Real-World Effectiveness of Intravenous and Oral Antibiotic Stepdown Strategies for Gram-Negative Complicated Urinary Tract Infection With Bacteremia

John J Veillette; Stephanie S May; Sameer Alzaidi; Jared Olson; Allison M Butler; C Dustin Waters; Katarina Jackson; Mary A Hutton; Brandon J Webb

doi:10.1093/ofid/ofae193

Real-World Effectiveness of Intravenous and Oral Antibiotic Stepdown Strategies for Gram-Negative Complicated Urinary Tract Infection With Bacteremia

Open Forum Infect Dis. 2024 Apr 4;11(4):ofae193. doi: 10.1093/ofid/ofae193. eCollection 2024 Apr.

Authors

John J Veillette^{1

2}, Stephanie S May^{1

2}, Sameer Alzaidi³, Jared Olson^{4

5}, Allison M Butler⁶, C Dustin Waters⁷, Katarina Jackson², Mary A Hutton⁸, Brandon J Webb⁹

Affiliations

¹ Infectious Diseases Telehealth Service, Intermountain Health, Murray, Utah, USA.
² Department of Pharmacy, Intermountain Medical Center, Murray, Utah, USA.
³ Pharmacy Services, Intermountain Health, Taylorsville, Utah, USA.
⁴ Department of Pharmacy, Primary Children's Hospital, Salt Lake City, Utah, USA.
⁵ Division of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
⁶ Statistical Data Center, Intermountain Health, Murray, Utah, USA.
⁷ Department of Pharmacy, McKay-Dee Hospital, Ogden, Utah, USA.
⁸ Department of Pharmacy, Utah Valley Hospital, Provo, Utah, USA.
⁹ Division of Clinical Epidemiology and Infectious Diseases, Intermountain Medical Center, Murray, Utah, USA.

Abstract

Background: Robust data are lacking regarding the optimal route, duration, and antibiotic choice for gram-negative bloodstream infection from a complicated urinary tract infection source (GN-BSI/cUTI).

Methods: In this multicenter observational cohort study, we simulated a 4-arm registry trial using a causal inference method to compare effectiveness of the following regimens for GN-BSI/cUTI: complete course of an intravenous β-lactam (IVBL) or oral stepdown therapy within 7 days using fluoroquinolones (FQs), trimethoprim-sulfamethoxazole (TMP-SMX), or high-bioavailability β-lactams (HBBLs). Adults treated between January 2016 and December 2022 for Escherichia coli or Klebsiella species GN-BSI/cUTI were included. Propensity weighting was used to balance characteristics between groups. The 60-day recurrence was compared using a multinomial Cox proportional hazards model with probability of treatment weighting.

Results: Of 2571 patients screened, 759 (30%) were included. Characteristics were similar between groups. Compared with IVBLs, we did not observe a difference in effectiveness for FQs (adjusted hazard ratio, 1.09 [95% confidence interval, .49-2.43]) or TMP-SMX (1.44 [.54-3.87]), and the effectiveness of TMP-SMX/FQ appeared to be optimal at durations of >10 days. HBBLs were associated with nearly 4-fold higher risk of recurrence (adjusted hazard ratio, 3.83 [95% confidence interval, 1.76-8.33]), which was not mitigated by longer treatment durations. Most HBBLs (67%) were not optimally dosed for bacteremia. Results were robust to multiple sensitivity analyses.

Conclusions: These real-world data suggest that oral stepdown therapy with FQs or TMP-SMX have similar effectiveness as IVBLs. HBBLs were associated with higher recurrence rates, but dosing was suboptimal. Further data are needed to define optimal dosing and duration to mitigate treatment failures.

Keywords: antimicrobial stewardship; complicated urinary tract infection; gram-negative bacteremia; real-world evidence; β-lactams.

Publication types

Clinical Trial