title: Nitrofurantoin's efficacy and safety as prophylaxis for urinary tract infections: a systematic review of the literature and meta-analysis of controlled trials.
abstract: OBJECTIVE
  Nitrofurantoin has been used for the prevention of urinary tract infection (UTI) for over 60 years. We conducted a systematic review and meta-analysis to assess its efficacy and safety in the prophylaxis of UTI.
  
  
  METHODS
  We performed a systematic review of all controlled trials in humans assessing nitrofurantoin for UTI prophylaxis published from 1946 to 2015. We further reviewed population-level cohort studies evaluating nitrofurantoin's toxicity. Meta-analyses assessing efficacy and adverse events were conducted on controlled trials.
  
  
  RESULTS
  Twenty-six controlled trials including 3052 patients fulfilled entry criteria for the systematic review and meta-analysis on efficacy and toxicity, and 16 population-level cohort studies were identified for review of toxicity. Overall quality was poor, with all studies at increased risk for various biases. When compared with no prophylaxis, nitrofurantoin is effective in the prevention of UTI (risk ratio 0.38 in favour of nitrofurantoin, 95% CI 0.30-0.48). Its prophylactic efficacy is superior to that of methenamine hippurate and comparable to that of other antibacterials. Compared with patients receiving other antibacterials, those receiving nitrofurantoin had an increased risk of 2.24 (95% CI 1.77-2.83) for a non-severe adverse effect. In all controlled trials, only one patient experienced a severe adverse effect (interstitial pneumonia). Cohort studies reported severe adverse effect frequencies of 0.02-1.5 per 1000 nitrofurantoin users.
  
  
  CONCLUSIONS
  Nitrofurantoin is effective in the prevention of UTI. Its use may be associated with increased non-severe adverse effects; severe adverse effects occur infrequently. The risk of severe toxicity seems to increase with the duration of nitrofurantoin prophylaxis.
authors.affiliation: Medical Centre Haaglanden-Bronovo, The Hague, The Netherlands. Electronic address: muller.research@gmail.com.
authors.forename: A E
authors.initials: AE
authors.lastname: Muller
authors.affiliation: Laboratory of Medical Microbiology and Immunology, St Elisabeth Hospital, Tilburg, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: Verhaegh
authors.affiliation: Infection Control Programme, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Harbarth
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Mouton
authors.affiliation: Infection Control Programme, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Huttner
mesh_terms: D000892:Anti-Infective Agents, Urinary / Q000009:adverse effects / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic; D005260:Female; D006801:Humans; D009582:Nitrofurantoin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000517:prevention & control*
chemical_list: D000892:Anti-Infective Agents, Urinary; D009582:Nitrofurantoin
keywords: Meta-analysis; Nitrofurantoin; Prophylaxis; Toxicity; Urinary tract infection