title: Steady-state pharmacokinetics and pharmacodynamics of piperacillin/tazobactam administered by prolonged infusion in hospitalised patients.
abstract: The objective of this study was to evaluate the steady-state pharmacokinetics and pharmacodynamics of piperacillin/tazobactam, administered by prolonged infusion, in hospitalised patients requiring antimicrobial therapy. Thirteen patients received 4.5 g every 8 h (q8h), infused over 4 h, and pharmacokinetic parameters were determined by non-compartmental methods. Monte Carlo simulations (10,000 patients) were performed to calculate the cumulative fraction of response (CFR) for seven gram-negative pathogens using minimum inhibitory concentration (MIC) data from the Meropenem Yearly Susceptibility Test Information Collection (2004-2007, USA) as well as the probability of target attainment (PTA) at MICs ranging from 1 microg/mL to 64 microg/mL. The pharmacodynamic target was free piperacillin concentration remaining above the MIC for 50% of the dosing interval. Mean+/-standard deviation maximum and minimum serum concentrations, half-life, volume of distribution at steady-state and systemic clearance of piperacillin were 108.2+/-31.7 microg/mL, 27.6+/-26.3 microg/mL, 2.1+/-1.2 h, 22.1+/-4.0 L and 8.6+/-3.0 L/h, respectively. The CFR was > 90% for Escherichia coli, Serratia marcescens and Citrobacter spp., 88.6% for Enterobacter spp., 87% for Klebsiella pneumoniae, 85.5% for Pseudomonas aeruginosa and 52.8% for Acinetobacter spp. The PTA was 100%, 81.1% and 12.3% at MICs of < or = 16 microg/mL, 32 microg/mL and 64 microg/mL, respectively. Piperacillin/tazobactam 4.5 g q8h infused over 4 h provides excellent target attainment for bacterial pathogens with MICs < or = 16 microg/mL. However, the CFR was < 90% for four of the seven gram-negative pathogens evaluated.
authors.affiliation: Clarian Health Partners, Inc., Methodist Hospital, Department of Pharmacy, Indianapolis, IN, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Shea
authors.forename: S Christian
authors.initials: SC
authors.lastname: Cheatham
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Wack
authors.forename: David W
authors.initials: DW
authors.lastname: Smith
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Sowinski
authors.forename: Michael B
authors.initials: MB
authors.lastname: Kays
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D007297:Inpatients; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D044967:Serum / Q000737:chemistry; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin