title: Evaluation of vancomycin in combination with piperacillin-tazobactam or oxacillin against clinical methicillin-resistant Staphylococcus aureus Isolates and vancomycin-intermediate S. aureus isolates in vitro.
abstract: Vancomycin with piperacillin-tazobactam is used as empirical therapy for critically ill patients. Studies of this combination against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S. aureus (VISA) are limited, but β-lactams in combination with vancomycin have shown synergistic activity against MRSA and VISA. The goal of this study was to evaluate whether piperacillin-tazobactam and vancomycin were synergistic against MRSA and VISA in vitro. Bloodstream MRSA (n = 20) and VISA (n = 4) strains were selected. In vitro antimicrobial activities of piperacillin-tazobactam and oxacillin were evaluated by disk diffusion, and MICs were determined by Etest using Muller-Hinton agar with and without vancomycin at one-half the MIC. Time-kill studies evaluated 14 MRSA and all 4 VISA isolates using piperacillin-tazobactam at 300/35 mg/liter or oxacillin at 40 mg/liter alone and with vancomycin at one-half the MIC. Mean zones of inhibition for piperacillin-tazobactam and oxacillin increased with vancomycin against MRSA and VISA (P < 0.001 for all), and the MIC90 decreased with vancomycin against MRSA and VISA to values meeting susceptibility criteria for S. aureus (P < 0.001 for both antibiotics against MRSA). In MRSA time-kill studies, the mean 24-h reductions in inoculum for piperacillin-tazobactam, piperacillin-tazobactam with vancomycin, and oxacillin with vancomycin were 3.53, 3.69, and 2.62 log10 CFU/ml, respectively. The mean 24-h reductions in VISA inoculum for piperacillin-tazobactam, piperacillin-tazobactam with vancomycin, and oxacillin with vancomycin were 2.85, 2.93, and 3.45 log10 CFU/ml, respectively. Vancomycin with piperacillin-tazobactam or oxacillin demonstrated synergistic activity against MRSA and VISA. The clinical implications of these combinations against MRSA and VISA should be investigated.
authors.affiliation: College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Dilworth
authors.forename: Jora
authors.initials: J
authors.lastname: Sliwinski
authors.forename: Keenan
authors.initials: K
authors.lastname: Ryan
authors.forename: Monique
authors.initials: M
authors.lastname: Dodd
authors.forename: Renée-Claude
authors.initials: RC
authors.lastname: Mercier
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D010068:Oxacillin / Q000494:pharmacology*; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D000077725:Piperacillin, Tazobactam Drug Combination; D014640:Vancomycin; D010397:Penicillanic Acid; D010068:Oxacillin; D010878:Piperacillin