2026 Southeastern Residency Conference

Oral Beta-lactam (BL) Versus Fluoroquinolone (FQ) or Sulfamethoxazole-Trimethoprim (SMXTMP) in Uncomplicated Gram-Negative Bacteremia (uGNB) Jared Robbins, Tyler Baumeister, Tracey Bastian Williamson Medical Center - Franklin, TN

Background/Purpose: Gram negative bacteremia is associated with significant morbidity and mortality. Historically, uncomplicated gram-negative bacteremia (uGNB) has been treated with highly bioavailable oral options like fluoroquinolones (FQ) or sulfamethoxazole/trimethoprim (SMX-TMP). This is primarily due to pharmacokinetic concerns and questionable bioavailability of other agents such as beta-lactam (BL) antibiotics. Therefore, optimal oral step-down agents for uGNB remains highly debated. The unfavorable safety profiles of FQs and SMX-TMP have sparked interest in investigating safer alternatives. Current literature including systematic reviews, meta-analyses, and cohort studies suggest beta-lactams may be an efficacious and safe alternative for uGNB. This study aims to compare the efficacy and safety of BLs versus FQs/SMX-TMP for oral step-down therapy in uGNB in a community hospital setting.

Methodology: This was a single-center, IRB-approved, retrospective study conducted at a 337- bed hospital in Franklin, Tennessee that evaluated clinical failure rates of 100 patients receiving either BLs or FQs/SMX-TMP for the treatment of uGNB. Eligible patients admitted between August 1, 2023, and August 1, 2025, who met inclusion and exclusion criteria were identified for analysis. Baseline characteristics included age, sex, weight, Charlson comorbidity score (CCS), and PITT bacteremia score. The primary outcome was a composite of clinical failure, defined by having 1 of the following; 30-day hospital readmission due to antibiotic intolerance, 30-day recurrent bacteremia caused by the same microorganism, or escalation in therapy. Secondary outcomes included individual components of the primary outcome at 90 days, 90-day incidence of Clostridioides difficile infection (CDI), duration of therapy (summative and breakdown components of IV/PO groups), and hospital length of stay. Safety outcomes included rates of hyponatremia, acute kidney injury, and hyperkalemia as primary cause of re-admission at 30 and 90 days, and a composite of these components.

Results: This trial included 100 total patients, 58 designated in the BL group, and 42 designated in the FQ/SMX-TMP group. Baseline characteristics were comparable between groups, with the exception of age (78.8 years vs 71.3 years, in the BL vs FQ/SMX-TMP groups, respectively; p=0.004) and CCS (5.2 vs 4.2, in the BL vs FQ/SMX-TMP groups, respectively; p=0.04). The primary outcome of 30-day composite clinical failure occurred in 4/58 patients (6.9%) in the BL group, and 4/42 patients (9.5%) in the FQ/SMX-TMP group. (RR 0.72; CI 0.19-2.73; p=0.72). For secondary outcomes, the 90-day clinical failure composite outcome occurred in 3/58 (5.2%) of patients in the BL group, and 4/42 (9.5%) in the FQ/SMX-TMP group. (RR 0.54; CI 0.13-2.3; p=0.449). Average length of stay, IV antimicrobial duration, and oral antimicrobial duration were similar between the two treatment groups. CDI did not occur in either treatment group. The 90-day composite safety outcomes occurred in 0/58 (0%) patients in the BL group, and 2/42 (4.8%) in the FQ/SMX-TMP group (RR 0.15; CI 0.007-3.02; p=0.174). Of the two events in the FQ/SMX-TMP group, both were due to hyponatremia leading to re-admission and occurred within 30 days post-discharge.