Retrospective analysis comparing oral stepdown therapy for enterobacteriaceae bloodstream infections: fluoroquinolones versus β-lactams

Abstract

Enterobacteriaceae bloodstream infections (EB-BSIs) are a common manifestation of Gram-negative sepsis and are initially managed with empirical intravenous antibiotics. Upon stabilisation and source control, patients are often transitioned to an oral agent. Fluoroquinolones (FQs) plays a prominent role in stepdown therapy for severe infections owing to favourable pharmacokinetic parameters; however, serious adverse events (AEs) have been documented with their use. A total of 224 adults with EB-BSI initiated on empirical intravenous antibiotics with stepdown to oral β-lactam (BLM) (n = 84) or FQ (n = 140) were studied to compare clinical success and identify risk factors for treatment failure. Subgroups of early versus late oral stepdown and short versus extended duration of therapy (DOT) were assessed. Stepdown therapy with oral BLM was non-inferior to oral FQ (86.9% vs. 87.1%; mean difference 0.2%, 97.5% CI -10.3 to 10.7). Microbiological success (94.0% vs. 97.9%; P > 0.05) and 30-day re-admission (14.3% vs. 14.3%; P > 0.05) were similar. Patients were more likely to complete their BLM course without an AE compared with FQs (91.7% vs. 82.1%; P = 0.049). Clinical success was comparable between early and late stepdown (86.7% vs. 87.5%; P > 0.05) and short versus extended DOT (88.2% vs. 86.7%; P > 0.05). Negative predictors of clinical success identified by logistic regression were complicated diabetes (OR = 0.35, 95% CI 0.15-0.83) and urinary abnormality (OR = 0.39, 95% CI 0.16-0.94). These findings suggest that oral BLMs were non-inferior to FQs as stepdown therapy for EB-BSI, with less AEs.

Keywords: Bacteraemia; Escherichia coli; Fluoroquinolone; Gram-negative; Oral antibiotics; β-Lactam.