Highly versus less bioavailable oral antibiotics in the treatment of gram negative bloodstream infections: a propensity-matched cohort analysis

Objectives — This study evaluated the clinical outcomes associated with use of highly bioavailable oral antibiotics (fluoroquinolones and trimethoprim-sulfamethoxazole) compared to less bioavailable oral antibiotics (beta-lactams) in Gram negative bloodstream infections (BSIs).

Methods — Among hospitalized older adult patients in Ontario, Canada, discharged home on oral treatment for Gram negative BSI between January 1, 2017, and December 31, 2019, we utilized a matched cohort design to compare outcomes among those receiving highly versus less bioavailable agents; hard-matching 1:1 on sex, BSI pathogen (Escherichia coli vs non-E. coli), and infection source (urinary vs. non-urinary/unknown source) along with a propensity score, incorporating specific pathogen, patient, and infection characteristics. The primary outcome was the composite of 90-day all-cause mortality, recurrent BSI with the same pathogen (genus and species), and re-admission to any Ontario hospital.

Results — A total of 2,012 patients were included in the study (1006 in each bioavailability category). Those who at discharge, received highly (compared to less) bioavailable antibiotics had lower rates of the composite outcome (171/1006 (17.0%) vs 216/1006 (21.5%), adjusted odds ratio (aOR) 0.74 (95% CI, 0.60 – 0.92). Recurrent BSI at 90 days was the main driver for the composite outcome occurring in 64 (5.4%) and 107 (9.4%) of the highly and less bioavailable group, respectively (p <0.001) (aOR 0.56 (95% CI, 0.40 – 0.78).

Conclusions — Use of highly (compared to less) bioavailable antibiotics at discharge was associated with significantly better clinical outcomes among patients with Gram negative BSIs.