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Chapter 5: Urethritis & Cystitis in Females

Urethritis, uncomplicated cystitis (hereafter referred to as cystitis) and vaginitis all produce a variety of overlapping symptoms, including dysuria, urgency, frequency, hesitancy, dyspareunia, or abnormal vaginal discharge. Therefore, taking a complete history, conducting a careful physical examination and ordering appropriate laboratory tests are crucial in establishing the diagnosis.

ETIOLOGY

The most common sexually transmitted agents producing acute urethritis in women are Chlamydia trachomatis, Neisseria gonorrhoeae, and herpes simplex virus. All three of these agents also commonly infect the cervix; thus, patients may have manifestations of cervical infection as well. Candida and Trichomonas vaginalis, which cause vaginitis, may also be isolated from the urethra of women, but are not usually considered causes of urethritis. Pathogens responsible for the bulk of cystitis in women include Escherichia coli (75-95%), Enterobacteriaceae (Proteus mirabilis, Klebsiella pneumonia) and Staphylococcus saprophyticus.

CLINICAL MANIFESTATIONS AND DIAGNOSIS

Women with urethritis or cystitis classically present with dysuria. A complete sexual history is helpful in differentiating dysuria secondary to an STD versus a non-STD pathogen. It is helpful to inquire about sexual partners (i.e., sex, number, new, multiple), specific sexual practices (vaginal sex, anal sex, oral sex), safer sex practices (male condoms, female condoms) and genitourinary symptoms (frequency, urgency, gross hematuria, abnormal vaginal discharge). The presence of abnormal vaginal discharge suggests cervicitis and/or vaginitis.   

Acute onset of symptoms and short duration of symptoms (<4 days before seeking treatment) also favor a diagnosis of cystitis, whereas a history of gradual onset and long duration of symptoms (>7days) before seeking therapy suggest urethritis or vaginitis.

Examination

The urethral examination may be normal in women with urethritis due to gonorrhea or chlamydia or may show erythema or an exudate. Vulvar or urethral lesions or inflammation may accompany genital herpes infection, and signs of cervical or labial infection are often also present (see Chapter 9 for further information on genital ulcer diseases).  Suprapubic or bladder tenderness are signs suggestive of cystitis. Findings typical of vaginitis and cervicitis are described more fully in Chapter 6 and Chapter 7.

LABORATORY

Microscopic urinalysis

Urinalysis can either be testing of leukocyte esterase on a first void urine or collection of a “clean catch” midstream urine specimen for microscopic evaluation.  A midstream urine specimen showing pyuria in a centrifuged specimen, usually defined as >10 PMNs/400X high-dry field (often with WBC clumps, RBC, or bacteria), suggests urethritis or cystitis.  Symptoms of dysuria but absence of pyuria on urinalysis is suggestive of vaginitis. The presence of squamous epithelial cells indicates poor clean-catch technique and markedly reduces the diagnostic value of the test.

Gram stain

A Gram stain of midstream, clean-catch uncentrifuged urine showing >1 organism/oil immersion field (1000X) suggests bacterial urinary tract infection (UTI), but the absence of bacteria does not exclude UTI.

Urine culture

Women without evidence of vaginitis or cervicitis on examination, but with pyuria and bacteriuria usually have a bacterial bladder infection. It is prudent to obtain a urine culture prior to initiation of therapy if a woman’s symptoms are not consistent with cystitis, if symptoms persist or recur after three months following therapy or if signs/symptoms are consistent with a complicated infection.

It is reasonable to manage such women without a urine culture if they:

  • have no fever, flank pain or other suspicion for pyelonephritis
  • have no history of previous urinary tract infections in the last 6 months
  • have not recently take antibiotics or
  • have no known urologic abnormalities or kidney stones

If urine cultures are obtained, ≥103 colony count of a single uropathogenic organism (E. coli, S. Saprophyticus, Proteus spp.) support the diagnosis of UTI.  Mixed organisms on urine culture indicate a possible contaminated specimen, but can still indicate UTI if there is a predominant organism with ≥103 colony count.

If the microscopic examination of the urine reveals only pyuria but not bacteriuria, the patient may have urethral infection with chlamydia or gonococci, but could alternatively have a bacterial urinary infection with lower counts of E. coli not visible on Gram stain.  Chlamydial and gonorrhea tests should be obtained from the cervix and urethra, and a urine culture should be done. If the patient has any lesions suggestive of herpes, both the lesions and the urethra should be assessed for HSV using a standard diagnostic test.

DIFFERENTIAL DIAGNOSIS

The differential diagnoses primarily include

  • urethritis, cystitis, and vaginitis (Table 5-1 and Figure 5-1 below)
  • upper urogenital tract diseases, such as pyelonephritis, endometritis, and salpingitis may occasionally also be present.
Table 5-1
Diagnostic Characteristics of Lower Genitourinary Tract Infections in Women
  CYSTITIS (UTI) URETHRITIS VAGINITIS/ CERVICITIS*
History

"Internal" dysuria, urgency, frequency, gross hematuria

Acute onset

Short duration (<4 days)

Previous cystitis or hematuria; suprapubic or low back pain

"Internal" dysuria

Gradual onset

Long duration (>7 days)

"External" dysuria

Vaginal discharge or odor, vulvar itching

Dyspareunia

Exam

Suprapubic or bladder tenderness

Genital exam usually normal except urethral erythema / exudate

Cervicitis often present

Candidal, trichomonal, or bacterial vaginosis (see Chapter 6)
Urinalysis

Pyuria; bacteriuria in most cases, hematuria in half of cases

Pyuria; no bacteriuria; no hematuria

No pyuria

Gram Stain

> 1 organism/1000x (uncentrifuged)

   
Urine Cultures

≥103/ml/single organism

Negative

Negative

Urethral/cervical Culture

Negative

Positive for CT, GC, HSV

Negative

* See Table 6-1 and Chapter 6 for further discussion of vaginitis and Chapter 7 for cervicitis.

Figure 5-1 Algorithm for management of sexually active woman with dysuria

TREATMENT

For a more detailed discussion of these regimens and other treatment considerations, please refer to the CDC 2010 STD Treatment Guidelines at http://www.cdc.gov/std/treatment/. For a more detailed discussion of management of UTI, refer to the recently updated IDSA guidelines at http://www.idsociety.org/Organ_System/#Genitourinary.

Urethritis and Cystitis in Women

Suspected Acute Cystitis/Urinary Tract Infection (UTI)

Recommended regimen

Nitrofurantoin monohydrate/macrocrystals 100 mg bid x 5 days

OR

Trimethoprim-sulfamethoxazole 160/800 mg (one DS tablet) bid x 3 days (avoid if resistance prevalence is known to exceed 20% or if used for UTI in previous 3 months)

OR

Fosfomycin trometamol 3 gm single dose (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected)

OR

Pivmecillinam 400 mg bid x 5 days (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected)

Presumed chlamydial or gonococcal urethritis

If suspicion for either of these is present, see testing and treatment recommendations for these infections. If the risk for STD is low, treatment for bacterial UTI should be given for suspected acute cystitis (above).

For women with recent history of UTI, recent antibiotic exposure, urologic abnormalities, or kidney stones, treatment should only be undertaken if urine culture and antibiotic sensitivities are available.

FOLLOW-UP

  • Patients who have no pyuria observed should be re-examined in 2 to 5 days if symptoms persist.
  • See follow-up regimens in specific chapters for women treated for vaginitis or cervicitis.
  • Women given empiric antimicrobials for acute cystitis should return PRN if symptoms persist/recur.
  • Practitioners should refer patients for specialty care if urine culture and susceptibilities reveal a challenging resistance profile.

SEQUELAE

Delay in treatment or inappropriate treatment of cystitis may lead to development of acute pyelonephritis. Untreated lower genital tract infection with chlamydia or gonorrhea may lead to morbid reproductive tract sequelae such as pelvic inflammatory disease, endometritis or salpingitis.


References:
Gupta K 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. CID 2011; 52: e103-120.

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