Assessment of Interindividual Variability of Plasma Concentrations after Administration of High Doses of Intravenous Amoxicillin or Cloxacillin in Critically Ill Patients

The aim of the present retrospective observational clinical study was to assess the interindividual pharmacokinetic variability of plasma concentrations of amoxicillin or cloxacillin administered in high doses intravenously in critically ill patients, related to renal function or administration method. Four hundred and two plasma concentrations were measured at steady-state with a high performance liquid chromatography technique in 162 patients treated with 100 - 300 mg/kg/day of intravenous amoxicillin or cloxacillin. For both drugs and administration methods, plasma concentrations were significantly higher for patients with creatinine clearance below 60 mL/min, even though doses were adapted for renal impairment. The correlations calculated between plasma concentrations and creatinine level, creatinine clearance or doses were all low. There were fewer outlying drug concentrations in patients receiving continuous rather than intermittent regimens. Our results are in favor of adapting dosages of these beta-lactam antibiotics based on plasma concentrations, especially in cases of renal impairment.