Meropenem Dosing Recommendations in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement...

Meropenem dosing regimens in critically ill patients undergoing prolonged intermittent renal replacement therapy (PIRRT) are limited. This study aimed to evaluate the probability of target attainment (PTA) of various meropenem regimens in these patients receiving PIRRT, using Monte Carlo simulations (MCS).

Mathematical models were developed using published pharmacokinetic (PK) data from critically ill patients. Simulations incorporated PIRRT modalities (haemodialysis [HD] and hemofiltration [HF]) with an effluent rate of 300 mL/min and various durations of 4, 6, 8, or 10 h. MCS assessed drug exposure over 48 h in 10 000 virtual patients per regimen. The pharmacodynamic (PD) targets were free drug concentrations that remained above 4 times the minimum inhibitory concentration (MIC) of 2 mg/L. Optimal regimens were those achieving ≥ 90% PTA in each PIRRT setting.

In alternate-day PIRRT, most session durations use a 1000 mg loading dose followed by 500 mg every 8 h, except for 10-h HD, which requires 1000 mg every 12 h. In daily PIRRT, HD requires 750 mg every 8 h for 4-8-h sessions and 1000 mg every 8 h for 10-h sessions. For HF, recommended regimens range from a 1000 mg loading dose followed by 500 mg every 8 h for 4-h sessions to 1000 mg every 12 h for 6-8-h sessions and 750 mg every 8 h for 10-h sessions.

Optimized daily meropenem doses of 2000-3000 mg for PIRRT are recommended to ensure safe and effective outcomes, though further clinical validation is needed before widespread use.