title: Nitrofurantoin vs other prophylactic agents in reducing recurrent urinary tract infections in adult women: a systematic review and meta-analysis.
abstract: BACKGROUND
  The clinical and financial burden from bladder infections is significant. Daily antibiotic use is the recommended strategy for recurrent urinary tract infection prevention. Increasing antibiotic resistance rates, however, require immediate identification of innovative alternative prophylactic therapies. This systematic review aims to provide guidance on gaps in evidence to guide future research.
  
  
  OBJECTIVE
  The objective of this review was to provide current pooled estimates of randomized control trials comparing the effects of nitrofurantoin vs other agents in reducing recurrent urinary tract infections in adult, nonpregnant women and assess relative adverse side effects.
  
  
  METHODS
  Data sources included the following: MEDLINE, Jan. 1, 1946, to Jan. 31, 2015; Cochrane Central Register of Controlled Trials the Cochrane Database of Systematic Reviews, and web sites of the National Institute for Clinical Excellence, and the National Guideline Clearinghouse from 2000 to 2015. Randomized control trials of women with recurrent urinary tract infections comparing nitrofurantoin with any other treatment were included.
  
  
  METHODS
  A protocol for the study was developed a priori. Published guidance was followed for assessment of study quality. All meta-analyses were performed using random-effects models with Stats Direct Software. Dual review was used for all decisions and data abstraction.
  
  
  RESULTS
  Twelve randomized control trials 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, methamine hippurate, estriol, or cefaclor were found in clinical or microbiological cure in adult nonpregnant women with recurrent urinary tract infections (9 randomized control trials, 673 patients, relative risk ratio, 1.06; 95% confidence interval, 0.89-1.27; I2, 65%; and 12 randomized control trials, 1063 patients, relative risk ratio, 1.06; 95% confidence interval, 0.90-1.26; I2, 76%, respectively). Duration of prophylaxis also did not have a significant impact on outcomes. There was a statistically significant difference in overall adverse effects, with nitrofurantoin resulting in greater risk than other prophylactic treatments (10 randomized control trials, 948 patients, relative risk ratio, 2.17; 95% confidence interval, 1.34-3.50; I2, 61%). Overall, the majority of nitrofurantoin adverse effects were gastrointestinal, with a significant difference for withdrawals (12 randomized control trials, 1063 patients, relative risk ratio, 2.14; 95% confidence interval, 1.28-3.56; I2, 8%).
  
  
  CONCLUSIONS
  Nitrofurantoin had similar efficacy but a greater risk of adverse events than other prophylactic treatments. Balancing the risks of adverse events, particularly gastrointestinal symptoms, with potential benefits of decreasing collateral ecological damage should be considered if selecting nitrofurantoin.
authors.affiliation: Division of Urogynecology and Reconstructive Pelvic Surgery, Oregon Health and Science University, Portland, OR. Electronic address: jamecap@hotmail.com.
authors.forename: Jameca Renee
authors.initials: JR
authors.lastname: Price
authors.affiliation: College of Medicine, Oregon Health and Science University, Portland, OR.
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Guran
authors.affiliation: Division of Urogynecology and Reconstructive Pelvic Surgery, Oregon Health and Science University, Portland, OR.
authors.forename: W Thomas
authors.initials: WT
authors.lastname: Gregory
authors.affiliation: Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, OR.
authors.forename: Marian S
authors.initials: MS
authors.lastname: McDonagh
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000892:Anti-Infective Agents, Urinary / Q000627:therapeutic use*; D002433:Cefaclor / Q000627:therapeutic use; D004964:Estriol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D009582:Nitrofurantoin / Q000627:therapeutic use*; D009643:Norfloxacin / Q000627:therapeutic use; D012008:Recurrence; D055502:Secondary Prevention; D014295:Trimethoprim / Q000627:therapeutic use; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D014552:Urinary Tract Infections / Q000517:prevention & control*
chemical_list: D000900:Anti-Bacterial Agents; D000892:Anti-Infective Agents, Urinary; D002433:Cefaclor; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D009582:Nitrofurantoin; D014295:Trimethoprim; D004964:Estriol; D009643:Norfloxacin
keywords: adult women; bladder infection; meta-analysis; prophylaxis; recurrence; systematic review; urinary tract infection