Abstract
BACKGROUND: Difficult-to-treat resistant (DTR) Pseudomonas aeruginosa infections have emerged as a significant global public health threat, characterized by limited treatment options and a heightened mortality risk. This study aimed to assess the appropriateness of initial antibiotic therapy, estimate 30-day all-cause mortality, and determine the impact of DTR P. aeruginosa infections on mortality. METHODS: A retrospective, multicenter study was conducted at four teaching hospitals in Beirut, Lebanon, between January 2021 and December 2023. The primary outcome was 30-day all-cause mortality. Kaplan-Meier survival analysis was used to assess time-to-mortality, and the log-rank test was applied to compare survival outcomes relative to DTR infections and the appropriateness of initial antibiotic therapy. Multivariable logistic regression was performed to identify predictors of mortality. RESULTS: Out of 2,639 screened cases, 477 patients met the inclusion criteria. Respiratory tract infections accounted for 38.8% of cases. Carbapenem-resistant P. aeruginosa (CRPA) comprised nearly one-third of isolates, and 15.3% were categorized as DTR. The most common empirical antibiotics were piperacillin-tazobactam (33.9%) and meropenem (24.5%). Inappropriate initial antibiotic therapy was observed in 43.8% of cases, with 33.8% of patients receiving antibiotics to which the pathogen was resistant. DTR infections were significantly more likely to be associated with inappropriate therapy (odds ratio [OR] = 4.21, 95% CI = 2.43-7.32, P < 0.001). The 30-day all-cause mortality rate was 14.8%, with a mean time-to-mortality of 13.29 ± 9.81 days. Patients who received inappropriate therapy had a shorter time-to-mortality (11.76 ± 8.80 days) compared to those receiving appropriate therapy (15.46 ± 10.90 days, P = 0.03). Predictors of mortality included DTR P. aeruginosa infection (adjusted odds ratio [AOR] = 2.48, 95% CI = 1.32-4.63, P < 0.01), and inappropriate initial therapy (AOR = 1.40, 95% CI = 1.04-2.35, P < 0.01). CONCLUSION: DTR P. aeruginosa infections and inappropriate initial antibiotic therapy are associated with increased mortality risk in hospitalized patients.