Extended vs Intermittent Infusion of Meropenem with Colistimethate Sodium and Risk of Acute Kidney Injury in Critically Ill Patients: A Propensity Score-Matched Retrospective Cohort Study.

Purpose: The objective of this study was to evaluate whether an extended-infusion strategy for meropenem is associated with a reduced incidence and severity of acute kidney injury in critically ill patients receiving combination therapy with colistimethate sodium for carbapenem-resistant gram-negative infections. While extended infusion is known to optimize pharmacokinetic/pharmacodynamic targets, its potential as a kidney-sparing intervention remains to be elucidated. Patients and methods: A single-center, retrospective cohort study was conducted in the intensive care unit between January 2021 and October 2025. Critically ill adults receiving combination therapy with colistimethate sodium and meropenem for at least 72 hours were included. Patients were stratified into prolonged infusion (at least 3 hours per dose) and intermittent infusion (less than 1 hour per dose) groups. Propensity score matching (1:1) was performed to balance baseline characteristics. To account for the variable duration of therapy and the competing risk of mortality, data were analyzed using the Fine-Gray proportional subdistribution hazards model. The primary outcome was the incidence of acute kidney injury according to the Kidney Disease: Improving Global Outcomes criteria. Secondary outcomes included severity of injury, requirement for renal replacement therapy, and in-hospital mortality. Results: After matching, 146 pairs (292 patients) were analyzed. The prolonged infusion group exhibited a significantly lower incidence of acute kidney injury than the intermittent infusion group (24.7% versus 39.7%, p=0.006). Severe acute kidney injury (stage 2 or 3) was also less frequent in the prolonged infusion group (9.6% versus 19.2%, p=0.019). In-hospital mortality (19.2% versus 28.1%, p=0.021) and renal replacement therapy requirements (5.5% versus 12.3%, p=0.034) were significantly lower with prolonged infusion. Multivariate Fine-Gray analysis confirmed that prolonged infusion was an independent protective factor against acute kidney injury (adjusted subdistribution hazard ratio 0.55, 95% confidence interval 0.35-0.86, p=0.009). Conclusion: Extended infusion of meropenem is independently associated with a reduced incidence and severity of acute kidney injury in critically ill patients receiving colistimethate sodium. This dosing strategy may also lower mortality and the need for renal replacement therapy. While these observational findings require validation in prospective trials, they support the consideration of extended infusion as a potential kidney-sparing intervention in this high-risk population.