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

Most adult patients receiving extracorporeal membrane oxygenation (ECMO) require antibiotic therapy, however the pharmacokinetics of beta-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 2 h 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 4-8x 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 V-d[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 (13141 vs. 12141), adequate (15141 vs. 19141) and excessive (13141 vs. 10141) drug concentrations was similar in ECM and non-ECMO patients. Achievement of target concentrations of these beta-lactams was poor in ECMO and non-ECMO patients. The influence of ECMO on MEM and TZP pharmacokinetics does not appear to be significant.