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Long-term antibiotics for prevention of recurrent urinary tract infection in older adults: systematic review and meta-analysis of randomised trials.

ABSTRACT:

Objective

To address clinical uncertainties about the effectiveness and safety of long-term antibiotic therapy for preventing recurrent urinary tract infections (UTIs) in older adults.

Design

Systematic review andmeta-analysis of randomised trials.

Method

We searched Medline, Embase, The Cumulative Index to Nursing and Allied Health Literature(CINAHL), and the Cochrane Register of Controlled Trials from inception to August 2016. Eligible studies compared long-term antibiotic therapy with non-antibiotic therapy or placebo in men or women aged over 65, or in postmenopausal women, with recurrent UTIs.

Results

We did not identify any studies that included older men. Three randomised controlled trials compared long-term antibiotics with vaginal oestrogens (n=150), oral lactobacilli (n=238) and D-mannose powder (n=94) in postmenopausal women. Long-term antibiotics reduced the risk of UTI recurrence by 24% (three trials, n=482; pooled risk ratio (RR) 0.76; 95% CI 0.61 to 0.95, number needed to treat=8.5). There was no statistically significant increase in risk of adverse events (mild adverse events: pooled RR 1.52; 95% CI 0.76 to 3.03; serious adverse events: pooled RR 0.90, 95% CI 0.31 to 2.66). One trial showed 90% of urinary and faecal Escherichia coli isolates were resistant to trimethoprim-sulfamethoxazole after 1 month of prophylaxis.

Conclusions

Findings from three small trials with relatively short follow-up periods suggest long-term antibiotic therapy reduces the risk of recurrence in postmenopausal women with recurrent UTI. We did not identify any evidence to inform several clinically important scenarios including, benefits and harms in older men or frail care home residents, optimal duration of prophylaxis, recurrence rates once prophylaxis stops and effects on urinary antibiotic resistance.

SUBMITTER: Ahmed H

PROVIDER: S-EPMC5729980 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:At least half of all adult women will experience infective cystitis (urinary tract infection: UTI) at least once in their life and many suffer from repeated episodes. Recurrent urinary tract infection (rUTI) in adult women is usually treated with long-term, low-dose antibiotics and current national and international guidelines recommend this as the 'gold standard' preventative treatment. Although they are reasonably effective, long-term antibiotics can result in bacteria becoming resistant not only to the prescribed antibiotic but to other antimicrobial agents. The problem of antimicrobial resistance is recognised as a global threat and the recent drive for antibiotic stewardship has emphasised the need for careful consideration prior to prescribing antibiotics. This has led clinicians and patients alike to explore potential non-antibiotic options for recurrent UTI prevention. DESIGN /METHODS:This is a multicentre, pragmatic, patient-randomised, non-inferiority trial comparing a non-antibiotic preventative treatment for rUTI in women, methenamine hippurate, against the current standard of daily low-dose antibiotics. Women who require preventative treatment for rUTI are the target population. This group is comprised of those with a diagnosis of rUTI, defined as three episodes in 1 year or two episodes in 6 months, and those with a single severe infection requiring hospitalisation. Participants will be recruited from secondary care urology / urogynaecology departments in the UK following referral with rUTI. Participants will be followed up during a 12-month period of treatment and in the subsequent 6 months following completion of the prophylactic medication. Outcomes will be assessed from patient recorded symptoms, quality of life questionnaires and microbiological examination of urine and perineal swabs. The primary outcome is the incidence of symptomatic antibiotic-treated UTI self-reported by participants during the 12-month period of preventative treatment. Health economic outcomes will also be assessed to define the cost-effectiveness of both treatments. A qualitative study will be conducted in the first 8 months of the trial to explore with participants/non-participants' and recruiting clinicians' views on trial processes and identify potential barriers to recruitment, reasons for participating and non-participation and for dropping out of the study. DISCUSSION:The study was commissioned and funded by the National Institute for Health Research (NIHR) and approved under the Medicines and Healthcare products Regulatory Agency (MHRA) notification scheme as a 'Type A' study. TRIAL REGISTRATION:International Standard Randomised Controlled Trial Number (ISRCTN), registry number: ISRCTN70219762 . Registered on 31 May 2016.

Project description:ImportanceRecurrent urinary tract infection (UTI) is a common debilitating condition in women, with limited prophylactic options. d-Mannose has shown promise in trials based in secondary care, but effectiveness in placebo-controlled studies and community settings has not been established.ObjectiveTo determine whether d-mannose taken for 6 months reduces the proportion of women with recurrent UTI experiencing a medically attended UTI.Design, setting, and participantsThis 2-group, double-blind randomized placebo-controlled trial took place across 99 primary care centers in the UK. Participants were recruited between March 28, 2019, and January 31, 2020, with 6 months of follow-up. Participants were female, 18 years or older, living in the community, and had evidence in their primary care record of consultations for at least 2 UTIs in the preceding 6 months or 3 UTIs in 12 months. Invitation to participate was made by their primary care center. A total of 7591 participants were approached, 830 responded, and 232 were ineligible or did not proceed to randomization. Statistical analysis was reported in December 2022.InterventionTwo grams daily of d-mannose powder or matched volume of placebo powder.Main outcomes and measuresThe primary outcome measure was the proportion of women experiencing at least 1 further episode of clinically suspected UTI for which they contacted ambulatory care within 6 months of study entry. Secondary outcomes included symptom duration, antibiotic use, time to next medically attended UTI, number of suspected UTIs, and UTI-related hospital admissions.ResultsOf 598 women eligible (mean [range] age, 58 [18-93] years), 303 were randomized to d-mannose (50.7%) and 295 to placebo (49.3%). Primary outcome data were available for 583 participants (97.5%). The proportion contacting ambulatory care with a clinically suspected UTI was 150 of 294 (51.0%) in the d-mannose group and 161 of 289 (55.7%) in the placebo group (risk difference, -5%; 95% CI, -13% to 3%; P = .26). Estimates were similar in per protocol analyses, imputation analyses, and preplanned subgroups. There were no statistically significant differences in any secondary outcome measures.Conclusions and relevanceIn this randomized clinical trial, daily d-mannose did not reduce the proportion of women with recurrent UTI in primary care who experienced a subsequent clinically suspected UTI. d-Mannose should not be recommended for prophylaxis in this patient group.Trial registrationisrctn.org Identifier: ISRCTN13283516.

Project description:IntroductionRecurrent urinary tract infections (RUTIs) have a significant negative impact on quality of life and healthcare costs. To date, daily prophylactic antibiotics are the only treatment which have been shown to help prevent RUTIs. D-mannose is a type of sugar which is believed to inhibit bacterial adherence to uroepithelial cells, and is already being used by some women in an attempt to prevent RUTIs. There is currently insufficient rigorous evidence on which to base decisions about its use. The D-mannose to prevent recurrent urinary tract infections (MERIT) study will evaluate whether D-mannose is clinically and cost-effective in reducing frequency of infection and symptom burden for women presenting to UK primary care with RUTI.Methods and analysisMERIT will be a two-arm, individually randomised, double blind placebo controlled, pragmatic trial. Participants will be randomised to take D-mannose powder or placebo powder daily for 6 months. The primary outcome will be the number of medical attendances attributable to symptoms of RUTI. With 508 participants we will have 90% power to detect a 50% reduction in the chance of a further clinically suspected UTI, assuming 20% lost to follow-up. Secondary outcomes will include: number of days of moderately bad symptoms of UTI; time to next consultation; number of clinically suspected UTIs; number of microbiologically proven UTIs; number of antibiotic courses for UTI; quality of life and healthcare utilisation related to UTI. A within trial economic evaluation will be conducted to examine cost-effectiveness of D-mannose in comparison with placebo. A nested qualitative study will explore participants' experiences and perceptions of recruitment to, and participation in a study requiring a daily treatment.Ethics and disseminationEthical approval has been obtained from South West-Central Bristol Research Ethics Committee. Publication of the MERIT study is anticipated to occur in 2021.Trial registration numberISRCTN 13283516.