Reducing antibiotic use in uncomplicated urinary tract infections in adult women: a systematic review and individual participant data meta-analysis

Kaußner Y, Röver C, Heinz J, Hummers E, Debray TPA, Hay AD, Heytens S, Vik I, Little P, Moore M, Stuart B, Wagenlehner F, Kronenberg A, Ferry S, Monsen T, Lindbæk M, Friede T, Gágyor I

Background: Randomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics and placebo to prevent overprescription of antibiotics in women with uncomplicated urinary tract infections (uUTI).

Objectives: To estimate the effect of these strategies and to identify symptoms, signs or other factors that indicate a benefit from these strategies.

Data sources: MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Database of Systematic Reviews and of Controlled Trials, and ClinicalTrials.

Study eligibility criteria, participants and interventions: RCTs investigating any strategies to reduce antibiotics versus immediate antibiotics in adult women with uUTI in primary care.

Data synthesis: We extracted individual participant data (IPD) if available, otherwise aggregate data (AD). Bayesian random-effects meta-analysis of the AD was used for pairwise comparisons. Candidate moderators and prognostic indicators of treatment effects were investigated using generalised linear mixed models based on IPD.

Results: We analysed IPD of 3524 patients from eight RCTs and AD of 78 patients. Non-antibiotic strategies increased the rates of incomplete recovery (odds ratio [OR] 3.0; 95% credible interval [CI] 1.7-5.5; Bayesian p-value pB=0.0017; ?=0.6), subsequent antibiotic treatment (OR 3.5 [95% CI 2.1, 5.8; pB=0.0003) and pyelonephritis (OR 5.6; 95% CI 2.3, 13.9; pB=0.0003). Conversely, they decreased overall antibiotic use by 63%. In patients positive for urinary erythrocytes and urine culture were at increased risk for incomplete recovery (OR 4.7; 95% CI 2.1-10.8; pB=0.0010), but no difference was apparent where both were negative (OR 0.8; 95% CI 0.3-2.0; pB=0.667). In patients treated with using non-antibiotic strategies, urinary erythrocytes and positive urine culture were independent prognostic indicators for subsequent antibiotic treatment and pyelonephritis.

Conclusions and relevance: Compared to immediate antibiotics, non-antibiotic strategies reduce overall antibiotic use but result in poorer clinical outcomes. The presence of erythrocytes and tests to confirm bacteria in urine could be used to target antibiotic prescribing.

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