Antibiotics and cure rates in childhood febrile urinary tract infections in clinical trials: a systematic review and meta-analysis

Purpose: Urinary tract infections (UTIs) are common bacterial infections among children. Objective: To systematically review the antimicrobials used for febrile urinary tract infections in pediatric clinical trials and meta-analyze the observed cure rates and reasons for treatment failure. Materials and Methods: We searched Medline, Embase and Cochrane central databases between January 1, 1990, and November 24, 2016, combining MeSH and free-text terms for: “urinary tract infections”, AND “therapeutics”, AND “clinical trials” in children (age range 0–18 years). Two independent reviewers assessed study quality and performed data extraction. The major outcome measures were clinical and microbiological cure rates according to different antibiotics. Results: We identified 2,762 published studies and included 30 clinical trials investigating 3913 cases of pediatric febrile urinary tract infections. Children with no underlying condition were the main population included in the trials (n=2,602; 66.5%). Cephalosporins were the most frequent antibiotics studied in trials (22/30, 73.3%). Only a few antibiotics active against resistant urinary tract infections have been tested in randomised clinical trials, mainly aminoglycosides. The average point cure rate of all investigational drugs was estimated to 95.3% [95% CI 93.5-96.9%]. Among 3,002 patients for whom cure and failure rates were reported, only 3.9% (3.9%; 118/3,002) were considered clinically to have treatment failure, while 135 (4.5%; 135/3,002) had microbiological failure. Conclusions: We observed high treatment cure rates, regardless of the investigational drug chosen, the route of administration, duration and dosing. This suggests that future research should prioritise observational studies and clinical trials on children with multi-drug resistant infections