Urinary Tract Infection Antibiotic Trial Study Design: A Systematic Review

Area of Science:

• Pediatric infectious diseases
• Clinical trial methodology
• Urology

Background:

• Urinary tract infections (UTIs) are common bacterial infections in children.
• No established guidance exists for conducting pediatric febrile UTI clinical trials (CTs).

Purpose of the Study:

• To evaluate patient selection criteria in pediatric febrile UTI CTs.
• To assess efficacy endpoints utilized in these trials.

Main Methods:

• Systematic search of Medline, Embase, Cochrane, and clinicaltrials.gov (1990-2016).
• Combined search terms for UTIs, therapeutics, and clinical trials in children (0-18 years).
• Two independent reviewers performed data extraction and quality assessment on 40 included CTs.

Main Results:

• Positive urine culture and fever were common inclusion criteria (93%, 78%).
• Significant variability observed in urine sampling, pyuria, and colony thresholds.
• Clinical (88%) and microbiological (93%) endpoints were assessed, but timing was inconsistent.
• Only 17% of trials post-1998 FDA guidance adhered to its endpoint assessment recommendations.

Conclusions:

• Wide variability exists in microbiological criteria and endpoint assessment timing for pediatric UTI CTs.
• Existing adult UTI guidance appears underutilized and potentially inapplicable to pediatric populations.
• A need for harmonized clinical trial designs for pediatric UTIs is evident.