A Multicenter Observational Study Evaluating Outcomes Associated With Antibiotic Combination Versus Monotherapy in Patients With Septic Shock

OBJECTIVES: To explore the association between antibiotic combination therapy and in-hospital mortality in patients with septic shock in two tertiary ICUs in different countries. DESIGN: Retrospective observational study. SETTING: ICUs of two tertiary hospitals, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia, and Rigshospitalet, Copenhagen, Denmark. PATIENTS: Adult patients with antibiotic treatment greater than or equal to 72 hours and vasopressor therapy greater than or equal to 24 hours. INTERVENTION: Combination versus mono antibiotic therapy. MEASUREMENTS AND MAIN RESULTS: Combination antibiotic therapy was defined as receiving two or more antibiotics from different classes, started within 12 hours of each other and with an overlapping duration of greater than or equal to 12 hours. Bivariate and multiple logistic regression analysis were performed comparing combination antibiotic therapy versus antibiotic monotherapy on in-hospital mortality. The analysis was adjusted for age, gender, centre, Acute Physiology and Chronic Health Evaluation II score, and chronic health evaluation. In total, 1,667 patients were included with 953 (57%) receiving combination therapy. Patients given combination therapy were older (60 ± 16 vs 56 ± 18), more likely admitted to Rigshospitalet (58% vs 16%), and had a higher Acute Physiology and Chronic Health Evaluation II score (26 ± 8 vs 23 ± 8). Combination therapy was associated with an increased mortality in univariate analysis (odds ratio = 1.33; 95% CI, 1.07–1.66); however, there was no significant association in the adjusted analysis (odds ratio = 0.88; 95% CI, 0.68–1.15). CONCLUSIONS: In this retrospective study, no association was found between use of combination therapy and in-hospital mortality. The large differences between centers probably reflect local traditions and lack of definitive evidence.