DESCRIPTION

• Colonization of urine with uropathogens and invasion of genitourinary (GU) tract
• Defined as urinary symptoms with ≥10² to 10⁵ CFU/mL of uropathogen and ≥10 WBC/mm³
• Lifetime risk of UTI in women is > 50%
• Uncomplicated cystitis:
  • Females aged 13–50
  • Symptoms < 2–3 days
  • Not pregnant
  • Afebrile (temperature < 38°C)
  • No flank pain
  • No costovertebral angle tenderness (CVAT)
  • Fewer than 4 UTIs in past year
  • No recent instrumentation or previous GU surgery
  • No functional/structural GU abnormality
  • Not immunocompromised
  • Neurologically intact
• Complicated cystitis:
  • Do not meet above criteria
  • Male gender
  • Patients with anatomic, functional, or metabolic abnormalities of GU tract
  • Postvoid residual urine
  • Catheters
  • Resistant pathogens
  • Recent antimicrobial use
• Uncomplicated pyelonephritis:
  • Renal parenchymal infection
  • Dysuria, frequency, urgency
  • Fever, chills, myalgias, nausea, vomiting
  • Flank, back, or abdominal pain
  • CVA tenderness
  • Leukocytosis (common)
• Complicated pyelonephritis:
  • Renal parenchymal infection
  • Temperature > 40°C
  • Urosepsis with septic shock
  • Intractable nausea, vomiting
  • Diabetes, other immunosuppression
  • Pregnancy (especially latter half)
  • Concomitant obstruction or stone
  • Asymptomatic (occult)

ETIOLOGY

• Mechanism:
  • Organisms colonize periurethral area and subsequently infect the GU tract.
• Risk factors:
  • Population:
    • Newborn, prepubertal girls, young boys
    • Sexually active young woman
    • Postmenopausal woman, elderly males
  • Behavior:
    • Sexual intercourse, spermicides, diaphragms
• Elderly females/postmenopausal state
• Less efficient bladder emptying, bladder prolapse, alteration of bladder defenses
• Increased vaginal pH
• Contamination due to urinary or fecal incontinence (Enterobacteriaceae)
• Instrumentation:
  • Elderly males due to prostatic hypertrophy and instrumentation
• Organisms:
  • Escherichia coli (80–85%)
  • Staphylococcus saprophyticus (10%)
  • Other (10%): Klebsiella, Proteus mirabilis, Enterobacter spp., Pseudomonas aeruginosa, group D streptococci

[Outline]

• DESCRIPTION
• ETIOLOGY

SIGNS AND SYMPTOMS

• Lower tract infection: Cystitis:
  • Dysuria, frequency, urgency, hesitancy
  • Suprapubic pain
  • Hematuria
• Upper tract infection: Pyelonephritis:
  • Symptoms of cystitis:
    • Fever, chills
    • Flank pain and/or tenderness
    • Nausea, vomiting, anorexia
  • Leukocytosis
  • Up to 50% of patients with cystitis may actually have pyelonephritis:
    • Symptom duration > 5 days, homelessness, and recent UTI are risk factors for upper tract infection
  • Elderly or frail patients:
    • Altered mental status
    • Anorexia
    • Decreased social interaction
    • Abdominal pain
    • Nocturia, incontinence
    • Syncope or dizziness

ESSENTIAL WORKUP

• Urinalysis (dipstick test, microscopy)
• Females: Rule out pregnancy, urethritis, vaginitis, pelvic inflammatory disease (PID)
• Males: Rule out urethritis, epididymitis, prostatitis; inquire about anal intercourse/HIV.
• Urologic evaluation in young healthy males with 1st UTI is not routinely recommended.

DIAGNOSIS TESTS & INTERPRETATION

Lab

• Rapid Urine Screen:
  • Dipstick (leukocyte esterase + nitrite) most effective when urine contains 10⁵ CFU/mL
  • Lab specimen unnecessary if pyuria and bacteriuria confirmed by dipstick
  • Leukocyte esterase: Positive likelihood ratio (LR+) ~5, negative likelihood ratio (LR–) ~0.3
  • Nitrite: LR+ ~30, LR– ~0.5
• Urinalysis/microscopy:
  • Obtain if rapid urine screen is unavailable or negative in patients with presumed UTI.
  • 10 WBC/mm³ in clean catch midstream urine indicates infection.
  • Bacteria detected in unspun urine indicates > 10⁵ CFU/mL. (LR+ ~20, LR– ~0.1)
• Indications for urine culture:
  • Complicated UTIs
  • Negative rapid urine screen or microscopy in patients with presumed UTI
  • Persistent signs and symptoms after 2–3 days of treatment
  • Recurrence (relapse vs. reinfection)
  • Recently hospitalized patients
  • Nosocomial infections
  • Pyelonephritis

Geriatric Considerations

• Asymptomatic bacteriuria (including positive cultures) occurs in 20% of women > 65 yr, 50% of women > 80 yr and generally should not be treated.
• Consider treating symptomatic geriatric patients for 5–10 days to decrease risk of recurrent or persistent bacteriuria.
• Fluoroquinolones may cause CNS side effects.

Imaging

• Indicated for complicated upper tract disease (see Pyelonephritis)
• Helical CT, renal ultrasound, or IV pyelogram if concomitant stone or obstruction suspected

Diagnostic Procedures/Surgery

Patients with significant hematuria, recurrent UTI with same uropathogen, or symptoms of obstruction need urologic evaluation to identify structural or functional abnormality.

DIFFERENTIAL DIAGNOSIS

• Appendicitis
• Diverticulitis
• Epididymitis
• Nephrolithiasis
• PID/cervicitis
• Prostatitis
• Pyelonephritis
• Urethritis
• Vulvovaginitis

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

INITIAL STABILIZATION/THERAPY

Urosepsis/septic shock:

• Manage airway and resuscitate as indicated
• IV crystalloid and vasopressors as needed
• Early goal-directed therapy

ED TREATMENT/PROCEDURES

Stable Patients

• For uncomplicated UTIs in women for most antibiotics, 3 days of therapy:
  • More effective than single dose
  • Clinically as effective as 5–10-day course with fewer side effects
• Resistance varies by place and changes over time:
  • In North America, 40–50% of E. coli are resistant to ampicillin; 3–17% to fluoroquinolones and is increasing.
  • Resistance to trimethoprim–sulfamethoxazole (TMP/SMX) is increasing (up to 30%).
  • Nitrofurantoin: In some studies, nitrofurantoin resistance is less than for other more widely used antibiotics.
  • Culture resistance may not correlate with clinical effect because urine antibiotic concentrations are much higher than those used in laboratory testing. However, symptom resolution may be delayed a few days in patients with resistant bacteria.
• Antibiotics of choice:
  • Nitrofurantoin
  • TMP/SMX
  • Fluoroquinolones 2nd-line treatment in women:
    • Sulfonamide intolerance
    • All quinolones equally effective (~95% susceptibility rates) but side effects vary
    • High frequency of antimicrobial resistance related to recent treatment
    • Live in areas with unknown or > 20% resistance to TMP/SMX
  • Oral cephalosporins may be reasonable alternatives in specific circumstances:
    • Require 7-day treatment regimens
  • Amoxicillin–clavulanate not as effective as ciprofloxacin, probably due to failure to eradicate vaginal E. coli
  • Diabetic women have increased risk of bacteriuria with Klebsiella spp.
  • Treat dysuria with phenazopyridine.
  • Treat pain with appropriate analgesics.
• Cranberry juice or tablets/products:
  • Prevents specific E. coli from adhering to uroepithelial cells but probably does not lower UTI recurrence rate in women with history of recurrent UTIs
  • Evidence suggests ineffective for treatment
• Treatment of upper tract disease—rule of 2s:
  • 2 L of IV crystalloid
  • 2 tablets of oxycodone/acetaminophen
  • 2 g of ceftriaxone or 2 mg/kg of gentamicin
  • If fever drops by 2°C and patient can retain 2 glasses of water
  • Discharge with fluoroquinolone for 2 wk.
  • Follow up in 2 days.

Pregnancy Considerations

• Treat asymptomatic bacteriuria in pregnancy with 4–7-day course of antibiotics:
  • Nitrofurantoin:
    • May cause birth defects if used in 1st trimester
    • Contraindicated in G6PD-deficiency
  • Amoxicillin (not 1st-line treatment due to high rate of resistance)
  • Fosfomycin (safe and effective)
  • TMP/SMX:
    • SMX should be avoided late in pregnancy as kernicterus can result.
    • TMP should be avoided in 1st trimester (folic acid antagonist; possible birth defects).
  • Quinolones should be avoided:
    • CNS reactions
    • Blood dyscrasias
    • Effects on collagen formation

MEDICATION

• Amoxicillin: 500 or 875 mg PO q12h
• Cefixime: 400 mg PO q24h
• Cefpodoxime: 400 mg PO q12h
• Ceftazidime: 1–2 g IV q8–12h
• Ceftriaxone: 1–2 g IV/IM q24h
• Cefuroxime: 250–500 mg PO q12h
• Cephalexin: 250–500 mg PO q6h
• Ciprofloxacin: 100–500 mg PO q12h
• Doripenem: 500 mg IV q8h
• Fosfomycin: 3 g single dose
• Gentamicin: 2 mg/kg IV or IM q8h
• Levofloxacin: 250 mg PO q24h
• Nitrofurantoin macrocrystals 100 mg PO q12h
• Norfloxacin: 400 mg PO q12
• Ofloxacin: 200 mg PO q12h or 400 mg IV q12h
• Phenazopyridine: 200 mg PO TID for 2 days:
  • For symptomatic treatment of dysuria
  • May turn urine and contact lenses orange
• TMP/SMX: 160 mg/800 mg PO q12h or 10 mg/kg/d IV div. q6–8–12h

[Outline]

• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

DISPOSITION

Admission Criteria

• Inability to comply with oral therapy
• Toxic appearing, unstable vital signs
• Pyelonephritis:
  • Intractable symptoms
  • Extremes of age
  • Immunosuppression
  • Urinary obstruction
  • Consider if coexisting urolithiasis
  • Significant comorbid disease
  • Outpatient treatment failure
  • Late in pregnancy

Discharge Criteria

• Well appearing, normal vital signs
• Can comply with oral therapy
• No significant comorbid disease
• Adequate follow-up (48–72 hr) as needed
• Healthy patients with uncomplicated pyelonephritis who respond to treatment in ED according to rule of 2s
• Pyelonephritis in early pregnancy with good follow-up may be treated as outpatients

Issues for Referral

Recurrent UTIs require workup for underlying pathology.

FOLLOW-UP RECOMMENDATIONS

Follow-up for UTIs should start with primary care physician.

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

• For women who have more than 2 episodes of acute cystitis in 6 mo or 3 episodes in 1 yr, consider long-term (6–12 mo) prophylactic antibiotics or postcoital prophylaxis
• Pregnant women should be screened and treated for asymptomatic bacteriuria (ASB) because 20–40% of women with ASB progress to pyelonephritis.
• ASB in pregnant women associated with increased risk of preterm birth, low birth weight, and perinatal mortality.
• Treat ASB in renal transplant recipients, patients who have recently undergone a urologic procedure, and neutropenic patients.
• Risk factors for acute cystitis in men: Increased age, uncircumsized, HIV infection (low CD4 counts), anatomic abnormalities (BPH or urethral strictures), and sexual activity (especially insertive anal intercourse).
• 25% of male GU complaints are attributable to prostatitis. TMP/SMX or fluoroquinolones are 1st-line treatment.
• In patients with indwelling catheters, pyuria is less strongly correlated with UTI than in patients without catheters.

ICD9

• 590.80 Pyelonephritis, unspecified
• 595.9 Cystitis, unspecified
• 599.0 Urinary tract infection, site not specified

ICD10

• N12 Tubulo-interstitial nephritis, not spcf as acute or chronic
• N30.90 Cystitis, unspecified without hematuria
• N39.0 Urinary tract infection, site not specified

[Outline]

• ICD9
• ICD10

• Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52:e103–e120.
• Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med. 2012;366(11):1028–1037.
• Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40:643–654.
• St. John A, Boyd JC, Lowes AJ, et al. The use of urinary dipstick tests to exclude urinary tract infection. Am J Clin Pathol. 2006;126:428–436.

See Also (Topic, Algorithm, Electronic Media Element)

• Pyelonephritis
• UTI, Pediatric

Paul A. Szucs

Barnet Eskin