The Experts below are selected from a list of 192 Experts worldwide ranked by ideXlab platform
Philippe Moreillon - One of the best experts on this subject based on the ideXlab platform.
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bal9141 a novel extended spectrum cephalosporin active against methicillin resistant staphylococcus aureus in treatment of experimental endocarditis
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: José M. Entenza, M. P. Glauser, P Hohl, I Heinzekrauss, Philippe MoreillonAbstract:The therapeutic efficacy of BAL9141 (formerly Ro 63-9141), a novel cephalosporin with broad in vitro activity that also has activity against methicillin-resistant Staphylococcus aureus (MRSA), was investigated in rats with experimental endocarditis. The test organisms were homogeneously methicillin-resistant S. aureus strain COL transformed with the Penicillinase-encoding plasmid pI524 (COL Bla+) and homogeneously methicillin-resistant, Penicillinase-producing isolate P8-Hom, selected by serial exposure of parent strain P8 to methicillin. The MICs of BAL9141 for these organisms (2 mg/liter) were low, and BAL9141was bactericidal in time-kill curve studies after 24 h of exposure to either two, four, or eight times the MIC. Rats with experimental endocarditis were treated in a three-arm study with a continuous infusion of BAL5788 (formerly Ro 65-5788), a carbamate prodrug of BAL9141, or with amoxicillin-clavulanate or vancomycin. The rats were administered BAL9141 to obtain steady-state target levels of 20, 10, and 5 mg of per liter or were administered either 1.2 g of amoxicillin-clavulanate (ratio 5:1) every 6 h or 1 g of vancomycin every 12 h at changing flow rates to simulate the pharmacokinetics produced in humans by intermittent intravenous treatment. Treatment was started 12 h after bacterial challenge and lasted for 3 days. BAL9141 was successful in the treatment of experimental endocarditis due to either MRSA isolate COL Bla+ or MRSA isolate P8-Hom at the three targeted steady-state concentrations and sterilized >90% of cardiac vegetations (P < 0.005 versus controls; P < 0.05 versus amoxicillin-clavulanate and vancomycin treatment groups). These promising in vivo results with BAL9141 correlated with the high affinity of the drug for PBP 2a and its stability to Penicillinase hydrolysis observed in vitro.
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The Impact of Penicillinase on Cefamandole Treatment and Prophylaxis of Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus
The Journal of infectious diseases, 1998Co-Authors: Yok-ai Que, José M. Entenza, Patrick Francioli, Philippe MoreillonAbstract:Beta-lactams active against methicillin-resistant Staphylococcus aureus (MRSA) must resist Penicillinase hydrolysis and bind penicillin-binding protein 2A (PBP 2A). Cefamandole might share these properties. When tested against 2 isogenic pairs of MRSA that produced or did not produce Penicillinase, MICs of cefamandole (8-32 mg/L) were not affected by Penicillinase, and cefamandole had a > or =40 times greater PBP 2A affinity than did methicillin. In rats, constant serum levels of 100 mg/L cefamandole successfully treated experimental endocarditis due to Penicillinase-negative isolates but failed against Penicillinase-producing organisms. This suggested that Penicillinase produced in infected vegetations might hydrolyze the drug. Indeed, cefamandole was slowly degraded by Penicillinase in vitro. Moreover, its efficacy was restored by combination with sulbactam in vivo. Cefamandole also uniformly prevented MRSA endocarditis in prophylaxis experiments, a setting in which bacteria were not yet clustered in the vegetations. Thus, while cefamandole treatment was limited by Penicillinase, the drug was still successful for prophylaxis of experimental MRSA endocarditis.
Henry F Chambers - One of the best experts on this subject based on the ideXlab platform.
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community associated mrsa resistance and virulence converge
The New England Journal of Medicine, 2005Co-Authors: Henry F ChambersAbstract:Laypeople and health care professionals alike recognize Staphylococcus aureus as an important cause of disease and understand that antibiotic-resistant strains pose a threat to the community. Before the availability of antibiotics, invasive staphylococcal disease was often fatal, and the introduction of penicillin in the 1940s dramatically improved survival. Although Penicillinase-producing strains soon emerged, methicillin and other Penicillinase-stable β-lactam agents filled the breach. However, methicillin-resistant strains of S. aureus (MRSA), which are resistant to the entire class of β-lactam agents, were identified almost immediately and are now found in hospitals worldwide. Despite the growing prevalence of MRSA in hospitals, these strains . . .
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the changing epidemiology of staphylococcus aureus
Emerging Infectious Diseases, 2001Co-Authors: Henry F ChambersAbstract:Strains of methicillin-resistant Staphylococcus aureus (MRSA), which had been largely confined to hospitals and long-term care facilities, are emerging in the community. The changing epidemiology of MRSA bears striking similarity to the emergence of Penicillinase-mediated resistance in S. aureus decades ago. Even though the origin (hospital or the community) of the emerging MRSA strains is not known, the prevalence of these strains in the community seems likely to increase substantially.
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the changing epidemiology of staphylococcus aureus
Emerging Infectious Diseases, 2001Co-Authors: Henry F ChambersAbstract:Author(s): Chambers, Henry | Abstract: Strains of methicillin-resistant Staphylococcus aureus (MRSA), which had been largely confined to hospitals and long-term care facilities, are emerging in the community. The changing epidemiology of MRSA bears striking similarity to the emergence of Penicillinase-mediated resistance in S. aureus decades ago. Even though the origin (hospital or the community) of the emerging MRSA strains is not known, the prevalence of these strains in the community seems likely to increase substantially.
David M Whiley - One of the best experts on this subject based on the ideXlab platform.
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Penicillinase producing plasmid types in neisseria gonorrhoeae clinical isolates from australia
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: David M Whiley, Ella Trembizki, Cameron Buckley, Andrew J Lawrence, Kevin Freeman, Athena Limnios, Julie C Pearson, Helen V Smith, Kerrie Stevens, Monica M LahraAbstract:Penicillinase-producing Neisseria gonorrhoeae (PPNG) carrying the blaTEM-135 gene is of particular concern, as it is considered a stepping stone toward resistance to extended-spectrum cephalosporins. Here, we sought to characterize plasmid types and the occurrence of the blaTEM-135 gene for N. gonorrhoeae clinical isolates from Australia. We found that blaTEM-135 was prevalent in Australian PPNG and was detected on all three major plasmid types.
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characterization of a novel neisseria gonorrhoeae Penicillinase producing plasmid isolated in australia in 2012
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: Ella Trembizki, Cameron Buckley, Andrew J Lawrence, Monica M Lahra, David M WhileyAbstract:Neisseria gonorrhoeae plasmids harboring a Penicillinase gene are responsible for dissemination of high-level penicillin resistance among gonococci worldwide. Penicillinase-producing N. gonorrhoeae (PPNG) strains are believed to have originally acquired such plasmids via horizontal genetic transfer
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enhancing gonococcal antimicrobial resistance surveillance a real time pcr assay for detection of Penicillinase producing neisseria gonorrhoeae by use of noncultured clinical samples
Journal of Clinical Microbiology, 2011Co-Authors: David M Whiley, Namraj Goire, Kevin Freeman, John W Tapsall, Stephen B Lambert, Michael D Nissen, Theo P SlootsAbstract:With increasing concerns regarding diminishing treatment options for gonorrhea, maintaining the efficacy of currently used treatments and ensuring optimal Neisseria gonorrhoeae antimicrobial resistance surveillance are of the utmost importance. Penicillin is still used to treat gonorrhea in some parts of the world. In this study, we developed and validated a real-time PCR assay for the detection of Penicillinase-producing N. gonorrhoeae (PPNG) in noncultured clinical samples with the aim of enhancing penicillin resistance surveillance. The assay (PPNG-PCR2) was designed to be an indirect marker of Penicillinase activity, by targeting a region of sequence predicted to be conserved across all N. gonorrhoeae plasmid types harboring the beta-lactamase gene while not specifically targeting the actual beta-lactamase-encoding sequence. The assay was evaluated by using a total of 118 N. gonorrhoeae clinical isolates and 1,194 clinical specimens, including 239 N. gonorrhoeae-positive clinical samples from which N. gonorrhoeae cells were isolated and for which phenotypic Penicillinase results are available. Overall, the PPNG-PCR2 assay provided 100% sensitivity and 98.7% specificity compared to bacterial culture results for the detection of PPNG in clinical specimens. PPNG-PCR2 false-positive results, presumably due to cross-reactions with unrelated bacterial species, were observed for up to 1.3% of clinical samples but could be distinguished on the basis of high cycle threshold values. In tandem with phenotypic surveillance, the PPNG-PCR2 assay has the potential to provide enhanced epidemiological surveillance of N. gonorrhoeae penicillin resistance and is of particular relevance to regions where penicillin is still used to treat gonorrhea.
José M. Entenza - One of the best experts on this subject based on the ideXlab platform.
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bal9141 a novel extended spectrum cephalosporin active against methicillin resistant staphylococcus aureus in treatment of experimental endocarditis
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: José M. Entenza, M. P. Glauser, P Hohl, I Heinzekrauss, Philippe MoreillonAbstract:The therapeutic efficacy of BAL9141 (formerly Ro 63-9141), a novel cephalosporin with broad in vitro activity that also has activity against methicillin-resistant Staphylococcus aureus (MRSA), was investigated in rats with experimental endocarditis. The test organisms were homogeneously methicillin-resistant S. aureus strain COL transformed with the Penicillinase-encoding plasmid pI524 (COL Bla+) and homogeneously methicillin-resistant, Penicillinase-producing isolate P8-Hom, selected by serial exposure of parent strain P8 to methicillin. The MICs of BAL9141 for these organisms (2 mg/liter) were low, and BAL9141was bactericidal in time-kill curve studies after 24 h of exposure to either two, four, or eight times the MIC. Rats with experimental endocarditis were treated in a three-arm study with a continuous infusion of BAL5788 (formerly Ro 65-5788), a carbamate prodrug of BAL9141, or with amoxicillin-clavulanate or vancomycin. The rats were administered BAL9141 to obtain steady-state target levels of 20, 10, and 5 mg of per liter or were administered either 1.2 g of amoxicillin-clavulanate (ratio 5:1) every 6 h or 1 g of vancomycin every 12 h at changing flow rates to simulate the pharmacokinetics produced in humans by intermittent intravenous treatment. Treatment was started 12 h after bacterial challenge and lasted for 3 days. BAL9141 was successful in the treatment of experimental endocarditis due to either MRSA isolate COL Bla+ or MRSA isolate P8-Hom at the three targeted steady-state concentrations and sterilized >90% of cardiac vegetations (P < 0.005 versus controls; P < 0.05 versus amoxicillin-clavulanate and vancomycin treatment groups). These promising in vivo results with BAL9141 correlated with the high affinity of the drug for PBP 2a and its stability to Penicillinase hydrolysis observed in vitro.
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The Impact of Penicillinase on Cefamandole Treatment and Prophylaxis of Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus
The Journal of infectious diseases, 1998Co-Authors: Yok-ai Que, José M. Entenza, Patrick Francioli, Philippe MoreillonAbstract:Beta-lactams active against methicillin-resistant Staphylococcus aureus (MRSA) must resist Penicillinase hydrolysis and bind penicillin-binding protein 2A (PBP 2A). Cefamandole might share these properties. When tested against 2 isogenic pairs of MRSA that produced or did not produce Penicillinase, MICs of cefamandole (8-32 mg/L) were not affected by Penicillinase, and cefamandole had a > or =40 times greater PBP 2A affinity than did methicillin. In rats, constant serum levels of 100 mg/L cefamandole successfully treated experimental endocarditis due to Penicillinase-negative isolates but failed against Penicillinase-producing organisms. This suggested that Penicillinase produced in infected vegetations might hydrolyze the drug. Indeed, cefamandole was slowly degraded by Penicillinase in vitro. Moreover, its efficacy was restored by combination with sulbactam in vivo. Cefamandole also uniformly prevented MRSA endocarditis in prophylaxis experiments, a setting in which bacteria were not yet clustered in the vegetations. Thus, while cefamandole treatment was limited by Penicillinase, the drug was still successful for prophylaxis of experimental MRSA endocarditis.
Namraj Goire - One of the best experts on this subject based on the ideXlab platform.
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multitarget pcr assay for direct detection of Penicillinase producing neisseria gonorrhoeae for enhanced surveillance of gonococcal antimicrobial resistance
Journal of Clinical Microbiology, 2015Co-Authors: Cameron Buckley, Ella Trembizki, Namraj Goire, Kevin Freeman, Robert W Baird, Marcus Y Chen, Basil Donovan, Rebecca Guy, Monica M LahraAbstract:A multitarget PCR was developed for the direct detection of Penicillinase-producing Neisseria gonorrhoeae (PPNG). The assay was validated by testing 342 PPNG isolates and 415 clinical samples. The method is suitable for routine detection of PPNG strains. Its multitarget approach reduces the potential for false-negative results caused by sequence variations.
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non culture neisseria gonorrhoeae molecular Penicillinase production surveillance demonstrates the long term success of empirical dual therapy and informs gonorrhoea management guidelines in a highly endemic setting
Journal of Antimicrobial Chemotherapy, 2014Co-Authors: David J Speers, Rachel E Fisk, Namraj Goire, Donna B MakAbstract:OBJECTIVES Unlike most of the world, penicillin resistance in Neisseria gonorrhoeae from remote regions of Western Australia (WA) with high gonorrhoea notification rates has not increased despite many years of empirical oral therapy. With the advent of non-culture molecular diagnosis of gonorrhoea and the consequent decline in culture-based susceptibility, it is imperative to ensure the ongoing reliability of combination oral azithromycin, amoxicillin and probenecid for uncomplicated gonorrhoea in this setting. PCR-based non-culture N. gonorrhoeae antimicrobial resistance surveillance for Penicillinase production was therefore employed. METHODS Genital and non-genital specimens that were PCR-positive for N. gonorrhoeae were assessed for Penicillinase production by detection of the N. gonorrhoeae TEM-1 plasmid using specific real-time PCR. RESULTS In remote regions of WA where gonorrhoea is highly endemic, <5% of N. gonorrhoeae isolates were Penicillinase-producing. This contrasts with rates of up to 20% observed in the more densely populated metropolitan and rural regions. CONCLUSIONS In the era of molecular diagnosis of gonorrhoea, non-culture-based antimicrobial resistance surveillance proved useful when developing evidence-based guidelines for the clinical management of locally acquired gonorrhoea in highly endemic regions in WA. The continued efficacy of combination oral amoxicillin, probenecid and azithromycin therapy despite many years of use in a setting highly endemic for gonorrhoea may explain the low rate of penicillin resistance in these remote regions and supports the concept of adding azithromycin to β-lactam antibiotics to help delay the emergence of multiresistant N. gonorrhoeae.
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enhancing gonococcal antimicrobial resistance surveillance a real time pcr assay for detection of Penicillinase producing neisseria gonorrhoeae by use of noncultured clinical samples
Journal of Clinical Microbiology, 2011Co-Authors: David M Whiley, Namraj Goire, Kevin Freeman, John W Tapsall, Stephen B Lambert, Michael D Nissen, Theo P SlootsAbstract:With increasing concerns regarding diminishing treatment options for gonorrhea, maintaining the efficacy of currently used treatments and ensuring optimal Neisseria gonorrhoeae antimicrobial resistance surveillance are of the utmost importance. Penicillin is still used to treat gonorrhea in some parts of the world. In this study, we developed and validated a real-time PCR assay for the detection of Penicillinase-producing N. gonorrhoeae (PPNG) in noncultured clinical samples with the aim of enhancing penicillin resistance surveillance. The assay (PPNG-PCR2) was designed to be an indirect marker of Penicillinase activity, by targeting a region of sequence predicted to be conserved across all N. gonorrhoeae plasmid types harboring the beta-lactamase gene while not specifically targeting the actual beta-lactamase-encoding sequence. The assay was evaluated by using a total of 118 N. gonorrhoeae clinical isolates and 1,194 clinical specimens, including 239 N. gonorrhoeae-positive clinical samples from which N. gonorrhoeae cells were isolated and for which phenotypic Penicillinase results are available. Overall, the PPNG-PCR2 assay provided 100% sensitivity and 98.7% specificity compared to bacterial culture results for the detection of PPNG in clinical specimens. PPNG-PCR2 false-positive results, presumably due to cross-reactions with unrelated bacterial species, were observed for up to 1.3% of clinical samples but could be distinguished on the basis of high cycle threshold values. In tandem with phenotypic surveillance, the PPNG-PCR2 assay has the potential to provide enhanced epidemiological surveillance of N. gonorrhoeae penicillin resistance and is of particular relevance to regions where penicillin is still used to treat gonorrhea.