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Clinical Trial
. 2024 Apr 4;11(4):ofae193.
doi: 10.1093/ofid/ofae193. eCollection 2024 Apr.

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

John J Veillette  1   2 , Stephanie S May  1   2 , Sameer Alzaidi  3 , Jared Olson  4   5 , Allison M Butler  6 , C Dustin Waters  7 , Katarina Jackson  2 , Mary A Hutton  8 , Brandon J Webb  9
Affiliations
Clinical Trial

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

John J Veillette et al. Open Forum Infect Dis. .

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.

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Conflict of interest statement

Potential conflicts of interest. All authors: No reported conflicts of interest.

Figures

Figure 1.
Figure 1.
Patient inclusion/exclusion. Abbreviations: FQ, fluoroquinolone; HBBL, high-bioavailability β-lactam; IVBL, intravenous β-lactam; LBBL, low-bioavailability β-lactam; TMP-SMX, trimethoprim-sulfamethoxazole; UTI, urinary tract infection.
Figure 2.
Figure 2.
Recurrence-free days for gram-negative bloodstream infection from a complicated urinary tract infection source, comparing intravenous β-lactam (IVBL) versus oral stepdown therapies. Data represent cumulative incidence curves generated from the propensity-weighted Cox proportional hazards models. Abbreviations: FQ, fluoroquinolone; HBBL, high-bioavailability β-lactam; TMP-SMX, trimethoprim-sulfamethoxazole (all taken orally).
Figure 3.
Figure 3.
Recurrence-free days through day 60 for gram-negative bloodstream infection from a complicated urinary tract infection source, based on treatment regimen and total duration. Data represent cumulative incidence curves generated from the propensity-weighted Cox proportional hazards models. Abbreviations: FQ, fluoroquinolone, HBBL, high-bioavailability β-lactam; IVBL, intravenous β-lactam; TMP-SMX, trimethoprim-sulfamethoxazole (all taken orally).
See this image and copyright information in PMC

References

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