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Non-Antibiotic UTI Prevention

Non-antibiotic strategies sit at the front of the recurrent-UTI prevention ladder per the AUA/CUA/SUFU 2022 guideline, the WikiGuidelines 2024 consensus, and the AGS Beers alternatives document. The rationale is identical across documents: comparable efficacy for many options, meaningfully lower resistance pressure, and better long-term tolerability than daily antibiotic prophylaxis.[1][2][3] A 2025 network meta-analysis of 50 RCTs (n = 10,495) comparing 14 non-antibiotic interventions found D-mannose (RR 0.34), vaccines (RR 0.65), probiotics (RR 0.69), and cranberry (RR 0.72) all significantly reduced UTI incidence vs placebo with no increase in adverse events — but as the individual-agent sections below show, the D-mannose network signal is not reproduced in the largest primary-care RCT, and head-to-head evidence is still evolving.[4]

This article is the prescribing-detail deep-dive for each modality. For the stepwise management framework, see UTI suppressive & prophylactic therapy; for treatment of active infection, see UTI treatment antibiotics.

Vaginal estrogen​

AUA/CUA/SUFU 2022 — Moderate Recommendation, Grade B: "In peri- and post-menopausal women with rUTIs, clinicians should recommend vaginal estrogen therapy to reduce the risk of future UTIs if there is no contraindication to estrogen therapy." Updated meta-analysis incorporating a new study showed RR 0.58 (95% CI 0.39–0.87) for UTI recurrence with vaginal estrogen.[1]

Mechanism​

GSM is a root cause of rUTI in postmenopausal women. Estrogen deprivation leads to vaginal and urethral atrophy, loss of Lactobacillus colonization, rising vaginal pH, and increased uropathogen colonization — vaginal estrogen reverses all three.[5]

Formulations and dosing​

FormulationTypical regimenPractical notes
Estradiol cream (0.01%)0.5–1 g intravaginally 2–3×/weekMost flexible dosing; messy
Estradiol tablets (10 µg)One tablet intravaginally 2×/week after loadingMinimal systemic absorption; patient-preferred
Estradiol ring (Estring, 7.5 µg/24 h)One ring every 90 daysBest adherence; insert-and-forget
Estriol cream / ring (not FDA-approved in US)0.5 mg 2×/weekThe Raz-Stamm trial agent; available in Europe
DHEA (prasterone) 6.5 mg vaginalNightlyNot formally studied for rUTI but treats GSM

Efficacy​

  • Raz & Stamm 1993 (landmark RCT, intravaginal estriol) — cumulative infection-free proportion dramatically higher vs placebo over 8 months; the trial that established the modality[6]
  • Chen 2021 meta-analysis (5 RCTs, n = 1,936) — vaginal estrogen reduced rUTI with RR 0.42 (95% CI 0.30–0.59); oral/systemic estrogen showed no benefit (RR 1.11; 95% CI 0.92–1.35) and should not be used for UTI prevention[7]
  • Tan-Kim 2023 (retrospective, n = 5,638 women prescribed vaginal estrogen for rUTI) — 51.9% reduction in UTI frequency in the year following prescription (3.9 → 1.8 episodes/year; p < 0.001) — the best real-world dataset[8]

Safety​

  • Local AEs: vaginal irritation, burning, or spotting in 6–20%; systemic absorption at labeled doses is minimal[9]
  • Breast cancer survivors: ACOG clinical consensus permits vaginal estrogen in appropriately counseled survivors when non-hormonal options have failed, with preference for ultra-low-dose estradiol (10 µg) or DHEA; coordinate with oncology
  • Endometrial safety: prolonged daily dosing can cause mild endometrial stimulation; the 2×/week maintenance regimen is the standard to minimize this

See GSM for the comprehensive genitourinary syndrome of menopause framework.

Methenamine hippurate​

Mechanism: methenamine hippurate is a urinary antiseptic — not an antibiotic (introduced 1899, FDA-approved 1967). It hydrolyzes to formaldehyde in acidic urine (pH < 6), producing non-specific bacteriostasis by alkylating microbial proteins and nucleic acids; the hippurate salt adds mild bacteriostasis and helps maintain urinary acidity. Because the active species forms in the bladder, it avoids systemic antimicrobial pressure. Optimal efficacy requires urinary acidification — concurrent ascorbic acid (1 g BID) or cranberry is sometimes recommended, though data for the combined approach are limited, and ascorbic acid has paradoxically raised urinary pH in catheterized elderly patients.[10]

Formaldehyde was long believed to be resistance-proof because it denatures proteins non-specifically. Hodgkinson 2026 analyzed E. coli isolates from the ALTAR trial and identified formaldehyde-detoxification resistance (FDHR) — 5.8% of isolates grew in > 1 mM formaldehyde via non-functional FrmR repressor variants or plasmid-encoded frmA homologues — showing methenamine carries some resistance risk, though clinical significance is undefined.[40]

Dosing​

  • Standard regimen: 1 g PO BID (adults and patients > 12 years; antibacterial activity is demonstrable in urine within ~ 30 minutes of a dose)
  • Use only after eradication of an active infection — methenamine is prophylactic / suppressive, not a treatment for acute UTI
  • Onset of prophylactic effect: ~ 1–2 weeks
  • Duration: an initial 6–12-month course is common; reassess periodically

Efficacy​

  • ALTAR trial (Harding 2022, n = 240, multicenter open-label non-inferiority RCT) — methenamine non-inferior to daily low-dose antibiotics (nitrofurantoin 50–100 mg, trimethoprim 100 mg, or cefalexin 250 mg) at 12 months (1.38 vs 0.89 episodes/person-year; within the 1-episode non-inferiority margin). Antibiotic resistance in perineal E. coli was higher in the antibiotic arm during treatment (72% vs 56%; p = 0.05), though post-treatment multidrug resistance was paradoxically higher in the methenamine arm (20% vs 5%; p = 0.06)[10][11]
  • ImpresU trial (Heltveit-Olsen 2025, n = 289 women ≥ 70 y, triple-blind placebo-controlled phase IV) — 25% reduction in antibiotic-treated UTIs at 6 months (IRR 0.75; 95% CI 0.57–1.0; p = 0.049); rebound increase in UTI rate after discontinuation (IRR 1.7; p < 0.05) — treatment may need to be continued long-term rather than for a fixed course[12]
  • Lee 2012 Cochrane review (13 studies, n = 2,032) — effective in patients without renal-tract abnormalities (RR 0.24; 95% CI 0.07–0.89) but not in those with renal-tract abnormalities or neuropathic bladder (RR 1.54; 95% CI 0.38–6.20)[41]
  • Davidson 2024 systematic review (7 studies) — consistent support across populations and clinical settings[13]

Special populations​

  • Neurogenic bladder / SCI — methenamine appears ineffective: incomplete emptying shortens formaldehyde contact time, and urea-splitting organisms alkalinize urine. The same caveat applies to catheterized patients.[41]
  • Renal transplant recipients — a single-center retrospective series found methenamine 1 g daily with vitamin C reduced UTI frequency and UTI-related hospitalizations without renal-function change, but this is low-quality evidence and the FDA label contraindicates use in renal insufficiency.[42]

Safety​

  • Generally well tolerated; GI upset most common (high doses > 4 g/day have caused dysuria, hematuria, hemorrhagic cystitis)
  • Contraindicated in renal insufficiency, severe hepatic impairment, severe dehydration, and concurrent sulfonamide use (sulfonamides form an insoluble precipitate with urinary formaldehyde)
  • Not effective against urea-splitting organisms (Proteus, Ureaplasma) — these alkalinize urine and block formaldehyde generation
  • The branded product contains FD&C Yellow No. 5 (tartrazine) — possible allergic reaction in susceptible patients, especially with aspirin hypersensitivity; periodic liver-function monitoring is advised

Cranberry products​

Mechanism: proanthocyanidins (PAC) — especially A-type PACs — inhibit P-fimbriae-mediated adherence of uropathogenic E. coli to uroepithelial cells. B-type PACs (apple juice, grape juice, chocolate) lack this anti-adhesion property. Because anti-adhesion activity wanes over hours, twice-daily dosing (morning and evening) is recommended for sustained effect.[30]

Dose — PAC content matters more than form​

  • WikiGuidelines 2024 recommends products containing ≥36 mg PAC per day for women, children, and people susceptible to UTI after interventions.[2]
  • Juice, capsules, and whole-fruit powder have all been studied; standardized capsule with declared PAC content is the most reproducible form. Cranberry products are regulated as dietary supplements, not drugs — PAC content and quality vary considerably between brands.[30]
  • Typical commercial dosing: 500 mg whole-cranberry powder or 36–72 mg PAC capsule daily
  • Trial PAC doses span 18–72 mg/day; the Cochrane review found no clear dose-response relationship across low, moderate (40–80 mg/day), and high (>80 mg/day) PAC doses[30]

Efficacy​

The 2023 Cochrane review (Williams, 50 RCTs, 8,857 participants) is the comprehensive synthesis, and the benefit is population-specific:[30]

PopulationRR (95% CI)Certainty
Women with recurrent UTI0.74 (0.55–0.99)Moderate
Children0.46 (0.32–0.68)Moderate
Susceptible after an intervention0.47 (0.37–0.61)Low
Elderly institutionalized0.93 (0.67–1.30)Moderate — no benefit
Pregnant women1.06 (0.75–1.50)Moderate — no benefit
Neurogenic bladder0.97 (0.78–1.19)Low — no benefit
  • Analyzed specifically as tablets / powder, cranberry reduced UTI risk in women with rUTI by ~ 55% (RR 0.45; 95% CI 0.28–0.72; 3 studies, n = 333)[30]
  • Stonehouse 2025 (multicenter, double-blind, placebo-controlled, n = 150 women with rUTI) — whole cranberry fruit powder 500 mg/day reduced culture-confirmed UTI by 52% (aRR 0.48; 95% CI 0.26–0.87; p = 0.01), delayed time to first UTI (HR 0.36; p = 0.01), and reduced total episodes (IRR 0.41; p = 0.01)[14]
  • Versus antibiotics, cranberry showed similar efficacy (RR 1.03; 95% CI 0.80–1.33); versus probiotics it was superior (RR 0.39; 95% CI 0.27–0.56)[30]
  • Xia 2021 meta-analysis with trial sequential analysis (23 trials, n = 3,979) judged the evidence for cranberry in susceptible populations conclusive (RR 0.70; 95% CI 0.59–0.83)[31]
  • Beerepoot 2013 meta-analysis — pooled RR 0.53 (95% CI 0.33–0.83)[9]
  • The Juthani-Mehta 2016 nursing-home RCT (72 mg PAC capsule) found no reduction in bacteriuria-plus-pyuria — consistent with the Cochrane elderly-institutionalized null[32]

Prevention only — not treatment​

A separate Cochrane review found no reliable evidence that cranberry products treat an active UTI. Cranberry is a preventive strategy only.[33]

Safety​

Well tolerated; the Cochrane review found only a possible mild increase in GI adverse events (RR 1.33; 95% CI 1.00–1.77) and no increase in mortality.[30] Warfarin: a theoretical CYP2C9-based interaction — moderate intake (standard supplement doses, 240–480 mL juice) does not meaningfully alter warfarin pharmacodynamics, and the US Pharmacopeial Convention concluded cautionary labeling is not warranted at standard doses; excessive intake (1–2 L/day juice or ≥ 3,000 mg/day extract) may, so monitor INR in that scenario.[34] Kidney stones: data are contradictory, with no clinically significant risk at standard doses.[34]

D-mannose​

Mechanism: D-mannose is a monosaccharide (a C-2 epimer of glucose) found naturally in cranberries, grapes, and apples. After oral absorption it is excreted largely unchanged into urine, where it binds the FimH adhesin on the tip of type 1 pili of uropathogenic E. coli, competitively blocking adherence to urothelial mannose receptors so bacteria are voided rather than colonizing. The effect is FimH-specific — primarily relevant to E. coli. Urinary half-life is ~ 4 hours, the rationale for multiple daily doses. Pharmacologically attractive; clinically underwhelming in recent rigorous data.[35]

Evidence — conflicting​

The evidence splits sharply between earlier open-label trials and the definitive blinded RCT:

  • Kranjčec 2014 — open-label 3-arm RCT (n = 308) in women with acute cystitis and rUTI history: 6-month recurrence 14.6% (D-mannose 2 g/day) vs 20.4% (nitrofurantoin) vs 60% (no treatment)[36]
  • Porru 2014 — randomized crossover (n = 60): mean time to recurrence 200 days (D-mannose) vs 52.7 days (co-trimoxazole)[37]
  • Lenger 2020 meta-analysis — pooled RR 0.23 (95% CI 0.14–0.37) vs placebo, driven by these open-label studies[38]
  • Han 2025 network meta-analysis — largest effect size of any non-antibiotic intervention (RR 0.34; 95% CI 0.21–0.56), again weighted by smaller / older studies[4]
  • MERIT RCT (Hayward 2024, JAMA Intern Med) — double-blind, placebo-controlled, n = 598 women with rUTI recruited from UK primary care: no significant benefit — 51.0% vs 55.7% with a medically attended UTI over 6 months (adjusted HR 0.92; 95% CI 0.73–1.16), with no difference in symptom burden, time to next UTI, antibiotic use, or serious adverse events, and consistency across pre-/postmenopausal subgroups[16]
  • WikiGuidelines 2024 concludes insufficient evidence to recommend for or against[2]

Reconciling the discrepancy: the favorable trials were open-label (vulnerable to expectation effects on symptom reporting and healthcare-seeking), enrolled women at the point of active cystitis, and recruited from specialist urology clinics; MERIT was blinded, enrolled women between infections, and recruited from primary care. A 2026 systematic review concluded D-mannose matched antibiotics in specialist settings but showed no benefit over placebo in broad primary care, and should be "reserved for selected patient populations."[39]

Dosing (when used despite the equivocal evidence)​

No standardized dose; trials span 200 mg–3 g/day. Typical regimen 2 g PO once daily or 1 g BID dissolved in water (the 2 g/day dose used in both Kranjčec and MERIT). Cannot be strongly recommended as a primary strategy given MERIT, but may retain a role in specialist-referred patients with high recurrence burden.

Safety​

Generally well tolerated; diarrhea is the most common adverse event, with rare vaginal burning, and MERIT found no excess serious adverse events.[16][35] Despite being a sugar, D-mannose has minimal effect on glucose metabolism at standard doses (most is excreted unmetabolized), though caution is reasonable in diabetic patients given that it does stimulate insulin secretion.[35]

Prevention only — not treatment​

The Cochrane review found no reliable evidence that D-mannose treats an active UTI; its anti-adhesion mechanism suits prevention, not established infection.[35]

Hydration (≥1.5 L/day increase)​

Hooton 2018 (JAMA Intern Med, RCT, n = 140 premenopausal women with rUTI and low baseline fluid intake) — adding 1.5 L of water daily cut recurrences by ~50% over 12 months (1.7 vs 3.2 episodes; p < 0.001) and reduced antimicrobial regimen use comparably.[17]

  • Low-risk, zero-resistance-pressure intervention
  • Confirmatory studies in postmenopausal women and patients with neurogenic bladder are awaited, but the intervention is cheap and reasonable to recommend broadly

Probiotics​

Heterogeneous evidence across strains, routes, and populations. The Han 2025 network meta-analysis found RR 0.69 (95% CI 0.50–0.94) with the strongest signal in pediatric subgroups (RR 0.50; 95% CI 0.28–0.89).[4] WikiGuidelines 2024 found inconclusive evidence and makes no formal recommendation.[2]

  • Most studied strains: vaginal Lactobacillus crispatus CTV-05 (Lactin-V), L. rhamnosus GR-1, L. reuteri RC-14
  • Route matters: vaginal delivery plausibly more directly relevant than oral for urinary colonization
  • Reasonable adjunct to vaginal estrogen in selected postmenopausal patients; not a stand-alone first-line option

Immunoprophylaxis​

None of these are FDA-approved in the US, but they are part of the global rUTI armamentarium and increasingly appear in patient-initiated queries.

OM-89 (Uro-Vaxom) — oral E. coli lysate​

  • Bauer 2005 RCT (n = 453, multicenter double-blind) — 34% reduction in UTI rate (0.84 vs 1.28 episodes; p < 0.001) with favorable safety[18]
  • Beerepoot 2013 meta-analysis — pooled RR 0.61 (95% CI 0.48–0.78)[9]
  • Volontè 2025 systematic review — confirmed reduced recurrence, good tolerability, and reduced antibiotic use[19]
  • Latin American consensus — Grade A recommendation[20]
  • Regimen: 6 mg PO once daily for 3 months (re-courses available)

MV140 (Uromune) — sublingual polybacterial spray​

  • Whole-cell heat-inactivated E. coli, K. pneumoniae, P. vulgaris, E. faecalis
  • Lorenzo-Gómez 2021 prospective cohort in frail elderly women — 7- to 40-fold reduction in UTI episodes after a 3-month course with improved QoL[21]
  • Large RCTs ongoing

Urovac — vaginal mucosal vaccine​

  • Modest reduction (RR 0.75; 95% CI 0.63–0.89); booster immunization extends time to reinfection[22]

Aziminia 2019 systematic review — 10 RCTs, n = 1,537​

Pooled RR 0.74 (95% CI 0.67–0.81) for vaccines vs placebo; evidence quality low with substantial heterogeneity.[22]

Vitamin D​

Mechanism: vitamin D induces cathelicidin (LL-37), a cationic antimicrobial peptide expressed by bladder urothelium and neutrophils.[23]

Evidence​

  • Jorde 2016 (RCT, n = 511 prediabetic subjects) — vitamin D3 20,000 IU/week for 5 years significantly reduced UTI reports vs placebo (18 vs 34 subjects; p < 0.05)[24]
  • D-Health Trial (Pham 2022, n = 21,315 older Australian adults) — modest reduction in antibiotic prescriptions with vitamin D supplementation, stronger in those with insufficient baseline levels[25]
  • Han 2025 network meta-analysis — RR 0.46 (95% CI 0.27–0.81) in the long follow-up subgroup (≥1 year)[4]

Not yet in major rUTI guideline recommendations. Reasonable as adjunct in patients with measured insufficiency — concurrent correction of a common deficiency that may also benefit bone and immune health.

Intravesical GAG replenishment (HA ± CS)​

Intravesical hyaluronic acid ± chondroitin sulfate is intended to restore the protective GAG layer of the bladder urothelium, reducing bacterial adherence and neurogenic inflammation. Primarily European practice; primarily deployed in refractory rUTI when non-antibiotic and antibiotic strategies have failed.

Evidence​

  • Damiano 2011 placebo-controlled RCT (n = 57) — HA-CS instillation reduced UTI rate by 86.6% vs 9.6% placebo (p = 0.0002) and extended time to first recurrence (185 vs 53 days; p < 0.05)[26]
  • Corona 2025 meta-analysis — HA-CS reduced infection rates vs placebo or standard care (OR 0.42; 95% CI 0.25–0.49; p < 0.001)[27]
  • Goddard 2018 systematic review + meta-analysis — HA ± CS decreased UTI rate per patient-year (pooled MD −2.56; 95% CI −3.86 to −1.26; p < 0.001)[28]

Practical notes​

  • Typical regimen: weekly instillation × 4, then monthly maintenance; protocol varies by product
  • Commercial products include iAluril (HA-CS), Cystistat (HA), Uracyst (CS)
  • Cross-covered in detail in Intravesical IC/BPS agents — same molecules used for bladder pain syndrome

Intravesical aminoglycoside instillation​

For refractory rUTI, intravesical gentamicin or amikacin — instilled as part of CIC regimens in neurogenic patients or through a Foley / suprapubic in non-neurogenic — has the strongest meta-analytic effect size among intravesical modalities.

  • Kwon 2026 systematic review + meta-analysis — intravesical aminoglycoside instillation produced the most marked reduction in recurrence among intravesical therapies (pooled IRR 0.23; 95% CI 0.15–0.37), with consistent benefit across neurogenic and non-neurogenic populations. Serum aminoglycoside levels were undetectable where measured; adverse events were mild and local[29]

Practical notes​

  • Typical regimen: gentamicin 30 mg in 50 mL normal saline instilled nightly, retained as long as tolerated; alternative amikacin 500 mg in 50 mL
  • No meaningful systemic absorption from intact urothelium — safety profile is excellent
  • Resistance can emerge; periodic urine cultures to monitor organism shift
  • Best suited to patients already doing CIC — delivery is straightforward; non-CIC patients require intermittent catheterization for each dose, which limits adherence

Behavioral modifications​

RCT evidence is limited, but these measures are low-risk and universally recommended:[6][15][17]

  • Post-coital voiding — widely recommended despite limited direct evidence
  • Avoid delaying urination — reduces bacterial dwell time
  • Wipe front-to-back — reduces fecal-perineal contamination
  • Avoid spermicides and diaphragms — associated with increased UTI risk in observational studies
  • Review contraceptive method with patients who develop rUTI after starting spermicide use

Evidence Summary​

InterventionStrength of evidenceEffect sizeGuideline status
Vaginal estrogenModerate (meta-analysis of RCTs)RR 0.42–0.58AUA Moderate / Grade B[1][7]
Methenamine hippurateModerate (non-inferiority RCT + placebo-controlled phase IV RCT)Non-inferior to daily antibiotics; 25% vs placeboAUA-endorsed alternative; WikiGuidelines recommended[10][12]
Cranberry (≥36 mg PAC)Moderate (multiple RCTs)RR 0.48–0.72AUA Conditional / Grade C; WikiGuidelines recommended[1][2][14]
Hydration +1.5 L/dayLow (single RCT)~50% reductionWikiGuidelines recommended[17]
D-mannoseConflicting (network meta positive; largest RCT negative)RR 0.34 vs nullWikiGuidelines insufficient evidence[4][16]
ProbioticsLow / inconclusiveRR 0.69WikiGuidelines inconclusive[4]
OM-89 (Uro-Vaxom)Moderate (multiple RCTs)RR 0.61Latin American Grade A; not FDA-approved[9][18][19]
MV140 (Uromune)Low (cohort)7–40× reductionOngoing RCTs; not FDA-approved[21]
Vitamin DLow (limited RCTs)RR 0.46 in long-follow-up subgroupNot in major guidelines[4][24]
Intravesical HA ± CSLow–moderate (small RCTs, meta-analysis)OR 0.42; MD −2.56/pyRefractory-rUTI option (mainly European)[27][28]
Intravesical aminoglycosidesLow–moderate (meta-analysis)IRR 0.23Refractory-rUTI option, strongest intravesical signal[29]
Behavioral modificationsVery low (observational)Not quantifiableUniversally recommended

Clinical Positioning​

  • Vaginal estrogen is first-line in postmenopausal women with rUTI regardless of whether GSM symptoms are the presenting complaint — the 2023 Tan-Kim real-world data (51.9% reduction, n = 5,638) and Chen meta-analysis (RR 0.42) are the anchor evidence.[7][8]
  • Systemic estrogen has no role in UTI prevention — use vaginal routes only.[7]
  • Methenamine hippurate is the highest-yield non-antibiotic oral agent and is non-inferior to daily antibiotics (ALTAR) with better resistance footprint.[10][11]
  • Cranberry works if the product has ≥36 mg PAC. Don't rely on cocktail juice — use a declared-PAC-content capsule or whole-fruit powder.[2][14]
  • D-mannose is no longer routinely recommended. The MERIT primary-care RCT is the largest, most rigorous, and negative.[16]
  • Add 1.5 L/day of water in every rUTI patient who is not volume-restricted. Cheap, zero-resistance, ~50% recurrence reduction in Hooton's RCT.[17]
  • Immunoprophylaxis (OM-89, MV140) is legitimate where available; not FDA-approved in the US but has Grade A support in Latin America and accumulating European evidence.[19][20][21]
  • Vitamin D is a reasonable adjunct in patients with measured insufficiency — biologically plausible (cathelicidin induction) with modest accumulating signal.[4][23][24]
  • Intravesical therapy (HA/CS, aminoglycoside) is for refractory rUTI — escalate to this tier when oral non-antibiotics and appropriate antibiotic strategies have failed. Intravesical aminoglycoside has the strongest meta-analytic signal (IRR 0.23) in the 2026 Kwon review.[29]
  • Always layer behavioral measures — post-coital voiding, spermicide avoidance, front-to-back wiping — on top of any pharmacologic strategy.

See Also​

References​

1. Anger JT, Bixler BR, Holmes RS, et al. "Updates to recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU guideline." J Urol. 2022;208(3):536–541. doi:10.1097/JU.0000000000002860

2. Nelson Z, Aslan AT, Beahm NP, et al. "Guidelines for the prevention, diagnosis, and management of urinary tract infections in pediatrics and adults: a WikiGuidelines group consensus statement." JAMA Netw Open. 2024;7(11):e2444495. doi:10.1001/jamanetworkopen.2024.44495

3. Steinman MA. "Alternative treatments to selected medications in the 2023 American Geriatrics Society Beers Criteria." J Am Geriatr Soc. 2025;73(9):2657–2677. doi:10.1111/jgs.19500

4. Han Z, Yi X, Li J, Liao D, Ai J. "Nonantibiotic prophylaxis for urinary tract infections: a network meta-analysis of randomized controlled trials." Infection. 2025;53(2):535–546. doi:10.1007/s15010-024-02357-z

5. Buck ES, Lukas VA, Rubin RS. "Effective prevention of recurrent UTIs with vaginal estrogen: pearls for a urological approach to genitourinary syndrome of menopause." Urology. 2021;151:31–36. doi:10.1016/j.urology.2020.05.058

6. Raz R, Stamm WE. "A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections." N Engl J Med. 1993;329(11):753–756. doi:10.1056/NEJM199309093291102

7. Chen YY, Su TH, Lau HH. "Estrogen for the prevention of recurrent urinary tract infections in postmenopausal women: a meta-analysis of randomized controlled trials." Int Urogynecol J. 2021;32(1):17–25. doi:10.1007/s00192-020-04397-z

8. Tan-Kim J, Shah NM, Do D, Menefee SA. "Efficacy of vaginal estrogen for recurrent urinary tract infection prevention in hypoestrogenic women." Am J Obstet Gynecol. 2023;229(2):143.e1–143.e9. doi:10.1016/j.ajog.2023.05.002

9. Beerepoot MA, Geerlings SE, van Haarst EP, van Charante NM, ter Riet G. "Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic review and meta-analysis of randomized controlled trials." J Urol. 2013;190(6):1981–1989. doi:10.1016/j.juro.2013.04.142

10. Harding C, Mossop H, Homer T, et al. "Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open-label, randomised, non-inferiority trial (ALTAR)." BMJ. 2022;376:e068229. doi:10.1136/bmj-2021-0068229

11. Harding C, Chadwick T, Homer T, et al. "Methenamine hippurate compared with antibiotic prophylaxis to prevent recurrent urinary tract infections in women: the ALTAR non-inferiority RCT." Health Technol Assess. 2022;26(23):1–172. doi:10.3310/QOIZ6538

12. Heltveit-Olsen SR, Arnljots ES, Sundvall PD, et al. "Methenamine hippurate as prophylaxis for recurrent urinary tract infections in older women — a triple-blind, randomised, placebo-controlled, phase IV trial (ImpresU)." Clin Microbiol Infect. 2025. doi:10.1016/j.cmi.2025.07.006

13. Davidson SM, Brown JN, Nance CB, Townsend ML. "Use of methenamine for urinary tract infection prophylaxis: systematic review of recent evidence." Int Urogynecol J. 2024;35(3):483–489. doi:10.1007/s00192-024-05726-2

14. Stonehouse W, Benassi-Evans B, Bednarz J, Vincent AD. "Whole cranberry fruit powder supplement reduces the incidence of culture-confirmed urinary tract infections in females with a history of recurrent urinary tract infection: a 6-month multicenter, randomized, double-blind, placebo-controlled trial." Am J Clin Nutr. 2025;121(4):932–941. doi:10.1016/j.ajcnut.2025.01.022

15. Schmiemann G, Kranz J, Mandraka F, et al. "The diagnosis, treatment, and prevention of recurrent urinary tract infection." Dtsch Arztebl Int. 2024;121(11):373–382. doi:10.3238/arztebl.m2024.0068

16. Hayward G, Mort S, Hay AD, et al. "D-mannose for prevention of recurrent urinary tract infection among women: a randomized clinical trial (MERIT)." JAMA Intern Med. 2024;184(6):619–628. doi:10.1001/jamainternmed.2024.0264

17. Hooton TM, Vecchio M, Iroz A, et al. "Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections: a randomized clinical trial." JAMA Intern Med. 2018;178(11):1509–1515. doi:10.1001/jamainternmed.2018.4204

18. Bauer HW, Alloussi S, Egger G, et al. "A long-term, multicenter, double-blind study of an Escherichia coli extract (OM-89) in female patients with recurrent urinary tract infections." Eur Urol. 2005;47(4):542–548. doi:10.1016/j.eururo.2004.12.009

19. Volontè S, De Vicari D, Cola A, Barba M, Frigerio M. "Efficacy and safety of Uro-Vaxom in urinary tract infection prevention: a systematic literature review." J Clin Med. 2025;14(11):3836. doi:10.3390/jcm14113836

20. Haddad JM, Ubertazzi E, Cabrera OS, et al. "Latin American consensus on uncomplicated recurrent urinary tract infection — 2018." Int Urogynecol J. 2020;31(1):35–44. doi:10.1007/s00192-019-04079-5

21. Lorenzo-Gómez MF, Padilla-Fernández B, Flores-Fraile J, et al. "Impact of whole-cell bacterial immunoprophylaxis in the management of recurrent urinary tract infections in the frail elderly." Vaccine. 2021;39(42):6308–6314. doi:10.1016/j.vaccine.2021.08.093

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