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BJU International Nov 2022To compare recurrent urinary tract infection (rUTI) guidelines from major urological and non-urological organisations internationally and identify areas of consensus and... (Review)
Review
OBJECTIVE
To compare recurrent urinary tract infection (rUTI) guidelines from major urological and non-urological organisations internationally and identify areas of consensus and discrepancy.
METHODS
PubMed, Google Scholar and the official webpages of major urological, gynaecological, infectious diseases and general practice organisations were searched for rUTI guidelines in March 2022. Nine guidelines were included for review: European Association of Urology, National Institute for Health and Care Excellence (NICE), Society of Obstetricians and Gynaecologists of Canada, American Academy of Family Physicians, Mexican College of Gynaecology and Obstetrics Specialists, Swiss Society of Gynaecology and Obstetrics, Spanish Society of Infectious Diseases and Clinical Microbiology, German Association of Scientific Medical Societies, and the combined American Urological Association/Canadian Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction.
RESULTS
The definition and evaluation of rUTIs, and antibiotic prophylaxis strategies, were mostly consistent across guidelines, and emphasised the importance of obtaining urine cultures and limiting cystoscopy and upper tract imaging in women without risk factors. Variable recommendations were noted for symptomatic treatment, self-initiated antibiotics, and antibiotic-sparing preventative strategies such as cranberry, vaginal oestrogen, immunoactive prophylaxis with OM-89, intravesical glycosaminoglycan instillation, and phytotherapeutics. Recent randomised evidence supports the use of methenamine hippurate. Either continuous or post-coital prophylactic antibiotics were supported by all guidelines. None of the guidelines were tailored to the management recurrent complicated UTI.
CONCLUSION
Multiple rUTI guidelines were identified and mostly limited their recommendations to otherwise healthy non-pregnant women with uncomplicated cystitis. Variation was noted, particularly in antibiotic-sparing preventative strategies. Some conflicting recommendations are due to more recent guidelines including updated evidence. Future guidelines should consider recommendations to assist management of complex patient groups, such as recurrent complicated UTI.
Topics: Pregnancy; Female; Humans; Canada; Urinary Tract Infections; Antibiotic Prophylaxis; Cystitis; Anti-Bacterial Agents
PubMed: 35579121
DOI: 10.1111/bju.15756 -
BMJ (Clinical Research Ed.) Mar 2022To test and compare the efficacy of methenamine hippurate for prevention of recurrent urinary tract infections with the current standard prophylaxis of daily low dose... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To test and compare the efficacy of methenamine hippurate for prevention of recurrent urinary tract infections with the current standard prophylaxis of daily low dose antibiotics.
DESIGN
Multicentre, open label, randomised, non-inferiority trial.
SETTING
Eight centres in the UK, recruiting from June 2016 to June 2018.
PARTICIPANTS
Women aged ≥18 years with recurrent urinary tract infections, requiring prophylactic treatment.
INTERVENTIONS
Random assignment (1:1, using permuted blocks of variable length via a web based system) to receive antibiotic prophylaxis or methenamine hippurate for 12 months. Treatment allocation was not masked and crossover between arms was allowed.
MAIN OUTCOME MEASURE
Absolute difference in incidence of symptomatic, antibiotic treated, urinary tract infections during treatment. A patient and public involvement group predefined the non-inferiority margin as one episode of urinary tract infection per person year. Analyses performed in a modified intention-to-treat population comprised all participants observed for at least six months.
RESULTS
Participants were randomly assigned to antibiotic prophylaxis (n=120) or methenamine hippurate (n=120). The modified intention-to-treat analysis comprised 205 (85%) participants (antibiotics, n=102 (85%); methenamine hippurate, n=103 (86%)). Incidence of antibiotic treated urinary tract infections during the 12 month treatment period was 0.89 episodes per person year (95% confidence interval 0.65 to 1.12) in the antibiotics group and 1.38 (1.05 to 1.72) in the methenamine hippurate group, with an absolute difference of 0.49 (90% confidence interval 0.15 to 0.84) confirming non-inferiority. Adverse reactions were reported by 34/142 (24%) in the antibiotic group and 35/127 (28%) in the methenamine group and most reactions were mild.
CONCLUSION
Non-antibiotic prophylactic treatment with methenamine hippurate might be appropriate for women with a history of recurrent episodes of urinary tract infections, informed by patient preferences and antibiotic stewardship initiatives, given the demonstration of non-inferiority to daily antibiotic prophylaxis seen in this trial.
TRIAL REGISTRATION
ISRCTN70219762.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Female; Hippurates; Humans; Methenamine; Middle Aged; Recurrence; Treatment Outcome; Urinary Tract Infections; Young Adult
PubMed: 35264408
DOI: 10.1136/bmj-2021-0068229 -
Health Technology Assessment... May 2022Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate, but comparative data on their efficacy and safety are lacking.
OBJECTIVE
To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex; Mylan NV, Canonsburg, PA, USA) compared with current standard care (antibiotic prophylaxis) for recurrent urinary tract infection prevention in adult women.
DESIGN
Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months' treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year.
SETTING
Eight UK NHS secondary care sites.
PARTICIPANTS
A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial.
INTERVENTIONS
A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted.
MAIN OUTCOME MEASURES
The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient's expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction.
RESULTS
Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months' data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in cultured from perineal swabs than participants in the methenamine hippurate arm (39/70; 56%) (-value = 0.05). Urine cultures revealed that during treatment higher proportions of participants and samples from the antibiotic arm grew resistant to trimethoprim/co-trimoxazole and cephalosporins, respectively. Conversely, post treatment, higher proportions of participants in the methenamine hippurate arm (9/45; 20%) demonstrated multidrug resistance in isolated from perineal swabs than participants in the antibiotic arm (2/39; 5%) ( = 0.06). All other secondary outcomes and adverse events were similar in both arms.
LIMITATIONS
This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation.
CONCLUSIONS
This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics.
RECOMMENDATIONS FOR RESEARCH
Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics.
TRIAL REGISTRATION
This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36.
FUNDING
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 26, No. 23. See the NIHR Journals Library website for further project information.
Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cost-Benefit Analysis; Escherichia coli; Female; Hippurates; Humans; Male; Methenamine; Trimethoprim; Urinary Tract Infections
PubMed: 35535708
DOI: 10.3310/QOIZ6538 -
Clinical Microbiology and Infection :... Jun 2017Nitrofurantoin has been used for the prevention of urinary tract infection (UTI) for over 60 years. We conducted a systematic review and meta-analysis to assess its... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Nitrofurantoin has been used for the prevention of urinary tract infection (UTI) for over 60 years. We conducted a systematic review and meta-analysis to assess its efficacy and safety in the prophylaxis of UTI.
METHODS
We performed a systematic review of all controlled trials in humans assessing nitrofurantoin for UTI prophylaxis published from 1946 to 2015. We further reviewed population-level cohort studies evaluating nitrofurantoin's toxicity. Meta-analyses assessing efficacy and adverse events were conducted on controlled trials.
RESULTS
Twenty-six controlled trials including 3052 patients fulfilled entry criteria for the systematic review and meta-analysis on efficacy and toxicity, and 16 population-level cohort studies were identified for review of toxicity. Overall quality was poor, with all studies at increased risk for various biases. When compared with no prophylaxis, nitrofurantoin is effective in the prevention of UTI (risk ratio 0.38 in favour of nitrofurantoin, 95% CI 0.30-0.48). Its prophylactic efficacy is superior to that of methenamine hippurate and comparable to that of other antibacterials. Compared with patients receiving other antibacterials, those receiving nitrofurantoin had an increased risk of 2.24 (95% CI 1.77-2.83) for a non-severe adverse effect. In all controlled trials, only one patient experienced a severe adverse effect (interstitial pneumonia). Cohort studies reported severe adverse effect frequencies of 0.02-1.5 per 1000 nitrofurantoin users.
CONCLUSIONS
Nitrofurantoin is effective in the prevention of UTI. Its use may be associated with increased non-severe adverse effects; severe adverse effects occur infrequently. The risk of severe toxicity seems to increase with the duration of nitrofurantoin prophylaxis.
Topics: Anti-Infective Agents, Urinary; Controlled Clinical Trials as Topic; Female; Humans; Nitrofurantoin; Treatment Outcome; Urinary Tract Infections
PubMed: 27542332
DOI: 10.1016/j.cmi.2016.08.003 -
Cureus Oct 2021Certain contemporary histology stains and methods are not the same as those used in the past. This progression has delved into the requirement for more precise, less... (Review)
Review
Certain contemporary histology stains and methods are not the same as those used in the past. This progression has delved into the requirement for more precise, less complex, and efficient staining procedures. The objective of this study is to assess historical and contemporary stains and procedures, as well as the challenges surrounding their improvement. Carmine, hematoxylin, silver nitrate, Giemsa, trichome stain, Gram stain, and mauveine were among the first histological stains discovered in nature. Aside from their utility in the study of tissues at the time, they also laid the groundwork for the development of commercial dyes that are still in use today. Hematoxylin and eosin, Ziehl-Nielsen (ZN) stain, periodic acid-Schiff stain, and Grocott-Gomori methenamine silver stain are some of the most recently developed histological stains. The future of histological stains and processes appears to be influenced by technological advancements and the demand for cost-effective diagnostic approaches in the healthcare system. Thus, currently used histological stains appear to be economical, quick, and reliable tools for interpreting, archiving, and delivering essential diagnoses that could not be achieved by any other means.
PubMed: 34754648
DOI: 10.7759/cureus.18486 -
Current Opinion in Nephrology and... Jul 2019The effect of the intestinal microbiome on urine chemistry and lithogenicity has been a popular topic. Here we review the evidence for exposure to antibiotics increasing... (Review)
Review
PURPOSE OF REVIEW
The effect of the intestinal microbiome on urine chemistry and lithogenicity has been a popular topic. Here we review the evidence for exposure to antibiotics increasing the risk of nephrolithiasis.
RECENT FINDINGS
Studies of the intestinal microbiome have focused on Oxalobacter formigenes, an anaerobe that frequently colonizes the human colon. As a degrader of fecal oxalate its presence is associated with lower urinary oxalate, which would be protective against calcium oxalate stone formation. It also appears capable of stimulating colonic oxalate secretion. A recent study showed that antibiotics can eliminate colonization with O. formigenes. In a case-control study, exposure to sulfa drugs, cephalosporins, fluoroquinolones, nitrofurantoin/methenamine, and broad spectrum penicillins prospectively increased the odds of nephrolithiasis. The effect was greatest for those exposed at younger ages and 3-6 months before being diagnosed with nephrolithiasis.
SUMMARY
Recent evidence suggests a possible, causal role of antibiotics in the development of kidney stones. A possible explanation for this finding includes alterations in the microbiome, especially effects on oxalate-degrading bacteria like O. formigenes. Ample reasons to encourage antibiotic stewardship already exist, but the possible role of antibiotic exposure in contributing to the increasing prevalence of kidney stones in children and adults is another rationale.
Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Gastrointestinal Microbiome; Humans; Kidney Calculi; Oxalates; Oxalobacter formigenes; Risk
PubMed: 31145705
DOI: 10.1097/MNH.0000000000000510