Treatment and outcomes of difficult-to-treat Stenotrophomonas maltophilia pneumonia in the intensive care unit: a multinational retrospective cohort study

Difficult-to-treat resistance (DTR) in Stenotrophomonas maltophilia is an emerging concern in ICU-acquired pneumonia, associated with high mortality and limited evidence to guide therapy. This study aimed to evaluate the association between antibiotic regimens and 30-day mortality in DTR S. maltophilia ICU-acquired pneumonia. We conducted a multicenter, international, retrospective study across 31 centers in eight countries, including all adult patients with DTR S. maltophilia ICU-acquired pneumonia treated with ≥24 hours of an in vitro–active antibiotic. The primary outcome was 30-day mortality. Secondary outcomes included clinical cure and a composite of 30-day survival with clinical cure. Each agent was analyzed as a separate exposure using modified Poisson regression with robust variance in a day-3 landmark cohort. Combination therapy and treatment duration were evaluated using overlap weighting. A total of 119 patients were included. Thirty-day mortality was 37.8%. Tigecycline was associated with higher 30-day mortality (aRR 1.95, 95% CI 1.21–3.13). Aztreonam/ceftazidime-avibactam showed a favorable but non-significant trend toward lower mortality (aRR 0.38, 95% CI 0.12–1.15), as did colistin (aRR 0.51, 95% CI 0.22–1.20). No agent other than tigecycline was significantly associated with any outcome, and the active agents had wide, overlapping confidence intervals. Neither combination therapy nor a treatment duration longer than 8 days was associated with any outcome. Tigecycline was associated with excess mortality and should be used with caution. Aztreonam/ceftazidime-avibactam and colistin trended toward lower mortality, whereas the other agents, including cefiderocol, appeared neutral. The study is underpowered to separate the active agents, and these hypothesis-generating findings require prospective confirmation.