Prospective evaluation of imipenem trough concentrations and clinical outcomes in critically ill patients.

BACKGROUND: Imipenem is a broad-spectrum antibiotic commonly used in critically ill patients, whose pharmacokinetic profile can be highly variable. While imipenem therapeutic drug monitoring (TDM) is being adopted increasingly, efficacy and toxicity plasma thresholds remain incompletely defined. Few studies have prospectively and systematically assessed imipenem concentrations in severely ill patients before clinical failure or toxicity events occur. METHODS: This prospective observational cohort study conducted at the University Hospitals of Geneva consecutively included all adult patients hospitalized for suspected or confirmed severe bacterial infections in the haematology, intermediate care and intensive care units whose clinicians prescribed imipenem. On inclusion, patients underwent imipenem plasma-concentration monitoring, with trough levels measured at steady state. We assessed the frequency of adverse events and clinical success over a 30-day period. RESULTS: Of 142 patients undergoing imipenem monitoring, 106 had trough levels drawn at steady state. The median trough concentration was 2.4 mg/L (IQR 1.2-4.0). Among all patients, adverse events occurred in 4.9% (7/142), while clinical success was achieved in 88/106 with trough levels (83%). No significant differences in trough levels were observed between patients with and without clinical success or with and without adverse events. Renal clearance had a significant impact on trough levels. CONCLUSION: Prospective, universally applied imipenem monitoring reveals lower trough levels than previously described. Nonetheless, this cohort of critically ill and/or immunosuppressed patients still experienced high rates of clinical success, with few adverse events. While low trough concentrations did not predict failure, rare outlying higher concentrations (10-20 mg/L) also did not predict toxicity.