Pharmacokinetics of imipenem in critically ill patients during empirical treatment of nosocomial pneumonia: A comparison of 0.5-h and 3-h infusions

In critically ill patients, pathophysiological changes alter the pharmacokinetics of antibiotics. Imipenem exhibits primarily time-dependent killing. Its administration by prolonged infusion may increase the time for which its plasma concentration exceeds the minimum inhibitory concentrations (MICs) of suspected pathogens. The objectives of this study were to compare the pharmacokinetic parameters of imipenem administered by standard short infusion (1 g imipenem/1 g cilastatin over 30 min three times daily) and by extended infusion with a reduced total dose (0.5 g imipenem/0.5 g cilastatin over 3 h four times daily) and to compare the target pharmacokinetic/pharmacodynamic indices, namely percentage of the dosing interval for which the free plasma concentration of imipenem exceeds the MIC and 4× MIC (%fT>MIC and %fT>4×MIC) of 0.5, 1, 2 and 4 mg/L, for these two regimens in critically ill adult patients with nosocomial pneumonia on Day 2 of empirical antibiotic therapy. The study included 22 patients. Whilst no significant differences were found between both groups for %fT>MIC, %fT>4×MIC was 87.4 ± 12.19%, 68.6 ± 15.08%, 47.31 ± 6.64% and 27.81 ± 9.52% of the 8-h interval in the short infusion group for MICs of 0.5, 1, 2 and 4 mg/L, respectively, and 85.15 ± 17.57%, 53.14 ± 27.27%, 13.55 ± 24.47% and 0 ± 0% of the 6-h interval for the extended infusion group. In conclusion, administration of 0.5 g of imipenem by a 3-h infusion every 6 h does not provide sufficient drug concentrations to treat infections caused by pathogens with a MIC of ≥2 mg/L.