Urinary Tract Infections

Objectives

Teaching Points

Sample Cases

Discussion

References

Objectives

1. Understand the categorization of UTI based on host factors and clinical findings
2. Know the most efficient use of laboratory testing in the workup of UTI
3. Know the considerations in the selection of treatment for UTI
4. Know indications for urologic referral

Teaching Points

The choice of antibiotic for treatment of UTI depends on one's suspicion for resistance. In general, TMP/SMX is the best agent to start with if the patient isn't allergic to it. Fluoroquinolones are best first agent for complicated UTI. Duration of treatment in uncomplicated UTI should probably be 3 days according to Stamm, though Komoroff still advocates single-dose treatment initially. Diabetics, diaphragm users, pregnant patients, and the elderly need 7 days. Pyelonephritis and complicated UTIs need 10-14 days. Relapses need 2-6 weeks. Sicker patients need IV antibiotics.

For women, urologic referral is necessary only for UTI relapsing with the same organism. For men, refer after one recurrence even with a different organism.

Important categories of patients with UTI:

• Acute uncomplicated cystitis in young women

  Differential diagnosis of dysuria in women:

  • Common causes: UTI (75-80%), vaginitis (10%). These two may also coexist.
  • Uncommon causes: urethritis, allergy/reaction to chemical, soap, or deodorant.
  • Rare causes: bladder CA, mycobacteria, urethral spasm without infection.

  History:

  • Elements favoring cystitis: "Internal" dysuria (deeper, dull pain, +/- suprapubic pain on voiding), frequency, urgency, nocturia.
    Risk factors for cystitis: sexual intercourse, diaphragm use, spermicide use (which may alter vaginal flora), delaying micturition.
  • Elements favoring vaginitis: Vaginal discharge, "external" dysuria (burning or sharp pain more localized to labia and urethral orifice).
  • Elements favoring urethritis: New sex partner, stuttering onset of symptoms over several days, purulent urethral discharge.
  • Also look for elements favoring other categories listed below: recurrent UTI, pyelonephritis, complicated UTI.

  Physical exam:

  • Flank tenderness indicates pyelonephritis. Suprapubic tenderness may be present in cystitis.
  • Pelvic exam is indicated if vaginitis or urethritis suspected.
  • Presence of vaginitis doesn't rule out cystitis-both are common and they may coexist.

  Lab:

  • A few pathogens cause the vast majority of illness (E. coli 80-90%, Staph. saprophyticus 2-20%, Proteus, Klebsiella, Enterococcus, other enteric pathogens all < 10% in outpatient setting).
  • Gold standard for diagnosis: culture of > 100 colony-forming units (CFU) of a single pathogen per ml of urine. Traditional cutoff of >= 10^5 CFU no longer used because it has low sensitivity.
  • Pyuria (defined as >2-5 WBC/hpf in centrifuged urine that is not contaminated [ie, contains no epithelial cells]: 80% sensitive, 95% specific
  • Leukocyte esterase: 75-96% sensitive for pyuria, 94-98% specific.
  • Nitrite: 35-85% sensitive for presence of bacteria.
  • Suggested workup strategy for dysuria without signs or symptoms of urethritis, vaginitis, pyelonephritis, recurrent UTI, or complicated UTI:
    • Leukocyte esterase is OK as a prescreen. Given its low false-positive rate, one may treat empirically with antibiotics based on a positive result. The disadvantage of using leukocyte esterase alone is that you don't see the urine sediment. Presence of WBC casts in sediment would indicate pyelonephritis; absence of bacteria might indicate urethritis.
    • Urinalysis with inspection of sediment: If pyuria is present one may treat empirically with antibiotics. Presence of hematuria with pyuria virtually rules out urethritis. If pyuria is absent antibiotics are unlikely to help.
    • Culture necessary only if risk factors for relapse: diabetes, immunosuppression, documented past relapse, pyelonephritis in the last year, indigent inner-city resident.

  Treatment: (see also Table 1, below)

  • Drugs: TMP/SMX (Double Strength [160mg/800mg] bid) & fluoroquinolones (eg, Cipro 250mg bid) eradicate pathogen from vagina, beta-lactams and nitrofurantoin don't and may therefore have higher rates of recurrence. Resistance in U.S. overall: amoxicillin 33%, nitrofurantoin 15-20%, TMP/SMX 5-15%, fluoroquinolones: <5%.

    Empiric treatment, therefore, should be TMP/SMX unless resistance is high locally or patient is allergic, then use fluoroquinolone. Use amoxicillin, cephalosporin, nitrofurantoin in special cases only-e.g. in pregnancy, amoxicillin and cephalosporins are favored, fluoroquinolones are contraindicated.

  • Duration: A 3-day regimen is as good as 7 days. Single-dose treatment favored by some (e.g. Komoroff), but its relapse rates are higher. Consider 7-day regimen if patient has diabetes mellitus, symptoms have persisted more than 7 days, use of diaphragm, age >65, pregnancy. These people are at increased risk for recurrence.

• Recurrent cystitis in young women
  Two subcategories must be differentiated:
  • Relapse
    History:
    • Recurrent UTI symptoms within 2 weeks of completion of treatment. Check for compliance with prior regimen.

    Physical Exam:

    • Check again for flank pain that would indicate pyelonephritis.

    Lab:

    • Always culture urine. If recurrence is a true relapse, the organism will be the same as the organism in the prior UTI. Followup culture post treatment is warranted.

    Treatment:

    • 2-6 weeks with antibiotic selection based on susceptibilities.

    Referral:

    • Consider IVP and urologic referral for cystoscopy as soon as the first relapse, if noncompliance is ruled out.

  • Reinfection
    History:
    • Recurrent UTI more than 2 weeks after completion of treatment. Document risk factors: spermicide, diaphragm, any temporal relation to coitus.

    Lab:

    • Culture urine once. Organism should usually be a different species or strain from prior UTI.

    Treatment:

    • If using diaphragm and spermicide consider changing contraceptive method. If temporal relation to coitus try postcoital voiding. If no identifiable risk factors for reinfection patient may just be more susceptible due to mucosal factors.
      < 3 UTI/yr: patient-initiated therapy with 3-day regimen
      >= 3 UTI/yr and temporal relation to coitus: postcoital prophylaxis with single dose (TMP/SMX 40/200, Keflex 250 mg, or nitrofurantoin 50-100 mg).
      >= 3 UTI/yr: continuous prophylaxis (once-daily trimethoprim 100mg, TMP/SMX 40/200, norfloxacin 200mg, Keflex 250 mg, or nitrofurantoin 50-100 mg).

    Referral:

    • Urologic referral not necessary for patients with reinfections according to Stamm. Komoroff says IVP positive in less than 1% of reinfections but that cystoscopy shows surgically amenable bladder diverticulum in up to 4%, which is he says justifies urologic referral for >= 3 UTI/yr.

• Postmenopausal women

  History & PE:

  • In addition to the usual approach outlined above, look for recurrence risk factors: bladder or uterine prolapsed causing postvoid residuals; vaginal atrophy causing loss of lactobacilli and colonization with pathogens.

  Treatment:

  • 7 days if age > 65
    
  • If recurring, continuous prophylaxis or topical estriol cream (Estriol cream significantly reduced recurrent episodes of UTI in one study: 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):753-6).

• Acute pyelonephritis in young women

  History & PE:

  • Findings range from cystitis with mild flank pain to sepsis.

  Lab:

  • Always culture acutely & consider follow-up culture 2 weeks after completion of treatment.
    
  • Komoroff recommends gram stain to look for enterococcus.
    
  • Culture blood if significantly ill.
    
  • Ultrasound or CT (for obstruction, perinephric or intrarenal abscess) is necessary only if fever, flank pain, or hematuria persist more than 72 hours.

  Treatment:

  • Duration should be 10-14 days.
    
  • Oral regimen acceptable for mild illness, without nausea and vomiting.
    
  • Outpatient parenteral ceftriaxone acceptable for intermediate degree of illness.
    
  • Hospitalize for more severe illness or if patient is pregnant. Use IV TMP/SMX, fluoroquinolone, or ceftriaxone. If enterococcus suspected use ampicillin & gentamicin. Switch to oral antibiotics after 48-72h and patient clinically improved.

• Complicated UTI

  Defined as UTI with any abnormality of the urinary tract (eg. congenital anomaly, known stones, diverticulum) or with resistant pathogens.

  History & PE:

  • May present with any syndrome from asymptomatic bacteriuria, mild cystitis, to urosepsis

  Lab:

  • Urine culture is essential
  • Repeat urine culture 1-2 weeks after completion of treatment

  Treatment:

  • Duration should be 10-14 days; possibly longer for Pseudomonas or enterococcus.
  • Start with empiric treatment:
    • If patient appears well: oral fluoroquinolone
    • If sick: ampicillin & gentamicin or imipenim & cilastatin; switch to orals when susceptibilities known and after clinical improvement.

• Men

  UTI is rare in men younger than 50 but not necessarily a sign of urologic abnormality.

  Differential diagnosis of dysuria in men:

  • Urethritis, epididymitis, prostatitis, UTI.

  History:

  • Risk factors for simple UTI: homosexuality, lack of circumcision, partner with vaginal colonization by pathogens, HIV with CD4 < 200.

  PE:

  • Low back or perineal pain, obstructive symptoms, prostatic tenderness indicate prostatitis.
  • Swollen, tender epididymis indicates epididymitis (or testicular torsion).

  Lab:

  • Always get urinalysis and urine culture on men.

  Treatment:

  • Treat empirically with TMP/SMX or fluoroquinolone 7 days
  • Urologic evaluation only needed for recurrent UTI or pyelonephritis.

• Catheter-associated UTI

  Three subcategories:

  • Symptomatic
    • Change the catheter if it's more than 2 weeks old-biofilms accumulate on catheters where pathogens can hide from antibiotics.
    • Treat with antibiotics as a complicated UTI.

  • Asymptomatic bacteriuria with a short-term catheter (i.e. anticipate less than 30 days):
    • Presence on urine culture of more than 100 CFU/ml means infection likely to worsen but benefit of empiric treatment is unproven

  • Asymptomatic bacteriuria, long term (>30 d) catheter
    • Bladder colonization is inevitable, prophylaxis is not effective.
    • If colonized, may consider switch from indwelling to intermittent catheter
    • Consider periodically changing any indwelling catheter (best frequency is not known)

• Asymptomatic bacteriuria without catheter
  • Pregnancy:

    Screen for bacteriuria in first trimester & treat bacteriuria with antibiotics even if asymptomatic-prevents pyelonephritis and risk of premature labor.

  • Elderly:

    Prevalence of asymptomatic bacteriuria is as high as 40% in nursing home populations. However, screening and treatment have not been shown to be cost effective (Boscia JA et al. Asymptomatic bacteriuria in elderly persons: to treat or not to treat? Ann Intern Med 1987;106:764-6).

Sample Cases

CASE 1:

What other elements of history & physical would be key in your initial approach to her illness?

How would you go about testing her urine?

Given pyuria, what drug and duration would you treat with in each of the following circumstances:

• no recent similar illnesses?
• she has diabetes mellitus?
• this is her fourth UTI this year?
• she had a UTI 10 days ago, treated with 3 days of TMP/SMX?

How would you counsel her about risk factors for UTI?

CASE 2:

What other elements of history & physical would be key in your initial approach to her illness?

How would you go about testing her urine?

What antibiotic regimen does she need, in what setting? What if she's vomiting or pregnant?

CASE 3:

What other elements of history & physical would be key in your initial approach?

How would you go about testing his urine?

What antibiotic regimen would you use?

Does he need to see a urologist?

CASE 4:

What other elements of history & physical would be key in your initial approach?

How would you go about testing her urine?

What treatment regimen would you use?

Discussion

CASE 1:

History:

• Consider vaginitis: vaginal discharge? internal vs. external dysuria?
• Consider recurrent or complicated UTI: H/O prior UTIs, diabetes, urinary tract abnormalities.
• Risk factors: including use of diaphragm, spermicide.

• Check for CVA tenderness.
• Pelvic exam if vaginitis or urethritis suspected

Given pyuria, what drug and duration would you treat with in each of the following circumstances? Treatment:

• No recent similar illnesses: Three days of TMP/SMX or if sulfa allergic a fluoroquinolone. See Table 1 for doses.

• diabetes mellitus: Seven days of TMP/SMX or if sulfa allergic a fluoroquinolone.

• her fourth UTI this year: Culture urine if no culture yet documented. Treat with three days of TMP/SMX or a fluoroquinolone. Then start either postcoital or continuous prophylaxis.

• a UTI 10 days ago, treated with 3 days of TMP/SMX: This is a relapse. Needs urine culture, a minimum of 2 weeks of TMP/SMX or a fluoroquinolone and may need urologic referral.

CASE 2:

History:

• Possibly pregnant?
• Diabetes?
• Urinary tract anomalies?
• History of stones?

• Her degree of illness warrants a more complete exam and a differential somewhat broader than just pyelonephritis.

How would you go about testing her urine? Urinalysis. Culture. Gram stain recommended by Komoroff to look for enterococcus.

What antibiotic regimen does she need, in what setting? What if she's vomiting or pregnant? If the patient isn't pregnant, her mild-moderate illness could be treated with oral TMP/SMX 10-14 days. If slightly more ill could start with a few days of outpatient IV ceftriaxone. If pregnant should hospitalize until fever is gone.

CASE 3:

Sexual history:

• Sexual preference and activity, new partner, female partner with recurrent UTI (may indicate vaginal colonization with pathogens).

• Testes for epididymitis.

What antibiotic regimen would you use? Seven days of TMP/SMX or if sulfa allergic a fluoroquinolone.

Does he need to see a urologist? Only if he has a recurrence or develops pyelonephritis.

CASE 4:

History:

• Symptoms of atrophic vaginitis, overflow incontinence, long-standing frequency and nocturia.

• CVA percussion tenderness. Pelvic exam: Evidence of uterine or bladder prolapse, atrophic vaginitis.

What treatment regimen would you use? Seven days of TMP/SMX or if sulfa allergic a fluoroquinolone. Consider estriol cream to treat atrophic vaginitis and reduce recurrence of UTIs

References

1. Stamm WE, Hooton TM. Management of urinary tract infections in adults. New Engl J Med 1993; 1328-34.
   A comprehensive summary of the categories of urinary tract infection and the best approaches to treatment. This article was the source for the majority of our teaching points. They advocate 3-day treatment of uncomplicated UTI over single-dose.

2. Komoroff AL. Urinalysis and urine culture in women with dysuria. In: Sox HC, ed. Common Diagnostic Tests: Use and Interpretation. Philadelphia: American College of Physicians, 1990: 287-301.
   Provides more data on sensitivity and specificity of urinalysis and other tests. Contains a detailed description of the methods for urine tests and a nice table of diagnostic tests recommended for each clinical syndrome.

3. Komoroff AL. Acute dysuria in adult women. In: Panzer RJ, et al, eds. Diagnostic Strategies for Common Medical Problems. Philadelphia: American College of Physicians, 1991: 239-48.
   A more succinct summary of the data and an approach to treatment. Advocates single-dose therapy of uncomplicated UTIs.

4. Hoole AJ. Urinary tract infections in women. In: Dornbrand L, et al, eds. Manual of Clinical Problems in Adult Ambulatory Care. Boston: Little Brown, 1991: 241-9.
   Provides more background on the pathophysiology of UTI, e.g. mucosal factors.