Uropathogen Resistance and Antibiotic Prophylaxis: A Meta-analysis

CONTEXT: Limited data exist regarding uropathogen resistance in randomized controlled trials of urinary tract infection (UTI) prevention and antibiotic prophylaxis. OBJECTIVE: To assess the effect of prophylaxis on developing a multidrug-resistant first recurrent UTI among children with vesicoureteral reflux. DATA SOURCES: Cochrane Kidney and Transplant Specialized Register through May 25, 2017. STUDY SELECTION: Randomized controlled trials of patients 18 years of age with a history of vesicoureteral reflux being treated with continuous antibiotic prophylaxis compared with no treatment or placebo with available antibiotic sensitivity profiles. DATA EXTRACTION: Two independent observers abstracted data and assessed quality and validity per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Adjusted meta-analyses were performed by using a mixed-effects logistic regression model. RESULTS: One thousand two hundred and ninety-nine patients contributed 224 UTIs. Patients treated with prophylaxis were more likely to have a multidrug-resistant infection (33% vs 6%, P < .001) and were more likely to receive broad-spectrum antibiotics (68% vs 49%, P = .004). Those receiving prophylaxis had 6.4 times the odds (95% confidence interval: 2.7-15.6) of developing a multidrug-resistant infection. One multidrug-resistant infection would develop for every 21 reflux patients treated with prophylaxis. LIMITATIONS: Variables that may contribute to resistance such as medication adherence and antibiotic exposure for other illnesses could not be evaluated. CONCLUSIONS: Prophylaxis increases the risk of multidrug resistance among recurrent infections. This has important implications in the risk-benefit assessment of prophylaxis as a management strategy and in the selection of empirical treatment of breakthrough infections in prophylaxis patients.