Urinary Tract Infection

Aka: Urinary Tract Infection, UTI, Bladder Infection, Acute Cystitis

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II. Causes

  1. Normal Host
    1. Escherichia coli (80-90%)
    2. Staphylococcus Saprophyticus (10-15% of young women, 4% overall)
      1. More aggressive and Recurrent Urinary Tract Infections
      2. Associated with Pyelonephritis
    3. Klebsiella Pneumoniae (3-6%)
    4. Enterococcus (5%)
    5. Group B Streptococcus (3%)
    6. Proteus Mirabilis (2-3%)
    7. Pseudomonas Aeruginosa (1%)
  2. Nephrolithiasis or Ureterolithiasis associated infection
    1. Proteus (urease positive)
    2. Klebsiella Pneumoniae
  3. Sexually Transmitted Infections
    1. Chlamydia
    2. Neisseria gonorrhoeae
    3. Herpes Simplex Virus II (Genital Herpes)

III. Risk factors: Complicated Cystitis

  1. Male gender
  2. Pregnancy
  3. Hospital acquired Urinary Tract Infection
  4. Prolonged urinary tract symptoms (>1 week)
  5. Poorly controlled Diabetes Mellitus
  6. Immunocompromised
  7. Underlying urologic disorder
    1. Vesicoureteral reflux
    2. Recurrent complicated Urinary Tract Infections
    3. Catheter associated Urinary Tract Infection
    4. Neurogenic Bladder dysfunction
    5. Polycystic Kidney Disease
    6. Urologic instrumentation or stenting
    7. Status Renal Transplant
    8. Urinary Tract Obstruction (e.g. Nephrolithiasis)
    9. Men with Prostatitis or BPH

IV. Symptoms

  1. Most suggestive of Urinary Tract Infection
    1. Dysuria (Likelihood Ratio 2.0)
      1. If absent, Likelihood Ratio 0.5
    2. Urinary Frequency (Likelihood Ratio 1.8)
    3. Hematuria (Likelihood Ratio 1.5)
      1. Occurs in 30% of cases
  2. Other symptoms with Urinary Tract Infection
    1. Urinary Urgency
    2. Suprapubic Pain (especially after voiding)
    3. Incomplete Bladder emptying

V. Differential Diagnosis

  1. Dysuria
    1. See Dysuria
    2. See Dysuria in Children
    3. See Dysuria in Men
    4. See Dysuria in Women
  2. Urethritis
    1. Pain at onset of urination
  3. Vaginitis
    1. External Dysuria
    2. Vaginal irritation or discharge
  4. Chlamydia Trachomatis
    1. Long, insidious onset
    2. Sexually active
  5. Acute Pyelonephritis
    1. Fever, Flank Pain, and Nausea or Vomiting
    2. Risk factors for cystitis with occult Pyelonephritis
      1. Women (30% have subclinical Pyelonephritis)
      2. Pregnancy
      3. Diabetes Mellitus
      4. Immunocompromised patients
      5. Urinary Tract Infection under age 12 years
      6. Genitourinary comorbid condition
  6. Acute Urethral syndrome (Sterile or low urine Bacterial count)
    1. Gonorrhea
    2. Chlamydia
    3. Herpes Simplex Virus
    4. Vaginitis
  7. Sterile Pyuria
    1. Chlamydia (most common)
    2. Genitourinary Tuberculosis (classic sterile pyuria)
  8. Asymptomatic Bacteriuria (organisms isolated on Urine Culture, but often not responsible for cystitis)
    1. Enterococcus
    2. Streptococcus agalactiae (Group B Streptococcus)
    3. Hooton (2013) N Engl J Med 369(20):1883-91 [PubMed]

VI. Labs

  1. Urinalysis
    1. Urine Leukocyte Esterase (high Test Sensitivity but low Test Specificity)
    2. Urine Nitrite (high Test Specificity approaches 90%, but low Test Sensitivity)
      1. Requires presence of Bacteria (e.g. E coli, Klebsiella, Proteus) capable of converting nitrates to nitrates
    3. Urine White Blood Cells on microscopy
  2. Urine Culture
    1. Positive for >100k organisms
      1. Women with Dysuria have <100k organisms in 30% cases
      2. Of those with positive Urinalysis for UTI, only half are culture positive
    2. Indications
      1. Not needed in uncomplicated UTI (young, healthy non-pregnant women)
      2. Complicated UTI or atypical presentations
      3. Suspected Pyelonephritis
      4. Older adults
      5. Women age <65 years with Recurrent UTI (2 in last 6 months, 3 in last year)
      6. Treatment failure despite first choice Antibiotics
      7. History of resistant Urinary Tract Infections
  3. Other labs to consider in complicated UTI or Pyelonephritis
    1. See Acute Pyelonephritis

VII. Diagnosis: Findings suggestive of upper Urinary Tract Infection (Pyelonephritis)

  1. See Pyelonephritis
  2. Fever, chills
  3. Flank Pain
  4. Vomiting
  5. Pregnancy (second and third trimester are higher risk)
  6. Underlying urinary tract disorder
  7. History of Ureteral Stenting or other instrumentation
  8. Male patients
    1. See Urinary Tract Infection in Men
  9. Insulin Dependent Diabetes Mellitus
  10. HIV Infection
  11. Immunosuppressants (Chronic Corticosteroid use, status-post transplant)
  12. Extremes of age (very young or very old)
    1. Underwhelming presentations of upper tract disease

VIII. Diagnosis: Factors suggestive of complicated UTI

  1. Extremes of age (preadolescent, or over age 65 years)
    1. See Urinary Tract Infection in Children
    2. See Elderly with Urinary Tract Infections
  2. Chronic renal disease
  3. Diabetes Mellitus
  4. Immunodeficiency
  5. Pyelonephritis (upper Urinary Tract Infection)
  6. Pregnancy
    1. See Urinary Tract Infection in Pregnancy
  7. Male patients (esp. uncircumsized)
    1. See Urinary Tract Infection in Men
  8. Recent Urinary Tract Instrumentation
    1. Ureteral Stents
    2. Indwelling catheters (>2 weeks)
      1. See Catheter-Associated Urinary Tract Infection (CAUTI)
  9. Ureterolithiasis
    1. Infected stone is an emergency
  10. Urologic abnormalities
    1. Neurogenic Bladder
    2. Polycystic Kidney Disease

IX. Diagnosis: Prediction Rule

  1. Background
    1. Self diagnosed UTI in women is a strong predictor of UTI
  2. Criteria
    1. New onset frequency and Dysuria
    2. Absent Vaginal Discharge and irritation
  3. Efficacy
    1. Pretest probability of UTI based on symptoms: 90%
    2. Probablity of UTI with negative Urinalysis: 23%
    3. Positive Predictive Value: 90%
  4. Interpretation
    1. May be treated without Urinalysis and Urine Culture
      1. Healthy patients without complicating risk factors or Pyelonephritis symptoms
    2. Editorial note: I do not recommended this (other Dysuria causes, Antibiotic Overuse)
      1. Alternative: Even dipstick testing alone is reasonably accurate, priced and fast
  5. Reference
    1. Bent (2002) JAMA 287:2701-10 [PubMed]

X. Precautions

  1. Consider Sexually Transmitted Infection in Vaginitis or male Dysuria
  2. Consider Ureterolithiasis with Urinary Tract Infection (emergency) when Flank Pain is severe
  3. Empiric Antibiotic regimens should be based on local resistance rates
  4. Urine Culture is not needed in occasional, uncomplicated Urinary Tract Infection (young, healthy, non-pregnant women)
  5. Assume upper tract disease in findings listed above
    1. Adjust management strategy to treat upper tract (e.g. avoid Macrobid/Nitrofurantoin)
  6. Asymptomatic Bacteriuria occurs in up to 20% of older women
    1. Resolves without Antibiotics within 1 week in 25-50% of patients
    2. Have adequate pretest probability for Urinary Tract Infection before Urinalysis in older women

XI. Management: General

  1. See UTI in Older Adults
  2. See UTI in Children
  3. See UTI in Pregnancy
  4. See Acute Pyelonephritis
  5. General measures
    1. Maintain hydration (e.g. 1.5 to 2 Liters/day, or 48 to 64 oz/day)
    2. Analgesics (Acetaminophen or Ibuprofen)
  6. Antibiotics
    1. Course
      1. Anticipate symptom relief within 36 hours of starting Antibiotics
      2. In uncomplicated UTI based on symptoms
        1. Considered delayed Antibiotics, starting if symptoms persist >2-3 days
    2. Antibiotic duration
      1. Uncomplicated treatment: 3 days (except as noted)
        1. Nitrofurantoin and Macrobid course is 5 days (was 7 days)
      2. Complicated treatment: 10 day course
    3. Antibiotic Resistance increasing (including multi-drug resistance)
      1. Nitrofurantoin and Macrobid resistance low (1-2%)
      2. Beta Lactams: 20 to 55%
      3. Ampicillin: 38%
      4. Trimethoprim Sulfamethoxazole (Septra): 18 to 22%
      5. Fluoroquinolone resistance had been low, but as of 2024 resistance is as high as 21%
        1. Avoid as first line agents if possible (due to other adverse effects)
        2. Consider in areas of high Septra resistance areas
    4. Cure may occur despite resistance to Antibiotic used
    5. Risks for Antibiotic Resistance
      1. Trimethoprim Sulfamethoxazole within last 3-6 months
      2. Diabetes Mellitus
      3. Recent hospitalization
      4. Travel outside United States
      5. Resistance rates in community >20%
  7. Acute Uncomplicated UTI: First-Line agents
    1. Note that Ciprofloxacin has been demoted from first-line agent due to adverse effects (see below)
    2. Trimethoprim-Sulfamethoxazole (Bactrim) DS one orally twice daily for 3 days
      1. Avoid if local resistance rate >20%
    3. Nitrofurantoin (Macrobid)
      1. Macrobid 100 mg orally twice daily for 5 days
      2. Avoid if GFR <30 ml/min (risk of interstitial pulmonary fibrosis)
    4. Fosfomycin (Monurol) 3 grams for one dose
      1. Consider as a single dose in Emergency Department (e.g. patient non-compliant)
      2. More expensive and may be less effective (58% efficacy compared with 70% for Nitrofurantoin)
        1. Huttner (2018) JAMA 319(17): 781-9 +PMID:29710295 [PubMed]
    5. First-line alternative agents for Acute Cystitis
      1. Cephalexin (Keflex) 500 mg orally twice daily for 5 to 7 days
      2. Cefuroxime (Ceftin) 500 mg orally twice daily for 5 to 7 days
  8. Acute Uncomplicated UTI with risks for resistance (prior Bactrim use or international travel in last 6 months)
    1. Nitrofurantoin
      1. Avoid if GFR <30 ml/min (risk of interstitial pulmonary fibrosis)
      2. Nitrofurantoin 100 mg orally four times daily for 5 days
      3. Macrobid 100 mg orally twice daily for 5 days
        1. Five days is sufficient course (previously used for 7 days)
        2. Gupta (2007) Arch Intern Med 167(20):2207-12 [PubMed]
    2. Fosfomycin (Monurol) 3 grams for one dose
    3. Also see Fluoroquinolones below
  9. More severe disease or resistant UTI organisms: Fluoroquinolones
    1. Precautions regarding Fluoroquinolones
      1. Risk of Tendinopathy (and Achilles Tendon Rupture) and Peripheral Neuropathy
      2. Avoid if local resistance rate >10%
      3. Renal dose adjustment required if GFR reduced
      4. Although 3 day courses are listed, complicated UTI is treated for 10 days (up to 6 weeks in men)
    2. Ciprofloxacin 250 mg PO bid for 3 days
      1. In healthy older women, 3 days equivalent to 7 days
      2. Vogel (2004) CMAJ 170:469-73 [PubMed]
    3. Levofloxacin 250 mg every 24 hours for 3 days
    4. Norfloxacin 400 mg PO bid for 3 days
    5. Ofloxacin 200 mg PO bid for 3 days
    6. Avoid Moxifloxacin and Gemifloxacin (poor penetration into urine)
  10. Antibiotics for UTI in Pregnancy
    1. See Urinary Tract Infection in Pregnancy
  11. Beta Lactam Antibiotics used in Urinary Tract Infection
    1. Precautions
      1. Beta Lactams have lower efficacy in UTI
    2. First-line alternative agents for Acute Cystitis (see above)
      1. Cephalexin (Keflex) 500 mg orally twice daily for 5 to 7 days
      2. Cefuroxime (Ceftin) 500 mg orally twice daily for 5 to 7 days
    3. Cefdinir (Omnicef) 300 mg orally twice daily for 3 to 7 days
      1. Oral Third Generation Cephalosporin with broader coverage
    4. Amoxicillin-Clavulanate (Augmentin) 875 mg orally twice daily for 5 to 7 days
      1. Higher resistance rates
  12. Sexually active young patients
    1. Avoid Nitrofurantoin (Macrobid)
      1. Staphylococcus Saprophyticus resistance
    2. Consider Chlamydia sceening
    3. Consider other Sexually Transmitted Disease Testing

XII. Management: Special Circumstances

  1. See Recurrent Urinary Tract Infection
  2. See Catheter-Associated Urinary Tract Infection (CAUTI)
  3. Lower tract, uncomplicated UTI with resistant Enterobacteriaceae
    1. Trimethoprim-Sulfamethoxazole (Bactrim)
    2. Nitrofurantoin or Fosfomycin
    3. Single IV Dose Aminoglycoside
  4. ESBL (Extended Spectrum Beta-Lactamase) producing E Coli, Proteus and Klebsiella
    1. Fosfomycin (cystitis)
    2. Trimethoprim-Sulfamethoxazole (Bactrim) may be effective
    3. Carbapenem (e.g. Ertapenem)
  5. Carbapenem-Resistant Enterobacteriaceae
    1. Trimethoprim-Sulfamethoxazole (Bactrim) or Fluoroquinolones may be effective
    2. Ceftazidime-Avibactam (Avycaz)
    3. Meropenem-Vaborbactam (Vabomere)
    4. Imipenem-Cilastin-relebactam (Recarbrio)
    5. Cefiderocol (Fetroja)
  6. Pseudomonas Aeruginosa resistant Bacteria
    1. Ceftolozane-Tazobactam (Zerbaxa)
    2. Ceftazidime-Avibactam (Avycaz)
    3. Imipenem-Cilastin-relebactam (Recarbrio)
    4. Cefiderocol (Fetroja)
  7. References
    1. Tamma (2023) Clin Infect Dis +PMID: 37463564 [PubMed]

XIII. Management: Asymptomatic Bacteriuria

  1. See Asymptomatic Bacteriuria

XIV. Prevention

  1. General measures in women
    1. Maintain adequate hydration
    2. Women should clean perineum wiping front to back
    3. Avoid Contraceptive Diaphragm
  2. Herbals and OTC products that are associated with reduced Recurrent Urinary Tract Infection
    1. See Prevention of Recurrent Urinary Tract Infection
    2. Methenamine hippurate
    3. Cranberry products
      1. Contains proanthocyanidins which inhibit E. coli and other p-fimbriated Bacteria from adhering to urothelial cells
      2. Number needed to treart (NNT): 16 in women, 8 in children, 9 following Bladder intervention
      3. Johari (2024) Am Fam Physician 110(1): 23B [PubMed]
  3. Sexually active women
    1. Women should empty Bladder before, after intercourse
    2. Post-coital Antibiotics may prevent Recurrent Urinary Tract Infections
      1. Trimethoprim 100 mg after intercourse
  4. Antibiotic prophylaxis (consider in Consultation with urology)
    1. Fosfomycin 3 grams every 10 days
    2. Nitrofurantion 50 to 100 mg daily
    3. Trimethoprim 100 mg once daily for 3 to 6 months
  5. Postmenopausal women
    1. Vaginal Estrogens may prevent Recurrent Urinary Tract Infections

XV. Complications: Surgical

  1. Perinephric Abscess
    1. Urinary Tract Infection contiguous spread
    2. Contrast with renal abscess (hematogenous spread)
  2. Emphysematous Pyelonephritis
    1. Seen in Diabetes Mellitus
    2. Requires surgical drainage (otherwise high mortality)

XVI. References

  1. McGann, Deal and Paparella (2024) Crit Dec Emerg Med 38(7): 25-30
  2. (2019) Sanford Guide, accessed on IOS 9/21/2019
  3. Colgan (2011) Am Fam Physician 84(7): 771-6 [PubMed]
  4. Ebell (2006) Am Fam Physician 73:293-6 [PubMed]
  5. Gupta (1999) JAMA 281:736-8 [PubMed]
  6. Gupta (2012) Ann Intern Med 156(5): ITC3-1 [PubMed]
  7. Hooton (1997) Infect Dis Clin North Am 11:551-81 [PubMed]
  8. Kurotschka (2024) Am Fam Physician 109(2): 167-74 [PubMed]
  9. Michels (2015) Am Fam Physician 92(9): 778-86 [PubMed]

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