title: In Vitro-In Vivo Discordance with Humanized Piperacillin-Tazobactam Exposures against Piperacillin-Tazobactam-Resistant/Pan-β-Lactam-Susceptible Escherichia coli.
abstract: Recent findings have identified Escherichia coli strains that are pan-β-lactam susceptible (PBL-S) but piperacillin-tazobactam resistant (TZP-R) in vitro We assessed the in vivo significance of this resistance profile in a neutropenic murine pneumonia model using humanized exposures of TZP with 18 clinical E. coli isolates, 8 TZP-S/PBL-S and 10 genotypically confirmed TZP-R/PBL-S. Despite phenotypically and genotypically defined resistance, TZP displayed efficacy against these isolates. Additional studies are required to define the clinical implications of these TZP-R/PBL-S strains.
authors: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
authors: M L
authors: ML
authors: Monogue
authors: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA david.nicolau@hhchealth.org.|Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA.
authors: D P
authors: DP
authors: Nicolau
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D003091:Colistin / Q000494:pharmacology; D003470:Culture Media / Q000494:pharmacology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D005260:Female; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009503:Neutropenia / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D010878:Piperacillin / Q000493:pharmacokinetics / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D014031:Tobramycin / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D003470:Culture Media; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D014031:Tobramycin; D010878:Piperacillin; D003091:Colistin