Recurrent Urinary Tract Infections in Children

Risk Factors and Association With Prophylactic Antimicrobials

Conway, Patrick H. MD, MSc
Cnaan, Avital PhD
Zaoutis, Theoklis MD, MSCE
Henry, Brandon V. BS
Grundmeier, Robert W. MD
Keren, Ron MD, MPH

Robert Wood Johnson Foundation Clinical Scholars Program (Dr Conway), Leonard Davis Institute of Health Economics (Drs Conway, Zaoutis, and Keren), Center for Clinical Epidemiology and Biostatistics (Drs Conway, Cnaan, Zaoutis, and Keren), and School of Medicine (Mr Henry), University of Pennsylvania, Philadelphia; Division of General Pediatrics (Drs Conway, Zaoutis, and Keren), Division of Biostatistics and Epidemiology (Dr Cnaan), and Center for Biomedical Informatics (Dr Grundmeier), Children's Hospital of Philadelphia; and Center for Health Care Quality and Division of General Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio (Dr Conway).

Corresponding Author: Patrick H. Conway, MD, MSc, Robert Wood Johnson Clinical Scholars Program, University of Pennsylvania, 423 Guardian Dr, Blockley Hall 1303A, Philadelphia, PA 19104 ([email protected]).

Author Contributions: Dr Conway had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Conway, Cnaan, Zaoutis, Grundmeier, Keren.

Acquisition of data: Conway, Cnaan, Henry, Grundmeier, Keren.

Analysis and interpretation of data: Conway, Cnaan, Zaoutis, Keren.

Drafting of the manuscript: Conway, Cnaan, Keren.

Critical revision of the manuscript for important intellectual content: Conway, Cnaan, Zaoutis, Henry, Grundmeier, Keren.

Statistical analysis: Conway, Cnaan, Henry, Keren.

Obtained funding: Conway, Zaoutis, Keren.

Administrative, technical, or material support: Henry, Grundmeier, Keren.

Study supervision: Cnaan, Keren.

Financial Disclosures: None reported.

Funding/Support: Dr Conway was supported by a training grant through the Robert Wood Johnson Clinical Scholars Training Program. This project was supported through a pilot grant from a University of Pennsylvania Center for Education and Research on Therapeutics (CERTS) grant. Dr Cnaan is supported by National Institutes of Health (NIH) Clinical and Translational Science Award U54 RR023567-01. Dr Keren was supported by grant K23 HD043179 from the National Institute of Child Health and Human Development, NIH.

Role of the Sponsors: None of the funding sources had any role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.

Additional Contributions: We thank the physicians and staff of the Practice-Based Research Network, especially Marguerite Swietlik, CRNP, and Louis Bell, MD, who facilitated the performance of this study. We thank Chris Bell for research support and data collection and Huaqing Zhao, MSc, The Children's Hospital of Pennsylvania Biostatistics and Data Management Core, for statistical support. None of those acknowledged received any compensation for their contributions.

JAMA: The Journal of the American Medical Association 298(2):p 179-186, July 11, 2007.

Context

The evidence regarding risk factors for recurrent urinary tract infection (UTI) and the risks and benefits of antimicrobial prophylaxis in children is scant.

Objectives

To identify risk factors for recurrent UTI in a pediatric primary care cohort, to determine the association between antimicrobial prophylaxis and recurrent UTI, and to identify the risk factors for resistance among recurrent UTIs.

Design, Patients, and Setting

From a network of 27 primary care pediatric practices in urban, suburban, and semirural areas spanning 3 states, a cohort of children aged 6 years or younger who were diagnosed with first UTI between July 1, 2001, and May 31, 2006, was assembled. Time-to-event analysis was used to determine risk factors for recurrent UTI and the association between antimicrobial prophylaxis and recurrent UTI, and a nested case-control study was performed among children with recurrent UTI to identify risk factors for resistant infections.

Main Outcome Measures

Time to recurrent UTI and antimicrobial resistance of recurrent UTI pathogens.

Results

Among 74 974 children in the network, 611 (0.007 per person-year) had a first UTI and 83 (0.12 per person-year after first UTI) had a recurrent UTI. In multivariable Cox time-to-event models, factors associated with increased risk of recurrent UTI included white race (0.17 per person-year; hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.22–3.16), age 3 to 4 years (0.22 per person-year; HR, 2.75; 95% CI, 1.37–5.51), age 4 to 5 years (0.19 per person-year; HR, 2.47; 95% CI, 1.19–5.12), and grade 4 to 5 vesicoureteral reflux (0.60 per person-year; HR, 4.38; 95% CI, 1.26–15.29). Sex and grade 1 to 3 vesicoureteral reflux were not associated with risk of recurrence. Antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI (HR, 1.01; 95% CI, 0.50–2.02), even after adjusting for propensity to receive prophylaxis, but was a risk factor for antibimicrobial resistance among children with recurrent UTI (HR, 7.50; 95% CI, 1.60–35.17).

Conclusion

Among the children in this study, antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI, but was associated with increased risk of resistant infections.