Abstract
BACKGROUND AND AIMS: Ventilator-associated pneumonia (VAP) caused by gram-negative bacteria is associated with significant complications, mortality, and resource utilization. Over the past decade, there has been growing interest in using fosfomycin to treat multidrug-resistant gram-negative infections, particularly when limited viable options remain. This study aimed to investigate the efficacy of inhaled colistin/fosfomycin as an adjunctive treatment for VAP. METHODS: In this triple-blind clinical trial, participants with VAP caused by extensively drug-resistant (XDR) Acinetobacter baumannii were randomly assigned to two groups. Both groups received meropenem (2 g as a 4 h extended infusion every 8 h) and intravenous colistin (9 million IU loading dose, followed by 4.5 million IU every 12 h). The control group was treated with inhaled colistin (1 million IU every 8 h), while the intervention group received a combination of inhaled colistin (1 million IU every 8 h) and fosfomycin (80 mg every 12 h). Clinical pulmonary infection score (CPIS) was measured at baseline and upon completion of the intervention. Acute kidney injury (AKI) rates during treatment, as well as clinical response and microbiological outcomes, were compared between the two groups. RESULTS: While the differences were not statistically significant (p = 0.19), the failure rate was lower in the colistin/fosfomycin group (n = 3; 7.7%) compared to the colistin group (n = 7; 18.9%). The colistin/fosfomycin group exhibited a higher microbiological response rate (n = 19; 48.7%) than the colistin group (n = 13; 35.1%), although the difference did not reach statistical significance (p = 0.23). Both groups showed a significant reduction in CPIS; however, there was no statistically significant difference in procalcitonin levels or CPIS changes between the groups. Treatment duration was significantly shorter in the colistin/fosfomycin group (8.97 ± 2.12 days) compared to the colistin group (14.06 ± 3.32 days) (p < 0.001). The incidence of AKI was similar between the groups, with 15 cases (38.5%) in the colistin/fosfomycin group and 13 cases (35.1%) in the colistin group (p = 0.76). CONCLUSION: The study demonstrated that the addition of inhaled colistin/fosfomycin to the treatment regimen may result in faster recovery and shorter treatment duration for patients with VAP caused by XDR Acinetobacter baumannii.