Urological group’s first-ever recurrent UTI guidelines encourage responsible evaluation, antibiotic, cranberry juice use
The American Urological Association has issued guidelines for the management of recurrent UTI for the first time, providing clinicians with recommendations for the evaluation and management of female patients with the condition, according to an article recently published in the Journal of Urology.
One of the critical areas the guidelines address is the appropriate use of antibiotics by identifying cases where antibiotics are inappropriate, decreasing the number of adverse events tied to antibiotic use and implementing antibiotic and nonantibiotic strategies for prevention.
“Over the past few decades, our ability to diagnose, treat and manage recurrent UTI long-term has evolved due to additional insights into the pathophysiology of recurrent UTI, a new appreciation for the adverse effects of repetitive antimicrobial therapy (“collateral damage”), rising rates of bacterial antimicrobial resistance, and better reporting of the natural history and clinical outcomes of acute cystitis and recurrent UTI,” Jennifer Anger, MD, of the department of urology at Cedars-Sinai Medical Center in Los Angeles, and colleagues wrote.
The authors acknowledged that while there are multiple ways to define recurrent UTI, they used the definition of either two episodes of acute bacterial cystitis within 6 months or three episodes within 1 year.
They also wrote that these recurrent UTI guidelines do not apply to women who are pregnant or are immunocompromised, who are pursuing UTI prevention in either procedural or operative settings, who have functional or anatomic urinary tract anomalies, who experience recurrent UTIs due to indwelling catheters or self-catheterization and/or who are exhibiting signs or symptoms of systemic bacteremia.
The AUA’s guidelines and evidence levels for assessment of recurrent UTI are:
- omit cystoscopy and upper tract imaging in index patients (Expert Opinion);
- acquire a complete patient history and performing a pelvic exam (Clinical Principle);
- obtain multiple urine studies when the first urine specimen may be contaminated and consider the possibility of acquiring a catheterized specimen (Clinical Principle);
- note positive urine cultures associated with previous symptomatic occurrences; (Clinical Principle);
- obtain urinalysis, urine culture and sensitivity with each symptomatic acute cystitis episode before commencing treatment (Moderate Recommendation; Evidence Level: Grade “C”); and
- extend the idea of patient-initiated treatment (self-start treatment) to select patients with acute episodes while anticipating urine cultures. (Moderate Recommendation; Evidence Level: Grade C).
The AUA’s guidelines and evidence levels for managing asymptomatic bacteriuria are:
- avoid treating asymptomatic bacteriuria (Strong Recommendation; Evidence Level: Grade B) and
- bypass surveillance urine testing, including urine culture, in asymptomatic patients. (Moderate Recommendation; Evidence Level: Grade C).
Anger and colleagues acknowledged the ongoing concerns in the medical community regarding antimicrobial stewardship and antibiotic resistance as they discussed treatment.
“While no evidence exists to support the concept of withholding antimicrobials from patients with recurrent UTIs, providers must bear in mind that continued intermittent courses of antibiotics are associated with significant adverse events, particularly in older patients. Substantial effort should be made to avoid unnecessary treatment unless there is a high suspicion of UTI,” they wrote.
Antibiotic-related prevention and treatment
The AUA’s guidelines and evidence levels for either antibiotic-related prevention or treatment are:
- treat acute cystitis episodes associated with urine cultures resistant to oral antibiotics with culture-directed parenteral antibiotics for as short a course as reasonable, generally no longer than 7 days (Expert Opinion);
- treat acute cystitis episodes with the minimum number of antibiotics as is reasonable, typically no more than 7 days. (Moderate Recommendation; Evidence Level: Grade B);
- prescribe antibiotic prophylaxis to lower the risk for future UTIs in women of all ages previously diagnosed with UTIs after discussing their risks, benefits and alternative treatments (Moderate Recommendation; Evidence Level: Grade B); and
- utilize first-line therapy (ie, nitrofurantoin, TMP-SMX, fosfomycin) dependent on the local antibiogram for treating women with symptomatic UTIs (Strong Recommendation; Evidence Level: Grade B).
Other prevention, treatment methods
Anger and colleagues also discussed the growing amount of medical literature examining the role that cranberry products — whether juice, cocktail or tablet — play in preventing recurrent UTI. After reviewing the available evidence, Anger and colleagues gave the recommendation a “C.”
“The availability of such products to the public is a severe limitation to the use of cranberries for recurrent UTI prophylaxis outside the research setting and must be discussed with patients,” they wrote.
“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 [proanthocyanidin] dosage. Further, clinical studies have also not routinely reported side effects,” they added.
Follow-up evaluations and estrogen therapy
The AUA guidelines for post-recurrent UTI evaluations and estrogen therapy are:
- perform multiple urine cultures to guide further management when UTI symptoms persist following antimicrobial therapy (Expert Opinion);
- recommend vaginal estrogen therapy in peri- and post-menopausal women to reduce their risk for future UTIs if there is no contraindication to estrogen therapy. (Moderate Recommendation; Evidence Level: Grade B); and
- avoid post-treatment test of cure urinalysis or urine culture in asymptomatic patients (Expert Opinion).
Putting the guidelines into practice
Healio Primary Care asked two physicians — Michael Durkin, MD, MPH, of the division of infectious diseases at Washington University School of Medicine in St. Louis, and Dimitri Drekonja, MD, MS, an associate professor of medicine within the infectious disease section at the University of Minnesota and physician with the U.S. Department of Veterans Affairs, who were not affiliated with the Anger and colleagues’ efforts — to review their feasibility in primary care.
Durkin said the guidelines were “feasible overall,” but added that some are more relevant than others to the primary care physician.
“Most of the recommendations are common sense and align with established evidence in the medical literature,” he said.
“In our experience, many health care providers are not familiar with antibiogram data. This is particularly true for providers who work primarily in outpatient clinic settings. In addition, providing antibiogram data for urinary pathogens — in particular for Escherichia coli — is not the standard at many facilities. Instead, antibiogram data will likely aggregate susceptibilities from E. coli infections in several sites, such as the lungs, blood and urine.”
He also took exception to the first-line therapy recommendations.
“I personally avoid using fosfomycin in my practice. First, a study in JAMA concluded that it is more expensive than the other oral options. Second, there are some recent data to suggest that it is inferior to nitrofurantoin. Third, from an antibiotic resistance standpoint, I would prefer to reserve it for patients who have infections that are resistant to other agents. Fosfomycin is one of the few antibiotics which remains active against many common multi-drug resistant UTIs that would otherwise require IV antibiotics,” Durkin said.
“I also discourage use of TMP-SMX as a first-line agent due to high resistance rates in our community. However, in terms of recommended first-line agents, all of the options are appropriate and consistent with the previous Infectious Diseases Society of America guidelines for uncomplicated UTIs,” he continued.
Drekonja told Healio Primary Care the guidelines are worth following “so long as they are applied to the same populations” they are intended for.
He agreed with Anger and colleagues that cranberry products are usually a reasonable prevention method for the cohort the AUA guidelines cover.
“Cranberry juice, cocktail and tablets are relatively benign with no other side effects linked to them. So long as the product is not contaminated, these products are not going to hurt anyone and might be worth a try,” Drekonja said.
Durkin discussed Ellura, a cranberry supplement that some patients have used to treat recurrent UTI.
Supplements in general are poorly regulated by the FDA, so the amount of active ingredient in each supplement may vary quite a bit. [But] from what I can find, it sounds like the manufacturer does a more rigorous job evaluating the contents of the supplement. It might work more reliably than other supplements, where the concentration may vary more from batch to batch. It might also work more favorably due to a higher amount of proanthocyanidins,” he said.
“[Patients] with recurrent UTIs should probably weigh the costs vs. benefits of taking Ellura, and I imagine that it would be more expensive than other over the counter cranberry-based supplements,” Dunkin continued.
For patients with recurrent UTIs who do not want or cannot take antibiotics or cranberry products, there are other options.
“Episodic therapy can help so long as the person does not have an active sex life, if UTIs occur post-intercourse. Or recommend drinking plenty of fluids and taking ibuprofen as needed. If you go this latter route, remind the patient these do not alleviate the symptoms recurrent UTIs cause as well as antibiotics do,” Drekonja said.
Durkin added that a research gap surrounds other nonantibiotic antimicrobials for recurrent UTIs.
“We need better data to evaluate the impact of such treatments. We often talk about methenamine and D-mannose instead of cranberry juice as patients have generally already tried cranberry over the counter. Further studies are also needed to evaluate the impact of a combination of these agents together,” he said.
Coordinated efforts are particularly helpful to clinicians managing recurrent UTIs.
“Multidisciplinary approaches are essential. At our institution, I work closely with the urologists and urogynecologists to manage recurrent UTIs as a team. I can help guide antibiotic selection and long-term suppression while they assist with advanced procedures and physical exam methods to diagnose and treat patients,” he said.
In addition, Durkin said he agreed with Anger and colleagues’ recommendation of avoiding post-treatment testing of cure urinalysis or urine culture in asymptomatic patients.
“I like that last point,” Durkin said in the interview. “Those clinicians who don’t follow it are in a difficult position if the result of a follow up urine culture is positive with the same pathogen or a new pathogen and the patient feels great.”
Drekonja offered a few pointers on assuring better patient compliance with guidelines.
“The key to successful implementation is to make sure you are treating the same exact group and condition that the guidelines are intended for,” he said.
Mindful that UTIs are one of many medical conditions that have multiple guidelines, Drekonja provided some general tips for primary care physicians to help determine which recommendations to follow.
“Look at the studies the guidelines utilized for things such as patient characteristics, such as age and other medications they were on. You may also want to look at the country the guidelines came from and consider how prevalent the condition is there or the country’s attitude toward treating the condition you are reading about,” he said. “For example, here in the United States we often prescribe antibiotics for strep throat, but in England the most common treatment for the same condition is acetaminophen.”
He added that PCPs need to remember that guidelines are designed to guide and that there is no rule that they must be followed exactly.
“Guidelines are only intended to lay overall principles. They intentionally leave room for variation based on patient preferences and needs,” Drekonja said in the interview. – by Janel Miller
Disclosures: Anger reports previous participation in studies or trials. Drekonja reports research funding from the department of Veterans Affairs. Durkin reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.