• July 08, 2008, Fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin, levofloxacin, moxifloxacin, gemifloxacin): A BOXED WARNING and Medication Guide are to be added to the prescribing information to strengthen existing warnings about the increased risk of developing tendinitis and tendon rupture in patients taking fluoroquinolones for systemic use.

Note from the National Guideline Clearinghouse (NGC) and the Institute for Clinical Systems Improvement (ICSI): In addition to updating their clinical guidance, ICSI has developed a new format for all guidelines. Key additions and changes include: combination of the annotation and discussion section; the addition of "Key Points" at the beginning of most annotations; the inclusion of references supporting the recommendations; and a complete list of references in the Supporting Evidence section of the guideline. For a description of what has changed since the previous version of this guidance, refer to Summary of Changes – July 2006.

The recommendations for uncomplicated urinary tract infection in women are presented in the form of an algorithm with 13 components, accompanied by detailed annotations. An algorithm is provided for Uncomplicated Urinary Tract Infection in Women; clinical highlights and selected annotations (numbered to correspond with the algorithms) follow.

Class of evidence (A-D, M, R, X) ratings are defined at the end of the "Major Recommendations" field.

Clinical Highlights

• Assess all women ages 18 to 65 with symptoms of urinary tract infection (UTI) for the presence of complicating factors. The presence of complicating factors warrants provider evaluation and may require additional diagnostic work-up. (Annotations #2, 4)
• Patients who have classic symptoms of UTI and no complicating factors can be offered the option of phone treatment, if preferred by both provider and patient. (Annotation #8)
• If laboratory evaluation is preferred by the provider, symptomatic women without complicating factors can be appropriately evaluated by a urinalysis rather than a urine culture. (Annotation #11)
• Symptomatic women without complicating factors can be effectively treated with the following recommended therapy: (Annotation #9)
  • Trimethoprim sulfamethoxazole double strength (D.S.) 1 twice a day (BID) x 3 days
  • Trimethoprim 100 mg 1 twice daily x 3 days

  If allergic to sulfa or trimethoprim:

  • Nitrofurantoin (Macrobid) 100 mg twice daily x 7 days
  • Ciprofloxacin 250 mg BID x 3 days

  Sulfa and ciprofloxacin may cause an increase in international normalized ratio (INR) values for patients taking warfarin.

• All patients should be provided patient education about the prescribed therapy and the need to return to clinic if the symptoms do not subside. (Annotation #9, 13)

Uncomplicated Urinary Tract Infection in Women Algorithm Annotations

1. Adult Female Presents or Calls with One or More of the Following Symptoms: Dysuria, Frequency, Urgency

   The classic symptoms of urinary tract infection (UTI) in women are dysuria, frequency, and urgency. One or more of these symptoms can trigger the initiation of the UTI guideline. Hematuria alone is not a classic uncomplicated UTI symptom. There is concern the presence of hematuria may be a sign of more significant disease. Patients whose symptoms do not subside should return to the clinic for a full examination.

2. Complicating Factors Present?

   History-taking is essential in differentiating uncomplicated from complicated urinary infection. Women should be screened for the presence of complicating factors when presenting or calling with symptoms of UTI. Depending upon which complicating factor is present, short course therapy may or may not be appropriate.

   Symptoms for which short course therapy with trimethoprim/sulfamethoxazole (TMP/SMX) is not appropriate:

   • Symptoms suggest pyelonephritis or other more severe infection: long duration, rigors, flank pain, or temperature greater than 101 degrees F.
   • Patient's medical history suggests likelihood of complicated urinary tract infection, or need for different investigation or therapy: diabetes, pregnancy, immunosuppression, underlying urinary tract disease or renal calculi, recent medical intervention (hospitalization or catheterization), or recurrent UTIs or failure of therapy.
   • Resident of an extended care facility

   Factors for which short course therapy may be appropriate at physician discretion:

   • Potential sexually transmitted infection (STI): an infected partner, other genitourinary symptoms. The patient should be seen and STIs ruled out.
   • Younger or older patients (less than 18 or greater than 65). There is little literature documentation of efficacy of short course therapy in these age groups.
   • Recent pyelonephritis or failure of antibiotic treatment. These patients may be at higher risk of complicated infection.

   Evidence supporting this recommendation is of classes: B, R

3. Urinalysis (UA)/Hold for Urine Culture (UC)/Patient Education

   Instructions on collecting a clean-catch, midstream urine specimen should be given to the patient. A dipstick and microscopic urinalysis is performed and the specimen is saved for possible culture. Education should also be given to the patient regarding urinary tract infection. (Refer to Support for Implementation section, "Other Resources Available" in the original guideline document.)

   The laboratory should be instructed to perform a urinalysis with microscopy and hold for possible urine culture. Urine specimens that are marked "Hold for UC" should be refrigerated.

   The final decision about culturing should be left to the provider.

4. Provider Evaluation

   Symptomatic women with complicating factors may have a more extensive infection and/or a UTI with lower colony counts. Sensitivities should be obtained; hospitalization and/or urological evaluation may be indicated.

   Women with a complicated history should be evaluated by a health care provider. The provider (physician or paraprofessional) will determine if a urine culture is necessary.

   Complicating factors are listed in detail on the algorithm page (floating box 2 of the original guideline document), and include the following categories:

   • Those that would preclude use of short course therapy
   • Those that would allow for discretionary use of short course therapy
   • Those that would necessitate a pelvic exam to rule out genitourinary disease

   Evidence supporting this recommendation is of class: R

5. Symptoms of or Risk for Other Genitourinary Diseases?

   Genitourinary disease symptoms may include a recent onset or change in vaginal discharge, odor, itching, or dyspareunia in women.

   Women with the following characteristics are at greater risk of an STI:

   Chlamydia Risk Factors

   • Contact with a partner who is infected with an STI

   or

   • New sexual partner within the last 3 months and no barrier contraception.

   Chlamydia trachomatis is an important sexually transmitted pathogen. In a low prevalence population for chlamydia, patients with dysuria, frequency, and urgency probably have a UTI. In a high prevalence population, these symptoms associated with sterile pyuria may be caused by chlamydia trachomatis. Other symptoms of chlamydial infection may include mucopurulent discharge (mucopus from the cervical os) and cervical friability. Gross hematuria is not a symptom of chlamydia.

   Evidence supporting this recommendation is of classes: C, M, R

7. Provider Evaluation

   Women with the symptoms and risk factors listed in Annotation #5, "Symptoms of or Risk for Other Genitourinary Disease," are at high risk for STIs and should receive closer evaluation. These patients should be scheduled for a provider (physician or paraprofessional) visit and should receive a pelvic exam.

   Finding an STI does not rule out concomitant UTI, which could be treated with short course therapy.

8. Patient/Provider Preference for Phone Treatment Without UA?

   Treatment of uncomplicated UTI over the phone (using a well developed protocol) for women between the ages of 18 and 65 is a reasonable practice. Patient education should be provided over the phone, handed out at the pharmacy, or mailed to the patient, and should include the following information:

   • Prescribed therapy
   • Prevention techniques
   • The need to return to the clinic if symptoms do not subside

   Of note, there is currently no data to suggest that risk of pregnancy increases with concomitant use of oral contraceptives and antibiotics recommended in this guideline.

   Evidence supporting this recommendation is of classes: D, R

9. Short Course Therapy/Patient Education

   Key Points:

   • Short course therapy (3-day) with trimethoprim-sulfamethoxazole (TMP/SMX) is as effective as 10-day therapy with TMP/SMX with fewer side effects.

   Short Course Therapy

   Symptomatic adult female patients with uncomplicated UTIs and a positive UA should be treated with short course therapy. After telephone screening to assess the symptomatology and presence of risk factors, short course therapy may be prescribed over the phone by a physician or via a clinic visit with a medical or paramedical provider.

   The drugs recommended for short course therapy are as follows:

   • Trimethoprim-sulfamethoxazole 1 twice daily x 3 days
   • Trimethoprim 100 mg 1 twice daily x 3 days (Trimethoprim may have lower side effect profile than Trimethoprim sulfamethoxazole)

   If allergic to Sulfa or Trimethoprim:

   • Nitrofurantoin (Macrobid) 100 mg twice daily x 7 days
   • Ciprofloxacin 250 mg twice daily x 3 days

   Sulfa and Ciprofloxacin may cause an increase in INR values for patients taking warfarin.

   Evidence supporting this recommendation is of class R

   Refer to the original guideline document for more information about the comparative effectiveness of treatment duration.

11. Pyuria or Dipstick Abnormal?

    A growing body of literature supports the practice of presumptive treatment of UTI in women without complicating factors on the basis of symptoms alone. For clinicians more comfortable with laboratory evaluation as an aid to the diagnosis of UTI, the use of clean-catch urinalysis is recommended. A variety of criteria for positive urinalysis in acutely dysuric women is reported in the literature. While microscopy is strongly supported by the literature, a positive leukocyte esterase may also be acceptable. However, a dipstick leukocyte esterase may not be sensitive enough to detect the degree of pyuria often associated with UTI.

    One method for measuring pyuria, determining cells per microscopic high-power field in a centrifuged urine specimen, does not correlate well with either the leukocyte excretion rate or the hemocytometer chamber technique. However, most practices do not use a hemocytometer for measurement of white blood cells in urine; therefore, defining a level of white blood cells per high-power field (wbc/hpf) that is abnormal is a matter of sensitivity and specificity. There is agreement that greater than or equal to 6 wbc/hpf demonstrates a reasonable predictive value for UTI, but it is also known that UTIs can occur in symptomatic women with less than or equal to 6 wbc/hpf.

    The presence of pyuria on urinalysis has high sensitivity (95%) but a relatively low specificity (71%) for infection. The presence of visible bacteria on microscopical examination is less sensitive but more specific (40 to 70% and 85 to 95%, respectively, depending on number of bacteria observed). Urinary dipstick testing has largely supplanted microscopy and urine-culture analysis, because the dipstick method is cheaper, faster, and more convenient. Dipsticks are most accurate when the presence of either nitrite or leukocyte esterase is positive, yielding a sensitivity of 75% and a specificity of 82%.

    Evidence supporting this recommendation is of classes: C, R

12. Provider Evaluation

    Symptomatic women with a negative urinalysis should receive further evaluation as clinically indicated.

    Within the population there may be some patients who do not appear to have a UTI by laboratory tests who will nonetheless respond to a trial of antibiotics. In addition, there may be patients who are well known to providers and who are known to be accurate historians who may not be able to come in for laboratory testing. In both cases, it may be reasonable to treat based on history without laboratory support.

13. Short Course Therapy/Phone Contact or Clinic Visit with a Medical Provider

    Patients should be encouraged to contact provider if symptoms have not resolved. Patients and providers should also understand that treatment with nitrofurantoin may take longer than treatment with TMP.

    Evidence supporting this recommendation is of classes: A, C

Definitions:

Classes of Research Reports:

1. Primary Reports of New Data Collection:

   Class A:

   • Randomized, controlled trial

   Class B:

   • Cohort study

   Class C:

   • Nonrandomized trial with concurrent or historical controls
   • Case-control study
   • Study of sensitivity and specificity of a diagnostic test
   • Population-based descriptive study

   Class D:

   • Cross-sectional study
   • Case series
   • Case reports
2. Reports that Synthesize or Reflect upon Collections of Primary Reports

   Class M:

   • Meta-analysis
   • Systematic review
   • Decision analysis
   • Cost-effectiveness analysis

   Class R:

   • Consensus statement
   • Consensus report
   • Narrative review

   Class X:

   • Medical opinion

A detailed and annotated clinical algorithm is provided for the management of Uncomplicated Urinary Tract Infection in Women.

For information about availability, see the "Availability of Companion Documents" and "Patient Resources" fields below.

• Uncomplicated urinary tract infection in women: percentage of women with uncomplicated urinary tract infection (UTI) with a urine culture performed at the initial encounter.


• Uncomplicated urinary tract infection in women: percentage of women with uncomplicated urinary tract infection (UTI) treated with recommended short course therapy.


• Uncomplicated urinary tract infection in women: percentage of women reporting satisfaction with their management of uncomplicated urinary tract infection (UTI) (patient survey).

ICSI, 8009 34th Avenue South, Suite 1200, Bloomington, MN 55425; telephone, (952) 814-7060; fax, (952) 858-9675; e-mail: icsi.info@icsi.org; Web site: www.icsi.org.

ICSI's conflict of interest policy and procedures are available for review on ICSI's website at www.icsi.org.

Electronic copies: Available from the Institute for Clinical Systems Improvement (ICSI) Web site.

Print copies: Available from ICSI, 8009 34th Avenue South, Suite 1200, Bloomington, MN 55425; telephone, (952) 814-7060; fax, (952) 858-9675; Web site: www.icsi.org; e-mail: icsi.info@icsi.org.

• Uncomplicated urinary tract infection in women. Executive summary. Bloomington (MN): Institute for Clinical Systems Improvement, 2006 Jul. 1 p. Electronic copies: Available from the Institute for Clinical Systems Improvement (ICSI) Web site.
• ICSI pocket guidelines. April 2006 edition. Bloomington (MN): Institute for Clinical Systems Improvement, 2006. 298 p.

Print copies: Available from ICSI, 8009 34th Avenue South, Suite 1200, Bloomington, MN 55425; telephone, (952) 814-7060; fax, (952) 858-9675; Web site: www.icsi.org; e-mail: icsi.info@icsi.org.

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