The 2025 Guideline update for Recurrent Uncomplicated Urinary Tract Infections (rUTIs) in Women takes a more patient-centered, risk-based, and microbiome-aware approach to rUTI management. The Guideline update tries to balance diagnostic accuracy with clinical judgment, redefining treatment success as symptom resolution rather than microbial eradication and placing a premium on antimicrobial stewardship and patient-centered care. These changes reflect a maturing understanding of the urinary microbiome, the limitations of existing diagnostics, and a public health imperative to reduce unnecessary antibiotic exposure.

Accumulating evidence suggests localized UTIs, infections restricted to the lower urinary tract, can be treated less aggressively than systemic infections such as pyelonephritis and sepsis.¹ To simplify clinical approaches and reduce confusion about factors defining “complicated” infections, the updated Guideline reframes the classification of rUTIs from uncomplicated vs complicated to localized vs systemic (Table). Unfortunately, most studies previously examining UTI therapeutics have utilized “uncomplicated” UTI for inclusion, questioning how older data can be applied to this newer classification framework.² Thus, the Guideline acknowledges that clinicians may consider more aggressive care for patients with “complicating factors,” patient features (eg, indwelling urinary devices, immunosuppression, bladder outlet obstruction) that place individuals at higher risk of poor outcomes.

Table. Guideline Definitions

The updated Guideline also reflects an expanded awareness of the human microbiome. It is accepted that humans harbor a diverse collection of microorganisms that perform beneficial functions. Antibiotics disturb those microbial communities throughout the body; this understanding demands a more thoughtful approach to diagnosis, treatment, and prevention. Understanding that the bladder harbors commensal microbes that may even prevent pathogenic infections informs our diagnosis of UTI. The updated Guideline stresses the importance of clinical judgment in interpreting patient symptoms, urinalysis, and culture (or equivalent) data together, rather than relying on culture positivity alone.

The updated Guideline places new importance on microscopic urinalysis as a diagnostic tool due to its high negative predictive value. In recognizing that urinary bacteria may be commensal, infection is better defined by the human’s reactionary inflammatory response. Thus, urinary leukocytes must be present for a diagnosis of UTI. The absence of urinary inflammation (pyuria) on microscopic urinalysis is strong evidence against a UTI diagnosis and should prompt consideration of other diagnoses.³ Given potential contamination, however, the presence of leukocytes is not sufficient for UTI diagnosis. To evaluate symptomatic episodes, the Guideline recommends microscopic urinalysis with urine culture only on reflex when pyuria is present; this practice drastically reduces both UTI overdiagnosis and antibiotic overprescription.

While the updated Guideline continues to recommend microbiological evaluation of each UTI episode, it recognizes the limitations of urine culture, including contamination, delayed results, and reduced sensitivity, particularly for non–Escherichia coli organisms. Also, no distinct cutoff for colony counts can predict UTI. Given the poor real-world performance of standard urine culture, alternative approaches to bacterial detection, such as multiplex PCR and next-generation sequencing, may be reasonable, although they lack sufficient validation to replace culture as the standard.⁴ These technologies detect a wider range of organisms, often in less time, but often detect bacteria when no infection is present, risking overdiagnosis if misapplied. Rather than endorse a specific test, organism list, or threshold, the Guideline emphasizes individualized interpretation and serial evaluation to improve outcomes, recognizing that all testing methods, including culture, are imperfect.

The shortcomings of urine culture may explain accumulating data suggesting UTI diagnoses are often inaccurate; as many as 60% to 80% of women diagnosed with UTI do not meet diagnostic criteria.^5,6 Widespread misdiagnosis not only subjects patients to unnecessary antibiotics but leaves the true etiology of their symptoms untreated.⁷ By focusing on the integration of clinical symptoms, urinalysis, and microbiologic evidence to guide clinical judgment, the updated Guideline seeks to reduce misdiagnosis. Patients with persistent or atypical symptoms, rapid recurrences after appropriate treatment, or lack of microbiological correlation with symptomatic episodes should be evaluated for alternative diagnoses such as interstitial cystitis, vaginal pathologies, pelvic floor dysfunction, or even malignancy.

The updated Guideline also high­lights working with patients and other clinicians to reframe the goals of rUTI care from bacterial eradication to symptom management and prevention of complications. As both clinicians and patients voice concerns about antibiotic overuse, the Guideline reemphasizes that not all bacteriuria warrants antibiotics. Instead, the Guideline prioritizes symptom relief and prevention of complications. This shift is supported by evidence showing that most cases of localized cystitis are self-limiting.⁸ Some patients may benefit from nonantibiotic symptomatic care (eg, hydration and analgesics) for the treatment of acute localized cystitis, as repeated antibiotics may perpetuate disturbances in the microbiome that can reinforce the rUTI cycle.⁹

Equally important is an emphasis on shared decision-making. The updated Guideline encourages clinicians to discuss with patients treatment risks, diagnostic uncertainties, and management options. Patients should be educated on the self-limiting nature of most rUTI episodes and the minimal benefit of antibiotics in most localized infections. The document encourages clinicians to discuss both antibiotic and nonantibiotic preventive options with patients. This focus on education, informed consent, and individualized care both improves long-term outcomes and addresses the fear and frustration expressed by rUTI patients.

For treatment, antibiotic stewardship remains a central pillar of the Guideline; empiric antibiotic use without microbiologic confirmation is discouraged. The Guideline supports using shorter, targeted courses of narrow-spectrum agents, reserving broad-spectrum agents for challenging situations such as multidrug resistance or allergies. While the previous Guideline stressed that asymptomatic bacteriuria should not be treated, the update also stresses that acute-onset symptoms are most suggestive of UTI, and chronic or fluctuating symptoms may warrant evaluation for alternative diagnoses.

The updated Guideline also expands the possible nonantibiotic options for rUTI prevention (Figure). New, stronger evidence supports the efficacy of cranberry for UTI prophylaxis. Recommendations supporting preventive vaginal estrogen were also strengthened for peri-/post-menopausal women without contraindications. New recommendations are made for methenamine hippurate and increased water intake (in patients who drink less than 1.5 L per day). The use of D-mannose in isolation is not recommended, as new studies have failed to demonstrate efficacy over placebo. These nonantibiotic options are promoted not only for their efficacy but also to reduce antibiotic dependence.

Conflicts of Interest: Dr Ackerman reported being a consultant or advisor for Watershed Medical, Abbvie, and Desert Harvest.