Outcomes of high-dose oral beta-lactam definitive therapy compared to fluoroquinolone or trimethoprim-sulfamethoxazole oral therapy for bacteremia secondary to a urinary tract infection

OBJECTIVE: Compare outcomes of patients receiving high-dose oral beta-lactam versus standard oral therapy for Enterobacterales bacteremia from a urinary tract infection (UTI). DESIGN: Retrospective, multicenter, observational cohort. SETTING: Three Michigan community teaching hospitals. PATIENTS: Adult patients admitted between February 1, 2020, and October 1, 2022, with gram-negative bacteremia from a urinary source were evaluated. Patients receiving active empiric intravenous (IV) antibiotics and transitioned to appropriately dosed oral cephalexin, amoxicillin, fluoroquinolone (FQ), or trimethoprim/sulfamethoxazole (TMP/SMX) were included. Patients receiving less than 72 hours of oral therapy, diagnosed with renal abscess, lobar nephronia, or expired during admission were excluded. METHODS: Standard oral therapy was defined as FQ or TMP/SMX. The primary outcome compared the composite of recurrent bacteremia or mortality within 30 days of therapy between groups. Secondary outcomes compared recurrent UTI, emergency department or hospital readmission, and Clostridioides difficile within 30 days. RESULTS: 194 patients were included (beta-lactam, n = 75 vs standard therapy, n =119). Patients in both groups were treated for a median of 11 days, with 4 days IV and 7 days oral therapy. There was no difference in the primary outcome between groups (beta-lactam 1.3% vs standard therapy 1.7%, OR 1.27 [95% CI 0.11–14.2]). No patients experienced C. difficile in either group (p = 1.0). Infectious disease consultation was independently associated with standard therapy prescribing (OR 4.4 [95% CI 2.24–8.26]). CONCLUSION: High-dose oral beta-lactams were as safe and effective as oral FQ or TMP/SMX for the treatment of bacteremia from a urinary source. Most patients received 8–10 days of therapy in both groups.