Seven versus 14 days of polymyxin-based therapy for ventilator-associated pneumonia due to carbapenem-resistant Acinetobacter baumannii: A randomised feasibility trial

ABSTRACT Background: Ventilator-associated pneumonia (VAP) due to carbapenem-resistant Acinetobacter baumannii ( CRAB ) is associated with substantial morbidity and mortality in intensive care units (ICUs), yet the optimal antibiotic duration of therapy remains uncertain. We compared outcomes of 7-day versus 14-day polymyxin-based therapy for CRAB-VAP. Methods: We conducted a single-centre, open-label, randomised feasibility trial in a tertiary-care respiratory ICU from March 2017 to October 2024. Patients with microbiologically confirmed CRAB-VAP who met predefined clinical stability criteria on day 7 were randomised 1:1 to either discontinue antibiotics on day 7 or continue treatment for 14 days. Treatment comprised intravenous colistin or polymyxin B with adjunctive nebulised colistin. The primary outcome was relapse of CRAB-VAP. Secondary outcomes included antibiotic-free days through day 28, duration of mechanical ventilation, ICU and hospital length of stay, and 28-day all-cause mortality. Results: We randomised 41 patients (7-day n = 22; 14-day n = 19). Relapse occurred in 1 (4.5%) versus 2 (10.5%) patients (risk ratio [RR] 0.43; 95% CI: 0.04, 4.31) in the 7-day versus 14-day groups, respectively. The 7-day group had more antibiotic-free days (mean difference: 6.9 days; 95% CI: 5.1, 8.7 days). Acute kidney injury occurred in 0% versus 31.6% (RR 0.07; 95% CI: 0.004, 1.15). Other outcomes, including 28-day mortality (45.5 vs 63.2%; RR 0.72; 95% CI: 0.40, 1.30), were similar. Conclusion: In clinically improving CRAB-VAP, a 7-day discontinuation strategy was feasible. Clinical outcome estimates, including relapse and mortality, were imprecise and should be interpreted as hypothesis-generating. These findings support evaluation in larger, adequately powered multicentre trials.