Rachel E Selekman1, Daniel J Shapiro2, John Boscardin3, Gabrielle Williams4, Jonathan C Craig4, Per Brandström5, Marco Pennesi6, Gwenalle Roussey-Kesler7, Pankaj Hari8, Hillary L Copp9. 1. Departments of Urology. 2. Boston Combined Residency Program, Boston Children's Hospital and Boston Medical Center, Boston, Massachusetts. 3. Medicine, and Biostatistics, University of California, San Francisco, San Francisco, California. 4. School of Public Health, University of Sydney, Camperdown, New South Wales, Australia. 5. Pediatric Uro-Nephrologic Center, Sahlgrenska Academy, University of Gothenburg and Queen Slivias Children's Hospital, Gothenburg, Sweden. 6. Department of Pediatrics, Institute for Child and Maternal Health, University of Trieste, Trieste, Italy. 7. Department of Pediatrics, University Hospital of Nantes, Nantes, France; and. 8. Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. 9. Departments of Urology, hillary.copp@ucsf.edu.
Abstract
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.
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.
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