β-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case-control study

Int J Antimicrob Agents. 2015 Mar;45(3):278-82. doi: 10.1016/j.ijantimicag.2014.11.005. Epub 2014 Dec 8.

Abstract

Most adult patients receiving extracorporeal membrane oxygenation (ECMO) require antibiotic therapy, however the pharmacokinetics of β-lactams have not been well studied in these conditions. In this study, data from all patients receiving ECMO support and meropenem (MEM) or piperacillin/tazobactam (TZP) were reviewed. Drug concentrations were measured 2h after the start of a 30-min infusion and just before the subsequent dose. Therapeutic drug monitoring (TDM) results in ECMO patients were matched with those in non-ECMO patients for (i) drug regimen, (ii) renal function, (iii) total body weight, (iv) severity of organ dysfunction and (v) age. Drug concentrations were considered adequate if they remained 4-8× the clinical MIC breakpoint for Pseudomonas aeruginosa for 50% (TZP) or 40% (MEM) of the dosing interval. A total of 41 TDM results (27 MEM; 14 TZP) were obtained in 26 ECMO patients, with 41 matched controls. There were no significant differences in serum concentrations or pharmacokinetic parameters between ECMO and non-ECMO patients, including Vd [0.38 (0.27-0.68) vs. 0.46 (0.33-0.79)L/kg; P=0.37], half-life [2.6 (1.8-4.4) vs. 2.9 (1.7-3.7)h; P=0.96] and clearance [132 (66-200) vs. 141 (93-197)mL/min; P=0.52]. The proportion of insufficient (13/41 vs. 12/41), adequate (15/41 vs. 19/41) and excessive (13/41 vs. 10/41) drug concentrations was similar in ECMO and non-ECMO patients. Achievement of target concentrations of these β-lactams was poor in ECMO and non-ECMO patients. The influence of ECMO on MEM and TZP pharmacokinetics does not appear to be significant.

Keywords: Antibiotic; ECMO; Extracorporeal membrane oxygenation; ICU; Pharmacokinetics; Sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Case-Control Studies
  • Extracorporeal Membrane Oxygenation*
  • Female
  • Humans
  • Male
  • Meropenem
  • Middle Aged
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / pharmacokinetics
  • Penicillanic Acid / therapeutic use
  • Piperacillin / pharmacokinetics
  • Piperacillin / therapeutic use
  • Piperacillin, Tazobactam Drug Combination
  • Pseudomonas Infections / drug therapy
  • Sepsis / drug therapy*
  • Sepsis / microbiology
  • Serum / chemistry
  • Thienamycins / pharmacokinetics
  • Thienamycins / therapeutic use
  • Treatment Outcome
  • beta-Lactams / pharmacokinetics*
  • beta-Lactams / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Thienamycins
  • beta-Lactams
  • Piperacillin, Tazobactam Drug Combination
  • Penicillanic Acid
  • Meropenem
  • Piperacillin