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Sample records for cefamandole

  1. Excretion of cephalothin and cefamandole by the normal pancreas and in acute pancreatitis in dogs.

    OpenAIRE

    Studley, J G; Schentag, J J; Schenk, W G

    1982-01-01

    Nine mongrel dogs were studied to evaluate the excretion of cefamandole (five dogs) and cephalothin (four dogs) in the pancreatic fluid. Each dog was studied before and after the induction of pancreatitis, with 2 weeks between studies. After intravenous administration of a 25-mg/kg dose of either cephalosporin, serum and pancreatic fluid concentrations were monitored for 6 h. Both cephalothin and cefamandole were excreted in bactericidal concentrations in the normal pancreas and in acute panc...

  2. DFT and TD-DFT theoretical studies on photo-induced electron transfer process on [Cefamandole].C60 nano-complex.

    Science.gov (United States)

    Taherpour, Avat Arman; Jamshidi, Morteza; Rezaei, Omid

    2017-08-01

    The C 60 fullerene displays a considerable electronegativity. It has a unique photophysical and electrochemical behavior that can be used as a suitable drug carrier. In the present study, the interaction of C 60 fullerene as an electron recipient with the Cefamandole antibiotic was investigated in both ground and excited states using DFT and TD-DFT methods. The study of the interaction of C 60 and Cefamandole via electron localization function (ELF) and reduced density gradient (RDG) revealed that the complex formation is of van der Waals type. The data from natural bonding orbitals (NBO) analysis also confirmed the interaction type. The study of absorption and emission spectrum via CAM-B3LYP in the TD-SCF state showed that the emission peak of C 60 fullerene in the 591.73nm after the complex formation results in the extinction of this emission spectrum due to charge transfer (CT) from chelator to fluorophore. The photoinduced electron transfer (PET) process was investigated using the electron hole theory. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Structures of the Michaelis Complex (1.2A) and the Covalent Acyl Intermediate (2.0A ) of Cefamandole Bound in the Active Sites of the Mycobacterium tuberculosis beta-Lactamase K72A and E166A Mutants

    Energy Technology Data Exchange (ETDEWEB)

    L Tremblay; h Xu; J Blanchard

    2011-12-31

    The genome of Mycobacterium tuberculosis (TB) contains a gene that encodes a highly active {beta}-lactamase, BlaC, that imparts TB with resistance to {beta}-lactam chemotherapy. The structure of covalent BlaC-{beta}-lactam complexes suggests that active site residues K73 and E166 are essential for acylation and deacylation, respectively. We have prepared the K73A and E166A mutant forms of BlaC and have determined the structures of the Michaelis complex of cefamandole and the covalently bound acyl intermediate of cefamandole at resolutions of 1.2 and 2.0 {angstrom}, respectively. These structures provide insight into the details of the catalytic mechanism.

  4. beta-Lactamases and beta-lactam resistance in Escherichia coli.

    OpenAIRE

    Jacoby, G A; Sutton, L

    1985-01-01

    Escherichia coli strains determining 17 different plasmid-determined beta-lactamases were tested for resistance to new broad-spectrum beta-lactam antibiotics. Several beta-lactamases demonstrated enhanced resistance to cefamandole but only low-level resistance to other agents. High production of cloned E. coli chromosomal beta-lactamase, however, provided resistance to cefamandole, cefoxitin, cefotaxime, ceftazidime, and aztreonam but not to BMY-28142 or imipenem.

  5. Cephalosporin susceptibility of methicillin-resistant, coagulase-negative staphylococci.

    Science.gov (United States)

    Menzies, R E; Cornere, B M; MacCulloch, D

    1987-01-01

    Coagulase-negative staphylococci were tested for susceptibility to methicillin, cephradine, ceftriaxone, cephalothin, and cefamandole by standard broth microdilution. Most of the 26 methicillin-resistant isolates were susceptible to cephalothin and cefamandole, but very few were susceptible to ceftriaxone, and none was susceptible to cephradine. The proportion of bacterial cells that grew in the presence of 128 micrograms of methicillin per ml was calculated for each methicillin-resistant isolate. Those with every cell or 1 in 10 cells resistant to 128 micrograms of methicillin per ml included the isolates that were most resistant to the cephalosporins and highly resistant to methicillin. Those with 1 cell resistant in 10(5) or 10(6) cells were the isolates most susceptible to the cephalosporins, and their methicillin MICs were lower. When cells resistant to 128 micrograms of methicillin per ml were used as inocula for broth microdilution tests, resistance to cephradine remained the same, but resistance to ceftriaxone, cephalothin, and cefamandole increased significantly. Cefamandole was the only cephalosporin which retained antibacterial activity against some methicillin-resistant isolates (12 of 26). Cephradine, ceftriaxone, cephalothin, and cefamandole resistance appeared to be expressed by the same cells that expressed methicillin resistance. In this way, cross resistance was demonstrated between methicillin and the cephalosporins. PMID:3646002

  6. Temperature Effect on the Susceptibility of Methicillin-Resistant Staphylococcus aureus to Four Different Cephalosporins

    OpenAIRE

    Canawati, Hanna N.; Witte, Joyce L.; Sapico, Francisco L.

    1982-01-01

    Forty isolates of methicillin-resistant Staphylococcus aureus were tested for in vitro susceptibility to cephalothin, cefamandole, cefotaxime, and moxalactam, using the disk diffusion and microbroth dilution methods at incubation temperatures of 30 and 35°C. Resistance to all four antibiotics was more clearly evident at an incubation temperature of 30°C.

  7. Activity of cephalosporins against methicillin-susceptible and methicillin-resistant, coagulase-negative staphylococci: minimal effect of beta-lactamase.

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    John, J F; McNeill, W F

    1980-01-01

    Eight cephalosporins were tested for their activity against methicillin-susceptible and methicillin-resistant, coagulase-negative staphylococci and for their resistance to beta-lactamase from methicillin-resistant, coagulase-negative staphylococci. Susceptibility testing by the agar plate method was evaluated for the effect of inoculum size and duration of incubation. Methicillin-susceptible, coagulase-negative staphylococci were highly susceptible to the cephalosporins, with cephapirin and cepahlothin showing the greatest activity, followed by cefazolin and cefamandole. Methicillin-resistant, coagulase-negative staphylococci displayed nearly total cross-resistance to the cephalosporins. Resistance increased with increasing inoculum size. Beta-Lactamases produced by methicillin-resistant, coagulase-negative staphylococci had a minimal hydrolytic effect on cepahlothin, cephapirin, cefazolin, and cefamandole and no measurable effect on cefoxitin. There was no correlation between the anti-staphylococcal activity and resistance to beta-lactamases. PMID:6966906

  8. Influence of growth medium on the in vitro activities of second- and third-generation cephalosporins against Streptococcus faecalis.

    OpenAIRE

    Sahm, D F; Baker, C N; Jones, R N; Thornsberry, C

    1984-01-01

    The influence of culture medium of the MICs of eight cephalosporins for 45 strains of Streptococcus faecalis was investigated. The MICs of cephalothin, cefamandole, and cefoperazone were not substantially influenced by the type of culture medium used. In contrast, MICs of cefuroxime, ceftizoxime, cefotaxime, cefmenoxime, and ceftriaxone varied markedly with both the commercial brand and the blood content of the broth used. The use of Mueller-Hinton broths (from Oxoid Ltd., GIBCO Diagnostics, ...

  9. Medium-dependent zone size discrepancies associated with susceptibility testing of group D streptococci against various cephalosporins.

    OpenAIRE

    Sahm, D F; Baker, C N; Jones, R N; Thornsberry, C

    1983-01-01

    Mueller-Hinton (MH) agar media from various commercial sources, either supplemented or not supplemented with 5% sheep blood, were studied to determine their effect on disk diffusion susceptibility testing results obtained with 90 strains of group D streptococci and four cephalosporins. The cephalosporins investigated included cephalothin, cefamandole, moxalactam, and cefotaxime. Results showed that a number of Streptococcus faecalis and Streptococcus faecium strains were susceptible to cephal...

  10. Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy.

    Science.gov (United States)

    Stigter, M; Bezemer, J; de Groot, K; Layrolle, P

    2004-09-14

    Carbonated hydroxyapatite (CHA) coatings were applied onto titanium implants by using a biomimetic precipitation method. Different antibiotics were incorporated into the CHA coatings and their release and efficacy against bacteria growth were studied in vitro. The following antibiotics were used within this study: cephalothin, carbenicillin, amoxicillin, cefamandol, tobramycin, gentamicin and vancomycin. Increased concentrations of antibiotics in the coating solution led to a higher quantity of antibiotic incorporated into the CHA coating. Some antibiotics were better incorporated than others depending on their chemical structure. Antibiotics, containing carboxylic groups such as cephalothin, carbenicillin and cefamandol, were better incorporated than antibiotics lacking these groups. A bacterial inhibition test on Staphylococcus aureus bacteria showed inhibition of growth for all antibiotics that were released from the CHA coating. A release test was conducted in phosphate buffer saline PBS at pH 7.4 and 37 degrees C and showed that antibiotics containing carboxylic groups like cephalothin were slower released from the CHA coating than others. These results suggest that certain antibiotics are able to bind/chelate with calcium, resulting in a better incorporation into the CHA coating and a slower release. Antibiotics incorporated in CHA coatings on titanium implants might be used to prevent post-surgical infections and to promote bone-bonding of orthopedic devices.

  11. Determination of in vitro susceptibility of Mycobacterium tuberculosis to cephalosporins by radiometric and conventional methods

    International Nuclear Information System (INIS)

    Heifets, L.B.; Iseman, M.D.; Cook, J.L.; Lindholm-Levy, P.J.; Drupa, I.

    1985-01-01

    Among eight cephalosporins and cephamycins tested in preliminary in vitro screening against Mycobacterium tuberculosis, the most promising for further study was found to be ceforanide, followed by ceftizoxime, cephapirin, and cefotaxime. Moxalactam, cefoxitin, cefamandole, and cephalothin were found to be not active enough against M. tuberculosis to be considered for further in vitro studies. The antibacterial activity of various ceforanide concentrations was investigated by three methods: (i) the dynamics of radiometric readings (growth index) in 7H12 broth; (ii) the number of CFU in the same medium; and (iii) the proportion method on 7H11 agar plates. There was a good correlation among the results obtained with these methods. The MIC for most strains ranged from 6.0 to 25.0 micrograms/ml. The BACTEC radiometric method is a reliable, rapid, and convenient method for preliminary screening and determination of the level of antibacterial activity of drugs not commonly used against M. tuberculosis

  12. Semiparametric mixed-effects analysis of PK/PD models using differential equations.

    Science.gov (United States)

    Wang, Yi; Eskridge, Kent M; Zhang, Shunpu

    2008-08-01

    Motivated by the use of semiparametric nonlinear mixed-effects modeling on longitudinal data, we develop a new semiparametric modeling approach to address potential structural model misspecification for population pharmacokinetic/pharmacodynamic (PK/PD) analysis. Specifically, we use a set of ordinary differential equations (ODEs) with form dx/dt = A(t)x + B(t) where B(t) is a nonparametric function that is estimated using penalized splines. The inclusion of a nonparametric function in the ODEs makes identification of structural model misspecification feasible by quantifying the model uncertainty and provides flexibility for accommodating possible structural model deficiencies. The resulting model will be implemented in a nonlinear mixed-effects modeling setup for population analysis. We illustrate the method with an application to cefamandole data and evaluate its performance through simulations.

  13. Determination of in vitro susceptibility of Mycobacterium tuberculosis to cephalosporins by radiometric and conventional methods

    Energy Technology Data Exchange (ETDEWEB)

    Heifets, L.B.; Iseman, M.D.; Cook, J.L.; Lindholm-Levy, P.J.; Drupa, I.

    1985-01-01

    Among eight cephalosporins and cephamycins tested in preliminary in vitro screening against Mycobacterium tuberculosis, the most promising for further study was found to be ceforanide, followed by ceftizoxime, cephapirin, and cefotaxime. Moxalactam, cefoxitin, cefamandole, and cephalothin were found to be not active enough against M. tuberculosis to be considered for further in vitro studies. The antibacterial activity of various ceforanide concentrations was investigated by three methods: (i) the dynamics of radiometric readings (growth index) in 7H12 broth; (ii) the number of CFU in the same medium; and (iii) the proportion method on 7H11 agar plates. There was a good correlation among the results obtained with these methods. The MIC for most strains ranged from 6.0 to 25.0 micrograms/ml. The BACTEC radiometric method is a reliable, rapid, and convenient method for preliminary screening and determination of the level of antibacterial activity of drugs not commonly used against M. tuberculosis.

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

    Science.gov (United States)

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

    1987-07-01

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

  15. Resistenza ai fluorochinoloni in Escherichia coli isolati da infezioni delle vie urinarie (IVU in pazienti ospedalizzati in unità di terapia intensiva (UTI.

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    Paola Pistarà

    2007-06-01

    Full Text Available Background: Fluoroquinolones are an important class of antibiotics for the treatment of urinary tract infections that have axcellent activity against Escherichia coli, one of the most frequently encountered pathogens. Several European studies have reported an increase of resistance to quinolones among uropathogenic E. coli. We conducted this study to update our knowledge on this evolution. Materials and methods: We evaluated the resistance phenotype of 203 clinical strains of E. coli collected from urine specimens. The following antimicrobial agents were tested: ampicillin, amoxiciclin-clavulanate, piperacillintazobactam, cefamandole, cefotaxime, ceftazidime, cefepime, aztreonam, imipenem, trimethoprimsulfamethoxazole, gentamicin, amikacin, ciprofloxacin, pipemidic acid, norfloxacin, nitrofurantoin. Disk diffusion tests were carried out as suggested by the CLSI (2006; strains were assigned to the susceptibility categories (susceptible, intermediate and resistant interpreting results according to the established breakpoints. Results: Resistance to quinolones (pipemidic acid, norfloxacin and ciprofloxacin was about of 45% and resistance to ampicillin, trimethoprim-sulfamethoxazole was 57. 1% and 55. 2%, respectively. Resistance rates less than 5% was found for cefepime, amikacin and imipenem. Conclusions: This study confirms the evolution through resistance to quinolones of uropathogenic E. coli isolates. The selective pressure exerted by fluoroquinolones may influence this evolution. Therapeutic alternatives, surveillance, and restriction of fluoroquinolones use are needed to control this spread of resistance.

  16. Influence of growth medium on the in vitro activities of second- and third-generation cephalosporins against Streptococcus faecalis.

    Science.gov (United States)

    Sahm, D F; Baker, C N; Jones, R N; Thornsberry, C

    1984-09-01

    The influence of culture medium of the MICs of eight cephalosporins for 45 strains of Streptococcus faecalis was investigated. The MICs of cephalothin, cefamandole, and cefoperazone were not substantially influenced by the type of culture medium used. In contrast, MICs of cefuroxime, ceftizoxime, cefotaxime, cefmenoxime, and ceftriaxone varied markedly with both the commercial brand and the blood content of the broth used. The use of Mueller-Hinton broths (from Oxoid Ltd., GIBCO Diagnostics, and Difco Laboratories) supplemented with 5% lysed sheep blood frequently resulted in MICs that were greater than or equal to 16 times lower than the MICs obtained with these same broths without blood. Similar, but less marked, patterns were observed when supplemented and unsupplemented brain heart infusion and Sceptor broths were used. The influence of the broth on MICs suggests a complex interaction between some cephalosporins, medium components, and organisms. The cephalosporins that were affected by media share an identical moiety at the 7-acyl position (cefuroxime is slightly different), but this structure is not shared by those cephalosporins that were not affected. This commonality in structure at the 7-acyl position may be partially responsible for the observed results.

  17. Validation of the cephalosporin intradermal skin test for predicting immediate hypersensitivity: a prospective study with drug challenge.

    Science.gov (United States)

    Yoon, S-Y; Park, S Y; Kim, S; Lee, T; Lee, Y S; Kwon, H-S; Cho, Y S; Moon, H-B; Kim, T-B

    2013-07-01

    Cephalosporin is a major offending agent in terms of drug hypersensitivity along with penicillin. Cephalosporin intradermal skin tests (IDTs) have been widely used; however, their validity for predicting immediate hypersensitivity has not been studied. This study aimed to determine the predictive value of cephalosporin intradermal skin testing before administration of the drug. We prospectively conducted IDTs with four cephalosporins, one each of selected first-, second-, third-, or fourth-generation cephalosporins: ceftezol; cefotetan or cefamandole; ceftriaxone or cefotaxime; and flomoxef, respectively, as well as with penicillin G. After the skin test, whatever the result, one of the tested cephalosporins was administered intravenously and the patient was carefully observed. We recruited 1421 patients who required preoperative cephalosporins. Seventy-four patients (74/1421, 5.2%) were positive to at least one cephalosporin. However, none of responders had immediate hypersensitivity reactions after a challenge dose of the same or different cephalosporin, which were positive in the skin test. Four patients who suffered generalized urticaria and itching after challenge gave negative skin tests for the corresponding drug. The IDT for cephalosporin had a sensitivity of 0%, a specificity of 97.5%, a negative predictive value of 99.7%, and a positive predictive value (PPV) of 0%, when challenged with the same drugs that were positive in the skin test. Routine skin testing with a cephalosporin before its administration is not useful for predicting immediate hypersensitivity because of the extremely low sensitivity and PPV of the skin test (CRIS registration no. KCT0000455). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. [Bacterial colangitis: therapeutic features

    Science.gov (United States)

    Russo, M.; Carmellino, S.; Russo, G.

    1999-01-01

    Cholangitis results from the combination of bactibilia and biliary tract obstruction. In recent years considerable progress has been made in the diagnosis and treatment of cholangitis; advances in endoscopic techniques and antibiotic therapy have ameliorated the prognosis of cholangitis. The choice of an antimicrobial regimen for cholangitis should take into account the antibiotic sensitivities of bacteria colonizing biliary tree, the antibiotic excretion into bile and whether biliary obstruction or bacteremia is present. Successful treatment depends on relieving biliary obstruction and administering antibiotics effective against bacteria implicated. The initial therapy should be active against E. coli and Klebsiella spp., while it is controversial whether the empirical antibiotic regimen should also include coverage against Enterococcus, Pseudomonas and anaerobes. The ureidopenicillins are the preferred initial treatment; the combination piperacillin-tazobactam may be active against the resistant species. Second generation cephalosporins like cefamandole and cefoxitin are still useful, cefoperazone gives excellent coverage against gram-negative bacteria, while cefepime may be suitable as treatment for acute cholangitis. In severe cholangitis an aminoglycoside can be added to the beta-lactamin; once-daily aminoglycoside administration is associated with a reduced incidence of nephrotoxicity also in patients with cholestasis. Whether the fluoroquinolones are effective in treatment for cholangitis has not been fully evaluated. In patients with suppurative cholangitis prompt endoscopic drainage is mandatory, since antibiotics alone will not sterilize the biliary tract in the face of obstruction. Antibiotic prophylaxis to prevent cholangitis after ERCP should be administered particularly to patients in whom biliary drainage is expected to be difficult; antimicrobial prophylaxis with piperacillin effectively prevents ERCPinduced cholangitis. Antibiotic maintenance

  19. Incidenza della meticillino-resistenza in Staphylococcus aureus e stafilococchi coagulasi-negativi isolati da emocolture

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    Alessandra Siddi

    2007-12-01

    Full Text Available Background: Staphylococci are major cause of nosocomial blood stream infections.This local surveillance study was carry out to monitor frequency of occurrence of Staphylococcus aureus and coagulase-negative staphylococci (CoNS in blood stream infections and the incidence of methicillin-resistant (MET-R strains. Materials and methods: During the period January – December 2006, 9840 blood specimens were analyzed and microrganisms from positive samples were collected. Bacterial identifications were performed according to the standard methods (Murray, 2003.We evaluated, in particular, the antibiotic-resistance phenotype of staphylococci employing disk diffusion test as suggested by the CLSI (2006. The following antimicrobial agents were tested: oxacillin, penicillin, amoxiciclin-clavulanate, cefalotin, cefamandole, imipenem, teicoplanin, linezolid, ciprofloxacin, erythromycin, clindamicin, rifampicin, trimethoprim-sulfamethoxazole, gentamicin, doxiciclin, fosfomycin. Results: The microrganisms isolated were 551: 370 Gram-positives (67%, 131 Gram-negatives (24%, 11 anaerobes (2% and 39 mycetes (7%. In particular, 121 S. epidermidis, 75 S. aureus, 42 S. haemolyticus and other 39 CoNS were analyzed: methicillin-resistance occurred in more than 80% of S.aureus strains collected from Intensive Care Units (ICU and in about 50 % of those isolated from other divisions. In CoNS the incidence of MET-R ranged from 30 to 80 %, the higher values were registered among S. epidermidis and S. haemolyticus. MET-R strains were characterized by high resistance rates even to ciprofloxacin (from 47 to 100%, erythromycin (from 70 to 100%, and in same cases to gentamicin (from 23 to 86% also. Conclusions: Staphylococci are the prevalent cause of blood stream infections.The distinctive feature of MET-R strains is their resistance not only to all b-lactam antibiotics, but also to a wide range of other antimicrobial agents. However, the glycopeptide teicoplanin remains 100

  20. Occurrence and antibiotic resistance of mesophilic Aeromonas in three riverine freshwaters of Marrakech, Morocco.

    Science.gov (United States)

    Imziln, B

    2001-12-01

    In order to evaluate the impact of pollution and sewage on the occurrence and antibiotic resistance of mesophilic aeromonads in riverine freshwaters of Marrakech, samples were collected from three rivers (Oukaimeden, Ourika, and Tensift) upstream and downstream from the principal bordering villages. During a 2-year study, indicators of pollution increased dramatically in the downstream waters. Bacterial indicators (faecal coliforms and faecal streptococci) correlated with mesophilic aeromonads only in heavily polluted waters. In low and moderately polluted sources, densities of mesophilic aeromonads were independent of water quality indicators and did not correlate statistically with faecal indicators. Average counts of Aeromonas in low and heavily polluted waters were 2.5 x 10(3) and 2.1 x 10(6) colony forming units per 100 ml, respectively. The biochemical identification of 841 isolates indicated a predominance of A. caviae in heavily and moderately polluted water and sediment. A. hydrophila was dominant only in low polluted waters and when the temperature was below 12 degrees C. High densities of A. sobria were found in low, moderately polluted, or cleaned waters and when the water temperature was above 18 degrees C. All selected isolates (total = 841) were tested for antibiotic susceptibility against 21 antibiotics. Antibiotic resistance frequencies recorded were: ampicillin and amoxicillin, 100%; novobiocin, 96%; cefalotin, 81%; colistin, 72%; sulfamethoxazole, 40%; cefamandole, 37%; polymyxin B, 23%; trimethoprim, 17%; erythromycin, 15%; streptomycin, 8%; amoxicillin-clavulanate, 5%. Resistance to cefotaxime, kanamycin, gentamycin, chloramphenicol, tetracycline, oxytetracycline, nalidixic acid, rifampicin, or trimethoprim-sulfameth-oxazole was found to be <5%. Antibiotic resistance rates did vary according to the source of a strain"s isolation, and high numbers of antibiotic resistant strains were recorded in polluted samples. Since no correlation between

  1. Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus

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    Nielsen Lene N

    2012-08-01

    Full Text Available Abstract Background The aim of this study was to investigate the effect of various classes of clinically relevant antibiotics at sub-lethal concentrations on virulence gene expression and biofilm formation in Staphylococcus aureus. Findings LacZ promoter fusions of genes related to staphylococcal virulence were used to monitor the effects of antibiotics on gene expression in a disc diffusion assay. The selected genes were hla and spa encoding α-hemolysin and Protein A, respectively and RNAIII, the effector molecule of the agr quorum sensing system. The results were confirmed by quantitative real-time PCR. Additionally, we monitored the effect of subinhibitory concentrations of antibiotics on the ability of S. aureus to form biofilm in a microtiter plate assay. The results show that sub-lethal antibiotic concentrations diversely modulate expression of RNAIII, hla and spa. Consistently, expression of all three genes were repressed by aminoglycosides and induced by fluoroquinolones and penicillins. In contrast, the β-lactam sub-group cephalosporins enhanced expression of RNAIII and hla but diversely affected expression of spa. The compounds cefalotin, cefamandole, cefoxitin, ceftazidime and cefixine were found to up-regulate spa, while down-regulation was observed for cefuroxime, cefotaxime and cefepime. Interestingly, biofilm assays demonstrated that the spa-inducing cefalotin resulted in less biofilm formation compared to the spa-repressing cefotaxime. Conclusions We find that independently of the cephalosporin generation, cephalosporins oppositely regulate spa expression and biofilm formation. Repression of spa expression correlates with the presence of a distinct methyloxime group while induction correlates with an acidic substituted oxime group. As cephalosporines target the cell wall penicillin binding proteins we speculate that subtle differences in this interaction fine-tunes spa expression independently of agr.

  2. Efficacy of collagen silver-coated polyester and rifampin-soaked vascular grafts to resist infection from MRSA and Escherichia coli in a dog model.

    Science.gov (United States)

    Schneider, Fabrice; O'Connor, Stephen; Becquemin, Jean Pierre

    2008-11-01

    The primary objective of this study was to compare the efficacy of a collagen silver-coated polyester graft, InterGard, with a gelatin-sealed graft, Gelsoft, both soaked in rifampin, for resistance to direct bacterial contamination in an animal model. The second objective was to confirm the lack of inflammation from silver acetate. Vascular grafts, 6 mm in diameter, were implanted in the infrarenal aorta of 28 dogs. Intravenous cefamandole (20 mg/kg) was injected intraoperatively in all dogs. The dogs were divided into three groups. Group I included 12 dogs. Six dogs received silver grafts and six dogs received gelatin-sealed grafts, all soaked with rifampin. Grafts implanted in group I were directly infected with methicillin-resistant Staphylococcus aureus (MRSA). Group II included also six silver grafts and six gelatin-sealed grafts, all soaked with rifampin. Dogs of group II were directly infected with Escherichia coli. Group III comprised four dogs, which received gelatin unsealed grafts, directly infected with MRSA, the control group. All dogs were followed by regular clinical examination, including blood cultures. Grafts in groups I and III and in group II were harvested at 30 days and 10 days, respectively. Bacterial analyses were performed on the explanted grafts. Histology was performed on both the tissue samples and the anastomotic sites of the harvested grafts. In group I, no grafts were infected with MRSA, irrespective of graft type. In group II, no silver grafts were infected with E. coli, whereas one (16.6%) of six gelatin-sealed grafts was infected (p = 0.317). In group III, three (75%) of the four grafts were infected with MRSA. The infection rate in the silver grafts and the gelatin-sealed grafts soaked in rifampin in group I compared with the unsealed gelatin grafts in group III was statistically significantly different (p anastomoses in three (25%) gelsoft grafts of 12 in groups I and II. There were no clinical or biological signs of inflammation