Author:
Paul A.Szucs
BarnetEskin
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 d
- 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:
- Organisms:
- Escherichia coli (80-85%)
- Staphylococcus saprophyticus (10%)
- Other (10%): Klebsiella, Proteus mirabilis, Enterobacter spp., Pseudomonas aeruginosa, group D streptococci
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, CVA tenderness
- Nausea, vomiting, anorexia
- Leukocytosis
- Up to 50% of patients with cystitis may actually have pyelonephritis:
- Symptom duration >5 d, 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 first UTI is not routinely recommended
Diagnostic 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 d of treatment
- Recurrence (relapse vs. reinfection)
- Recently hospitalized patients
- Nosocomial infections
- Pyelonephritis
- Urine color:
- White/cloudy/murky:
- Red/pink:
- Beets, blackberries, rhubarb
- Chlorpromazine, phenazopyridine, phenolphthalein, rifampin, senna, thioridazine
- Blood
- Brown:
- Aloe, fava beans, rhubarb
- Cascara, chloroquine, levodopa, methocarbamol, metronidazole, nitrofurantoin, primaquine, senna
- Bilirubin, myoglobin
- Orange:
- Blue/green:
- Asparagus, food dyes, vitamins B
- Amitriptyline, cimetidine, indomethacin, promethazine, propofol, triamterene
- Familial benign hypercalcemia
- Purple (rare):
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
- Treating symptomatic geriatric patients for a shorter duration than the typical 7-10 d appears to be effective with no increased risk of recurrent or persistent bacteriuria
- The FDA has reported that fluoroquinolones may cause serious side effects, including but not limited to, CNS side effects and tendon ruptures
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Imaging
- Indicated for complicated upper tract disease (see Pyelonephritis)
- Helical CT, renal US, 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
- Asymptomatic bacteriuria in pregnancy or elderly
- Diverticulitis
- Epididymitis
- Nephrolithiasis
- PID/cervicitis
- Prostatitis
- Pyelonephritis
- Urethritis
- Vulvovaginitis
Initial Stabilization/Therapy
Urosepsis/septic shock:
- Manage airway and resuscitate as indicated
- Early goal-directed therapy
- IV crystalloid (30 mL/kg)
- Antibiotics
- Vasopressors as needed
ED Treatment/Procedures
Stable Patients
- Considerations for antibiotic selection include: Clinical efficacy, side-effects, resistance rates, cost, drug availability
- Individualize treatment regimens based on patient characteristics (allergy, tolerability, cost, compliance) and local community resistance prevalence
- Optimal antibiotic treatment duration is similar for any adult woman regardless of age (3-7 d)
- For uncomplicated UTIs in women for most antibiotics, 3 d of therapy:
- More effective than single dose
- Clinically as effective as 5-10 d course with fewer side effects
- Beta-lactams should be prescribed for 7 d
- Resistance varies by community and changes over time:
- In North America, 40-50% of E. coli are resistant to ampicillin; 3-17% to fluoroquinolones
- Resistance to trimethoprim-sulfamethoxazole (TMP/SMX) is increasing (up to 30%)
- Nitrofurantoin: In some studies, 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 lab testing
- Avoid antibiotic if community resistance prevalence >20%
- Cranberry juice or tablets/products:
- Evidence suggests ineffective for treatment
- Prevents specific E. coli from adhering to uroepithelial cells but probably does not lower UTI recurrence rate in women with h/o recurrent UTIs
- Historic treatment of upper tract disease - rule of 2s:
- 2 L of IV crystalloid
- 2 tablets of oxycodone/acetaminophen
- 1 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 d
- Antibiotics of choice:
- Nitrofurantoin:
- Avoid if creatinine clearance < 30 mL/min
- Inadequate if early pyelonephritis is suspected
- TMP/SMX
- Fosfomycin:
- Inadequate if early pyelonephritis is suspected
- β-lactams are second-line agents:
- Less effective than TMP/SMX and fluoroquinolones
- Oral cephalosporins are reasonable alternatives in specific circumstances:
- Require 7-d treatment regimens
- Ampicillin or amoxicillin should not be used for empiric treatment due to high-resistance rates
- Amoxicillin-clavulanate not as effective as ciprofloxacin probably due to failure to eradicate vaginal E. coli
- Fluoroquinolones:
- Alternative treatment for women
- Risks outweigh benefits for uncomplicated UTI
- Tendon ruptures; CNS side effects
- All quinolones equally effective (∼95% susceptibility rates) but side effects vary
- High prevalence of antimicrobial resistance
- Live in areas with unknown or >20% resistance to Nitrofurantoin and /or TMP/SMX
- Diabetic women have increased risk of bacteriuria with Klebsiella spp.
- Treat dysuria with phenazopyridine
- Treat pain with appropriate analgesics
Pregnancy Prophylaxis |
- Treat asymptomatic bacteriuria in pregnancy with 4-7 d course of antibiotics:
- Nitrofurantoin:
- May cause birth defects if used in first trimester
- Contraindicated in G6PD-deficiency
- TMP/SMX:
- SMX should be avoided late in pregnancy as kernicterus can result
- TMP should be avoided in first trimester (folic acid antagonist; possible birth defects)
- Fosfomycin is safe and effective
- Amoxicillin not recommended due to high resistance rates
- Quinolones should be avoided:
- CNS reactions
- Blood dyscrasias
- Effects on collagen formation
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Medication
- Amoxicillin-Clavulanate: 875 mg PO q12h
- Cefadroxil: 1-2 g PO q24
- Cefdinir: 600 mg PO q24
- 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: 500 mg PO q12h
- Doripenem: 500 mg IV q8h
- Fosfomycin: 3 g single dose
- Gentamicin: 2 mg/kg IV/IM q8h
- Levofloxacin: 250-500 mg PO q24h
- Nitrofurantoin: 100 mg PO q12h
- Phenazopyridine: 200 mg PO t.i.d for 2 d:
- For symptomatic treatment of dysuria
- May turn urine, tears and contact lenses orange
- TMP/SMX: 160 mg/800 mg PO q12h or 10 mg/kg/d IV div q6-8-12h
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 the 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
- FDA Drug Safety Communication. FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together . http://www.fda.gov/Drugs/DrugSafety/ucm500143.htm. Accessed September 25, 2017.
- GuptaK, HootonTM, NaberKG, 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(5):e103-e120.
- HootonTM. Clinical practice. Uncomplicated urinary tract infection . N Engl J Med. 2012;366(11):1028-1037.
- LuttersM, Vogt-FerrierNB. Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women . Cochrane Database Syst Rev. 2008;CD001535.
- NicolleLE, BradleyS, ColganR, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults . Clin Infect Dis. 2005;40(5):643-654.
- St. JohnA, BoydJC, LowesAJ, et al. The use of urinary dipstick tests to exclude urinary tract infection: A systematic review of the literature . Am J Clin Pathol. 2006;126(3):428-436.
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