2025 Southeastern Residency Conference

Title: Oral β-lactam versus Fluoroquinolone or Trimethoprim-sulfamethoxazole for Directed Short Course Therapy in Uncomplicated Enterobacterales Bacteremia
 
Authors: Colby Jordan Osborne, Allison M. Field, Christopher Dennis, David Laurent

Background/Purpose: Gram-negative bacteremia is prevalent and a significant cause of morbidity and mortality in hospitalized patients. Evidence suggests that transitioning to oral (PO) antibiotics after initial intravenous (IV) therapy results in comparable outcomes, while reducing hospital length of stay. Due to their favorable oral bioavailability, fluoroquinolones (FQs) and trimethoprim/sulfamethoxazole (TMP-SMX), have historically been preferred when selecting a PO agent. However, rising resistance rates and potential adverse effects may limit their use. Recent data suggest that PO β-lactam antibiotics may be an effective alternative. However, data on short course therapy with PO β-lactams remains limited. This study aims to evaluate the efficacy and safety of utilizing short PO β-lactam courses as directed therapy in uncomplicated Enterobacterales bacteremia.

Methods: This retrospective, cohort study assesses hospitalized patients ≥18 years of age with uncomplicated Enterobacterales bacteremia between January 1, 2020, and May 31, 2024. Patients receiving a short course, defined as 6 to 9 consecutive active antibiotic days, with transition to a PO β-lactam, FQ, or TMP-SMX as directed therapy with <96 hours of active IV therapy were included for analysis. The primary endpoint is a 30-day composite of treatment failure, defined as all-cause mortality, hospital readmission, recurrent bacteremia, or primary site infection due to the same microorganism. Secondary endpoints include individual components of the primary outcome at 30 and 90 days, as well as 90-day incidence of Clostridioides difficile infection (CDI) and multidrug-resistant organism (MDRO) colonization.

Results: Of 2046 patients screened, 281 patients (n=179 FQ/TMP-SMX and n=102 β-lactam) were included in the study. Baseline characteristics were similar between groups. The main source of infection was the urinary tract, with 79.3% in FQ/TMP-SMX group and 82.4% in β-lactam group. The most common pathogen identified was Escherichia coli (76.5% for both groups). The primary outcome occurred in 15/179 patients (8.4%) in the FQ/TMP-SMX group verses 8/102 patients (7.8%) in the β-lactam group (P=0.875). There were no statistically significant differences in secondary outcomes between groups, including 90-day all-cause mortality, hospital readmission, or recurrent bacteremia. Confirmed CDI at 90 days occurred in 1/179 (0.56%) in FQ/TMP-SMX group with no cases observed in β-lactam group.

Conclusion: Short-course oral β-lactam therapy demonstrated similar effectiveness and safety outcomes compared to FQ or TMP-SMX regimens in patients with uncomplicated Enterobacterales bacteremia. These findings support that in patients with uncomplicated Enterobacterales bacteremia, a 7-day treatment course utilizing a PO β-lactam for definitive therapy may be appropriate.