High-dose versus standard-dose intermittent meropenem in critically ill patients: An observational cohort study

Background: The impact of high-dose versus standard-dose meropenem on outcomes in critically ill patients remains uncertain. Methods: We conducted an observational cohort study in Vienna, Austria, including critically ill patients treated with meropenem from March 2014 to March 2024. Eligible patients had an intensive care unit (ICU) stay of ≥3 days and received either high-dose (6 g/day) or standard-dose (3 g/day) meropenem via intermittent infusion (or equivalent doses in patients with impaired renal function). We applied 2:1 propensity score matching with covariate adjustment to adjust for confounding by indication. The primary outcome was 90-day all-cause mortality. Secondary outcomes included 30-day mortality, emergence of antimicrobial resistance, initiation of extracorporeal membrane oxygenation (ECMO), new onset of acute respiratory distress syndrome (ARDS) and length of ICU and hospital stay. Occurrence of acute kidney injury (AKI) was evaluated as a safety endpoint. Results: Of 4,210 critically ill patients who received meropenem, we matched 1144 treated with high-dose intermittent infusions with 572 patients who received standard-dose therapy. The 90-day all-cause mortality was significantly lower in the high-dose meropenem group (adjusted risk, 31.5%; 95% CI, 28.5-34.5) compared to the standard-dose group (adjusted risk, 40.9%; 95% CI, 36.7-45.1), with an adjusted risk difference of 9.4% (95% CI, 4.8-14.1; p < 0.001). Secondary outcomes did not differ between groups, with adjusted risks for 30-day mortality (high-dose vs. standard-dose: adjusted risks, 20.0% vs. 22.2%), resistance emergence (5.0% vs. 6.2%), ECMO initiation (6.1% vs. 7.3%), and new-onset ARDS (20.8% vs. 24.9%) showing no significant differences. Adjusted mean ICU and hospital length of stay were comparable (21.5 vs. 21.4 days and 44.3 vs. 41.7 days, respectively). High-dose therapy was associated with a lower adjusted risk of AKI (60.6% vs. 68.2%). Conclusions: High-dose intermittent meropenem was independently associated with lower 90-day all-cause mortality compared with standard-dose therapy in critically ill patients.