Abstract
BACKGROUND: Stenotrophomonas maltophilia, a multidrug-resistant nosocomial pathogen, is associated with high mortality and therapeutic challenges due to resistance. Empiric Gram-negative antibiotic regimens often lack activity against S. maltophilia, delaying effective therapy. This study evaluated timely versus delayed antibiotic therapy's impact on clinical outcomes in S. maltophilia pneumonia patients. METHODS: This retrospective cohort study included adults hospitalized with S. maltophilia pneumonia at the University of Kentucky HealthCare (2014-2023). Patients received active monotherapy or combination therapy with trimethoprim/sulfamethoxazole, minocycline, or levofloxacin. Timely therapy was defined as initiation ≤48 hours from index culture collection; delayed therapy as >48 hours. Propensity score matching minimized baseline differences. The Desirability of Outcome Ranking (DOOR) framework evaluated outcomes, prioritizing clinical efficacy and safety. Kaplan-Meier analysis assessed 30-day mortality. A Cox proportional hazards model with time-dependent covariates assessed therapy timing, adjusting for calendar year and COVID-19 time period. RESULTS: Of 430 patients (215 per group), DOOR analysis showed a 72.8% probability (95% CI, 67.9%-77.1%; P < .001) that timely therapy resulted in patients being alive with fewer or no clinical events. Kaplan-Meier analysis confirmed higher survival with timely therapy (log-rank P < .001), with a 22.8% absolute reduction in 30-day mortality (survival rates: 87.9% timely vs 65.1% delayed). A time-dependent Cox model, adjusted for calendar year and COVID-19 time period, confirmed timely therapy reduced death hazard (adjusted hazard ratio: 0.48; 95% CI: .27-.86; P = .013). CONCLUSIONS: Timely therapy significantly improved survival and clinical outcomes in S. maltophilia pneumonia, highlighting the need for rapid, targeted treatment in managing resistant Gram-negative infections.