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Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women.

ABSTRACT: OBJECTIVES: To compare the effectiveness of cranberry extract with low-dose trimethoprim in the prevention of recurrent urinary tract infections (UTIs) in older women. PATIENTS AND METHODS: One hundred and thirty-seven women with two or more antibiotic-treated UTIs in the previous 12 months were randomized to receive either 500 mg of cranberry extract or 100 mg of trimethoprim for 6 months. RESULTS: Thirty-nine of 137 participants (28%) had an antibiotic-treated UTI (25 in the cranberry group and 14 in the trimethoprim group); difference in proportions relative risk 1.616 (95% CI: 0.93, 2.79) P = 0.084. The time to first recurrence of UTI was not significantly different between the groups (P = 0.100). The median time to recurrence of UTI was 84.5 days for the cranberry group and 91 days for the trimethoprim group (U = 166, P = 0.479). There were 17/137 (12%) withdrawals from the study, 6/69 (9%) from the cranberry group and 11/68 (16%) from the trimethoprim group (P = 0.205), with a relative risk of withdrawal from the cranberry group of 0.54 (95% CI: 0.19, 1.37). CONCLUSIONS: Trimethoprim had a very limited advantage over cranberry extract in the prevention of recurrent UTIs in older women and had more adverse effects. Our findings will allow older women with recurrent UTIs to weigh up with their clinicians the inherent attractions of a cheap, natural product like cranberry extract whose use does not carry the risk of antimicrobial resistance or super-infection with Clostridium difficile or fungi.

SUBMITTER: McMurdo ME

PROVIDER: S-EPMC2639265 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women.

McMurdo Marion E T ME Argo Ishbel I Phillips Gabby G Daly Fergus F Davey Peter P

The Journal of antimicrobial chemotherapy 20081128 2

<h4>Objectives</h4>To compare the effectiveness of cranberry extract with low-dose trimethoprim in the prevention of recurrent urinary tract infections (UTIs) in older women.<h4>Patients and methods</h4>One hundred and thirty-seven women with two or more antibiotic-treated UTIs in the previous 12 months were randomized to receive either 500 mg of cranberry extract or 100 mg of trimethoprim for 6 months.<h4>Results</h4>Thirty-nine of 137 participants (28%) had an antibiotic-treated UTI (25 in the ...[more]

PMID: 19042940

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Project description:Urinary tract infections (UTIs) are the most common bacterial infections requiring medical attention and a leading justification for antibiotic prescription. Trimethoprim is prescribed empirically for uncomplicated cases. UTIs are primarily caused by extraintestinal pathogenic Escherichia coli (ExPEC) and ExPEC strains play a central role in disseminating antimicrobial-resistance genes worldwide. Here, we describe the whole-genome sequences of trimethoprim-resistant ExPEC and/or ExPEC from recurrent UTIs (67 in total) from patients attending a regional Australian hospital from 2006 to 2008. Twenty-three sequence types (STs) were observed, with ST131 predominating (28 %), then ST69 and ST73 (both 7 %). Co-occurrence of trimethoprim-resistance genes with genes conferring resistance to extended-spectrum β-lactams, heavy metals and quaternary ammonium ions was a feature of the ExPEC described here. Seven trimethoprim-resistance genes were identified, most commonly dfrA17 (38 %) and dfrA12 (18 %). An uncommon dfrB4 variant was also observed. Two blaCTX-M variants were identified - blaCTX-M-15 (16 %) and blaCTX-M-14 (10 %). The former was always associated with dfrA12, the latter with dfrA17, and all blaCTX-M genes co-occurred with chromate-resistance gene chrA. Eighteen class 1 integron structures were characterized, and chrA featured in eight structures; dfrA genes featured in seventeen. ST131 H30Rx isolates possessed distinct antimicrobial gene profiles comprising aac(3)-IIa, aac(6)-Ib-cr, aph(3')-Ia, aadA2, blaCTX-M-15, blaOXA-1 and dfrA12. The most common virulence-associated genes (VAGs) were fimH, fyuA, irp2 and sitA (all 91 %). Virulence profile clustering showed ST131 H30 isolates carried similar VAGs to ST73, ST405, ST550 and ST1193 isolates. The sole ST131 H27 isolate carried molecular predictors of enteroaggregative E. coli/ExPEC hybrid strains (aatA, aggR, fyuA). Seven isolates (10 %) carried VAGs suggesting ColV plasmid carriage. Finally, SNP analysis of serial UTI patients experiencing worsening sequelae demonstrated a high proportion of point mutations in virulence factors.

Project description:One in three women will experience a clinically significant urinary tract infection (UTI) by age twenty-four and almost half will have at least one in their lifetime. Recurrent UTIs (rUTIs) are defined as having greater than two infections in a 6-month period, or three infections over twelve months, with complete resolution for at least two weeks. These may be due to relapse from incomplete treatment (persistence) or re-infection (new source). It may be difficult to distinguish between the two, where the same organism is cultured. There are several risk factors for rUTIs including an impairment of the body's immune system and virulence factors. Reversible or treatable causes are sought and excluded in the patient's initial review. Patient's with rUTI are often complex and difficult to manage. The long-term management options in women are multimodal and should focus on prevention of relapse and recurrence. Behavioural factors include adequate hydration, care with sexual hygiene, reducing one's body mass index (BMI) and post-void residual (PVR) volume. There are several non-antimicrobial options for rUTIs which have become a multi-billion-dollar business. Unfortunately, there are numerous studies which fail to show any major benefit or having conflicting data. Vaccines are currently being explored as a prevention strategy, delivered through injection, intra-nasal sprays, or vaginal suppositories, which are made from combinations of heat killed uro-pathogenic strains. There are no widely available vaccines at present due to limited clinical success. It is well established that appropriate antibiotic therapy results in higher rates of symptom relief and bacterial eradication in women with uncomplicated cystitis. There are several options for antimicrobial use which have been shown to be highly effective in reducing the risk of rUTI in women. The pain and discomfort of the UTI must be balanced with the cost and risk of developing resistance when using antimicrobials. Continuous prophylaxis, pre- and post-coital voiding, and self-starting are the three commonly accepted options for prophylaxis. The choice between these will depend upon patient preference, cultures and previous pattern of infection. Intra-vesical instillation of hyaluronic acid and chondroitin sulphate have been used for glycosaminoglycan (GAG) layer replenishment for many indications, including interstitial cystitis, overactive bladder syndrome, radiation cystitis and prevention of rUTI. At present, intra-vesical therapies are reserved for only those with the most unresponsive rUTIs. The principles of treating rUTI are to break the cycle and to treat any reversible causes. With our ever-expanding research knowledge, there are now many useful products that may be used for the successful treatment of rUTI. A management plan including a combination of a non-antimicrobial and selective antimicrobial regime for a minimum of six months should be considered. It is a prudent clinician that clearly defines this management plan, with reassurance of a finite period of therapy.

Project description:PurposeOur objective was to assess the efficacy of a high dose cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection.Material and methodsWe recruited 145 healthy, adult women with a history of recurrent urinary tract infection, defined as ≥ 2 in the past 6 months or ≥ 3 in the past 12 months in this randomized, controlled, double-blind clinical trial. Participants were randomized to receive a high dose of standardized, commercially available cranberry proanthocyanidins (2 × 18.5 mg daily, n = 72) or a control low dose (2 × 1 mg daily, n = 73) for a 24-week period. During follow-up, symptomatic women provided urine samples for detection of pyuria and/or bacteriuria and received an appropriate antibiotic prescription. The primary outcome for the trial was the mean number of new symptomatic urinary tract infections during a 24-week intervention period. Secondary outcomes included symptomatic urinary tract infection with pyuria or bacteriuria.ResultsIn response to the intervention, a non-significant 24% decrease in the number of symptomatic urinary tract infections was observed between groups (Incidence rate ratio 0.76, 95%CI 0.51-1.11). Post-hoc analyses indicated that among 97 women who experienced less than 5 infections in the year preceding enrolment, the high dose was associated with a significant decrease in the number of symptomatic urinary tract infections reported compared to the low dose (age-adjusted incidence rate ratio 0.57, 95%CI 0.33-0.99). No major side effects were reported.ConclusionHigh dose twice daily proanthocyanidin extract was not associated with a reduction in the number of symptomatic urinary tract infections when compared to a low dose proanthocyanidin extract. Our post-hoc results reveal that this high dose of proanthocyanidins may have a preventive impact on symptomatic urinary tract infection recurrence in women who experienced less than 5 infections per year.Trial registrationClinicaltrials.gov, identifier NCT02572895.

Project description:BackgroundUrinary tract infections (UTIs) are amongst the most common bacterial infections affecting women. Although antibiotics are the treatment of choice for UTI, cranberry derived products have been used for many years to prevent UTIs, with limited evidence as to their efficacy. Our objective is to assess the efficacy of a cranberry extract capsule standardized in A-type linkage proanthocyanidins (PACs) for the prevention of recurrent urinary tract infection.MethodsWe will perform a 1:1 randomized, controlled, double blind clinical trial in women aged 18 years or more who present ≥2 UTIs in 6 months or ≥ 3 UTIs in 12 months. One hundred and forty-eight women will be recruited and randomized in two groups to either receive an optimal dose of cranberry extract quantified and standardized in PACs (2 × 18.5 mg PACs per day) or a control dose (2 × 1 mg PACs per day). The primary outcome for the trial is the mean number of new symptomatic UTIs in women during a 6-month intervention period. Secondary outcomes are: (1) To evaluate the mean number of new symptomatic UTIs with pyuria as demonstrated by a positive leucocyte esterase test; (2) To detect the mean number of new symptomatic culture-confirmed UTIs; (3) To quantify urinary PACs metabolites in women who take a daily dose of 37 mg PACs per day compared to women who take a daily dose of 2 mg per day for 6 months; (4) To characterize women who present recurrent UTI based on known risk factors for recurrent UTI; (5) To describe the side effects of daily intake of cranberry extract containing 37 mg PACs compared to 2 mg PACs. This report provides comprehensive methodological data for this randomized controlled trial.DiscussionThe results of this trial will inform urologists, gynaecologists, family physicians and other healthcare professionals caring for healthy women with recurrent UTI, as to the benefits of daily use of an optimal dose of cranberry extract for the prevention of recurrent UTI.Trial registrationClinicaltrials.gov, identifier: NCT02572895 October 8th 2015.

Dataset Information

Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women.

Publications

Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women.

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