Assessment of treatment outcomes in patients receiving high- versus low-dose sulfamethoxazole-trimethoprim for oral stepdown therapy in gram-negative bacteremia: a multi-center, retrospective cohort study.

Abstract

Objective: Many studies have evaluated the safety and efficacy of oral stepdown therapy for treatment of gram-negative bacteremia (GNB). There are currently no studies comparing the safety and effectiveness of various dosing strategies of sulfamethoxazole-trimethoprim (SMX-TMP) in these patients.

Methods: This retrospective cohort study included adult patients at 6 hospitals within a health system with GNB, excluding Stenotrophomonas spp. that received at least 72 hours of oral SMX-TMP. Patients were grouped based on high- (≥8 mg/kg) or low-dose (<8 mg/kg) SMX-TMP. The primary outcome was a composite of all-cause mortality and recurrence at 30 days. Secondary outcomes included readmission, hyperkalemia requiring intervention, acute kidney injury, and intolerance leading to SMX-TMP discontinuation.

Results: There were 176 patients included (25.6% high-dose, 74.4% low-dose) in this study. Baseline characteristics were similar except for age, sex, and dosing body weight. Median total duration of therapy for both groups was approximately 14 days; time to initiation of antibiotics was similar between groups. Six patients met the composite outcome (high-dose: 4.4% vs. low-dose: 3.1%; P = .646). Secondary outcomes did not differ significantly between groups.

Conclusions: SMX-TMP is commonly used as oral stepdown therapy in GNB. Results of this study indicate that low-dose (<8 mg/kg) SMX-TMP may be sufficient, as outcomes were similar between the groups. To date, this is the first study evaluating different dosing strategies of SMX-TMP for this indication.