Oral Beta-Lactams, Fluoroquinolones, or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Uncomplicated Escherichia coli or Klebsiella species Bacteremia from a Urinary Source

Abstract

Abstract Background Fluoroquinolones (FQs) are effective for oral stepdown therapy for Gram-negative bloodstream infections (GN-BSIs) but are associated with unfavorable toxicities. Robust data are lacking for trimethoprim-sulfamethoxazole (TMP-SMX) and high-bioavailability β-lactams (HBBLs). Methods In this multicenter observational cohort study, we simulated a three-arm registry trial using causal inference methodology to compare effectiveness of FQs, TMP-SMX, or HBBLs for GN-BSI oral stepdown therapy. Adults treated between 1/2016-12/2022 for uncomplicated E. coli or Klebsiella species bacteremia of urinary tract origin who were who were transitioned to an oral regimen after ≤ 4 days of effective intravenous (IV) antibiotics were included. Propensity weighting was used to balance characteristics between groups. 60-day recurrence was compared using a multinomial Cox proportional hazards model with probability of treatment weighting. Results Of 2,571 patients screened, 648 (25%) were included. Median age was 67 years (IQR 45-78) with only 103 males (16%). Characteristics were well-balanced between groups. Compared to FQs, TMP-SMX had similar effectiveness (adjusted hazard ratio, aHR 0.91 [95% CI, 0.30-2.78]), and HBBLs had higher risk of recurrence (aHR 2.19 [0.95-5.01]), although the difference was not statistically significant. Most (70%) of HBBLs were not optimally dosed for bacteremia. Total antibiotic duration ≤ 8 days was associated with higher recurrence in select patients with risk factors for failure. Conclusions FQs and TMP-SMX had similar effectiveness in this real-world dataset. HBBLs were associated with higher recurrence rates, but suboptimal dosing may have contributed. Further studies are needed to define optimal BL dosing and duration to mitigate treatment failures.