Transition to oral beta-lactam therapy in uncomplicated gram-negative bacteremia: A systematic review and meta-analysis

Introduction

Gram-negative bacteremia (GNB) is associated with significant morbidity and mortality. Transition to oral therapy has traditionally utilized fluoroquinolones or trimethoprim-sulfamethoxazole rather than beta-lactams due to concerns about pharmacokinetics and bioavailability despite a dearth of clinical data. The purpose of this meta-analysis is to evaluate the clinical efficacy of transition to oral beta-lactam therapy in uncomplicated GNB.

Methods

We performed a meta-analysis of published articles in MEDLINE, Embase, and Web of Science databases from inception to September 2024. Inclusion criteria included any study with adults (age >18 years of age) with uncomplicated GNB from any source. Primary outcomes included 30-day all-cause mortality and 30-day antibiotic failure rate.

Results

Eight retrospective cohort studies were reviewed comprising 7500 patients. Twice as many patients were in the fluoroquinolones/trimethoprim-sulfamethoxazole group compared with the beta-lactams group (4998 vs. 2482). Patients in each group had similar average age (70 vs. 71), percent male (54% vs. 56%), percent urinary source (78% vs. 80%), duration of IV antibiotics (4.2 vs. 4.5), Pitt bacteremia score (1.1 vs. 1.4) and Charleston comorbid index (2 vs. 2). There was no statistically significant difference in the 30-day all-cause mortality rate between the fluoroquinolones/trimethoprim-sulfamethoxazole and the beta-lactams group: 2.06% versus 1.89% with a weighted relative risk ratio of 1.24 (95% confidence interval [CI]: 0.86–1.77) or the 30-day antibiotic failure rate: 2.08% vs. 3.42%, weighted relative risk ratio of 1.29 (95% CI: 0.97–1.71).

Conclusions

There is no statistically significant difference in 30-day mortality or antibiotic failure rates between BL and FQ/TMP-SMX as transition to oral therapy in treating uncomplicated GNB.