Influence of empirical double-active combination antimicrobial therapy compared with active monotherapy on mortality in patients with septic shock: A propensity score-adjusted and matched analysis

Objectives: To evaluate the influence on mortality of empirical double-active combination antimicrobial therapy (DACT) compared with active monotherapy (AM) in septic shock patients. Methods: A retrospective study was performed of monomicrobial septic shock patients admitted to a university centre during 2010-15. A propensity score (PS) was calculated using a logistic regression model taking the assigned therapy as the dependent variable, and used as a covariate in multivariate analysis predicting 7, 15 and 30 day mortality and for matching patients who received DACT or AM. Multivariate models comprising the assigned therapy group and the PS were built for specific patient subgroups. Results: Five-hundred and seventy-six patients with monomicrobial septic shock who received active empirical antimicrobial therapy were included. Of these, 340 received AM and 236 DACT. No difference in 7, 15 and 30 day all-cause mortality was found between groups either in the PS-adjusted multivariate logistic regression analysis or in the PS-matched cohorts. However, in patients with neutropenia, DACT was independently associated with a better outcome at 15 (OR 0.29, 95% CI 0.09-0.92) and 30 (OR 0.25, 95% CI 0.08-0.79) days, while in patients with Pseudomonas aeruginosa infection DACT was associated with lower 7 (OR 0.12, 95% CI 0.02-0.7) and 30 day (OR 0.26, 95% CI 0.08-0.92) mortality. Conclusions: All-cause mortality at 7, 15 and 30 days was similar in patients with monomicrobial septic shock receiving empirical double-active combination therapy and active monotherapy. However, a beneficial influence of empirical double-active combination on mortality in patients with neutropenia and those with P. aeruginosa infection is worthy of further study.