Antibiotics and Cure Rates in Childhood Febrile Urinary Tract Infections in Clinical Trials: A Systematic Review and Meta-analysis
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Urinary tract infections (UTIs) are common bacterial infections among children.
To systematically review the antimicrobials used for febrile UTIs in paediatric clinical trials and meta-analyse 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.
We identified 2762 published studies and included 30 clinical trials investigating 3913 cases of paediatric febrile urinary tract infections. Children with no underlying condition were the main population included in the trials (n = 2602; 66.5%). Cephalosporins were the most frequent antibiotics studied in trials (22/30, 73.3%). Only a few antibiotics active against resistant UTIs 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 3002 patients for whom cure and failure rates were reported, only 3.9% (3.9%; 118/3002) were considered clinically to have treatment failure, while 135 (4.5%; 135/3002) had microbiological failure.
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.
KV, RB and YH conceptualized and designed the work. KV, RB, JB and LF identified eligible studies. KV, RB and LF appraised study quality; data were extracted, transformed and analysed by KV and RB. Data analysis was guided by YH. MS and TZ contributed substantially to data interpretation. KV and RB drafted the initial manuscript. JB, LF, TZ, MS and YH critically revised the manuscript for important intellectual content. All authors contributed to, reviewed, and approved the final version to be published. All authors received access to all the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. YH is the guarantor.
Compliance with Ethical Standards
No external funding for this manuscript.
Conflict of interest
MS reports grants from GlaxoSmithKline, Pfizer and Cubist Pharmaceuticals, outside the submitted work. JB’s husband is senior corporate counsel at Novartis International AG, Basel, Switzerland, and holds Novartis stock and stock options. The other authors have no conflicts of interest to disclose.
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