Imipenem levels are not predictable in the critically ill patient

Background: Critically ill patients often demonstrate extremely unusual volumes of distribution (Vd) and half-lives (t(1/2)) of drugs. Imipenem is a widely used antibiotic in critically ill patients. Methods: We performed high-performance liquid chromatography analysis of imipenem in samples from 50 critically ill patients treated with either 500 or 1,000 mg. Results: Peak imipenem levels varied from 1.56 mug/mL to 58.8 mug/mL. Trough levels varied between 0.0 mug/mL and 15.62 mug/mL. Only 54% of patients maintained a trough level greater than 4 mug/mL. Both the Vd and the t(1/2) of imipenem were much greater than observed in other patient populations. Conclusions: The pharmacokinetic activity of imipenem in critically ill patients is different from that in other patient populations. There is a very weak correlation between dosage and serum concentrations. Therapeutic failures of imipenem may be because of unpredictable pharmacodynamics (Vd and t(1/2)) in critically ill surgical patients.