What Drives Mortality in S. maltophilia Bloodstream Infections? An Outcome-Focused Cohort Study of Treatment Strategies and Resistance Profiles

Stenotrophomonas maltophilia bloodstream infection (SM-BSI) carries high mortality and limited therapeutic options. We conducted a single-center retrospective cohort of adults with first SM-BSI (2018–2024) to describe treatment patterns and identify factors associated with survival. Demographic, clinical, and microbiological data were extracted and analyzed. Forty-three patients were included (median age: 63 years; 61% male). Appropriate antimicrobial therapy was given to 74%; trimethoprim–sulfamethoxazole-based regimens were used in 61%; and combination therapy in 23%. The median time from BSI to treatment initiation was 4 days (IQR: 3–5) and the treatment duration averaged 7 days (IQR: 0–12). Thirty-day mortality was 37% (16/43). The survival analysis found that a 14–21-day course was associated with better 30-day survival than a 7–13-day course (0/9 vs. 5/15 deaths; log-rank p = 0.045), whereas monotherapy and combination therapy did not differ (p = 0.855). Multidrug resistance was linked to worse survival (log-rank p = 0.001). In multivariable models for 30-day mortality, only active treatment (aHR: 0.14; 95% CI: 0.02–0.88) and microbiological cure (aHR: 0.08; 95% CI: 0.01–0.47) remained independently protective. These data suggest that outcomes in SM-BSI are driven primarily by the receipt of appropriate therapy and achievement of microbiological clearance, reinforcing the need for prompt source control, optimized antimicrobial treatment, and continued development of novel therapeutic strategies to improve outcomes in this challenging infection.