Pharmacokinetics of meropenem and piperacillin in critically ill patients with indwelling surgical drains

摘要

Meropenem and piperacillin are two commonly prescribed antibiotics in critically ill surgical patients. To date, the pharmacokinetics of these antibiotics in the presence of indwelling abdominal surgical drains is poorly defined. This was a prospective pharmacokinetic study of meropenem and piperacillin. Serial plasma, urine and surgical drain fluid samples were collected over one dosing interval of antibiotic treatment in ten patients (meropenem, n = 5; piperacillin n = 5). Drug concentrations were measured using a validated high-performance liquid chromatography assay. Median (interquartile range) pharmacokinetic parameter estimates for meropenem were as follows: area under concentration-time curve (AUC), 128.7 mg h/L (95.3-176.7 mg h/L); clearance (CL), 5.7 L/h (5.1-10.5 L/h); volume of distribution (V_d), 0.41 L/kg (0.35-0.56 L/kg); AUC ratio (drain:plasma), 0.2 (0.1-0.2); and calculated antibiotic clearance via surgical drain, 3.8% (2.8-5.4%). For piperacillin, unbound pharmacokinetic results were as follows; AUC, 344.3 mg h/L (341.1-348.4 mg h/L); CL, 13.1 L/h (12.9-13.2 L/h); V_d, 0.63 L/kg (0.38-1.28 L/kg); AUC ratio (drain:plasma), 0.2 (0.2-0.3); and calculated antibiotic clearance via surgical drain 8.2% (3.3-14.0%). A linear correlation was present between the percentage of antibiotic cleared through the drain and the volume of surgical drain fluid output for meropenem (r~2 = 0.89; P = 0.05) and piperacillin (r~2 = 0.63; P = 0.20). Meropenem and piperacillin have altered pharmacokinetics in critically ill patients with indwelling surgical drains. We propose that only when very high drain fluid output is present (>1000 mL/day) would an additional dose of antibiotic be necessary.