Systematic Review
Nitrofurantoin vs other prophylactic agents in reducing recurrent urinary tract infections in adult women: a systematic review and meta-analysis

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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.

Data Sources

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.

Study Design

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%).

Conclusion

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.

Section snippets

Materials and Methods

A detailed description of the methods is available online in a protocol registered a priori with the PROSPERO registry (www.crd.york.ac.uk/PROSPERO; record number 23966). An investigational review board reviewed and exempted this study.

Description of included studies

The literature search yielded 1061 articles, of which 78 were reviewed in full text (Figure 1). Of these studies, 12 randomized control trials met the inclusion criteria. These trials included a total of 1063 patients, in whom 344 bacterial urinary tract infections were reported from 10 studies. The remaining studies reviewed in full text were excluded for the following reasons: studies without nitrofurantoin prophylaxis therapy, nitrofurantoin therapy with acute bacterial infections, other

Comment

Twelve randomized, clinical trials involving 1063 patients were included in this review. No significant differences in prophylactic antibiotic treatment with nitrofurantoin, norfloxacin, trimethoprim, sulfamethoxazole/trimethoprim, methenamine hippurate, 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%,

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  • Cited by (0)

    The authors report no conflict of interest.

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