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Discordant Clinical and Microbiological Outcomes Are Associated With Late Clinical Relapse in Clinical Trials for Complicated Urinary Tract Infections

Journal Article · · Clinical Infectious Diseases
DOI:https://doi.org/10.1093/cid/ciad010· OSTI ID:2425644
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Abstract Background

Current US Food and Drug Administration guidance recommends that the primary endpoint for complicated urinary tract infection clinical trials be a composite of the clinical and microbiological responses, assessed at a fixed point after therapy. Although some participants meet the criteria for clinical success, they do not meet the criteria for microbiological eradication and are classified as treatment failures. These discordant outcomes have raised questions about the utility of the microbiological endpoint.

Methods

We analyzed participant data from 13 phase 3 clinical trials submitted to the US Food and Drug Administration (N = 4842). Outcomes were determined at the test of cure (TOC) visit, recommended to occur at least 5 days after therapy and at the late follow-up visit, recommended to occur 21 to 28 days after randomization. Clinical and microbiological success were defined as the resolution of complicated urinary tract infection symptoms present at study entry, with no new symptoms (clinical cure), and a reduction in density of the original pathogen to <103 CFU/mL on urine culture (microbiological eradication).

Results

Among included participants, 70.7% were concordant successes at the TOC visit, 18.0% were discordant failures (clinical cure/microbiological persistence), and 6.7% were concordant failures (clinical failure/microbiological persistence). Discordant participants were at an increased risk for clinical failure at the late follow-up visit, and the risk of late clinical failure increased with time.

Conclusions

Discordant clinical and microbiological outcomes at the TOC visit were associated with an increased risk of late clinical failure. Microbiological outcomes appear to be an important component of the endpoint.

Research Organization:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
DOE Contract Number:
SC0014664
OSTI ID:
2425644
Journal Information:
Clinical Infectious Diseases, Journal Name: Clinical Infectious Diseases Journal Issue: 10 Vol. 76; ISSN 1058-4838
Publisher:
Oxford University Press
Country of Publication:
United States
Language:
English

References (12)

An update on the management of urinary tract infections in the era of antimicrobial resistance journal October 2016
Risk of recurrent acute lower urinary tract infections and prescription pattern of antibiotics in women with and without diabetes in primary care journal May 2010
The Asymptomatic Bacteriuria Escherichia coli Strain 83972 Outcompetes Uropathogenic E. coli Strains in Human Urine journal January 2006
Management of urinary tract infection in women: A practical approach for everyday practice journal January 2019
Urine testing is associated with inappropriate antibiotic use and increased length of stay in emergency department patients journal October 2022
Corrigendum to: Longitudinal, Nationwide, Cohort Study to Assess Incidence, Outcomes, and Costs Associated With Complicated Urinary Tract Infection journal January 2020
Genetic Control of the Variable Innate Immune Response to Asymptomatic Bacteriuria journal November 2011
Conducting Meta-Analyses in R with the metafor Package journal January 2010
Random-effects model for meta-analysis of clinical trials: An update journal February 2007
Extending DerSimonian and Laird's methodology to perform multivariate random effects meta‐analyses journal May 2010
Urinary Tract Infection journal July 2013
Molecular determinants of disease severity in urinary tract infection journal June 2021

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