MIC for metronidazole was 16 mg/L. Although the strain was intermediate according the CLSI criteria, it was resistant (> 4 mg/L) according to EUCAST criteria. The isolate was nim gene positive, and nucleotide sequencing of the PCR product shared 100% similarity with nimE gene (emb |AM042593.1 |). On the other hand the isolate was susceptible to carbapenems and sulbactam-ampicillin. Following administration of ampicillin-sulbactam, the patient's fever disappeared after 24 hours. The clinical condition improved considerably and he was discharged at day 8. The patient was followed up at the medical oncology clinic; however he died due to disease

  18. Synthetic Beta-Lactam Antibiotic as a Selective Breast Cancer Cell Apoptosis Inducer: Significance in Breast Cancer Prevention and Treatment

    Science.gov (United States)

    2005-04-01

    954. 48 Wan SB, Chen D, Dou OP, and Chan TH. Study of the green tea polyphenols catechin -3-gallate (CG) and epicatechin-3-gallate (ECG) as proteasome... tea polyphenol epigallocatechin inhibits [26] Coultas L, Strasser A. The molecular control of DNA damage-induced DNA replication and consequently...Pommier Y. [20] Nam S, Smith DM, Dou QP. Ester bond-containing tea polyphenols Protein-linked DNA strand breaks induced by NSC 314622, a novel potently

  19. Synthetic Beta-Lactam Antibiotics as a Selective Breast Cancer Cell Apoptosis Inducer: Significance in Breast Cancer Prevention and Treatment

    Science.gov (United States)

    2008-03-01

    with Ph.D. on August, 2007. Dissertation Title: “Synthetic Green Tea Catechin Analogs and Their Prodrugs: A Structural and Biological Analysis of...State University School of Medicine, Graduate Student Research Day, September 21, 2006. “A Novel Pro-drug of Green Tea Catechin (-)-EGCG as a Potential...Wan SB, Chen D, Dou QP, and Chan TH. Study of the green tea polyphenols catechin -3-gallate (CG) and epicatechin-3-gallate (ECG) as proteasome

  20. Synthetic Beta-Lactam Antibiotics as a Selective Breast Cancer Cell Apoptosis Inducer: Significance in Breast Cancer Prevention and Treatment

    Science.gov (United States)

    2007-03-01

    648. 56. Parodi FE, Mao D, Ennis TL, Bartoli MA, Thompson RW: Suppres- sion of experimental abdominal aortic aneurysms in mice by treatment with...children. J Trop Pediatr 1994, 40:185-187. 64. Jayadeep A, Raveendran Pillai K, Kannan S, Nalinakumari KR, Mathew B, Krishnan Nair M, Menon VP: Serum

  1. Are new antibiotics better than beta-lactams for non-critical inpatients with community-acquired pneumonia?

    Directory of Open Access Journals (Sweden)

    Tomás Reyes B.

    2016-09-01

    Full Text Available Resumen El tratamiento de la neumonía adquirida en la comunidad en el adulto inmunocompetente es empírico, siendo tradicionalmente los antibióticos betalactámicos la terapia de primera línea. Se ha postulado que nuevos antibióticos podrían ser más efectivos, pero hasta el momento este planteamiento no ha sido corroborado por la evidencia disponible y su uso podría asociarse a mayor costo, aumento de la resistencia bacteriana y otros efectos adversos. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas realizadas en 30 bases de datos, identificamos seis revisiones sistemáticas que en conjunto incluyen 36 estudios aleatorizados pertinentes a la pregunta. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que los nuevos antibióticos no son mejores que los antibióticos betalactámicos en pacientes adultos hospitalizados con neumonía no severa en cuanto a riesgo de fracaso clínico o efectos adversos.

  2. Pharmacokinetic drug interactions of antimicrobial drugs : a systematic review on oxazolidinones, rifamycines, macrolides, fluoroquinolones, and Beta-lactams

    NARCIS (Netherlands)

    Bolhuis, Mathieu S; Panday, Prashant N; Pranger, Arianna D; Kosterink, Jos G W; Alffenaar, Jan-Willem C

    2011-01-01

    Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactio

  3. [Improvement of the knowledge on allergic cross-reactions between two drug groups: beta-lactams and NSAIDS].

    Science.gov (United States)

    Sánchez-Quiles, I; Nájera-Pérez, M D; Calleja-Hernández, M Á; Martinez-Martínez, F; Belchí-Hernández, J; Canteras, M

    2013-01-01

    Objetivos: Identificar oportunidades de mejora, sobre el conocimiento disponible del personal sanitario (en concreto a personal médico, farmacéutico y de enfermería), sobre reacciones alérgicas cruzadas (RAC) de penicilinas y AINEs. Método: Estudio prospectivo cuasiexperimental pre-exposición en un hospital de 412 camas. Se realizó una valoración del conocimiento sobre RAC de penicilinas y AINEs, a través de encuestas anónimas, antes (1a encuesta) y después (2a encuesta) de la implantación de una serie de medidas de mejora: protocolo “paciente alérgico a medicamentos”, tarjeta de bolsillo, póster resumen de información y charlas divulgativas. Las propias encuestas sirvieron de hoja de recogida de datos y el análisis estadístico se llevó a cabo con el programa SPSS v18.0. Resultados: La media de errores en las 1as encuestas sobre “RAC en paciente alérgico a penicilinas” y sobre “RAC en paciente alérgico a AINEs”, fue de 20,53 y 27,62, respectivamente. La media de errores en las 2as encuestas sobre “RAC en paciente alérgico a penicilinas” y sobre “RAC en paciente alérgico a AINEs”, fue de 2,27 y 7,26, respectivamente. Todos los resultados se consideraron significativos para un nivel 945;conocimiento sobre RAC de penicilinas y AINEs, lo que justifica la realización de un ciclo de mejora. - Tras la implantación de las medidas de mejora se aprecia un aumento en el nivel de conocimiento sobre RAC en penicilinas y AINEs, en los grupos de estudio.

  4. Effect of clavulanic acid on the activities of ten beta-lactam agents against members of the Bacteroides fragilis group.

    Science.gov (United States)

    Lamothe, F; Auger, F; Lacroix, J M

    1984-01-01

    Clavulanic acid reduced the MICs of amoxicillin, carbencillin , cefamandole, cefotaxime, ceftazidime, ceftizoxime, cephalothin, and penicillin G, but not of cefoxitin or moxalactam, against 77 isolates of the Bacteroides fragilis group, all rapidly beta-lactamase positive by the nitrocefin slide test. It had no effect on the susceptibilities of eight Bacteroides distasonis strains that were slowly beta-lactamase positive (18 h of incubation). PMID:6732233

  5. Exposure of Staphylococcus aureus to subinhibitory concentrations of β-lactam antibiotics induces heterogeneous vancomycin-intermediate Staphylococcus aureus.

    Science.gov (United States)

    Roch, Mélanie; Clair, Perrine; Renzoni, Adriana; Reverdy, Marie-Elisabeth; Dauwalder, Olivier; Bes, Michèle; Martra, Annie; Freydière, Anne-Marie; Laurent, Frédéric; Reix, Philippe; Dumitrescu, Oana; Vandenesch, François

    2014-09-01

    Glycopeptides are known to select for heterogeneous vancomycin-intermediate Staphylococcus aureus (h-VISA) from susceptible strains. In certain clinical situations, h-VISA strains have been isolated from patients without previous exposure to glycopeptides, such as cystic fibrosis patients, who frequently receive repeated treatments with beta-lactam antibiotics. Our objective was to determine whether prolonged exposure to beta-lactam antibiotics can induce h-VISA. We exposed 3 clinical vancomycin-susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains to ceftazidime, ceftriaxone, imipenem, and vancomycin (as a control) at subinhibitory concentrations for 18 days in vitro. Population analyses showed progressive increases in vancomycin resistance; seven of the 12 derived strains obtained after induction were classified as h-VISA according to the following criteria: area under the curve (AUC) on day 18/AUC of Mu3 of ≥90% and/or growth on brain heart infusion (BHI) agar with 4 mg/liter vancomycin. The derived isolates had thickened cell walls proportional to the level of glycopeptide resistance. Genes known to be associated with glycopeptide resistance (vraSR, yvqF, SA1703, graRS, walKR, and rpoB) were PCR sequenced; no de novo mutations were observed upon beta-lactam exposure. To determine whether trfA, a gene encoding a glycopeptide resistance factor, was essential in the selection of h-VISA upon beta-lactam pressure, a trfA-knockout strain was generated by allelic replacement. Indeed, beta-lactam exposure of this mutated strain showed no capacity to induce vancomycin resistance. In conclusion, these results showed that beta-lactam antibiotics at subinhibitory concentrations can induce intermediate vancomycin resistance in vitro. This induction required an intact trfA locus. Our results suggest that prior use of beta-lactam antibiotics can compromise vancomycin efficacy in the treatment of MRSA infections.

  6. Emergence of quinolone resistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae in the Central African Republic: genetic characterization

    Directory of Open Access Journals (Sweden)

    Frank Thierry

    2011-08-01

    Full Text Available Abstract Background Cross-resistance to quinolones and beta-lactams is frequent in Enterobacteriaceae, due to the wide use of these antibiotics clinically and in the food industry. Prescription of one of these categories of antibiotic may consequently select for bacteria resistant to both categories. Genetic mechanisms of resistance may be secondary to a chromosomal mutation located in quinolone resistance determining region of DNA gyrase or topoisomerase IV or to a plasmid acquisition. The insertion sequence ISCR1 is often associated with qnr and may favour its dissemination in Gram-negative bacteria. The aim of this study was to determine the genetic mechanism of quinolone resistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae strains in the Central African Republic. Findings Among seventeen ESBL-producing Enterobacteriaceae isolated from urine, pus or stool between January 2003 and October 2005 in the Central African Republic, nine were resistant to ciprofloxacin (seven from community patients and two from hospitalized patients. The ESBL were previously characterized as CTX-M-15 and SHV-12. Susceptibility to nalidixic acid, norfloxacin and ciprofloxacin, and the minimal inhibitory concentrations of these drugs were determined by disc diffusion and agar dilution methods, respectively. The presence of plasmid-borne ISCR1-qnrA region was determined by PCR and amplicons, if any, were sent for sequencing. Quinolone resistance determining region of DNA gyrase gyrA gene was amplified by PCR and then sequenced for mutation characterization. We found that all CTX-M-producing strains were resistant to the tested quinolones. All the isolates had the same nucleotide mutation at codon 83 of gyrA. Two Escherichia coli strains with the highest MICs were shown to harbour an ISCR1-qnrA1 sequence. This genetic association might favour dissemination of resistance to quinolone and perhaps other antibiotics among Enterobacteriaceae

  7. Resistance to Third-Generation Cephalosporins and Other Antibiotics by Enterobacteriaceae in Western Nigeria

    Directory of Open Access Journals (Sweden)

    A. O. Okesola

    2009-01-01

    Full Text Available Problem statement: The emergence and spread of resistance to third-generation cephalosporins are threatening to create species resistant to all currently available agents. The most common cause of bacterial resistance to beta-lactam antibiotics is the production of beta-lactamases and many of the 2nd and 3rd-generation penicillins and cephalosporins were specifically designed to resist the hydrolytic action of major ß-lactamases. However new ß-lactamases emerged against each of the new classes of ß-lactams that were introduced and caused resistance. This study was designed to determine the rate of resistance to 3rd-generation cephalosporins and other classes of antibiotics by the Enterobacteriaceae in this environment. Approach: One hundred bacteria isolates belonging to the family Enterobacteriaceae identified from different clinical specimens between October and December 2007 using standard bacteriological methods. These were subjected to antibiotic susceptibility testing to third-generation cephalosporins and other classes of antibiotics which included quinolones and an aminoglycoside using the Kirby-Bauer method of disc diffusion test. Results: Out of the total number of Enterobacteriaceae isolated in the study period, only 54.8% of the klebsiella species isolated were sensitive to ceftazidime, 48.4% to ceftriaxone and 30.7% to cefotaxime. With Escherichia coli however, the susceptibility pattern to the 3rd-generation cephalosporins was better (65.6% were sensitive to ceftazidime, 62.5% to ceftriaxone and 71.9% to cefotaxime. In proteus species, the susceptibility pattern was generally poor to the three classes of antibiotics(50% were sensitive to ceftazidime and ceftriaxone, 0% to cefotaxime, 33.3% to ciprofloxacin, 50% to gentamycin and 0% to amoxycillin/clavulanate. Conclusion/Recommendations: The poor susceptibility to amoxicillin/clavulanate demonstrated by all the isolates in this

  8. When one drug affects 2 patients: a review of medication for the management of nonlabor-related pain, sedation, infection, and hypertension in the hospitalized pregnant patient.

    Science.gov (United States)

    Bulloch, Marilyn N; Carroll, Dana G

    2012-06-01

    One of the most difficult challenges health care providers encounter is drug selection for pregnant patients. Drug selection can be complex as efficacy and maternal side effects must be weighed against potential risk to the embryo or fetus. Verification of an individual drug's fetal safety is limited as most evidence is deduced from epidemiologic, prospective cohort, or case-control studies. Medication selection for the pregnant inpatient is a particularly complex task as the illnesses and conditions that require hospitalization mandate different medications, and the risk versus benefit ratio can vary significantly compared to the outpatient setting. Some degree of acute pain is not uncommon among inpatients. Acetaminophen is generally considered the drug of choice in pregnancy for mild to moderate acute pain, while most opioids are thought to be safe for short-term use to manage moderate to severe pain. Providing sedation is particularly challenging as the few options available for the general population are further limited by either known increased risk of congenital malformations or very limited human pregnancy data. Propofol is the only agent recommended for continuous sedation, which has a Food and Drug Administration classification as a pregnancy category B medication. Treatment of infections in hospitalized patients requires balancing the microbiology profile against the fetal risk. Older antimicrobials proven generally safe include beta-lactams, and those with proven fetal risks include tetracyclines. However, little to no information regarding gestational use is available on the newer antimicrobials that are frequently employed to treat resistant infections more commonly found in the inpatient setting. Management of maternal blood pressure is based on the severity of blood pressure elevations and not the hypertensive classification. Agents generally considered safe to use in hypertensive pregnant patients include methyldopa, labetolol, and hydralazine

  9. Factors that affect transfer of the IncI1 β-lactam resistance plasmid pESBL-283 between E. coli strains

    NARCIS (Netherlands)

    Händel, N.; Otte, S.; Jonker, M.J.; Brul, S.; ter Kuile, B.H.

    2015-01-01

    The spread of antibiotic resistant bacteria worldwide presents a major health threat to human health care that results in therapy failure and increasing costs. The transfer of resistance conferring plasmids by conjugation is a major route by which resistance genes disseminate at the intra- and inter

  10. Transgenic insect-resistant corn affects the fourth trophic level: effects of Bacillus thuringiensis-corn on the facultative hyperparasitoid Tetrastichus howardi

    Science.gov (United States)

    Prütz, Gernot; Brink, Andreas; Dettner, Konrad

    2004-09-01

    As hyperparasitoids may have a considerable influence on the control of herbivorous arthropods, analyzing the host-mediated impact of Bacillus thuringiensis-plants (“Bt-plants”) on hyperparasitoids is of interest. Laboratory-scale experiments were conducted in order to assess the potential effect of Bt-corn leaf material on the facultative hyperparasitoid Tetrastichus howardi (Olliff) (Hymenoptera: Eulophidae), mediated through the herbivore Chilo partellus Swinhoe (Lepidoptera: Crambidae) and its primary parasitoid Cotesia flavipes (Cameron) (Hymenoptera: Braconidae). In the Bt-group, significantly less C. flavipes larvae per host spun cocoons and pupated than in the control, and the mean fresh weight of a single C. flavipes cocoon was significantly reduced compared to the control. All C. flavipes cocoons of one host formed cocoon clusters. T. howardi females of the Bt-group parasitized significantly less cocoon clusters than in the control. Moreover, significantly fewer C. flavipes cocoons per cocoon cluster were successfully parasitized as compared to the control. As a consequence, T. howardi females of the control had more offspring than in the Bt-group. Adult female T. howardi offspring of the Bt-group weighed significantly less than in the control, but there was no significant weight difference between males of both groups. Our results suggest that transgenic insect-resistant plants could affect hyperparasitoids indirectly. However, it remains to be determined whether facultative hyperparasitoids prefer to develop as primary or secondary parasitoids under field conditions.

  11. Proactive infection control measures to prevent nosocomial transmission of carbapenem-resistant Enterobacteriaceae in a non-endemic area

    Institute of Scientific and Technical Information of China (English)

    CHENG Vincent Chi-Chung; CHAN Jasper Fuk-Woo; WONG Sally Cheuk-Ying; CHEN Jonathan Hon-Kwan; TAI Josepha Wai-Ming; YAN Mei-Kum; KWAN Grace See-Wai

    2013-01-01

    Background Identification of hospitalized carbapenem-resistant Enterobacteriaceae (CRE)-positive patient is important in preventing nosocomial transmission.The objective of this study was to illustrate the implementation of proactive infection control measures in preventing nosocomial transmission of CRE in a healthcare region of over 3200 beds in Hong Kong between October 1,2010 and December 31,2011.Methods The program included active surveillance culture in patients with history of medical tourism with hospitalization and surgical operation outside Hong Kong within 12 months before admission,and "added test" as an opportunistic CRE screening in all fecal specimens submitted to the laboratory.Outbreak investigation and contact tracing were conducted for CRE-positive patients.Serial quantitative culture was performed on CRE-positive patients and the duration of fecal carriage of CRE was analyzed.Results During the study period,a total of 6533 patients were screened for CRE,of which 76 patients were positive (10 from active surveillance culture,65 from "added test",and 1 secondary case from contact tracing of 223 patients with no nosocomial outbreak),resulting in an overall rate of CRE fecal carriage of 1.2%.The median time of fecal carriage of CRE was 43 days (range,13-119 days).Beta-lactam-beta-lactamase-inhibitors,cephalosporins,and fluoroquinolones were associated significantly with high fecal bacterial load when used 90 days before CRE detection,while use of cephalosporins,carbapenems,and fiuoroquinolones after CRE detection are significantly associated with longer duration of carriage.The duration of fecal carriage of CRE also correlates significantly with the initial fecal bacterial load (Pearson correlation:0.53; P=0.02).Conclusion Proactive infection control measures by enhanced surveillance program identify CRE-positive patients and data obtained are useful for the planning of and resource allocation for CRE control.

  12. Prevalence of SHV/CTX-M/TEM (ESBL Beta-lactamase Resistance Genes in Escherichia Coli Isolated from Urinary Tract Infections in Tehran, Iran

    Directory of Open Access Journals (Sweden)

    Yazdi M

    2010-01-01

    Full Text Available Background and objectives: Beta-lactamase enzymes are the most causes ofresistance to antibiotics among gram-negative bacteria. Nowadays, Infectionsdue to ESBLs are being increased throughout the world and is considered as anew burden to the health systems. This study aimed at determining thesensitivity pattern of E.coli isolates to beta-lactam antibiotics, andinvestigating the presence of blaCTX-M, blaTEM, and blaSHV genes in the urinesamples..Material and Methods: In this study, 244 E.coli isolates were screened in2009-2010. The antibiotic susceptibility of E. coli isolates were determined bydisc-diffusion method. Antimicrobial agents tested were cefoxatime,ceftazidime, imipenem, nalidixic acid, and ciprofloxacin. The combined disctest was used to confirm the results. The results were compared to the Clinicaland Laboratory Standards Institute (CLSI and ESBL positive isolates werefurther investigated for the presence of blaCTX-M, blaTEM, and blaSHV genes byPCR.Results: Of 244 E. coli isolates, 116 (47.1% are resistant to Ceftazidime, and96 (39.2% to cefoxatime. Also, 109 (44.3% isolates are ESBL positive.blaCTX-M, blaTEM, and blaSHV genes are found among 95 (87.1%, 75 (68.8%,and 77 (70.6% ESBL positive isolates, respectively. Forty (36.6% isolateshave all three genes, while 68 (62.3% include blaTEM and blaSHV genes.Moreover, 61 (55.9% isolates carry blaCTX-M and blaTEM genes, and 54(49.5%have blactx-M and blashv.Conclusion: Regarding the high frequency of resistance to the thirdgeneration cephalosporin antibiotics, precise antibiogram testing is highlyrecommended before any antibiotic prescription in cases of infections withESBL producing microorganisms.Key words: ESBL; Escherichia coli; blaCTX-M; blaTEM; blaSHV

  13. Structure-based Design and In-Parallel Synthesis of Inhibitors of AmpC b-lactamase

    Energy Technology Data Exchange (ETDEWEB)

    Tondi, D.; Powers, R.A.; Negri, M.C.; Caselli, M.C.; Blazquez, J.; Costi, M.P.; Shoichet, B.K. (NWU)

    2010-03-08

    Group I {beta}-lactamases are a major cause of antibiotic resistance to {beta}-lactams such as penicillins and cephalosporins. These enzymes are only modestly affected by classic {beta}-lactam-based inhibitors, such as clavulanic acid. Conversely, small arylboronic acids inhibit these enzymes at sub-micromolar concentrations. Structural studies suggest these inhibitors bind to a well-defined cleft in the group I {beta}-lactamase AmpC; this cleft binds the ubiquitous R1 side chain of {beta}-lactams. Intriguingly, much of this cleft is left unoccupied by the small arylboronic acids. To investigate if larger boronic acids might take advantage of this cleft, structure-guided in-parallel synthesis was used to explore new inhibitors of AmpC. Twenty-eight derivatives of the lead compound, 3-aminophenylboronic acid, led to an inhibitor with 80-fold better binding (2; K{sub i} 83 nM). Molecular docking suggested orientations for this compound in the R1 cleft. Based on the docking results, 12 derivatives of 2 were synthesized, leading to inhibitors with K{sub i} values of 60 nM and with improved solubility. Several of these inhibitors reversed the resistance of nosocomial Gram-positive bacteria, though they showed little activity against Gram-negative bacteria. The X-ray crystal structure of compound 2 in complex with AmpC was subsequently determined to 2.1 {angstrom} resolution. The placement of the proximal two-thirds of the inhibitor in the experimental structure corresponds with the docked structure, but a bond rotation leads to a distinctly different placement of the distal part of the inhibitor. In the experimental structure, the inhibitor interacts with conserved residues in the R1 cleft whose role in recognition has not been previously explored. Combining structure-based design with in-parallel synthesis allowed for the rapid exploration of inhibitor functionality in the R1 cleft of AmpC. The resulting inhibitors differ considerably from {beta}-lactams but

  14. Identification of quantitative trait loci affecting resistance to gastrointestinal parasites in a double backcross population of Red Maasai and Dorper sheep.

    Science.gov (United States)

    Silva, M V B; Sonstegard, T S; Hanotte, O; Mugambi, J M; Garcia, J F; Nagda, S; Gibson, J P; Iraqi, F A; McClintock, A E; Kemp, S J; Boettcher, P J; Malek, M; Van Tassell, C P; Baker, R L

    2012-02-01

    A genome-wide scan for quantitative trait loci (QTL) affecting gastrointestinal nematode resistance in sheep was completed using a double backcross population derived from Red Maasai and Dorper ewes bred to F(1) rams. This design provided an opportunity to map potentially unique genetic variation associated with a parasite-tolerant breed like Red Maasai, a breed developed to survive East African grazing conditions. Parasite indicator phenotypes (blood packed cell volume - PCV and faecal egg count - FEC) were collected on a weekly basis from 1064 lambs during a single 3-month post-weaning grazing challenge on infected pastures. The averages of last measurements for FEC (AVFEC) and PCV (AVPCV), along with decline in PCV from challenge start to end (PCVD), were used to select lambs (N = 371) for genotyping that represented the tails (10% threshold) of the phenotypic distributions. Marker genotypes for 172 microsatellite loci covering 25 of 26 autosomes (1560.7 cm) were scored and corrected by Genoprob prior to qxpak analysis that included Box-Cox transformed AVFEC and arcsine transformed PCV statistics. Significant QTL for AVFEC and AVPCV were detected on four chromosomes, and this included a novel AVFEC QTL on chromosome 6 that would have remained undetected without Box-Cox transformation methods. The most significant P-values for AVFEC, AVPCV and PCVD overlapped the same marker interval on chromosome 22, suggesting the potential for a single causative mutation, which remains unknown. In all cases, the favourable QTL allele was always contributed from Red Maasai, providing support for the idea that future marker-assisted selection for genetic improvement of production in East Africa will rely on markers in linkage disequilibrium with these QTL.

  15. Interleukin-6 -174G/C gene polymorphism affects muscle damage response to acute eccentric resistance exercise in elderly obese women.

    Science.gov (United States)

    Funghetto, Silvana Schwerz; Prestes, Jonato; Silva, Alessandro de Oliveira; Farias, Darlan L; Teixeira, Tatiane G; Vieira, Denis Cesar Leite; Souza, Vinícius C; Sousa, Nuno M F; Navalta, James W; Melo, Gislane F; Karnikowski, Margô Gomes de Oliveira

    2013-11-01

    The IL-6 gene polymorphism has been associated with disease prevalence and different physiological responses to exercise. Eccentric resistance exercise (ERE) is considered a nonpharmacological tool to prevent the chronic degenerative profile associated with aging and obesity. Consequently, the aim of the present study was to investigate the influence of IL-6 -174G/C polymorphism on acute interleukin-6 (IL-6) and creatine kinase (CK) temporal response to ERE in elderly obese women. Ninety women completed seven sets of ten repetitions (eccentric only) of an acute ERE session at 110% of the ten repetitions maximum (10RM). IL-6 genotypes displayed no difference at baseline. ERE induced changes in CK concentration over time occurred only in the GG group, F(2.619, 136.173)=5.199, p=0.003, with CK activity increased from 106.8±6.9 U/l pre-intervention to 122.7±11.2 U/l at 24 h and 131.9±14.4 U/l at 48 h post-exercise. IL-6 concentration in the GG group was lower than the CC/CG group only at 0 h post-exercise (3.78±0.58 pg/ml versus 6.51±1.91 pg/ml, p=0.030). Only the GG genotype group had higher CK activity 24-48 h following ERE and greater CK integral values, while IL-6 activity over 48 h was higher in the CC/CG genotype group. In conclusion, IL-6 genotype affects CK and IL-6 in response to ERE. It is of interest that the ERE protocol induced an elevation in CK, indicating possible muscle damage without exacerbating IL-6 and CK for the GG genotype.

  16. Resistance and the management of complicated skin and skin structure infections: the role of ceftobiprole

    Directory of Open Access Journals (Sweden)

    April Barbour

    2010-09-01

    Full Text Available April Barbour1, Hartmut Derendorf21GlaxoSmithKline, King of Prussia, PA, USA; 2Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USAAbstract: Antimicrobial resistant bacteria are an increasing concern due to the resulting increase in morbidity, mortality, and health-care costs associated with the administration of inadequate or delayed antimicrobial therapy. The implications of inadequate antimicrobial therapy in complicated skin and skin structure infections (cSSSIs have gained more attention recently, most likely due to the recent emergence of community-acquired methicillin resistant Staphylococcus aureus (MRSA and the already high prevalence of MRSA in the nosocomial setting. Due to the continuous threat of resistance arising and the limitations of currently available agents for the treatment of cSSSIs, it is necessary to develop new antimicrobials for this indication. Ceftobiprole medocaril, the prodrug of ceftobiprole, is a parental investigational cephalosporin for the treatment of cSSSIs displaying a wide-spectrum of activity against both Gram-positive and Gram-negative species, including MRSA. Ceftobiprole displays noncomplex linear pharmacokinetics, is eliminated primarily by glomerular filtration, and distributes to extracellular fluid. Additionally, it has been shown that the extent of distribution to the site of action with regard to cSSSIs, ie, the extracellular space fluid of subcutaneous adipose tissue and skeletal muscle, is expected to be efficacious, as free concentrations meet efficacy targets for most pathogens. Similar to other beta-lactams, it displays an excellent safety and tolerability profile with the primary adverse events being dysgeusia in healthy volunteers, resulting from the conversion of the prodrug to the active, and nausea in patients. Ceftobiprole has demonstrated noninferiority in two large-scale pivotal studies comparing it to vancomycin, clinical cure rates 93.3% vs

  17. Efflux kinetics and intracellular distribution of daunorubicin are not affected by major vault protein/lung resistance-related protein (vault) expression.

    NARCIS (Netherlands)

    Zon, van A; Mossink, MH; Schoester, M.; Scheper, R.J.; Sonneveld, P.; Wiemer, EA

    2004-01-01

    Vaults may contribute to multidrug resistance by transporting drugs away from their subcellular targets. To study the involvement of vaults in the extrusion of anthracyclines from the nucleus, we investigated the handling of daunorubicin by drug-sensitive and drug-resistant non-small lung cancer cel

  18. Bacillus subtilis from Soybean Food Shows Antimicrobial Activity for Multidrug-Resistant Acinetobacter baumannii by Affecting the adeS Gene.

    Science.gov (United States)

    Wang, Tieshan; Su, Jianrong

    2016-12-28

    Exploring novel antibiotics is necessary for multidrug-resistant pathogenic bacteria. Because the probiotics in soybean food have antimicrobial activities, we investigated their effects on multidrug-resistant Acinetobacter baumannii. Nineteen multidrug-resistant A. baumannii strains were clinifcally isolated as an experimental group and 11 multidrug-sensitive strains as controls. The growth rates of all bacteria were determined by using the analysis for xCELLigence Real-Time Cell. The combination of antibiotics showed synergistic effects on the strains in the control group but no effect on the strains in the experimental group. Efflux pump gene adeS was absent in all the strains from the control group, whereas it exists in all the strains from the experimental group. Furthermore, all the strains lost multidrug resistance when an adeS inhibitor was used. One strain of probiotics isolated from soybean food showed high antimicrobial activity for multidrug-resistant A. baumannii. The isolated strain belongs to Bacillus subtilis according to 16S RNA analysis. Furthermore, E. coli showed multidrug resistance when it was transformed with the adeS gene from A. baumannii whereas the resistant bacteria could be inhibited completely by isolated Bacillus subtilis. Thus, probiotics from soybean food provide potential antibiotics against multidrug-resistant pathogenic bacteria.

  19. Prevalence of coagulase-negative staphylococci and determination of antimicrobial resistance in accompany with types of SCCmec in isolated of nosocomial infections

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Arabestani

    2016-03-01

    Full Text Available Background: Coagulase-negative staphylococci (CoNS were considered as contaminats previously, but, during the past decade considered as one of the most common photogenic bacteria in hospital. Resistance to beta-lactams especially methicillin in staphylococcus species is being worrying in hospitals. Rapid identification of mechanisms of resistance and confirmation of their resistance to methicillin is a basic principle for antibiotic treatment. The aim of this study was to determine antibiotic resistance, frequency of mecA gene, and determination of SCCmec types in CoNS isolates from teaching hospitals in Iran. Methods: The descriptive cross-sectional study was carried out one hundred clinical samples isolated from patients with an average age of 7-69 years at teaching hospitals in Hamadan City, Iran, from September 2014 to February 2015. After confirmation of isolates by microbiological standard biochemical tests, antimicrobial susceptibility testing was performed by disk agar diffusion (DAD method. After extraction of isolated genomicm, mecA gene was detected. Then, the types of SCCmec were performed by PCR. Results: In this study, 387 clinical samples were collected which among 100 CoNS isolated, Staphylococcus epidermidis was the most prevalent species with frequency 55 (55%, followed by S. haemolyticus 40(40% and S. saprophyticus 5(5%. The highest antibiotic susceptibility was to rifampin 96(96% and the lowest resistance was detected for trimethoprim/sulfamethoxazole (TMP/SMX 47(47%. None of the strains were resistant to vancomycin. Resistance to methicillin was detected in 50% of CoNS isolates. Typing of SCCmec was performed by The polymerase chain reaction (PCR. Frequency types of SCCmec was type III with frequency 13(13%, type V 11(11%, type II 6(6%, type IV 4 (4%, type I 3(3% respectively. Thirteen isolated was not typable in this study. Conclusion: The result of this study showed that a large percentage of coagulase

  20. pbp2229-mediated nisin resistance mechanism in Listeria monocytogenes confers cross-protection to class IIa bacteriocins and affects virulence gene expression.

    Science.gov (United States)

    Gravesen, Anne; Kallipolitis, Birgitte; Holmstrøm, Kim; Høiby, Poul Erik; Ramnath, Manilduth; Knøchel, Susanne

    2004-03-01

    It was previously shown that enhanced nisin resistance in some mutants was associated with increased expression of three genes, pbp2229, hpk1021, and lmo2487, encoding a penicillin-binding protein, a histidine kinase, and a protein of unknown function, respectively. In the present work, we determined the direct role of the three genes in nisin resistance. Interruption of pbp2229 and hpk1021 eliminated the nisin resistance phenotype. Interruption of hpk1021 additionally abolished the increase in pbp2229 expression. The results indicate that this nisin resistance mechanism is caused directly by the increase in pbp2229 expression, which in turn is brought about by the increase in hpk1021 expression. We also found a degree of cross-protection between nisin and class IIa bacteriocins and investigated possible mechanisms. The expression of virulence genes in one nisin-resistant mutant and two class IIa bacteriocin-resistant mutants of the same wild-type strain was analyzed, and each mutant consistently showed either an increase or a decrease in the expression of virulence genes (prfA-regulated as well as prfA-independent genes). Although the changes mostly were moderate, the consistency indicates that a mutant-specific change in virulence may occur concomitantly with bacteriocin resistance development.

  1. Cross-Resistance between Cry1 Proteins in Fall Armyworm (Spodoptera frugiperda May Affect the Durability of Current Pyramided Bt Maize Hybrids in Brazil.

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    Daniel Bernardi

    Full Text Available Genetically modified plants expressing insecticidal proteins from Bacillus thuringiensis (Bt offer valuable options for managing insect pests with considerable environmental and economic benefits. Despite the benefits provided by Bt crops, the continuous expression of these insecticidal proteins imposes strong selection for resistance in target pest populations. Bt maize (Zea mays hybrids have been successful in controlling fall armyworm (Spodoptera frugiperda, the main maize pest in Brazil since 2008; however, field-evolved resistance to the protein Cry1F has recently been reported. Therefore it is important to assess the possibility of cross-resistance between Cry1F and other Cry proteins expressed in Bt maize hybrids. In this study, an F2 screen followed by subsequent selection on MON 89034 maize was used to select an S. frugiperda strain (RR able to survive on the Bt maize event MON 89034, which expresses the Cry1A.105 and Cry2Ab2 proteins. Field-collected insects from maize expressing the Cry1F protein (event TC1507 represented most of the positive (resistance allele-containing (isofamilies found. The RR strain showed high levels of resistance to Cry1F, which apparently also conferred high levels of cross resistance to Cry1A.105 and Cry1Ab, but had only low-level (10-fold resistance to Cry2Ab2. Life history studies to investigate fitness costs associated with the resistance in RR strain revealed only small reductions in reproductive rate when compared to susceptible and heterozygous strains, but the RR strain produced 32.2% and 28.4% fewer females from each female relative to the SS and RS (pooled strains, respectively. Consistent with the lack of significant resistance to Cry2Ab2, MON 89034 maize in combination with appropriate management practices continues to provide effective control of S. frugiperda in Brazil. Nevertheless, the occurrence of Cry1F resistance in S. frugiperda across Brazil, and the cross-resistance to Cry1Ab and Cry1A

  2. Cross-Resistance between Cry1 Proteins in Fall Armyworm (Spodoptera frugiperda) May Affect the Durability of Current Pyramided Bt Maize Hybrids in Brazil.

    Science.gov (United States)

    Bernardi, Daniel; Salmeron, Eloisa; Horikoshi, Renato Jun; Bernardi, Oderlei; Dourado, Patrick Marques; Carvalho, Renato Assis; Martinelli, Samuel; Head, Graham P; Omoto, Celso

    2015-01-01

    Genetically modified plants expressing insecticidal proteins from Bacillus thuringiensis (Bt) offer valuable options for managing insect pests with considerable environmental and economic benefits. Despite the benefits provided by Bt crops, the continuous expression of these insecticidal proteins imposes strong selection for resistance in target pest populations. Bt maize (Zea mays) hybrids have been successful in controlling fall armyworm (Spodoptera frugiperda), the main maize pest in Brazil since 2008; however, field-evolved resistance to the protein Cry1F has recently been reported. Therefore it is important to assess the possibility of cross-resistance between Cry1F and other Cry proteins expressed in Bt maize hybrids. In this study, an F2 screen followed by subsequent selection on MON 89034 maize was used to select an S. frugiperda strain (RR) able to survive on the Bt maize event MON 89034, which expresses the Cry1A.105 and Cry2Ab2 proteins. Field-collected insects from maize expressing the Cry1F protein (event TC1507) represented most of the positive (resistance allele-containing) (iso)families found. The RR strain showed high levels of resistance to Cry1F, which apparently also conferred high levels of cross resistance to Cry1A.105 and Cry1Ab, but had only low-level (10-fold) resistance to Cry2Ab2. Life history studies to investigate fitness costs associated with the resistance in RR strain revealed only small reductions in reproductive rate when compared to susceptible and heterozygous strains, but the RR strain produced 32.2% and 28.4% fewer females from each female relative to the SS and RS (pooled) strains, respectively. Consistent with the lack of significant resistance to Cry2Ab2, MON 89034 maize in combination with appropriate management practices continues to provide effective control of S. frugiperda in Brazil. Nevertheless, the occurrence of Cry1F resistance in S. frugiperda across Brazil, and the cross-resistance to Cry1Ab and Cry1A.105

  3. Beta-lactamase characterization in Escherichia coli isolates with diminished susceptibility or resistance to extended-spectrum cephalosporins recovered from sick animals in Spain.

    Science.gov (United States)

    Briñas, Laura; Moreno, Miguel Angel; Teshager, Tirushet; Zarazaga, Myriam; Sáenz, Yolanda; Porrero, Concepción; Dominguez, Lucas; Torres, Carmen

    2003-01-01

    A total of 1439 Escherichia coli isolates from sick animals were received from the Spanish Network of Veterinary Antimicrobial Resistance Surveillance (VAV) from 1997 to 2001. Antimicrobial susceptibility tests were performed and diminished susceptibility to cefotaxime and ceftazidime was identified in 2.5% and 2.8% of the isolates, respectively. Beta-lactamase characterization was carried out in the group of 20 E. coli isolates with both characteristics. The MIC ranges of different beta-lactams showed by these 20 isolates were as follows (in microg/ml): ampicillin (64-->256), amoxicillin-clavulanic acid (4-64), ticarcillin (8-->128), cefazolin (32-->256), cefoxitin (4-->128), cefotaxime (1-64), ceftazidime (2-->64), ceftriaxone (0.5-64), imipenem (32). TEM, SHV, CMY, and FOX beta-lactamase genes were analyzed by PCR and sequencing. The beta-lactamase genes detected were the following ones (number of isolates): bla(TEM-1b) (3), bla(TEM-1a) (1), bla(TEM-30f) (2), bla(TEM-1b) + bla(CMY-2) (2), and bla(SHV-12) (1). Sequences of the promoter and/or attenuator region of the chromosomal ampC gene were studied in all the 20 isolates. Mutations at position -42 or -32 were detected in 16 isolates and these mutations were associated with the presence of a TEM type beta-lactamase in 6 isolates. Besides, a high variety of plasmidic beta-lactamases was detected including TEM-30 and CMY-2. To our knowledge, this is the first time that TEM-30 beta-lactamase has been detected in E. coli isolates of animal origin.

  4. Antimicrobial activity of ceftobiprole, a novel anti-methicillin-resistant Staphylococcus aureus cephalosporin, tested against contemporary pathogens: results from the SENTRY Antimicrobial Surveillance Program (2005-2006).

    Science.gov (United States)

    Fritsche, Thomas R; Sader, Helio S; Jones, Ronald N

    2008-05-01

    Ceftobiprole is a 1st-in-class anti-methicillin-resistant Staphylococcus aureus (MRSA) extended-spectrum cephalosporin currently in clinical trials for the treatment of complicated skin and skin structure infections (cSSSIs) and nosocomial pneumonia. This agent is also active against other prominent Gram-positive and Gram-negative pathogens, making it an attractive candidate for broad-spectrum therapy. We evaluated the in vitro potency of ceftobiprole tested against the most commonly occurring bacterial pathogens as part of a global surveillance study for the years 2005 to 2006 (>60 medical centers in North America, Latin America, and Europe). All isolates (40 675) were susceptibility tested using reference broth microdilution methods. Ceftobiprole inhibited 100% and >99% of tested S. aureus and coagulase-negative staphylococci at Ceftobiprole was also broadly active against Streptococcus pneumoniae, beta-hemolytic and viridans group streptococci, inhibiting >98% of isolates at ceftobiprole was generally inactive against Enterococcus faecium, the majority of Enterococcus faecalis strains (95.7%) were inhibited at ceftobiprole and ceftazidime), ceftobiprole and cefepime were superior to ceftazidime against Enterobacter spp. and Citrobacter spp. Against Pseudomonas aeruginosa, ceftobiprole was equal in potency to ceftazidime (MIC50, 2 microg/mL) and 2-fold more potent than cefepime. None of these agents inhibited >45% of Acinetobacter spp. at 8 mug/mL. Ceftobiprole is a new anti-MRSA beta-lactam with recognized activity against the most commonly occurring Enterobacteriaceae and P. aeruginosa, similar to that of extended-spectrum cephems. These characteristics warrant continued evaluation of the agent as empiric therapy for cSSSIs, and in pneumonia, especially in those institutions/regions where MRSA and P. aeruginosa may be prevalent.

  5. Extended spectrum β-lactamase and plasmid mediated quinolone resistance in Escherichia coli fecal isolates from healthy companion animals in Algeria.

    Science.gov (United States)

    Yousfi, Massilia; Mairi, Assia; Touati, Abdelaziz; Hassissene, Lila; Brasme, Lucien; Guillard, Thomas; De Champs, Christophe

    2016-07-01

    The aim of this study was to evaluate the rate of fecal carriage of Escherichia coli strains producing Extended-spectrum β-lactamases (ESBLs) and plasmid-mediated quinolone resistance (PMQR) isolated from healthy pets (dogs and cats) in Algeria. Fecal samples from 171 healthy pets (102 dogs and 69 cats) in one veterinary practice and private owners were included. After isolates identification, antibiotic susceptibility was determined by disk diffusion procedure. ESBL were detected by combination disk tests. PCR and sequencing were used to characterize genes encoding ESBLs and PMQR. Transfer of ESBL and PMQR genes was assessed by conjugation experiments. Phylogenetic groups of E. coli were determined by PCR. Of the 171 animals, 20 carried an ESBL producing E. coli giving a prevalence of ESBL fecal carriage of 11.7%. All isolates were susceptible to carbapenems, cefoxitin, piperacillin-tazobactam, amikacin and fosfomycine. For the rest of the tested β-lactams, susceptibility rates ranged from 35% to 70% for cefepime and amoxicillin-clavulanic acid respectively. Concerning the non-beta-lactams antibiotics, the rates of susceptibility ranged between 5% to trimethoprim and 95% for chloramphenicol. The beta-lactamase genes identified in E. coli isolates were blaCTX-M-15, blaCTX-M-1, blaSHV-12 and blaTEM-1. The PMQR determinants aac(6')-Ib-cr, qnrS1 and qnrB5 genes were identified in 15 isolates. Transconjugants were obtained for two isolates. Phylogenetic analysis showed that E. coli isolates belong to commensal phylogroups of A and B1. We reported here for the first time in Algeria ESBL and PMQR-producing E. coli in healthy cats and dogs.

  6. The influence of antimicrobial peptides and mucolytics on the integrity of biofilms consisting of bacteria and yeasts as affecting voice prosthetic air flow resistances

    NARCIS (Netherlands)

    Oosterhof, JJH; Elving, GJ; Stokroos, [No Value; Amerongen, AV; van der Mei, HC; Busscher, HJ; van Weissenbruch, R; Albers, FWJ

    2003-01-01

    The integrity of biofilms on voice prostheses used to rehabilitate speech in laryngectomized patients causes unwanted increases in airflow resistance, impeding speech. Biofilm integrity is ensured by extracellular polymeric substances (EPS). This study aimed to determine whether synthetic salivary p

  7. AtMYB44 regulates resistance to the green peach aphid and diamondback moth by activating EIN2-affected defences in Arabidopsis.

    Science.gov (United States)

    Lü, B-B; Li, X-J; Sun, W-W; Li, L; Gao, R; Zhu, Q; Tian, S-M; Fu, M-Q; Yu, H-L; Tang, X-M; Zhang, C-L; Dong, H-S

    2013-09-01

    Recently we showed that the transcription activator AtMYB44 regulates expression of EIN2, a gene essential for ethylene signalling and insect resistance, in Arabidopsis thaliana (Arabidopsis). To link the transactivation with insect resistance, we investigated the wild-type and atmyb44 mutant plants, genetically Complemented atmyb44 (Catmyb44) and AtMYB44-Overexpression Transgenic Arabidopsis (MYB44OTA). We found that AtMYB44 played a critical role in Arabidopsis resistance to the phloem-feeding generalist green peach aphid (Myzus persicae Sulzer) and leaf-chewing specialist caterpillar diamondback moth (Plutella xylostella L.). AtMYB44 was required not only for the development of constitutive resistance but also for the induction of resistance by both herbivorous insects. Levels of constitutive and herbivore-induced resistance were consistent with corresponding amounts of the AtMYB44 protein constitutively produced in MYB44OTA and induced by herbivory in Catmyb44. In both cases, AtMYB44 promoted EIN2 expression to a greater extent in MYB44OTA than in Catmyb44. However, AtMYB44-promoted EIN2 expression was arrested with reduced resistance levels in the EIN2-deficient Arabidopsis mutant ein2-1 and the MYB44OTA ein2-1 hybrid. In the different plant genotypes, only MYB44OTA constitutively displayed phloem-based defences, which are specific to phloem-feeding insects, and robust expression of genes involved in the biosynthesis of glucosinolates, which are the secondary plant metabolites known as deterrents to generalist herbivores. Phloem-based defences and glucosinolate-related gene expression were not detected in ein2-1 and MYB44OTA ein2-1. These results establish a genetic connection between the regulatory role of AtMYB44 in EIN2 expression and the development of Arabidopsis resistance to insects.

  8. Two-spotted spider mite reared on resistant eggplant affects consumption rate and life table parameters of its predator, Typhlodromus bagdasarjani (Acari: Phytoseiidae).

    Science.gov (United States)

    Khanamani, Mostafa; Fathipour, Yaghoub; Hajiqanbar, Hamidreza; Sedaratian, Amin

    2014-06-01

    The study of interactions between host plant cultivars and biological control agents is important in integrated pest management programs. In this study, the life table parameters and predation rate of Typhlodromus bagdasarjani Wainstein & Arutunjan were determined on two-spotted spider mites reared on a susceptible (Isfahan) or a resistant (Neishabour) eggplant cultivar. All experiments were carried out under laboratory conditions, at 25 ± 1 °C, 60 ± 5 % RH and a photoperiod of 16:8 (L:D) h. A significant difference was observed between mean developmental time of immature stages of T. bagdasarjani on the two eggplant cultivars: 6.6 versus 7.5 days, on the susceptible and resistant cultivar, respectively. Net reproductive rate (R 0) of T. bagdasarjani did not differ between the cultivars. Doubling time on the susceptible and resistant cultivars was 3.48 versus 5.72 days, mean generation time (T) was 10.13 versus 16.08 days, respectively. Total fecundity was higher on susceptible than on resistant eggplants, the intrinsic rate of population increase (r) was 0.188 versus 0.119 day(-1), respectively. Daily and total prey consumption of various life stages of T. bagdasarjani on two-spotted spider mite reared on susceptible versus resistant eggplant differed; total consumption was higher on spider mites reared on the resistant cultivar. However, the lower intrinsic rate of increase and higher mortality of the predator on the resistant eggplant (Neishabour) revealed that more attention should be devoted to integrated control of spider mites using resistant cultivars and phytoseiid mites.

  9. Antibiotic innovation may contribute to slowing the dissemination of multiresistant Streptococcus pneumoniae: the example of ketolides.

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    Lulla Opatowski

    Full Text Available BACKGROUND: Despite increasingly frequent bacterial resistance to antibiotics, antibacterial innovation is rare. Ketolides constitute one of the very few new antibiotic classes active against Streptococcus pneumoniae developed during the last 25 years. Their mechanism of action resembles that of macrolides, but they are unaffected by common resistance mechanisms. However, cross-resistance to ketolides has been observed in some macrolide-resistant strains. We examined how new antibiotic exposure may affect overall pneumococcal resistance patterns in the population. The aims of this study were to assess the potential dissemination of newly emerged resistances and to control the selection of strains already multiresistant to existing antimicrobials. METHODOLOGY/PRINCIPAL FINDINGS: We developed an age-structured population model for S. pneumoniae transmission in a human community exposed to heptavalent vaccine, and beta-lactams, macrolides and ketolides. The dynamics of intra-individual selection of resistant strains under antibiotic exposure and interindividual transmission were simulated, with antibiotic-specific resistance mechanisms defining the path to co-resistances and cross-resistances, and parameters concerning the French situation. Results of this simulation study suggest that new antibiotic consumption could markedly slow the diffusion of multiresistant strains. Wider use was associated with slower progression of multiresistance. When ketolides were prescribed to all ages, resistance to them reached 10% after >15 years, while it took >40 years when they were prescribed only to adults. In the scenario according to which new antibiotics totally replaced former antimicrobials, the beta-lactam resistance rate was limited at 70%. CONCLUSIONS: In a context of widespread vaccination and rational use of antibiotics, innovative antibiotic, prescribed to all age groups, may have an added impact on multiresistant-strain dissemination in the

  10. Evaluation of a Mixing versus a Cycling Strategy of Antibiotic Use in Critically-Ill Medical Patients: Impact on Acquisition of Resistant Microorganisms and Clinical Outcomes.

    Directory of Open Access Journals (Sweden)

    Nazaret Cobos-Trigueros

    Full Text Available To compare the effect of two strategies of antibiotic use (mixing vs. cycling on the acquisition of resistant microorganisms, infections and other clinical outcomes.Prospective cohort study in an 8-bed intensive care unit during 35- months in which a mixing-cycling policy of antipseudomonal beta-lactams (meropenem, ceftazidime/piperacillin-tazobactam and fluoroquinolones was operative. Nasopharyngeal and rectal swabs and respiratory secretions were obtained within 48h of admission and thrice weekly thereafter. Target microorganisms included methicillin-resistant S. aureus, vancomycin-resistant enterococci, third-generation cephalosporin-resistant Enterobacteriaceae and non-fermenters.A total of 409 (42% patients were included in mixing and 560 (58% in cycling. Exposure to ceftazidime/piperacillin-tazobactam and fluoroquinolones was significantly higher in mixing while exposure to meropenem was higher in cycling, although overall use of antipseudomonals was not significantly different (37.5/100 patient-days vs. 38.1/100 patient-days. There was a barely higher acquisition rate of microorganisms during mixing, but this difference lost its significance when the cases due to an exogenous Burkholderia cepacia outbreak were excluded (19.3% vs. 15.4%, OR 0.8, CI 0.5-1.1. Acquisition of Pseudomonas aeruginosa resistant to the intervention antibiotics or with multiple-drug resistance was similar. There were no significant differences between mixing and cycling in the proportion of patients acquiring any infection (16.6% vs. 14.5%, OR 0.9, CI 0.6-1.2, any infection due to target microorganisms (5.9% vs. 5.2%, OR 0.9, CI 0.5-1.5, length of stay (median 5 d for both groups or mortality (13.9 vs. 14.3%, OR 1.03, CI 0.7-1.3.A cycling strategy of antibiotic use with a 6-week cycle duration is similar to mixing in terms of acquisition of resistant microorganisms, infections, length of stay and mortality.

  11. Ectopically expressed sweet pepper ferredoxin PFLP enhances disease resistance to Pectobacterium carotovorum subsp. carotovorum affected by harpin and protease-mediated hypersensitive response in Arabidopsis.

    Science.gov (United States)

    Ger, Mang-Jye; Louh, Guan-Yu; Lin, Yi-Hsien; Feng, Teng-Yung; Huang, Hsiang-En

    2014-12-01

    Plant ferredoxin-like protein (PFLP) is a photosynthesis-type ferredoxin (Fd) found in sweet pepper. It contains an iron-sulphur cluster that receives and delivers electrons between enzymes involved in many fundamental metabolic processes. It has been demonstrated that transgenic plants overexpressing PFLP show a high resistance to many bacterial pathogens, although the mechanism remains unclear. In this investigation, the PFLP gene was transferred into Arabidopsis and its defective derivatives, such as npr1 (nonexpresser of pathogenesis-related gene 1) and eds1 (enhanced disease susceptibility 1) mutants and NAHG-transgenic plants. These transgenic plants were then infected with the soft-rot bacterial pathogen Pectobacterium carotovorum subsp. carotovorum (Erwinia carotovora ssp. carotovora, ECC) to investigate the mechanism behind PFLP-mediated resistance. The results revealed that, instead of showing soft-rot symptoms, ECC activated hypersensitive response (HR)-associated events, such as the accumulation of hydrogen peroxide (H2 O2 ), electrical conductivity leakage and expression of the HR marker genes (ATHSR2 and ATHSR3) in PFLP-transgenic Arabidopsis. This PFLP-mediated resistance could be abolished by inhibitors, such as diphenylene iodonium (DPI), 1-l-trans-epoxysuccinyl-leucylamido-(4-guanidino)-butane (E64) and benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), but not by myriocin and fumonisin. The PFLP-transgenic plants were resistant to ECC, but not to its harpin mutant strain ECCAC5082. In the npr1 mutant and NAHG-transgenic Arabidopsis, but not in the eds1 mutant, overexpression of the PFLP gene increased resistance to ECC. Based on these results, we suggest that transgenic Arabidopsis contains high levels of ectopic PFLP; this may lead to the recognition of the harpin and to the activation of the HR and other resistance mechanisms, and is dependent on the protease-mediated pathway.

  12. In vitro efficacy of bioactive extracts of 15 medicinal plants against ESbetaL-producing multidrug-resistant enteric bacteria.

    Science.gov (United States)

    Ahmad, Iqbal; Aqil, Farrukh

    2007-01-01

    Alcoholic crude extracts and some fractions from 15 traditionally used Indian medicinal plants were investigated for their ability to inhibit the growth of extended spectrum beta-lactamases (ESbetaL)-producing multidrug-resistant enteric bacteria. The test bacteria Eschrichia coli and Shigella were resistant to 16-23 antibiotics with intermediate or resistance to beta-lactams (minimum inhibitory concentration (MIC) value range 16-1024 microg/ml). The crude plant extracts demonstrated zone of inhibition in the range of 11-29 mm against one or more test bacteria. On the basis of promising activity, 12 plants were selected to determine their efficacy in terms of MIC, which ranged from 0.64 mg/ml to 10.24 mg/ml. The extracts of Acorus calamus, Hemidesmus indicus, Holarrhena antidysenterica and Plumbago zeylanica demonstrated relatively high activity as compared to other plant extracts and were fractionated into acetone, ethyl acetate and methanol. Acetone fraction in most of the cases exhibited higher potency (low MIC value) as compared to ethyl acetate and methanol fraction. However, in Plumbago zeylanica, ethyl acetate fraction was most active. Synergistic interactions among crude extracts were demonstrated in the 12 different combinations against ESbetaL-producing E. coli (ESbetaL-02). Certain combinations exhibited significant synergy with enlargement of combined inhibition zone size by 5 mm. Interaction of crude extracts with five antibiotics (Tetracycline, ciprofloxacin, nalidixic acid, chloramphenicol and streptomycin) demonstrated synergistic interaction with tetracycline and ciprofloxacin by 10 and 3 plant extracts respectively. Phytochemical analysis and thin layer chromatography (TLC) bioautography of crude extracts showed the presence of alkaloids, phenols and flavonoids as active phytoconstituents. Most active fractions of four plants were subjected to Infrared spectroscopy and the major groups of compounds were detected. The plant extracts were further

  13. Characteristics of Quinolone Resistance in Escherichia coli Isolates from Humans, Animals, and the Environment in the Czech Republic

    Science.gov (United States)

    Röderova, Magdalena; Halova, Dana; Papousek, Ivo; Dolejska, Monika; Masarikova, Martina; Hanulik, Vojtech; Pudova, Vendula; Broz, Petr; Htoutou-Sedlakova, Miroslava; Sauer, Pavel; Bardon, Jan; Cizek, Alois; Kolar, Milan; Literak, Ivan

    2017-01-01

    Escherichia coli is a common commensal bacterial species of humans and animals that may become a troublesome pathogen causing serious diseases. The aim of this study was to characterize the quinolone resistance phenotypes and genotypes in E. coli isolates of different origin from one area of the Czech Republic. E. coli isolates were obtained from hospitalized patients and outpatients, chicken farms, retailed turkeys, rooks wintering in the area, and wastewaters. Susceptibility of the isolates grown on the MacConkey agar with ciprofloxacin (0.05 mg/L) to 23 antimicrobial agents was determined. The presence of plasmid-mediated quinolone resistance (PMQR) and ESBL genes was tested by PCR and sequencing. Specific mutations in gyrA, gyrB, parC, and parE were also examined. Multilocus sequence typing and pulsed-field gel electrophoresis were performed to assess the clonal relationship. In total, 1050 E. coli isolates were obtained, including 303 isolates from humans, 156 from chickens, 105 from turkeys, 114 from the rooks, and 372 from wastewater samples. PMQR genes were detected in 262 (25%) isolates. The highest occurrence was observed in isolates from retailed turkey (49% of the isolates were positive) and inpatients (32%). The qnrS1 gene was the most common PMQR determinant identified in 146 (56%) followed by aac(6′)-Ib-cr in 77 (29%), qnrB19 in 41 (16%), and qnrB1 in 9 (3%) isolates. All isolates with high level of ciprofloxacin resistance (>32 mg/L) carried double or triple mutations in gyrA combined with single or double mutations in parC. The most frequently identified substitutions were Ser(83)Leu; Asp(87)Asn in GyrA, together with Ser(80)Ile, or Glu(84)Val in ParC. Majority of these isolates showed resistance to beta-lactams and multiresistance phenotype was found in 95% isolates. Forty-eight different sequence types among 144 isolates analyzed were found, including five major clones ST131 (26), ST355 (19), ST48 (13), ST95 (10), and ST10 (5). No isolates

  14. Ceftobiprole: first cephalosporin with activity against methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Vidaillac, Céline; Rybak, Michael J

    2009-05-01

    Ceftobiprole medocaril is the first member of a new series of advanced cephalosporins with activity against methicillin-resistant Staphylococcus aureus (MRSA). The drug received an approvable letter from the United States Food and Drug Administration (FDA) in March 2008 and from Health Canada in June 2008 for the treatment of complicated skin and skin structure infections including diabetic foot infections. Ceftobiprole exerts its antibacterial activity by inhibiting the penicillin-binding proteins (PBPs) involved in cell wall synthesis. It has an established stability against hydrolysis by many gram-positive beta-lactamases and a higher affinity for various PBPs (such as PBP2a of MRSA or PBP2x of Streptococcus pneumoniae), which leads to a wider spectrum of activity compared with older beta-lactams. Ceftobiprole activity does not cover extended-spectrum beta-lactamase-producing Enterobacteriaceae and some other pathogens, including Enterococcus faecium or Acinetobacter baumanii. Generally well tolerated, with nausea and taste disturbance being the most common adverse events, ceftobiprole appeared noninferior to empiric therapy in several clinical trials. Ceftobiprole is available only for intravenous administration; recommended dosage regimens have not been approved by the FDA as of this writing. However, based on the Canadian package insert, expected dosage recommendations are 500 mg as a 1-hour intravenous infusion every 12 hours for the treatment of complicated skin and skin structure infections caused by certain gram-positive pathogens, and 500 mg as a 2-hour infusion every 8 hours when susceptible gram-negative or both gram-positive and susceptible gram-negative pathogens are involved. Dosage adjustments are indicated for patients with moderate or severe renal impairment, and dosage recommendations are expected to be 500 or 250 mg, respectively, as a 2-hour infusion every 12 hours. Several precautions regarding hypersensitivity and drug incompatibility are

  15. Chemokine-like receptor 1 deficiency does not affect the development of insulin resistance and nonalcoholic fatty liver disease in mice

    NARCIS (Netherlands)

    Gruben, Nanda; Vergara, Marcela Aparicio; Kloosterhuis, Niels J.; van der Molen, Henk; Stoelwinder, Stefan; Youssef, Sameh; de Bruin, Alain; Delsing, Dianne J.; Kuivenhoven, Jan Albert; van de Sluis, Bart; Hofker, Marten H.; Koonen, Debby P. Y.

    2014-01-01

    The adipokine chemerin and its receptor, chemokine-like receptor 1 (Cmklr1), are associated with insulin resistance and nonalcoholic fatty liver disease (NAFLD), which covers a broad spectrum of liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). It is possible that

  16. Apramycin treatment affects selection and spread of a multidrug-resistant Escherichia coli strain able to colonize the human gut in the intestinal microbiota of pigs

    DEFF Research Database (Denmark)

    Herrero-Fresno, Ana; Zachariasen, Camilla; Hansen, Monica Hegstad;

    2016-01-01

    The effect of apramycin treatment on transfer and selection of an Escherichia coli strain (E. coli 912) in the intestine of pigs was analyzed through an in vivo experiment. The strain was sequenced and assigned to the sequence type ST101 and serotype O11. It carried resistance genes to apramycin...

  17. Release from native root herbivores and biotic resistance by soil pathogens in a new habitat both affect the alien Ammophila arenaria in South Africa

    NARCIS (Netherlands)

    Knevel, IC; Lans, T; Menting, FBJ; Hertling, UM; van der Putten, WH

    2004-01-01

    Many native communities contain exotic plants that pose a major threat to indigenous vegetation and ecosystem functioning. Therefore the enemy release hypothesis (ERH) and biotic resistance hypothesis (BRH) were examined in relation to the invasiveness of the introduced dune grass Ammophila arenaria

  18. Early Onset Inflammation in Pre-Insulin-Resistant Diet-Induced Obese Rats Does Not Affect the Vasoreactivity of Isolated Small Mesenteric Arteries

    DEFF Research Database (Denmark)

    Blædel, Martin; Raun, Kirsten; Boonen, Harrie C M;

    2012-01-01

    Background: Obesity is an increasing burden affecting developed and emerging societies since it is associated with an increased risk of diabetes and consequent cardiovascular complications. Increasing evidence points towards a pivotal role of inflammation in the etiology of vascular dysfunction...

  19. Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.

    Science.gov (United States)

    Venkatesan, Meera; Gadalla, Nahla B; Stepniewska, Kasia; Dahal, Prabin; Nsanzabana, Christian; Moriera, Clarissa; Price, Ric N; Mårtensson, Andreas; Rosenthal, Philip J; Dorsey, Grant; Sutherland, Colin J; Guérin, Philippe; Davis, Timothy M E; Ménard, Didier; Adam, Ishag; Ademowo, George; Arze, Cesar; Baliraine, Frederick N; Berens-Riha, Nicole; Björkman, Anders; Borrmann, Steffen; Checchi, Francesco; Desai, Meghna; Dhorda, Mehul; Djimdé, Abdoulaye A; El-Sayed, Badria B; Eshetu, Teferi; Eyase, Frederick; Falade, Catherine; Faucher, Jean-François; Fröberg, Gabrielle; Grivoyannis, Anastasia; Hamour, Sally; Houzé, Sandrine; Johnson, Jacob; Kamugisha, Erasmus; Kariuki, Simon; Kiechel, Jean-René; Kironde, Fred; Kofoed, Poul-Erik; LeBras, Jacques; Malmberg, Maja; Mwai, Leah; Ngasala, Billy; Nosten, Francois; Nsobya, Samuel L; Nzila, Alexis; Oguike, Mary; Otienoburu, Sabina Dahlström; Ogutu, Bernhards; Ouédraogo, Jean-Bosco; Piola, Patrice; Rombo, Lars; Schramm, Birgit; Somé, A Fabrice; Thwing, Julie; Ursing, Johan; Wong, Rina P M; Zeynudin, Ahmed; Zongo, Issaka; Plowe, Christopher V; Sibley, Carol Hopkins

    2014-10-01

    Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.

  20. Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in S. cerevisiae.

    Science.gov (United States)

    Ayyadevara, Srinivas; Tazearslan, Cagdas; Alla, Ramani; Jiang, James C; Jazwinski, S Michal; Shmookler Reis, Robert J

    2014-01-01

    A quantitative trait locus (QTL) in the nematode C. elegans, "lsq4," was recently implicated by mapping longevity genes. QTLs for lifespan and three stress-resistance traits coincided within a span of thermal stresses, and lower male frequency (reflecting X-chromosome non-disjunction), traits reversed uniquely by rec-8 knockdown. A strain bearing the longer-lived lsq4 allele, differing from the short-lived strain at resistance response mediated by innate immunity. Replicative lifespan was extended 20% in haploid S. cerevisiae (BY4741) by deletion of REC8, orthologous to nematode rec-8, implying that REC8 disruption of mitotic-cell survival is widespread, exemplifying antagonistic pleiotropy (opposing effects on lifespan vs. reproduction), and/or balancing selection wherein genomic disruption increases genetic variation under harsh conditions.

  1. Thirty-seven transcription factor genes differentially respond to a harpin protein and affect resistance to the green peach aphid in Arabidopsis

    Indian Academy of Sciences (India)

    Ruoxue Liu; Beibei Lü; Xiaomeng Wang; Chunling Zhang; Shuping Zhang; Jun Qian; Lei Chen; Haojie Shi; Hansong Dong

    2010-09-01

    The harpin protein HrpNEa induces Arabidopsis resistance to the green peach aphid by activating the ethylene signalling pathway and by recruiting EIN2, an essential regulator of ethylene signalling, for a defence response in the plant. We investigated 37 ethylene-inducible Arabidopsis transcription factor genes for their effects on the activation of ethylene signalling and insect defence. Twenty-eight of the 37 genes responded to both ethylene and HrpNEa, and showed either increased or inhibited transcription, while 18 genes showed increased transcription not only by ethylene but also by HrpNEa. In response to HrpNEa, transcription levels of 22 genes increased, with AtMYB44 being the most inducible, six genes had decreased transcript levels, and nine remained unchanged. When Arabidopsis mutants previously generated by mutagenicity at the 37 genes were surveyed, 24 mutants were similar to the wild type plant while four mutants were more resistant and nine mutants were more susceptible than wild type to aphid infestation. Aphid-susceptible mutants showed a greater susceptibility for atmyb15, atmyb38 and atmyb44, which were generated previously by T-DNA insertion into the exon region of AtMYB15 and the promoter regions of AtMYB38 and AtMYB44. The atmyb44 mutant was the most susceptible to aphid infestation and most compromised in induced resistance. Resistance accompanied the expression of PDF1.2, an ethylene signalling marker gene that requires EIN2 for transcription in wild type but not in atmyb15, atmyb38, and atmyb44, suggesting a disruption of ethylene signalling in the mutants. However, only atmyb44 incurred an abrogation in induced EIN2 expression, suggesting a close relationship between AtMYB44 and EIN2.

  2. The Arabidopsis thaliana lectin receptor kinase LecRK-I.9 is required for full resistance to Pseudomonas syringae and affects jasmonate signalling.

    Science.gov (United States)

    Balagué, Claudine; Gouget, Anne; Bouchez, Olivier; Souriac, Camille; Haget, Nathalie; Boutet-Mercey, Stéphanie; Govers, Francine; Roby, Dominique; Canut, Hervé

    2016-07-11

    On microbial attack, plants can detect invaders and activate plant innate immunity. For the detection of pathogen molecules or cell wall damage, plants employ receptors that trigger the activation of defence responses. Cell surface proteins that belong to large families of lectin receptor kinases are candidates to function as immune receptors. Here, the function of LecRK-I.9 (At5g60300), a legume-type lectin receptor kinase involved in cell wall-plasma membrane contacts and in extracellular ATP (eATP) perception, was studied through biochemical, gene expression and reverse genetics approaches. In Arabidopsis thaliana, LecRK-I.9 expression is rapidly, highly and locally induced on inoculation with avirulent strains of Pseudomonas syringae pv. tomato (Pst). Two allelic lecrk-I.9 knock-out mutants showed decreased resistance to Pst. Conversely, over-expression of LecRK-I.9 led to increased resistance to Pst. The analysis of defence gene expression suggests an alteration of both the salicylic acid (SA) and jasmonic acid (JA) signalling pathways. In particular, LecRK-I.9 expression during plant-pathogen interaction was dependent on COI1 (CORONATINE INSENSITIVE 1) and JAR1 (JASMONATE RESISTANT 1) components, and JA-responsive transcription factors (TFs) showed altered levels of expression in plants over-expressing LecRK-I.9. A similar misregulation of these TFs was obtained by JA treatment. This study identified LecRK-I.9 as necessary for full resistance to Pst and demonstrated its involvement in the control of defence against pathogens through a regulation of JA signalling components. The role of LecRK-I.9 is discussed with regard to the potential molecular mechanisms linking JA signalling to cell wall damage and/or eATP perception.

  3. The barley HvNAC6 transcription factor affects ABA accumulation and promotes basal resistance against powdery mildew

    DEFF Research Database (Denmark)

    Chen, Yan-Jun; Perera, Venura; Wagner, Michael

    2013-01-01

    a transgenic approach to constitutively silence HvNAC6 expression, using RNA interference (RNAi), to investigate the in vivo functions of HvNAC6 in basal resistance responses in barley in relation to the phytohormone ABA. The HvNAC6 RNAi plants displayed reduced HvNAC6 transcript levels and were more...... susceptible to Bgh than wild-type plants. Application of exogenous ABA increased basal resistance against Bgh in wild-type plants, but not in HvNAC6 RNAi plants, suggesting that ABA is a positive regulator of basal resistance which depends on HvNAC6. Silencing of HvNAC6 expression altered the light....../dark rhythm of ABA levels which were, however, not influenced by Bgh inoculation. The expression of the two ABA biosynthetic genes HvNCED1 and HvNCED2 was compromised, and transcript levels of the ABA conjugating HvBG7 enzyme were elevated in the HvNAC6 RNAi lines, but this effect was not clearly associated...

  4. Highly variable penicillin resistance determinants PBP 2x, PBP 2b, and PBP 1a in isolates of two Streptococcus pneumoniae clonal groups, Poland 23F-16 and Poland 6B-20.

    Science.gov (United States)

    Izdebski, Radoslaw; Rutschmann, Jens; Fiett, Janusz; Sadowy, Ewa; Gniadkowski, Marek; Hryniewicz, Waleria; Hakenbeck, Regine

    2008-03-01

    Penicillin-binding proteins (PBPs) in representatives of two Streptococcus pneumoniae clonal groups that are prevalent in Poland, Poland 23F-16 and Poland 6B-20, were investigated by PBP profile analysis, antibody reactivity pattern analysis, and DNA sequence analysis of the transpeptidase (TP) domain-encoding regions of the pbp2x, pbp2b, and pbp1a genes. The isolates differed in their MICs of beta-lactam antibiotics. The majority of the 6B isolates were intermediately susceptible to penicillin (penicillin MICs, 0.12 to 0.5 microg/ml), whereas all 23F isolates were penicillin resistant (MICs, >or=2 microg/ml). The 6B isolates investigated had the same sequence type (ST), determined by multilocus sequence typing, as the Poland 6B-20 reference strain (ST315), but in the 23F group, isolates with three distinct single-locus variants (SLVs) in the ddl gene (ST173, ST272, and ST1506) were included. None of the isolates showed an identical PBP profile after labeling with Bocillin FL and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and only one pair of 6B isolates and one pair of 23F isolates (ST173 and ST272) each contained an identical combination of PBP 2x, PBP 2b, and PBP 1a TP domains. Some 23F isolates contained PBP 3 with an apparently higher electrophoretic mobility, and this feature also did not correlate with their STs. The data document a highly variable pool of PBP genes as a result of multiple gene transfer and recombination events within and between different clonal groups.

  5. Macrophytes may not contribute significantly to removal of nutrients, pharmaceuticals, and antibiotic resistance in model surface constructed wetlands.

    Science.gov (United States)

    Cardinal, Pascal; Anderson, Julie C; Carlson, Jules C; Low, Jennifer E; Challis, Jonathan K; Beattie, Sarah A; Bartel, Caitlin N; Elliott, Ashley D; Montero, Oscar F; Lokesh, Sheetal; Favreau, Alex; Kozlova, Tatiana A; Knapp, Charles W; Hanson, Mark L; Wong, Charles S

    2014-06-01

    Outdoor shallow wetland mesocosms, designed to simulate surface constructed wetlands to improve lagoon wastewater treatment, were used to assess the role of macrophytes in the dissipation of wastewater nutrients, selected pharmaceuticals, and antibiotic resistance genes (ARGs). Specifically, mesocosms were established with or without populations of Typha spp. (cattails), Myriophyllum sibiricum (northern water milfoil), and Utricularia vulgaris (bladderwort). Following macrophyte establishment, mesocosms were seeded with ARG-bearing organisms from a local wastewater lagoon, and treated with a single pulse of artificial municipal wastewater with or without carbamazepine, clofibric acid, fluoxetine, and naproxen (each at 7.6μg/L), as well as sulfamethoxazole and sulfapyridine (each at 150μg/L). Rates of pharmaceutical dissipation over 28d ranged from 0.073 to 3.0d(-1), corresponding to half-lives of 0.23 to 9.4d. Based on calculated rate constants, observed dissipation rates were consistent with photodegradation driving clofibric acid, naproxen, sulfamethoxazole, and sulfapyridine removal, and with sorption also contributing to carbamazepine and fluoxetine loss. Of the seven gene determinants assayed, only two genes for both beta-lactam resistance (blaCTX and blaTEM) and sulfonamide resistance (sulI and sulII) were found in sufficient quantity for monitoring. Genes disappeared relatively rapidly from the water column, with half-lives ranging from 2.1 to 99d. In contrast, detected gene levels did not change in the sediment, with the exception of sulI, which increased after 28d in pharmaceutical-treated systems. These shallow wetland mesocosms were able to dissipate wastewater contaminants rapidly. However, no significant enhancement in removal of nutrients or pharmaceuticals was observed in mesocosms with extensive aquatic plant communities. This was likely due to three factors: first, use of naïve systems with an unchallenged capacity for nutrient assimilation and

  6. Effects of the exposure to self- and other-referential bodies on state body image and negative affect in resistance-trained men.

    Science.gov (United States)

    Cordes, Martin; Vocks, Silja; Düsing, Rainer; Waldorf, Manuel

    2017-03-09

    Previous body image research suggests that first, exposure to body stimuli can negatively affect men's body satisfaction and second, body concerns are associated with dysfunctional gaze behavior. To date, however, the effects of self- vs. other-referential body stimuli and of gaze behavior on body image in men under exposure conditions have not been investigated. Therefore, 49 weight-trained men were presented with pictures of their own and other bodies of different builds (i.e., normal, muscular, hyper-muscular) while being eye-tracked. Participants completed pre- and post-exposure measures of body image and affect. Results indicated that one's own and the muscular body negatively affected men's body image to a comparable degree. Exposure to one's own body also led to increased negative affect. Increased attention toward disliked own body parts was associated with a more negative post-exposure body image and affect. These results suggest a crucial role of critical self-examination in maintaining body dissatisfaction.

  7. On conditions of negativity of friction resistance for non-stationary modes of blood flow and possible mechanism of affecting of environmental factors on energy effectiveness of cardio-vascular system functioning

    CERN Document Server

    Chefranov, S G

    2013-01-01

    It is shown that initiated by action of molecular viscosity impulse flow, directed usually from the moving fluid to limiting it solid surface, can, under certain conditions, turn to zero and get negative values in the case of non-stationary flow caused by alternating in time longitudinal (along the pipe axis) pressure gradient. It is noted that this non-equilibrium mechanism of negative friction resistance in the similar case of pulsating blood flow in the blood vessels, in addition to the stable to turbulent disturbances swirled blood flow structure providing, can also constitute hydro-mechanical basis of the observed but not explained yet paradoxically high energy effectiveness of the normal functioning of the cardio-vascular system (CVS). We consider respective mechanism of affecting on the stability of the normal work of CVS by environmental variable factors using shifting of hydro-dynamic mode with negative resistance realization range boundaries and variation of linear hydro-dynamic instability leading ...

  8. Exercise order affects the total training volume and the ratings of perceived exertion in response to a super-set resistance training session

    OpenAIRE

    Balsamo S; Tibana RA; Nascimento DC; Farias GL; Petruccelli Z; Santana FS; Martins OV; Aguiar F; Pereira GB; Souza JC; Prestes J.

    2012-01-01

    Sandor Balsamo1–3, Ramires Alsamir Tibana1,2,4, Dahan da Cunha Nascimento1,2, Gleyverton Landim de Farias1,2, Zeno Petruccelli1,2, Frederico dos Santos de Santana1,2, Otávio Vanni Martins1,2, Fernando de Aguiar1,2, Guilherme Borges Pereira4, Jéssica Cardoso de Souza4, Jonato Prestes41Department of Physical Education, Centro Universitário UNIEURO, Brasília, 2GEPEEFS (Resistance training and Health Research Group), Brasília/DF, 3G...

  9. The sheet resistance of the cells affects the efficiency%方块电阻对电池片效率的影响

    Institute of Scientific and Technical Information of China (English)

    吴姣; 常乐

    2015-01-01

    solar cel production process diffusion process analysis and study on the impact of different size sheet resistance of solar cel efficiency , thereby enhancing the conversion efficiency of solar cels .%通过对太阳能电池生产过程中的扩散工艺的分析与研究,探讨不同大小的方块电阻对太阳能电池片效率的影响,从而提高太阳能电池转换效率。

  10. Exercise order affects the total training volume and the ratings of perceived exertion in response to a super-set resistance training session

    Directory of Open Access Journals (Sweden)

    Balsamo S

    2012-02-01

    Full Text Available Sandor Balsamo1–3, Ramires Alsamir Tibana1,2,4, Dahan da Cunha Nascimento1,2, Gleyverton Landim de Farias1,2, Zeno Petruccelli1,2, Frederico dos Santos de Santana1,2, Otávio Vanni Martins1,2, Fernando de Aguiar1,2, Guilherme Borges Pereira4, Jéssica Cardoso de Souza4, Jonato Prestes41Department of Physical Education, Centro Universitário UNIEURO, Brasília, 2GEPEEFS (Resistance training and Health Research Group, Brasília/DF, 3Graduate Program in Medical Sciences, School of Medicine, Universidade de Brasília (UnB, Brasília, 4Graduation Program in Physical Education, Catholic University of Brasilia (UCB, Brasília/DF, BrazilAbstract: The super-set is a widely used resistance training method consisting of exercises for agonist and antagonist muscles with limited or no rest interval between them – for example, bench press followed by bent-over rows. In this sense, the aim of the present study was to compare the effects of different super-set exercise sequences on the total training volume. A secondary aim was to evaluate the ratings of perceived exertion and fatigue index in response to different exercise order. On separate testing days, twelve resistance-trained men, aged 23.0 ± 4.3 years, height 174.8 ± 6.75 cm, body mass 77.8 ± 13.27 kg, body fat 12.0% ± 4.7%, were submitted to a super-set method by using two different exercise orders: quadriceps (leg extension + hamstrings (leg curl (QH or hamstrings (leg curl + quadriceps (leg extension (HQ. Sessions consisted of three sets with a ten-repetition maximum load with 90 seconds rest between sets. Results revealed that the total training volume was higher for the HQ exercise order (P = 0.02 with lower perceived exertion than the inverse order (P = 0.04. These results suggest that HQ exercise order involving lower limbs may benefit practitioners interested in reaching a higher total training volume with lower ratings of perceived exertion compared with the leg extension plus leg curl

  11. Bacillus volatiles adversely affect the physiology and ultra-structure of Ralstonia solanacearum and induce systemic resistance in tobacco against bacterial wilt

    Science.gov (United States)

    Tahir, Hafiz Abdul Samad; Gu, Qin; Wu, Huijun; Niu, Yuedi; Huo, Rong; Gao, Xuewen

    2017-01-01

    Volatile organic compounds (VOCs) produced by various bacteria have significant potential to enhance plant growth and to control phytopathogens. Six of the most effective antagonistic Bacillus spp. were used in this study against Ralstonia solanacearum (Rsc) TBBS1, the causal agent of bacterial wilt disease in tobacco. Bacillus amyloliquefaciens FZB42 and Bacillus artrophaeus LSSC22 had the strongest inhibitory effect against Rsc. Thirteen VOCs produced by FZB42 and 10 by LSSC22 were identified using gas chromatography-mass spectrometry analysis. Benzaldehyde, 1,2-benzisothiazol-3(2 H)-one and 1,3-butadiene significantly inhibited the colony size, cell viability, and motility of pathogens and negatively influenced chemotaxis. Transmission and scanning electron microscopy revealed severe morphological and ultra-structural changes in cells of Rsc. Furthermore, VOCs altered the transcriptional expression level of PhcA (a global virulence regulator), type III secretion system (T3SS), type IV secretion system (T4SS), extracellular polysaccharides and chemotaxis-related genes, which are major contributors to pathogenicity, resulting in decreased wilt disease. The VOCs significantly up-regulated the expression of genes related to wilt resistance and pathogen defense. Over-expression of EDS1 and NPR1 suggest the involvement of SA pathway in induction of systemic resistance. Our findings provide new insights regarding the potential of antibacterial VOCs as a biocontrol tool against bacterial wilt diseases. PMID:28091587

  12. KPC-mediated resistance in Klebsiella pneumoniae in two hospitals in Padua, Italy, June 2009-December 2011: massive spreading of a KPC-3-encoding plasmid and involvement of non-intensive care units

    Directory of Open Access Journals (Sweden)

    Richter Sara N

    2012-07-01

    Full Text Available Abstract Background Klebsiella pneumoniae carbapenemases (KPCs producing bacteria have emerged as a cause of multidrug-resistant nosocomial infections worldwide. KPCs are plasmid-encoded enzymes capable of hydrolysing a broad spectrum of beta-lactams, including carbapenems and monobactams, therefore worryingly limiting antimicrobial treatment options. Analysis of circulating bacterial strains and KPC alleles may help understanding the route of KPC dissemination and therefore help containing the infection. Methods KPC-producing Klebsiella pneumoniae dissemination in two 1580- and 300- bed hospitals in Padua, Italy, from initial outbreak in 2009 to late 2011 was analysed. Molecular and clinical epidemiology, including bacterial strains, KPC-encoding plasmid sequences and associated resistance genes, involved hospital wards and relocation of patients were described. Routine antimicrobial susceptibility testing and MIC of carbapenems on clinical isolates were performed. Detection of resistance genes was obtained by PCR and sequencing. MLST, PFGE and ERIC were used for molecular genotyping. Plasmid analysis was obtained by digestion with restriction enzymes and deep sequencing. Results KPC-positive clinical samples were isolated from nearly 200 patients. In the initial outbreak intensive care units were almost exclusively involved, while medical, surgical and long-term wards were successively massively concerned. Analysis of KPC alleles, plasmids and bacterial sequence types (STs indicated that during the initial outbreak KPC-3 in ST258 and KPC-2 in ST147 were each confined in one of the two surveilled hospitals. While KPC-2 dissemination was effectively contained, KPC-3 in ST258 cross-spreading was observed. The simultaneous presence of two carbapenemases, VIM-1 and KPC-2, in the same isolate was also observed in three patients. Total sequencing of plasmid content of two KPC-3 strains showed novel association of resistance plasmids. Conclusions The

  13. Proteinase K-resistant material in ARR/VRQ sheep brain affected with classical scrapie is composed mainly of VRQ prion protein.

    Science.gov (United States)

    Jacobs, J G; Bossers, A; Rezaei, H; van Keulen, L J M; McCutcheon, S; Sklaviadis, T; Lantier, I; Berthon, P; Lantier, F; van Zijderveld, F G; Langeveld, J P M

    2011-12-01

    Classical scrapie is a prion disease in sheep and goats. In sheep, susceptibility to disease is genetically influenced by single amino acid substitutions. Genetic breeding programs aimed at enrichment of arginine-171 (171R) prion protein (PrP), the so-called ARR allele, in the sheep population have been demonstrated to be effective in reducing the occurrence of classical scrapie in the field. Understanding the molecular basis for this reduced prevalence would serve the assessment of ARR adaptation. The prion formation mechanism and conversion of PrP from the normal form (PrP(C)) to the scrapie-associated form (PrP(Sc)) could play a key role in this process. Therefore, we investigated whether the ARR allele substantially contributes to scrapie prion formation in naturally infected heterozygous 171Q/R animals. Two methods were applied to brain tissue of 171Q/R heterozygous sheep with natural scrapie to determine the relative amount of the 171R PrP fraction in PrP(res), the proteinase K-resistant PrP(Sc) core. An antibody test differentiating between 171Q and 171R PrP fragments showed that PrP(res) was mostly composed of the 171Q allelotype. Furthermore, using a novel tool for prion research, endoproteinase Lys-C-digested PrP(res) yielded substantial amounts of a nonglycosylated and a monoglycosylated PrP fragment comprising codons 114 to 188. Following two-dimensional gel electrophoresis, only marginal amounts (scrapie-infected animals. This is suggestive of a poor adaptation of classical scrapie to this resistance allele under these natural conditions.

  14. Using steric hindrance to design new inhibitors of class C beta-lactamases

    Energy Technology Data Exchange (ETDEWEB)

    Trehan, Indi; Morandi, F.; Blaszczak, L.C.; Shoichet, Brian K. (NWU)

    2010-03-08

    {beta}-lactamases confer resistance to {beta}-lactam antibiotics such as penicillins and cephalosporins. However, {beta}-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of {beta}-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R1 side chain of {beta}-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective {beta}-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of the penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.

  15. Polyclonal KPC-3-producing Enterobacteriaceae in Portugal

    OpenAIRE

    Manageiro, Vera; Ferreira, Eugénia; Louro, Deolinda; Caniça, Manuela; Antimicrobial Resistance Surveillance Program in Portugal (ARSIP)

    2012-01-01

    Water has been recognized as a reservoir for antibiotic resistance genes (ARG), where the presence of mobile genetic elements, including plasmids, favors their dissemination. It is noteworthy that nonpathogenic environmental organisms, where plasmids encoding multiple ARG are prevalent, can provide resistance to most classes of antimicrobials including beta-lactams, aminoglycosides, chloramphenicol, trimethoprim, streptomycin, fosfomycin, quinolones, among others. The main goal of...

  16. Hygiene quality and presence of ESBL-producing Escherichia coli in raw food diets for dogs

    Directory of Open Access Journals (Sweden)

    Oskar Nilsson

    2015-10-01

    CMY-2 group and only one of them was also resistant to a non-beta-lactam antibiotic. Conclusion: The results of this study indicate that raw food diets could be a source of ESC-resistant E. coli to dogs and highlight the need for maintaining good hygiene when handling these products to prevent infection.

  17. Comparison of Factors Affecting Seed Germination of Beckmannia syzigachne Resistant and Susceptible Populations to Fenoxaprop-p-ethyl%精(噁)唑禾草灵抗性及敏感菵草种群萌发条件的比较

    Institute of Scientific and Technical Information of China (English)

    艾萍; 吕波; 李俊; 董立尧

    2011-01-01

    In order to investigate and compare the seed germination characteristics of Beckmannia syzigachne between the resistant and susceptible population to fenoxiaprop - p - ethyl, some factors affecting seed germination including temperture, light, pH value, water potential and NaCl stress have heen tested and evaluated via dish dipping method. The results showed that there was no significant difference to be found in seed germination rate between the resistant and susceptible population when pH values ranged from 4 to 10. Seed germination rate of the resistant population was signifcant lower than that of susceptible population under the whole light condition or at the temperature of 10 ℃. The inhibiting effect of water potential and NaCl stress on seed germination in the resistant population was higher than that of susceptible population. The germination in resistant population was completely inhibited under -0.5 MPa water potential,while the germination rate in susceptible population reached to 41.9%. The germination in resistant population was completely inhibited with 160 mmol/L NaCl treatment,while germination rate in the susceptible population reached to 51.7%.%为了比较对精(噁)唑禾草灵抗性及敏感菵草种群在萌发特性上的差异,采用培养皿法研究了温度、光照、pH值、水势、盐胁迫对其萌发的影响.结果表明,pH值为4~10条件下,2个种群的萌发率无显著性差异;全光照条件下,抗性菵草的萌发率显著低于敏感菵草;10℃条件下,抗性菵草的萌发率显著低于敏感菵草;水势胁迫和盐分胁迫对抗性茼草萌发的影响大于敏感菵草,当水势为-0.5 MPa时,抗性菵草无萌发,敏感菵草萌发率为41.9%;当NaCl溶液浓度为160 mmol/L时,抗性菵草无萌发,敏感菵草的萌发率为51.7%.

  18. Relationship between the degree of insulin resistance during late gestation and postpartum performance in dairy cows and factors that affect growth and metabolic status of their calves

    Science.gov (United States)

    KAWASHIMA, Chiho; MUNAKATA, Megumi; SHIMIZU, Takashi; MIYAMOTO, Akio; KIDA, Katsuya; MATSUI, Motozumi

    2016-01-01

    This study aimed to investigate the effects of insulin resistance (IR) during the close-up dry period on the metabolic status and performance of dairy cows as well as to determine the effects on body weight (BW) and metabolic status of their calves. An insulin tolerance test (ITT) was conducted by administering 0.05 IU/kg BW of insulin to 34 multiparous Holstein cows at 3 weeks prepartum. Blood samples were collected at 0, 30, 45 and 60 min after insulin injection, and cows were divided into two groups based on the time required for glucose to reach the minimum levels [non-IR (NIR), 45 min (n=28); and IR, 60 min (n=6)]. Blood or milk sampling and body condition score (BCS) estimation were performed twice weekly during the experimental period. Blood samples from calves were collected immediately after birth. Cows with IR showed lower BCS (Pmilk yield (Pcows is related to postpartum metabolic status and performance along with growth and metabolic status of their calves. PMID:26781705

  19. Factors affecting thermal resistance of Salmonella enterica serovar enteritidis ODA 99-30581-13 in shell egg contents and use of heat-ozone combinations for egg pasteurization.

    Science.gov (United States)

    Perry, Jennifer J; Yousef, Ahmed E

    2013-02-01

    Infection of laying hens with Salmonella enterica serovar Enteritidis leads to deposition of the pathogen into the albumen or yolk of forming eggs. Heat treatment can inactivate internalized Salmonella Enteritidis in shell eggs, but factors such as the nature and location of contamination may influence the efficacy of thermal treatments. In the current research, natural contamination was mimicked by introducing small inocula of Salmonella Enteritidis into different locations of shell eggs and incubating inoculated eggs. These pathogen-containing eggs were heated at 57°C for 40 min, and temperature within eggs was monitored at the locations of inocula. Comparison of inactivation at equivalent internal temperatures revealed similar levels of lethality regardless of inoculum location. Refrigeration between incubation and heat treatment did not increase thermal resistance of cells in albumen but decreased cell inactivation in yolk. Sequential application of heat and gaseous ozone allows for the development of a process capable of decontaminating shell eggs with minimal thermal treatment and impact on egg quality. Inoculated eggs were subjected to (i) an immersion heating process similar to that used in commercial pasteurization or (ii) immersion heating, at reduced duration, followed by vacuum (50.8 kPa) and treatment with ozone gas (maximum 160 g/m(3)) under pressure (∼187.5 kPa). All treatments tested produced greater than 5-log inactivation, which is required for "pasteurization" processes. Differences were observed in the visual quality of eggs depending on treatment parameters. Application of ozone subsequent to heating allows for a significant reduction in heating time without decreasing process lethality.

  20. Fish oil supplementation suppresses resistance exercise and feeding-induced increases in anabolic signaling without affecting myofibrillar protein synthesis in young men.

    Science.gov (United States)

    McGlory, Chris; Wardle, Sophie L; Macnaughton, Lindsay S; Witard, Oliver C; Scott, Fraser; Dick, James; Bell, J Gordon; Phillips, Stuart M; Galloway, Stuart D R; Hamilton, D Lee; Tipton, Kevin D

    2016-03-01

    Fish oil (FO) supplementation potentiates muscle protein synthesis (MPS) in response to a hyperaminoacidemic-hyperinsulinemic infusion. Whether FO supplementation potentiates MPS in response to protein ingestion or when protein ingestion is combined with resistance exercise (RE) remains unknown. In a randomized, parallel group design, 20 healthy males were randomized to receive 5 g/day of either FO or coconut oil control (CO) for 8 weeks. After supplementation, participants performed a bout of unilateral RE followed by ingestion of 30 g of whey protein. Skeletal muscle biopsies were obtained before and after supplementation for assessment of muscle lipid composition and relevant protein kinase activities. Infusion of L-[ring-(13)C6] phenylalanine was used to measure basal myofibrillar MP Sat rest (REST), in a nonexercised leg following protein ingestion (FED) and following RE and protein ingestion (FEDEX).MPS was significantly elevated above REST during FEDEX in both the FO and CO groups, but there was no effect of supplementation. There was a significant increase in MPS in both groups above REST during FED but no effect of supplementation. Supplementation significantly decreased pan PKB activity at RESTin the FO group but not the CO group. There was a significant increase from REST at post-RE for PKB and AMPKα2 activity in the CO group but not in the FO group. In FEDEX, there was a significant increase in p70S6K1 activity from REST at 3 h in the CO group only. These data highlight that 8 weeks of FO supplementation alters kinase signaling activity in response to RE plus protein ingestion without influencing MPS.

  1. L-Alanylglutamine inhibits signaling proteins that activate protein degradation, but does not affect proteins that activate protein synthesis after an acute resistance exercise.

    Science.gov (United States)

    Wang, Wanyi; Choi, Ran Hee; Solares, Geoffrey J; Tseng, Hung-Min; Ding, Zhenping; Kim, Kyoungrae; Ivy, John L

    2015-07-01

    Sustamine™ (SUS) is a dipeptide composed of alanine and glutamine (AlaGln). Glutamine has been suggested to increase muscle protein accretion; however, the underlying molecular mechanisms of glutamine on muscle protein metabolism following resistance exercise have not been fully addressed. In the present study, 2-month-old rats climbed a ladder 10 times with a weight equal to 75 % of their body mass attached at the tail. Rats were then orally administered one of four solutions: placebo (PLA-glycine = 0.52 g/kg), whey protein (WP = 0.4 g/kg), low dose of SUS (LSUS = 0.1 g/kg), or high dose of SUS (HSUS = 0.5 g/kg). An additional group of sedentary (SED) rats was intubated with glycine (0.52 g/kg) at the same time as the ladder-climbing rats. Blood samples were collected immediately after exercise and at either 20 or 40 min after recovery. The flexor hallucis longus (FHL), a muscle used for climbing, was excised at 20 or 40 min post exercise and analyzed for proteins regulating protein synthesis and degradation. All supplements elevated the phosphorylation of FOXO3A above SED at 20 min post exercise, but only the SUS supplements significantly reduced the phosphorylation of AMPK and NF-kB p65. SUS supplements had no effect on mTOR signaling, but WP supplementation yielded a greater phosphorylation of mTOR, p70S6k, and rpS6 compared with PLA at 20 min post exercise. However, by 40 min post exercise, phosphorylation of mTOR and rpS6 in PLA had risen to levels not different than WP. These results suggest that SUS blocks the activation of intracellular signals for MPB, whereas WP accelerates mRNA translation.

  2. Constitutive expression of pathogen-inducible OsWRKY31 enhances disease resistance and affects root growth and auxin response in transgenic rice plants

    Institute of Scientific and Technical Information of China (English)

    Juan Zhang; Youliang Peng; Zejian Guo

    2008-01-01

    WRKY transcription factors have many regulatory roles in response to biotic and abiotic stresses. In this study, we isolated a rice WRKY gene (OsWRKY31) that is induced by the rice blast fungus Magnaporthe grisea and auxin. This gene encodes a polypeptide of 211 amino-acid residues and belongs to a subgroup of the rice WRKY gene family that probably originated after the divergence of monocot and dicot plants. OsWRKY31 was found to be localized to the nucleus of onion epidermis cells to transiently express OsWRKY31-eGFP fusion protein. Analysis of 0sWRKY31 and its mutants fused with a Cal4 DNA-binding domain indicated that OsWRKY31 has transactivation activity in yeast. Overexpression of the OsWRKY31 gene was found to enhance resistance against infection with M. grisea, and the transgenic lines exhibited reduced lateral root formation and elongation compared with wild-type and RNAi plants. The lines with overexpression showed constitutive expression of many defense-related genes, such as PBZ1 and OsSci2, as well as early auxin-response genes, such as OsIAA4 and OsCrll genes. Furthermore, the plants with overexpression were less sensitive to exogenously supplied IBA, NAA and 2,4-D at high concentrations, suggesting that overexpression of the OsWRKY31 gene might alter the auxin response or transport. These results also suggest that OsWRKY31 might be a common component in the signal transduction pathways of the auxin response and the defense response in rice.

  3. Factors affecting soil cohesion

    Science.gov (United States)

    Soil erodibility is a measure of a soil’s resistance against erosive forces and is affected by both intrinsic (or inherent) soil property and the extrinsic condition at the time erodibility measurement is made. Since soil erodibility is usually calculated from results obtained from erosion experimen...

  4. 不同沟灌方式下玉米叶片气孔阻力差异%Leaf stomatal resistance of maize affected by different furrow irrigation methods

    Institute of Scientific and Technical Information of China (English)

    李彩霞; 周新国; 孙景生; 李新强

    2014-01-01

    maize leaf, regardless of irrigation methods, the stomatal resistance decreased gradually from the base to the tip of the maize leaf. At the population level, the stomatal resistance of maize leaf increased gradually from canopy top to bottom. For the change of the leaf stomatal resistance in time, diurnal variation of leaf stomatal resistance was in a Wshape. Diurnal and daily changes in the leaf stomatal resistance in the upper canopy were relatively small. The upper surface of maize leaf contributed more to CO2 and water vapor transfer than the ones underside. Except at the seedling stage, the leaves in the upper and middle part of maize canopy contributed more than 80% of the total CO2 and water vapor. Stomatal resistances of maize leaves decreased with the increase in leaf age during the vegetative growth stage. Differences in stomatal resistance among maize leaves of different ages were increased by the alternative deficit water supply. During the reproductive growth phase, leaf age had no significant influence on the stomatal resistance in matured leaves. Compared with the conventional furrow irrigation with sufficient water supply, the alternative deficit water supply increased the ratio of the stomatal resistances between the upper side and underside of maize leaves. The vertical gradient of stomatal resistance from canopy top to bottom increased significantly (P<0.05), decreasing leaf stomatal conductivity rapidly, and improving the contribution of the stomatal aperture in the upper canopy to water vapor transfer. Therefore, the leaf stomatal resistance of maize was regulated by furrow irrigation methods and soil water condition, and it was affected by the leaf age, leaf area index and natural feature of stomatal aperture. The study is useful for controllable irrigation technology and water vapor cycle in soil plant atmosphere continuum (SPAC).

  5. Prolonged extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome in a child affected by rituximab-resistant autoimmune hemolytic anemia: a case report

    Directory of Open Access Journals (Sweden)

    Beretta Chiara

    2009-04-01

    Full Text Available Abstract Introduction Autoimmune hemolytic anemia in children younger than 2 years of age is usually characterized by a severe course, with a mortality rate of approximately 10%. The prolonged immunosuppression following specific treatment may be associated with a high risk of developing severe infections. Recently, the use of monoclonal antibodies (rituximab has allowed sustained remissions to be obtained in the majority of pediatric patients with refractory autoimmune hemolytic anemia. Case presentation We describe the case of an 8-month-old Caucasian girl affected by a severe form of autoimmune hemolytic anemia, which required continuous steroid treatment for 16 months. Thereafter, she received 4 weekly doses of rituximab (375 mg/m2/dose associated with steroid therapy, which was then tapered over the subsequent 2 weeks. One month after the last dose of rrituximab, she presented with recurrence of severe hemolysis and received two more doses of rrituximab. The patient remained in clinical remission for 7 months, before presenting with a further relapse. An alternative heavy immunosuppressive therapy was administered combining cyclophosphamide 10 mg/kg/day for 10 days with methylprednisolone 40 mg/kg/day for 5 days, which was then tapered down over 3 weeks. While still on steroid therapy, the patient developed an interstitial pneumonia with Acute Respiratory Distress Syndrome, which required immediate admission to the intensive care unit where extracorporeal membrane oxygenation therapy was administered continuously for 37 days. At 16-month follow-up, the patient is alive and in good clinical condition, with no organ dysfunction, free from any immunosuppressive treatment and with a normal Hb level. Conclusions This case shows that aggressive combined immunosuppressive therapy may lead to a sustained complete remission in children with refractory autoimmune hemolytic anemia. However, the severe life-threatening complication presented by our

  6. Resistance to antibiotics in Gram-negative bacteria isolated from broiler carcasses Resistência a antibióticos em bactérias Gram-negativas isoladas de carcaças de frangos

    Directory of Open Access Journals (Sweden)

    M.A.S. Moreira

    2002-02-01

    Full Text Available One hundred and ninety-seven isolates of Gram-negative bacteria, comprising 10 genera, were isolated from poultry carcasses at a processing plant in order to investigate resistance to low levels of antibiotics. The samples were taken just after evisceration and before inspection. Most of the isolates were of Samonella and Escherichia. Other genera present were Enterobacter, Serratia, Klebsiella, Kluyvera, Erwinia, Citrobacter, Pseudomonas and Aeromonas. Distinct profiles of antibiotic resistance were detected. Resistance to more than two antibiotics predominated and spanned several classes of antibiotics. Salmonellae and escherichiae were mainly resistant to the aminoglycosides, followed by tetracycline, nitrofuran, sulpha, macrolide, chloramphenicol, quinolones and beta-lactams. Most isolates were sensitive to 30mug/ml olaquindox, the growth promoter in use at the time of sampling. However, many were resistant to a level of 10mug/ml and 13mug/ml olaquindox, levels present in the gut due to the dilution in the feed. The results suggest a possible role of low level administration of antibiotics to broilers in selecting multi-resistant bacteria in vivo.Para verificar a resistência a baixos níveis de antibióticos foram obtidos e identificados 197 isolados de bactérias Gram negativas pertencentes a 10 gêneros. Os isolados foram coletados em abatedouro industrial, imediatamente após a evisceração e antes do serviço de inspeção. Salmonella e Escherichia foram os gêneros identificados com maior freqüência. Os demais gêneros foram Aeromonas, Enterobacter, Serratia, Klebsiella, Citrobacter, Erwinia, Kluyvera, Pseudomonas e Aeromonas. Diferentes perfis de resistência a antibióticos foram detectados. A resistência a mais de dois antibióticos foi freqüente na maioria dos isolados e incluiu diversas classes de antibióticos. As bactérias dos gêneros Salmonella e Escherichia apresentaram maior percentagem de isolados resistentes

  7. Neonatal pneumonia etiology analysis and gram negative bacteria resistant gene research%新生儿肺炎病原学分析及革兰阴性菌耐药基因的研究

    Institute of Scientific and Technical Information of China (English)

    谭礼洪; 方座华; 徐俊

    2014-01-01

    Objective To observe and study the newborn pneumonia etiology analysis and gram negative bacteria resistant genes, guide clinical rational use of antibiotics treatment. Methods Choose from June 2011 to December 2011, for clinical diagnosis of patients with infectious pneumonia of newborn, sterile to ordinary the phlegm cultivation and high permeability, system identification of bacteria, with the French of France Egypt to K - B method to analyze drug susceptibility. Results 160 strains of gram-negative pathogenic bacteria mainly for: klebsiel a pneumoniae and e. coli, eosinophilic malt oligotrophic food, bacterium acinetobacter baumanni , pseudomonas aeruginosa, sewer intestine bacil us, etc. Drug susceptibility results showed that in beta lactam antimicrobial drugs (except with enzyme inhibitors) common resistance, of quinolone and aminoglycoside sensitive. Conclusions Neonatal infectious pneumonia gram negative bacil i isolated from the drug resistance in severe cases, clinical should be more choose antimicrobial agents according to antimicrobial susceptibility test results, avoid type induced resistant bacteria to produce.%目的:观察和研究新生儿肺炎病原学分析及革兰阴性菌耐药基因,指导临床合理选用抗生素治疗。方法:选择2011年6月~2013年12月对临床诊断为感染性肺炎的新生儿患者,无菌取痰进行普通培养和高渗培养,用法国生物梅里埃系统鉴定细菌,以 K-B法进行药敏分析。结果:160株革兰阴性病原菌主要分布为:肺炎克雷伯菌、大肠埃希菌、嗜麦芽寡养食单胞菌、鲍曼不动杆菌、铜绿假单胞菌、阴沟肠杆菌等。药敏结果显示:对β-内酰胺类抗菌药物(加酶抑制剂除外)普遍耐药,对喹诺酮类和氨基糖苷类较敏感。结论:新生儿感染性肺炎分离出的革兰阴性杆菌耐药情况严重,临床应根据药敏试验结果合理选用抗菌药物,避免诱导型耐药菌的产生。

  8. Reversible antibiotic tolerance induced in Staphylococcus aureus by concurrent drug exposure

    DEFF Research Database (Denmark)

    Haaber, Jakob Krause; Friberg, Cathrine; McCreary, Mark

    2015-01-01

    UNLABELLED: Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second...

  9. Temporal trends in invasive pneumococcal disease and pneumococcal serotypes over 7 decades

    DEFF Research Database (Denmark)

    Harboe, Zitta B; Benfield, Thomas; Valentiner-Branth, Palle

    2010-01-01

    by serotype 19A increased before introduction of PCV. Between 1993 and 2007, the level of resistance to macrolides and beta-lactams was 6%. CONCLUSIONS: The epidemiology of IPD and single serotypes has constantly changed over the past 7 decades. PCV serotypes appeared to dominate the pneumococcal population....

  10. Quantitative analysis of the IgG and IgG subclass immune responses to chromosomal Pseudomonas aeruginosa beta-lactamase in serum from patients with cystic fibrosis by western blotting and laser scanning densitometry

    DEFF Research Database (Denmark)

    Petersen, T D; Ciofu, O; Pressler, T

    1996-01-01

    BACKGROUND: Antibodies against chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) are markers of the development of resistance of P aeruginosa to beta-lactam antibiotics in patients with cystic fibrosis and chronic lung infection. The role of these antibodies in patients with chronic...

  11. One-year incidence of prosthetic joint infection in total hip arthroplasty

    DEFF Research Database (Denmark)

    Gundtoft, P H; Pedersen, Alma Becic; Schønheyder, Henrik Carl

    2016-01-01

    . The most common micro-organisms identified in the 271 PJI were Staphylococcus aureus (36%) and coagulase-negative staphylococci (CoNS) (33%); others commonly identified included Enterobacteriaceae, enterococci, and streptococci. Antimicrobial resistance to beta-lactams and gentamicin did not change during...

  12. Xenobiotic remediation in niche domination of soil-borne mycotoxigenic fungi: The deletion analysis of fungal lactamases in Fusarium verticillioides

    Science.gov (United States)

    Beta-lactamase enzymes are well studied because of their huge impact on medicine. Their prominent role is in resistance to beta-lactam (four membered lactam ring) antibiotics including the first and most famous fungus derived medically important antibiotic, penicillin. These antibiotics primarily fu...

  13. It’s War Out There: Fighting for life with xenobiotic degrading enzymes

    Science.gov (United States)

    It’s War Out There: Fighting for life with xenobiotic degrading enzymes Beta-lactamase enzymes are well studied because of their tremendous impact on medicine. Their prominent role is in resistance to beta-lactam (four membered lactam ring) antibiotics including the first and most famous fungally d...

  14. Reversible antibiotic tolerance induced in Staphylococcus aureus by concurrent drug exposure

    DEFF Research Database (Denmark)

    Haaber, Jakob Krause; Friberg, Cathrine; McCreary, Mark;

    2015-01-01

    UNLABELLED: Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second...... antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram......-negative pathogens. We show that colistin-induced vancomycin tolerance persists only as long as the inducer is present and is accompanied by gene expression changes similar to those resulting from mutations that produce stably inherited reduction of vancomycin sensitivity (vancomycin-intermediate S. aureus [VISA...

  15. Characterization of the beta-lactam binding site of penicillin acylase of Escherichia coli by structural and site-directed mutagenesis studies

    NARCIS (Netherlands)

    Alkema, WBL; Hensgens, CMH; Kroezinga, EH; de Vries, E; Floris, R; van der Laan, JM; Dijkstra, BW; Janssen, DB

    2000-01-01

    The binding of penicillin to penicillin acylase was studied by X-ray crystallography, The structure of the enzyme-substrate complex was determined after soaking crystals of an inactive beta N241A penicillin acylase mutant with penicillin G, Binding of the substrate induces a conformational change, i

  16. Factors Affecting Sulfate Resistance of Mortars.

    Science.gov (United States)

    1980-10-01

    31295 80 i 11 119 I Destroy this report when no longer needed. Do not return it to the originator . The findings in this report are not to be construed...la pouzzolane, y compris les cendres volantes produites par ]a combustion de charbons bitumineux, subbitumineux et lignitiques, le verre volcanique...pour cent de SiO2 ; elles sont un sous-produit de la production de metal au silicium. Les cendres volantes produites par les charbons subbitumineux et

  17. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    Urban design and architecture are increasingly used as material and affective strategies for setting the scene, for manipulation and the production of urban life: The orchestration of atmospheres, the framing and staging of urban actions, the programming for contemplation, involvement, play, expe...... affects can be choreographed and designed intentionally or whether it arises from unpredictable circumstances within urbanity itself....

  18. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    of environmental knowledge production. It uses InfoAmazonia, the databased platform on Amazon rainforests, as an example of affective geo-visualization within information mapping that enhances embodiment in the experience of the information. Amazonia is defined as a digitally created affective (map)space within...

  19. Univariate analysis of the factors affecting treatment compliance of 98 multidrug-resistant tuberculosis patients%98例耐多药结核病患者治疗管理依从性单因素分析

    Institute of Scientific and Technical Information of China (English)

    郝宝林; 刘占峰; 马丽萍

    2014-01-01

    Objective To explore influencing factors on compliance of multidrug-resistant tuberculosis(MDR-TB) treatment. Methods From January 2007 to December 2009, questionnaire survey on 98 cases of MDR-TB patients treated in one year, x2 was adopted to analyze the factors affecting compliance of MDR-TB treatment. Results Types of drug resistant, adverse reactions, inconvenient transportation, economic difficulties, awareness of TB Knowledge, were risk factors for compliance of MDR-TB patients treatment and management. Conclusion Many factors could affect the compliance of MDR-TB treatment and management, took appropriate countermeasures could improve treatment compliance and reduce treatment failure and mortality of MDR-TB.%目的:探讨耐多药结核病患者治疗管理依从性的影响因素。方法于2007-2009年对河南省12个市级结核病防治机构治疗满一年的98例耐多药肺结核病患者治疗进行问卷调查,利用卡方对影响治疗依从性的可能因素进行单因素分析。结果观察1年的治疗,耐药种类、不良反应的发生、交通不便、经济困难、结核病防治知识的知晓情况对患者治疗管理依从性均有影响,其对比均有显著性差异。结论耐多药结核病患者依从性受多种因素的影响,积极采取相应对策,可以提高耐多药肺结核患者的治疗依从性,降低治疗失败率和病死率。

  20. Resistance-resistant antibiotics.

    Science.gov (United States)

    Oldfield, Eric; Feng, Xinxin

    2014-12-01

    New antibiotics are needed because drug resistance is increasing while the introduction of new antibiotics is decreasing. We discuss here six possible approaches to develop 'resistance-resistant' antibiotics. First, multitarget inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy owing to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, repurposing existing drugs can lead to combinations of multitarget therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and, in some cases, suggest that sensitivity to existing antibiotics may be restored in otherwise drug-resistant organisms.

  1. Resistance to change

    NARCIS (Netherlands)

    Dow, J.; Perotti, E.

    2009-01-01

    Established firms often fail to maintain leadership following disruptive market shifts. We argue that such firms are more prone to internal resistance. A radical adjustment of assets affects the distribution of employee rents, creating winners and losers. Losers resist large changes when strong cust

  2. Resistance to change

    NARCIS (Netherlands)

    Dow, J.; Perotti, E.

    2013-01-01

    Established firms often fail to maintain leadership following disrup tive market shifts. We argue that such firms are more prone to internal resistance. A radical adjustment of assets affects the distribution of employee rents, creating winners and losers. Losers resist large changes when strong cus

  3. Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Nielsen, Lene Nørby; Roggenbuck, Michael; Haaber, Jakob Krause

    2012-01-01

    , expression of all three genes were repressed by aminoglycosides and induced by fluoroquinolones and penicillins. In contrast, the beta-lactam sub-group cephalosporins enhanced expression of RNAIII and hla but diversely affected expression of spa. The compounds cefalotin, cefamandole, cefoxitin, ceftazidime...

  4. Pattern of antimicrobial usage in livestock animals in south-western Nigeria: The need for alternative plans

    Directory of Open Access Journals (Sweden)

    Hezekiah K. Adesokan

    2015-02-01

    Full Text Available Resistance to antibiotics has continued to increase, placing future animal and human disease management in real danger. The developing countries characterised by widespread indiscriminate antibiotic use and in which ‘third-generation’ antibiotics are not readily available or affordable are the worst affected. A 3-year (2010–2012 retrospective survey of antibiotic usage in livestock production in three selected states of south-western Nigeria was conducted. Data obtained from eight purposively selected licensed veterinary pharmaceutical sales establishments in the area, based on keeping detailed sales records for the study period, were analysed using Stata Version 12. Results showed that tetracyclines (33.6%, fluoroquinolones (26.5% and beta-lactams/aminoglycosides (20.4% constituted the majority of the antibiotics used over the 3 years. The differences in the quantities of antibiotic types used within each antimicrobial class were statistically significant for tetracyclines (F = 59.87; p < 0.0001 and fluoroquinolones (F = 43.97; p < 0.0001 but not for beta-lactams/aminoglycosides (F = 3.21; p = 0.148. Furthermore, antibiotic consumption increased by 40.4% between 2010 and 2012. Although statistically insignificant (F = 0.277; p = 0.762, the increasing trend across the years was at rates of 23.5% between 2010 and 2011 and 13.8% between 2011 and 2012. In addition, the findings show a significantly higher consumption rate (t = 15.21; df = 5; p < 0.0001 during the rainy (52.5% than the dry (47.5% seasons. The current increasing trend in antibiotic usage holds a serious danger for the future and therefore calls for alternative plans to safeguard future livestock production, food security and human health. This becomes more imperative considering emerging resistance against tetracyclines and fluoroquinolones, the foremost remedies for livestock diseases in most developing countries.

  5. Affect Regulation

    DEFF Research Database (Denmark)

    Pedersen, Signe Holm; Poulsen, Stig Bernt; Lunn, Susanne

    2014-01-01

    Gergely and colleagues’ state that their Social Biofeedback Theory of Parental Affect Mirroring” can be seen as a kind of operationalization of the classical psychoanalytic concepts of holding, containing and mirroring. This article examines to what extent the social biofeedback theory of parenta...

  6. Anthelmintic resistance.

    Science.gov (United States)

    Waller, P J

    1997-11-01

    simple commercial fact that by far the greatest anthelmintic sales are associated with the cattle industry. However, this market is specific and sectoral, with by far the greatest sales in North America and Western Europe, where the prevalence of resistance is likely to be low and remain so, more-or-less indefinitely. So the chances of the above scenario occurring must be considered low. Remarkable developments have recently occurred in non-chemotherapeutic parasite control options, for example worm vaccines, host selection and biological control. Also, there seems to be greater acceptance of various grazing management practices designed to reduce the frequency of anthelmintic treatment. However, they collectively cannot be expected to offer immediate salvation to farmers now faced with chemotherapeutic failure to control nematode parasites in their flocks. The future for these farmers must be considered bleak, because compounded with these problems are the poor commodity prices for sheep and goat meat and fibre, resulting in relentless reductions in funding for research to support these industries. Perhaps the major social issues associated with re-structuring and possibly abandonment of sheep and goat farming in affected areas may precipitate action? As veterinary parasitologists, who in general have an interest and expertise in parasite control, we must promote the importance of the problem of anthelmintic resistance and ways to tackle it.

  7. DETERMINATION OF THE SPECTRUM OF ANTIBIOTIC RESISTANCE GENES HAVE PHENOTYPIC RESISTANT STRAINS OF PARIETAL INTESTINAL MICROBIOTA IN RATS BY RT-PCR

    Directory of Open Access Journals (Sweden)

    Bukina Y.V.

    2016-06-01

    Full Text Available Introduction. The problem of formation of bacterial resistance to glycopeptides and beta-lactam antibiotics (cephalosporins and carbapenems are used worldwide for the treatment of severe community acquired and nosocomial infections, especially caused by polymicrobial flora has become global and is a major factor limiting the effectiveness of antibiotic therapy. In this regard, the study of genetic microbial resistance determinants allows not only to carry out an effective antibiotic therapy, but also to identify two main processes leading to the development of epidemiologically significant events: the introduction of the agent in the risk population from the outside and in situ pathogen (spontaneous genetic drift targeted restructuring of the population. Therefore, the aim of our study was to investigate the resistance genes to carbapenems, cephalosporins, glycopeptides have clinically important phenotype of resistant strains of microorganisms families Enterobacteriaceae, Pseudomonadaceae, Bacteroidaceae, Enterococcaceae, Peptostreptococcaceae. Materials and methods. As a material for PCR studies 712 phenotypically resistant strains of microorganisms isolated from 80 rats "Wistar" line in microbiological study microflora of the wall were used. During the investigation 474 isolates of bacteria of the family Enterobacteriaceae, 39 - Pseudomonadaceae, 71 - Bacteroidaceae, 96 - Enterococcaceae, 32 - Peptostreptococcaceae were studied. Isolation of DNA from bacteria in the study was performed using reagents "DNA-Express" ("Litekh", Russia. For the detection of resistance genes by PCR in real time (RT-PCR reagent kits "FLUOROPOL-RV" ("Litekh", Russia were used. During the experiment, the VIM genes, OXA-48, NDM, KPC, responsible for the resistance of microorganisms to carbapenems, CTX-M - resistance to cephalosporins, as well as genes Van A and van B, the development of resistance to glycopeptides (vancomycin and teicoplanin were determined. Analysis

  8. Affective Networks

    Directory of Open Access Journals (Sweden)

    Jodi Dean

    2010-02-01

    Full Text Available This article sets out the idea of affective networks as a constitutive feature of communicative capitalism. It explores the circulation of intensities in contemporary information and communication networks, arguing that this circulation should be theorized in terms of the psychoanalytic notion of the drive. The article includes critical engagements with theorists such as Guy Debord, Jacques