OBJECTIVE: The objective of this review was to provide current pooled estimates of randomized controlled trials (RCTs) comparing the effects of nitrofurantoin versus all other treatments including other antibiotics in reducing recurrent urinary tract infections in adult, non-pregnant women and assess relative adverse side effects.
DATA SOURCES: MEDLINE January 1, 1946 to January 31, 2015; Cochrane Central Register of Controlled Trials (CENTRAL), tCochrane Database of Systematic Reviews, ClinicalTrials.gov, and Web sites of the National Institute for Clinical Excellence, and the National Guideline Clearinghouse from 2000 to 2015.
STUDY ELIGIBILITY CRITERIA: This systematic review aims to provide guidance on gaps in evidence to guide future research.
A description of the inclusion criteria is available online. (www.crd.york.ac.uk/PROSPERO; Record number 23966) STUDY APPRAISAL AND SYNTHESIS METHODS: Quality of included studies was assessed using the Drug Effectiveness Review Project (DERP) tool. Studies were synthesized by pooling data on similar outcomes across studies with similar design, methodology, and patient populations.
RESULTS: Twelve RCTs involving 1063 patients were included. One study that had a serious flaw was rated poor in quality, one study rated good, and the remainder fair. No significant differences in prophylactic antibiotic treatment with nitrofurantoin and norfloxacin, trimethoprim, sulfamethoxazole/trimethoprim, methenamine hippurate, estriol, or cefaclor were found in clinical (9 RCTs, 673 patients, RR = 1.06, 95% CI = 0.89 - 1.27, I2 65%) or microbiological cure in adult non-pregnant women with recurrent UTIs (12 RCTs, 1063 patients, RR = 1.06, 95% CI = 0.90 to 1.26, I2 76% ). Duration of prophylaxis also did not significantly impact outcomes. There was a statistically significant difference in overall adverse effects with nitrofurantoin resulting in greater risk than other prophylactic treatments (10 RCTS, 948 patients, RR = 2.17, 95% CI = 1.34 to 3.50; I2 61%) with a significant difference for withdrawals (12 RCTs, 1063 patients, RR = 2.14, 95% CI = 1.28 to 3.56, I2 8%). Overall, the majority of nitrofurantoin adverse effects were gastrointestinal.
CONCLUSIONS: Nitrofurantoin had similar efficacy, but greater risk of adverse events than other prophylactic treatments. Balancing the risks of adverse events, particularly gastrointestinal symptoms, should be considered if selecting nitrofurantoin.