Propensity-Matched Comparison of Timely vs Delayed Antibiotic Therapy in Pneumonia.

BACKGROUND

, 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 , delaying effective therapy. This study evaluated timely versus delayed antibiotic therapy's impact on clinical outcomes in pneumonia patients.

METHODS

This retrospective cohort study included adults hospitalized with 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%; < .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 < .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; = .013).

CONCLUSIONS

Timely therapy significantly improved survival and clinical outcomes in pneumonia, highlighting the need for rapid, targeted treatment in managing resistant Gram-negative infections.