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Some women continue continuous or post-coital prophylaxis for years to maintain the benefit without adverse events, but it should be noted that continuing prophylaxis for years is not evidence-based. Continuous antimicrobial prophylaxis regimens for women with rUTIs have been recommended by several trials. In women who experience UTIs temporally related to sexual activity, antibiotic prophylaxis taken before or after sexual intercourse has been shown to be effective and safe.
This use of antibiotics is associated with a significant reduction in recurrence rates. Additionally, intermittent dosing is associated with decreased risk of adverse events including gastrointestinal symptoms and vaginitis. In a randomized double-blind placebo-controlled trial of 27 sexually active women with a median age of 23, post-coital antibiotics were shown to be more effective than placebo in reducing UTI recurrences. In one study of women, post-coital dosing was as effective as daily dosing.
The antibiotic prophylaxis approach targets the preventive therapy to the time frame when these women are most vulnerable to UTIs, thus minimizing use of antibiotics, decreasing risk of adverse events, and potentially reducing direct and indirect costs of rUTIs. Recommended instructions for antibiotic prophylaxis related to sexual intercourse include taking a single dose of an antibiotic immediately before or after sexual intercourse.
Dosing options for prophylaxis include the following:. There has been a growing concern regarding antibiotic resistance in the setting of recurrent UTI. In the World Health Organization increased awareness of the issue of the growing world-wide phenomenon of antimicrobial resistance through its publication Global Action Plan on Antimicrobial Resistance AMR. Cranberries have been studied as a preventative measure for UTI for decades, but recently cranberry has been the subject of an increasing number of randomized clinical trials.
These studies have used cranberry in a variety of formulations including juice, cocktail, and tablets.
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The proposed mechanisms of action is thought to be related to proanthocyanidins PACs present in cranberries and their ability to prevent the adhesion of bacteria to the urothelium. It must be noted that PACs are found in varying concentrations depending on formulation used, and many of the cranberry products used in the studies noted below were explicitly formulated for research purposes. The availability of such products to the public is a severe limitation to the use of cranberries for rUTI prophylaxis outside the research setting and must be discussed with patients. Juice studies have used a variety of juices and cocktails in varying volumes of daily consumption and have included cranberry of varying concentrations within the overall volume of product ingested.
Likewise, cranberry tablets include variability in dosing and are not subject to the same regulatory environment as antimicrobial drugs. Many studies do not include validation of PAC dosage. Further, clinical studies have also not routinely reported side effects. Risk of bias was variable across the studies. Cranberry was associated with decreased risk of experiencing at least 1 UTI recurrence than placebo or no cranberry 5 trials, RR 0. In a subgroup analysis of women aged 50 years or more, relapse of UTI was observed in 16 of 55 patients The study found cranberry was associated with a decreased number of clinical UTI recurrences mean 4.
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Researchers noted cranberry was associated with a lower risk of resistance in E. Additionally, it was found that Not all studies have included a methodology to examine a hypothesized mechanism of action in humans, which have included both inhibition of adherence mechanisms and urinary content changes that make the urine generally less habitable to uropathogens. Clinical studies have also not routinely reported side effects. Cranberry, in a formulation that is available and tolerable to the patient, may be offered as prophylaxis including oral juice and tablet formulations as there is not sufficient evidence to support one formulation over another when considering this food-based supplement.
In addition, there is little risk to cranberry supplements, further increasing their appeal to patients. However, it must be noted that fruit juices can be high in sugar content, which is a consideration that may limit use in diabetic patients. While lactobacillus probiotics have been studied with greater interest in recent years given growing concerns for antibiotic resistance, the Panel is unable to recommend the use of lactobacillus as a prophylactic agent for rUTI given the current lack of data indicating benefit in comparison to other available agents.
The systematic review identified five trials evaluating lactobacillus for prevention of recurrent UTI. Three trials compared lactobacillus versus placebo, ,, one trial compared lactobacillus versus an antibiotic, and one trial compared lactobacillus versus skim milk-based lactobacillus growth factor. Lactobacillus species were rhamnosus, reuteri, and crispatus. The increased fluid intake intervention was based on provision of three mL bottles of water to be consumed daily.
Daily fluid intake increased from 0.
While these data are promising, no conclusions can be drawn as to whether or not increased water intake is beneficial to women who regularly drink higher quantities of fluids than those reported in this study or those who may be at a lower risk for UTI recurrence. In both studies, antibiotics were associated with shorter time to UTI recurrence 24 versus 43 and Two high risk of bias trials compared a prophylactic antibiotic nitrofurantoin or TMP versus methenamine 1g every 12 hours for up to 1 year.
Results were similar in both trials. One of the trials also compared antibiotics versus topical povidone iodine and found no difference between trimethoprim versus topical iodine in risk of UTI recurrence. Herbal Therapies.
Two trials evaluated herbal therapies for prevention of rUTI. Two small, medium risk of bias trials evaluated intravesical hyaluronic acid plus chondroitin for prevention of rUTI. Harms were not reported. While these studies show promise, further study is needed to assess generalizability, long-term outcomes, and overall feasibility. Biofeedback and Immunoactive Therapy. There are no studies that address whether or not screening urinalysis or urine culture following clinical cure of a documented UTI is beneficial in those with a history of rUTI.
Extrapolating from the ASB literature, the Panel does not endorse microbiological reassessment i. The Panel does recognize, however, that certain clinical scenarios, such as planned surgical intervention in which mucosal bleeding is anticipated, may prompt screening. It should again be emphasized that symptom clearance is sufficient.
In patients with rapid recurrence particularly with the same organism , clinicians may consider evaluation on and off therapy to help identify those patients who warrant further urologic evaluation. Additionally, repeated infection with bacteria associated with struvite stone formation e. After initiating antimicrobial therapy for UTI, clinical cure i.
UTI symptom resolution is expected within three to seven days. Although there is no evidence, the Panel felt it reasonable to repeat a urine culture if UTI symptoms persist beyond seven days. Although a second antibiotic can be given empirically, this should only be done after a urine sample is obtained for culture.
Clinicians should recommend vaginal estrogen therapy to all peri- and post-menopausal women with rUTI to reduce the risk of rUTI. This is in contrast to oral or other formulations of systemic estrogen therapy, which have not been shown to reduce UTI and are associated with different risks and benefits. Patients who present with rUTI and are already on systemic estrogen therapy can and should still be placed on vaginal estrogen therapy.
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There is no substantially increased risk of adverse events. However, systemic estrogen therapy should not be recommended for treatment of rUTI. Multiple randomized trials using a variety of formulations of vaginally applied estrogen therapy demonstrated a decreased incidence and time to recurrence of UTI in hypoestrogenic women.
Table 4 shows the formulations and dosing of several commonly used types of vaginal estrogen therapy. A systematic review of vaginal estrogen therapy for genitourinary syndrome of menopause concluded there was insufficient evidence to favor one formulation of vaginal estrogen over another. One trial evaluating estriol vaginal cream 0. As part of shared decision-making, the clinician should weigh the risks associated with vaginal estrogen therapy with its benefits in reducing UTIs.
Given low systemic absorption, systemic risks association with vaginal estrogen therapy are minimal. Vaginal estrogen therapy has not been shown to increase risk of cancer recurrence in women undergoing treatment for or with a personal history of breast cancer. A better understanding of rUTI pathophysiology will greatly aid in our ability to design more effective, mechanistically-based treatments.
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Critical expansion of our understanding of both host and pathogen factors that result in rUTI is mandated. Additionally, refinement of how UTI is defined must be considered. In this context, defining initiatives for partnering with our primary care colleagues and patients to provide education regarding rUTI definitions, evaluation, and treatment will provide an impactful narrative for the future. Urine culture results, even those from extended quantitative urine culture techniques, do not reflect any aspect of the host response.
Investigations of more defined host biomarkers, such as cytokines or serum inflammatory markers, may allow more precise analysis of the host response which reflects a true UTI. Further refinements of bacterial molecular genetic technologies may help point-of-care testing with faster identification of potential uropathogens. By extension, the types and content of bacteria which inhabit the urinary tract as part of the native microbiome will change our understanding of how host-bacterial interactions contribute to development of rUTI.
Emerging data regarding the microbiome of the human bladder, bowel, and vagina, including the contribution of both traditional and viable but non-culturable bacteria, viruses, bacteriophages, fungi, and helminths, will define a more accurate portrait of the healthy balance, as well as pathogenic dysbiosis that may contribute to rUTIs.
Depletion or alteration of the normal host microbiome and host innate barriers and innate immune system may lead to development of rUTI. Modulation of the host response to bacterial infection is a key dynamic for which limited information currently exists.
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A worldwide crisis has emerged due to rapid expansion of MDR bacteria, foreshadowing the devastating implications of the eventual inefficacy of many of our broad-spectrum antimicrobial agents. On a more immediate time frame is the need for comprehensive randomized controlled trials for non-antibiotic prevention therapies, including probiotics and cranberry formulations. The influence of our environments including the foods we eat, how they are prepared, and their source may become increasingly important as the area of food science expands.
Future efforts may uncover other food sources with preventative mechanisms. Implementation of novel technologies, such as vaccines for urinary pathogens, may represent a future direction for prevention strategies. Use of mannosides as therapeutic entities to prevent bacterial adhesion to the urothelium may represent a narrow-spectrum treatment strategy associated with few systemic manifestations. We must also expand our perspective of rUTI to include prevention. The PLUS consortium also seeks to identify modifiable risk factors for acute cystitis which can be tested in a prospective prevention trial.
Through multiple efforts, which include identifying modifiable socioecological risk factors, understanding host responses involved in UTI and understanding pathogen virulence factors, we will discover new methods in diagnosis and treatment of rUTI. Website Tip! While viewing Guideline Statements on a desktop computer, use the left navigation to jump to different parts of the page.