Recurrent Cystitis

Aka: Recurrent Cystitis, Recurrent UTI, Recurrent Urinary Tract Infection, Prevention of Recurrent Urinary Tract Infection

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II. Definitions

  1. Recurrent Urinary Tract Infection in young women
    1. One year with 3 or more symptomatic, culture positive Urinary Tract Infections
  2. Recurrent Urinary Tract Infection in Pregnancy
    1. Two or more episodes of Urinary Tract Infection in Pregnancy
    2. See UTI in Pregnancy
  3. Recurrent Urinary Tract Infection in postmenopausal women
    1. One year with 3 or more symptomatic, culture positive Urinary Tract Infections OR
    2. Six months with 2 or more Urinary Tract Infections
  4. UTI Relapse
    1. UTI with same organism and serotype presents within 2 weeks of last UTI treatment

III. Epidemiology

  1. Incidence of bacteriuria
    1. School age child: 1.2%
    2. Late Teenage years: 2-5%
    3. Additional 1% per decade of life
  2. UTI recurrence rate in women: 14 to 25%
  3. Incidence of UTIs for those prone: 2-3 per year
    1. Reduced to <1 per year on prophylaxis

IV. Pathophysiology

  1. Causative organisms
    1. Escherichia coli (75% of Recurrent UTI)
    2. Enterococcus faecalis
    3. Proteus Mirabilis
    4. Klebsiella
    5. Staphylococcus Saprophyticus
  2. Inherited factors (esp. in first degree relative with >5 UTIs)
    1. Immune susceptibility (e.g. variation in Neutrophil receptors)
      1. May reduce Bacterial clearance or not preventing uroepithelial adherence
    2. Urogenital anatomy variation
      1. Shorter anal-Urethral distance
  3. Other factors predisposing to UTI
    1. Protective Lactobacillus decreased

V. Types: Infection Classification

  1. General
    1. Reinfection represents 99% of Recurrent UTI in women
    2. Vaginal colonization is the most common cause
  2. First Infection
  3. Unresolved Bacteriuria (Refractory Infection)
    1. Bacterial resistance to drug selected for treatment
      1. Resistance developed by sensitive Bacteria
      2. Bacteriuria with 2 different species
      3. Rapid reinfection with a second resistant organism
    2. Azotemia
    3. Analgesic abuse causing papillary necrosis
    4. Giant staghorn calculi
    5. Noncompliance
  4. Bacterial persistance (Same organism recurs)
    1. Infected Renal Calculi
    2. Chronic Bacterial Prostatitis
    3. Unilateral infected atrophic Pyelonephritis
    4. Infected pericalyceal Diverticulae
    5. Infected nonrefluxing ureteral stumps
      1. Follows Nephrectomy
    6. Medullary sponge Kidneys
    7. Polycystic Kidney Disease
    8. Infected Urachal Cysts
    9. Analgesic abuse causing infected papillary necrosis
  5. Reinfection (Urine cleared, but new infection occurs)
    1. Colonization of vaginal introitus
    2. Vesicoenteric fistulae
    3. Vesicovaginal fistulae
    4. Vesicoureteral Reflux
    5. Voiding dysfunction
      1. Cystocele
      2. Multiple Sclerosis
      3. Neurogenic Bladder
    6. Immunosuppression
      1. Chronic Renal Insufficiency
      2. Diabetes Mellitus
      3. Immunosuppressant medications
    7. Instrumentation
      1. Ureteral Stent
      2. Nephrostomy Tube
      3. Intermittent catheterization or indwelling Urinary Catheter

VI. Risk Factors

  1. Young women with Recurrent UTI (prior to Menopause)
    1. Intercourse in the past month >9 times: Odds Ratio 10.3
    2. Intercourse in the past month 4-8 times: Odds Ratio 5.8
    3. Age at first UTI >15 years: Odds Ratio 3.9
    4. Mother with Recurrent UTI: Odds Ratio 2.3
    5. New sex partner in the last year: Odds Ratio 1.9
    6. Spermicide use in the last year: Odds Ratio 1.8
    7. Scholes (2000) J Infect Dis 182(4): 1177-82 [PubMed]
  2. Postmenopausal women
    1. Estrogen deficiency
      1. Vaginal Atrophy (Genitourinary Syndrome of Menopause, responds to Topical Estrogens)
      2. Also alters Vaginal pH and decreases Lactobacillus colonization
    2. Urinary Incontinence
    3. Urinary Retention (residual Urine Volume >150 ml)
    4. Structural abnormalities (e.g. Cystocele)
    5. Type II Diabetes Mellitus
    6. History of Urinary Tract Infection (>5)
    7. Activities that increase intraabdominal pressure (e.g. long distance travel or walking)
  3. Transgender or Gender-Affirming Surgery
    1. Female to Male (FTM) Transgender
      1. Testosterone results in Vaginal Atrophy (responds to Topical Estrogens)
    2. Female to Male Gender-Affirming Surgery (Metoidioplasty, Phalloplasty)
      1. Increased UTI complications
    3. Male to Female Gender-Affirming Surgery (Vaginoplasty)
      1. Small increased UTI risk

VII. History

  1. UTI Frequency
  2. Prior infection severity
  3. Symptom evolution over time
    1. Classic UTI symptoms
      1. Dysuria, Frequency, Urgency and Suprapubic Pain
    2. Atypical or subtle symptoms (esp. postmenopausal women)
      1. Mild discomfort with urination
      2. Incomplete Bladder emptying
      3. Minor pelvic discomfort
  4. Laboratory data (Urinalysis, Urine Culture with Microbe identification)
    1. Exclude Asymptomatic Bacteriuria (positive UA/UC without urinary tract symptoms)
    2. Exclude pyuria or Dysuria with negative cultures (see Dysuria for alternative diagnoses)
    3. Differentiate recurrence from relapse
      1. Relapsed UTI occurs with same organism and serotype presents within 2 weeks of last UTI treatment
  5. General recurrence contributing factors (see above)
    1. Antibiotic exposure
    2. Increased sexual activity
    3. Spermicidal agents
    4. Contraceptive Diaphragms
    5. Perimenopause or Postmenopause
  6. Urinary stasis risk
    1. Incomplete Bladder emptying
    2. Pelvic Organ Prolapse
    3. Voiding dysfunction
  7. Comorbid medical conditions
    1. Diabetes Mellitus
    2. Nephrolithiasis
    3. Neurogenic Bladder
    4. Urinary structural abnormalities

VIII. Differential Diagnosis

  1. See Dysuria
  2. Consider Vaginitis or Sexually Transmitted Infection (presentations similar to UTI)
  3. Consider other noninfectious causes (e.g. Interstitial Cystitis, Bladder Cancer, Urethral Diverticulum)
  4. Consider Genitourinary Syndrome of Menopause (Atrophic Vaginitis)
    1. Vulvovaginal dryness, Pruritus, and Dyspareunia

IX. Labs

  1. Consider Urine Pregnancy Test
  2. Urinalysis
  3. Urine Culture is recommended with each Recurrent UTI
    1. Microbe identification and susceptibility testing
      1. Recommended for each Recurrent UTI
      2. Obtain sample via catheter when patient is unable to provide a reliable clean catch sample
    2. Replaces older Urine Culture indications in Recurrent UTI
      1. Obtain in at least one of Recurrent Urinary Tract Infections
      2. Breakthrough Urinary Tract Infection while on UTI prophylaxis
      3. UTI symptoms >48 hours despite Antibiotic treatment
      4. Symptomatic bacteriuria at 2 weeks after 2 weeks of culture-directed Antibiotics
        1. Evaluate for Antibiotic Resistance or persistent infection nidus

X. Diagnostics

  1. Precautions
    1. Cystoscopy and imaging have low yield in general for Recurrent UTI that responds to treatment
    2. Consider advanced diagnostics when specifically indicated as below
  2. Post-void Residual Volume and urodynamic testing indications
    1. Urinary Incontinence or Overactive Bladder
    2. Incomplete Bladder emptying
  3. Structural evaluation (pelvic exam, Ultrasound, CT, cystoscopy) indications
    1. Hematuria persists after infection clearance
    2. Urinary tract malignancy history
    3. Urogenital surgery or Trauma History
    4. Diverticulitis history
    5. Nephrolithiasis or Urolithiasis
      1. Especially if Urine Culture with Proteus, Klebsiella, Pseudomonas (associated with Struvite Stones)
    6. Multi-drug resistant organisms
    7. Persistent symptoms and bacteriuria despite 2 weeks of culture directed Antibiotics
    8. Pneumaturia or fecaluria
    9. Urine Culture with anaerobic organisms (except E. coli, Staphylococcus)
    10. Recurrent or treatment-resistant Pyelonephritis
    11. Voiding dysfunction
      1. Urinary obstructive symptoms
      2. Increased post-void Residual Volume
      3. Urinary Incontinence

XI. Management: Urinary Tract Infection Treatment

  1. See Urinary Tract Infection for acute management
  2. See UTI in Pregnancy
  3. See UTI associated with Urinary Catheter
  4. See UTI in Children
  5. See UTI in Men
  6. See UTI in Older Adults
  7. First-line agents (less likely to induce Antibiotic Resistance)
    1. Trimethoprim-sulfamethoxazole or Septra, Bactrim orally twice daily for 3 days
      1. Avoid if local resistance rates are >20%
    2. Nitrofurantoin or Macrobid 100 mg orally twice daily for 5 days
      1. Avoid if eGFR <30-60 ml/min, or upper tract infection is possible
    3. Fosfomycin or monurol 3 grams orally for 1 dose (1 day)
  8. Other agents
    1. Reserve Fluoroquinolones (e.g. Ciprofloxacin, Levofloxacin) for more complicated infections
    2. Beta Lactam agents (Penicillins, Cephalosporins) are less effective in Recurrent UTI
  9. Precautions
    1. Use prior Urine Culture susceptibility to choose empiric Antibiotics while awaiting repeat Urine Culture
    2. Treat uncomplicated cystitis with three day course (avoid Antibiotic courses >7 days)
    3. Treat uncomplicated cystitis in Diabetes Mellitus with same agents as those without diabetes
    4. Avoid repeat follow-up urine testing in asymptomatic patients after treatment
      1. Avoid treating residual Asymptomatic Bacteriuria after treatment
      2. Exceptions
        1. Pregnancy
        2. Prior to invasive urologic procedure
        3. Persistent Hematuria
        4. Suspected Ureterolithiasis
        5. Recurrent Pyelonephritis
        6. Genitourinary structural abnormalities
  10. Urology Consultation indications
    1. Hematuria without Dysuria
    2. Serum Creatinine increased
    3. Recurrent Proteus infections
    4. Urinary Retention and Incontinence

XII. Management: Antibiotic self-starting regimen for symptomatic UTI

  1. Consider in patients who are not candidates for UTI prophylaxis
  2. Emergency prescription available to start after onset of classic Urinary Tract Infection symptoms
    1. Self diagnosis based on Dysuria, Urinary Frequency, urinary hesitancy is 85% accurate
    2. Preferably patient also submits a Urine Culture sample before starting on Antibiotics
  3. Choose a 3 day Antibiotic course
    1. See Urinary Tract Infection for Antibiotic options and dosing
  4. Indications for medical evaluation
    1. Symptoms last more than 48 hours despite Antibiotics
    2. Fever
    3. Nausea or Vomiting
    4. Acute back pain
    5. Vaginal Discharge
    6. Pelvic Pain
    7. STD Exposure
  5. Contraindications
    1. Prior urogenital surgery
    2. Bladder Catheterization
  6. References
    1. Schaeffer (1999) J Urol 161(1):207-11 +PMID:10037399 [PubMed]

XIII. Management: UTI Prophylaxis in women

  1. Indications
    1. Recurrent Urinary Tract Infections occurring 3 or more times annually
  2. Precautions
    1. Confirm pregnancy and Lactation status when prescribing prophylaxis
  3. Continuous UTI Prophylaxis (Average Course: Taken daily for 6 months, up to 12 months)
    1. Discontinue after 6-12 months without UTI
    2. Preferred first-line continuous prophylaxis (choose one)
      1. Nitrofurantoin 50-100 mg once daily (avoid in GFR <30 ml/min)
      2. Trimethoprim Sulfamethoxazole 40/200 daily or three times per week
    3. Other agents used for continuous prophylaxis (choose one)
      1. Trimethoprim 100 mg daily
      2. Cephalexin 125-250 mg daily
      3. Fosfomycin 3 grams every 10 days
    4. Generally avoid for continuous prophylaxis (risk of increasing resistance)
      1. Ciprofloxacin 125 mg daily
      2. Norfloxacin 200 mg daily
  4. Postcoital Prophylaxis
    1. Precaution: Recurrence is common after stopping prophylaxis
    2. One dose taken within 2 hours of intercourse
    3. Preferred first-line post-coital prophylaxis (choose one)
      1. Nitrofurantoin 100 mg once
      2. Trimethoprim Sulfamethoxazole 40/200 to 80/400 once
    4. Other agents used for post-coital prophylaxis (choose one)
      1. Trimethoprim 100 mg once
      2. Cephalexin 250 mg once
    5. Generally avoid for post-coital prophylaxis (risk of increasing resistance)
      1. Ciprofloxacin 125 mg once
      2. Norfloxacin 200 mg once
  5. Peri-Menopausal and Post-menopausal women
    1. Manage Urinary Incontinence (risk for Recurrent UTI)
    2. Topical Estrogen for Atrophic Vaginitis
      1. Estriol Cream 0.5 mg intravaginal daily for 2 weeks initially, then twice weekly
      2. May reduce Recurrent UTI risk by up to 60%
      3. Perotta (2008) Cochrane Database Syst Rev (2):CD005131 +PMID:18425910 [PubMed]

XIV. Management: Other prophylactic agents

  1. General Measures
    1. Maintain adequate hydration each day (e.g. 51 oz fluid per day, 1.5 Liters/day)
      1. Alternatively, maintain fluid intake sufficient to maintain clear or light yellow Urine Color
  2. Probiotics
    1. Lactobacillus Probiotics used orally or vaginally reduce Recurrent UTI frequency in premenopausal women
    2. Vaginal Probiotics (with or without oral Probiotics) are most effective
    3. Gupta (2024) Clin Infect Dis 78(5):1154-61 [PubMed]
  3. Methenamine
    1. Indications
      1. Short term prophylaxis in patients without renal tract abnormalities
    2. Contraindications
      1. Renal Impairment
      2. Bladder catheter
    3. Mechanism
      1. Metabolized to formaldehyde in the urine, killing local Microbes
      2. Anticipate Recurrent UTI after Methenamine discontinuation at 6 months
      3. Requires acidic urine
        1. Less effective in UTIs due to urea splitting Bacteria (e.g. Proteus, Pseudomonas)
    4. Medications
      1. Methenamine Hippurate 1 g orally twice daily (preferred)
      2. Methenamine Mandelate 1 g orally four times daily
        1. Older preparation with less evidence (released before 1938 FDA reviews started)
    5. Drug Interactions
      1. Trimethoprim Sulfamethoxazole (TMP-SMZ)
        1. Formaldehyde (Methenamine metabolite) reacts with Sulfonamides, forming precipitates
        2. Results in Crystalluria
    6. References
      1. Weidner (2018) Email communication, received 9/1/2018
      2. Lee (2012) Cochrane Database Syst Rev (10): CD003265 +PMID: 23076896 [PubMed]
  4. Cranberry Juice (variable evidence)
    1. Mechanism
      1. Contains proanthocyanidin compounds
      2. Inhibits E. coli and other p-fimbriated Bacteria from adhering to urothelial cells in the urinary tract
    2. Recommended daily dosing of cranberry juice
      1. Cranberry extract 300 to 500 mg tablet once to twice daily
      2. Pure cranberry unsweetened juice 8 ounces once to three times daily
    3. Efficacy
      1. Number needed to treart (NNT) to prevent Recurrent Urinary Tract Infections
        1. Women NNT 16
        2. Children NNT 8
        3. Following Bladder interventions NNT 9
        4. Johari (2024) Am Fam Physician 110(1): 23B [PubMed]
      2. Some reviews have reported no high quality evidence for significant benefit
        1. Guay Drugs (2009) 69(7):775-807 [PubMed]
      3. Not effective in older women living in Nursing Homes
        1. Juthani-Mehta (2016) JAMA 316(18):1879-87 +PMID: 27787564 [PubMed]
      4. Daily cranberry juice may decrease recurrent symptomatic UTIs in women over 1 year
        1. Jepson (2008) Cochrane Database Syst Rev (1):CD001321 +PMID:18253990 [PubMed]
      5. Older, original studies suggesting more broad efficacy in UTI prevention
        1. Kontiokari (2001) BMJ 322:1571-3 [PubMed]
        2. Howell (1998) N Engl J Med 339(15): 1085-86 [PubMed]
        3. Lynch (2004) Am Fam Physician 70(11): 2175-77 [PubMed]
  5. Immunoactive therapy (Vaccines targetting common UTI Bacteria)
    1. Used internationally (but not FDA approved for use in U.S.)
    2. Agents
      1. Bacterial lysate OM-89
        1. Oral Vaccine against E. coli
      2. MV 140
        1. Sublingual spray
        2. Active against 4 Bacteria (E. coli, K. Pneumoniae, E. faecalis, and P. vulgaris)
      3. Solco-Urovac
        1. Vaginal suppository
        2. Active against 10 Bacteria (6 strains E. coli, 2 Proteus species, K. Pneumoniae, E. faecalis)
      4. ExPEC4V/ExPEC10V
        1. IM Vaccine against E. coli

XV. Prevention: Behavior Modification

  1. Measures that may offer benefit
    1. Women should empty Bladder before and after intercourse
    2. Avoid postponing urination when there is an urge to urinate
    3. Avoid Contraceptive Diaphragm
    4. Avoid spermacide
    5. Increased hydration (1.5 Liters/day)
      1. Alternatively, maintain fluid intake sufficient to maintain clear or light yellow Urine Color
      2. Hooton (2018) JAMA Intern Med 178(11):1509-15 [PubMed]
  2. Measures NOT found to reduce UTI risk
    1. Women wiping perineum front to back after stooling
    2. Cotton underwear
    3. Reduced exposure to hot tubs
    4. Reduced use of tampons
    5. Avoid douching (did not decrease UTI risk, but should be avoided due to other risks)
    6. Glover (2014) Urol Sci 25(1): 1-8 [PubMed]

XVI. References

  1. (2026) Presc Ins 33(6): 1-3
  2. Arnold (2016) Am Fam Physician 93(7): 560-9 [PubMed]
  3. Gupta (2013) BMJ 346:f3140 [PubMed]
    1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688544/
  4. Kodner (2011) Am Fam Physician 82(6): 638-43 [PubMed]
  5. Sen (2006) Clin Evid 15:2558-64 [PubMed]
  6. Zwahlen (2026) Am Fam Physician 113(6): 568-77 [PubMed]

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