Combination Antibiotic Therapy with Colistin, Meropenem, and Ampicillin-Sulbactam for Carbapenem-Resistant Acinetobacter Infections: A Randomized Controlled Trial

Background: Multidrug-resistant Acinetobacter baumannii infections present significant therapeutic challenges in intensive care unit (ICU) settings. Current evidence on optimal antimicrobial combinations remains limited. Objectives: This randomized controlled trial aims to compare the efficacy of dual versus triple antibiotic therapy in critically ill patients with carbapenem-resistant Acinetobacter infections. Methods: We conducted a single-center randomized controlled trial at Bohlool Hospital, Gonabad, Iran, between June 2024 and April 2025. Adult ICU patients with culture-confirmed carbapenem-resistant A. baumannii (CRAB) infections were randomly assigned (1:1) using block randomization to receive either dual therapy (colistin and ampicillin–sulbactam) or triple therapy (colistin, meropenem, and ampicillin–sulbactam). Outcome assessors were blinded to the treatment assignment. The primary outcome was 14-day clinical success. Secondary outcomes included 14- and 28-day mortality, final outcome, and hospital length of stay. Results: At day 14, clinical success was achieved in 14/23 (60.9%) dual-therapy versus 19/23 (82.6%) triple-therapy patients (P = 0.102). By day 28, mortality was significantly lower in the triple-therapy group (34.8% vs 65.2%; P = 0.039). There was no significant difference in overall in-hospital mortality (dual: 65.2% vs triple: 73.9%; P = 0.522). Time to discharge among survivors did not differ (P = 0.155). Conclusions: In this randomized controlled trial, adding meropenem to colistin and ampicillin–sulbactam was associated with reduced 28-day mortality in critically ill carbapenem-resistant Acinetobacter infections patients but did not significantly affect final outcome. Larger multicenter trials are warranted to confirm these findings and optimize combination regimens.