title: Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients.
abstract: OBJECTIVE
  To evaluate the steady-state pharmacokinetic and pharmacodynamic parameters of piperacillin in morbidly obese, surgical intensive care patients.
  
  
  METHODS
  Open-label single-center prospective study.
  
  
  METHODS
  Level I trauma center and university-affiliated teaching institution.
  
  
  METHODS
  Nine morbidly obese (body mass index [BMI] 40.0 kg/m² or higher) hospitalized patients admitted to the trauma and surgical intensive care service who were treated with piperacillin-tazobactam between December 15, 2010, and April 18, 2012.
  
  
  METHODS
  Patients received intravenous piperacillin-tazobactam 4.5 g every 6 hours, administered as a 30-minute infusion.
  
  
  RESULTS
  Patients' blood samples were collected after the administration of the fourth, fifth, or sixth dose (i.e., at steady state). Serum piperacillin concentrations were determined by using a validated high-performance liquid chromatography assay; these concentrations were used to estimate pharmacokinetic parameters, and 5000-patient Monte Carlo simulations were performed. The probability of target attainment for 50% or higher of the dosing interval during which free (unbound) drug concentrations exceeded the minimum inhibitory concentration (%fT > MIC) of likely pathogens was calculated for piperacillin at various MICs. Patient demographic and clinical characteristics included a mean ± SD total body weight of 164 ± 50 kg, BMI of 57 ± 15.3 kg/m², and age 57 ± 11 years, and a median Acute Physiology and Chronic Health Evaluation II score of 22 (interquartile range 21-26). Compared with values previously reported in other populations, the volume of distribution was increased in the study patients, and total system clearance was decreased. The net result was a mean ± SD half-life of 3.7 ± 1.2 hours compared with ~1 hour reported in other populations. This contributed to an extended %fT > MIC for likely pathogens. Results from all nine patients showed %fT > MIC of 100% at the susceptibility breakpoint MIC of 16 mg/L and 85% or higher at an MIC of 32 mg/L.
  
  
  CONCLUSIONS
  The pharmacokinetics of piperacillin is altered in morbidly obese, surgical intensive care patients. The use of standard-dosage piperacillin-tazobactam 4.5 g intravenously every 6 hours was shown to be an appropriate dosage for this study population.
authors.affiliation: Department of Pharmacy, Vidant Medical Center, Greenville, North Carolina.
authors.forename: Ashley W
authors.initials: AW
authors.lastname: Sturm
authors.forename: Nichole
authors.initials: N
authors.lastname: Allen
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Rafferty
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Fish
authors.forename: Eric
authors.initials: E
authors.lastname: Toschlog
authors.forename: Mark
authors.initials: M
authors.lastname: Newell
authors.forename: Brett
authors.initials: B
authors.lastname: Waibel
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016638:Critical Illness / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009767:Obesity, Morbid / Q000188:drug therapy*; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077725:Piperacillin, Tazobactam Drug Combination; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin
keywords: antibiotic dosing; infectious disease; morbidly obese; obese; pharmacodynamics; pharmacokinetics; piperacillin-tazobactam