Non-steroidal anti-inflammatory drugs for treating symptomatic uncomplicated urinary tract infections in non-pregnant adult women.

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Almost half of all women will have at least one symptomatic urinary tract infection (UTI) in their lifetime. Although usually self-remitting, 74% of women contacting a health professional are prescribed an antibiotic, and in rare instances, they may progress to more severe infections. Therefore, the standard of care for the treatment of symptomatic uncomplicated UTIs is oral antibiotic therapy, which aims to achieve symptom resolution and prevent the development of complications such as pyelonephritis. Given that a number of UTIs are self-remitting, non-antibiotic treatments that may help reduce the severity or duration of symptoms or reduce the need for antibiotics may be of benefit. This review aims to investigate the benefits and risks associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of symptomatic uncomplicated UTIs in non-pregnant adult women. We searched the Cochrane Kidney and Transplant Register of Studies up to 18 November 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. We included all randomised controlled trials (RCTs) and quasi-RCTs looking at the effectiveness of NSAIDs in the treatment of symptomatic uncomplicated UTIs in non-pregnant adult women. The outcomes of interest were: 1) short-term resolution of symptoms (days 1 to 4); 2) medium-term resolution of symptoms (days 5 to 10); and 3) incidence of adverse events (including progression to sepsis or complicated UTI, hospitalisation or need for intravenous antibiotics, gastrointestinal complications, or death) up to 30 days from randomisation. Screening, abstract selection, and data extraction were carried out independently by two authors, and any disagreements were resolved by discussion with a third author. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Six studies (1646 randomised women) published between 2010 and 2019 met our inclusion criteria. The mean age ranged from 28 to 50 years; previous UTIs were reported in 7.2% to 77% of participants. There were five multicentre studies, and studies were carried out in Denmark, Germany, Korea, Norway, Sweden, Switzerland, and the UK. Overall, the risk of bias was low or unclear. Compared to antibiotics, NSAIDs probably result in less short-term resolution of symptoms (4 studies, 1144 participants: RR 0.67, 95% CI 0.49 to 0.91; I2 = 75%; moderate certainty) and may also result in less medium-term resolution of symptoms (4 studies, 1140 participants: RR 0.84, 95% CI 0.71 to 1.01; I2 = 78%; low certainty). NSAIDs probably make little or no difference to the number of adverse events by day 30 (4 studies, 1165 participants: RR 1.08, 95% CI 0.88 to 1.33; I2 = 64%; moderate certainty). NSAIDs may result in longer duration of symptoms (2 studies, 553 participants: MD 1.00 day, 95% CI 0.61 to 1.39; I2 = 0%; low certainty). NSAIDs may result in a lower proportion of women experiencing microbiological resolution by day 10 compared to antibiotics (2 studies, 322 participants: RR 0.76, 95% CI 0.68 to 0.85; I2 = 0%; low certainty) and probably result in more women using rescue antibiotic treatment by day 30 (4 studies, 1165 participants: RR 3.14, 95% CI 2.23 to 4.42; I2 = 49%; moderate certainty). Compared to placebo, NSAIDs may reduce the use of rescue antibiotic treatment (1 study, 183 participants: RR 0.56, 95% CI 0.36 to 0.87; low certainty evidence) but may make little or no difference to adverse events at day 30. Compared to the herbal product Uva-Ursi, NSAIDs may make little or no difference to adverse events by day 30. The use of NSAIDs for symptomatic management of uncomplicated UTIs probably results in less short-term resolution of symptoms and greater use of rescue antibiotics by day 30 compared to primary antibiotic treatment. Future studies should consider the various confounders such as degree of symptoms, microbiology, type and resistance patterns of bacteria involved and number of UTI episodes in the months prior to commencement of treatment.