Urethritis Treatment in Males

The material below has been excerpted from the Centers for Disease Control, Morbidity and Mortality Weekly Report, May 10, 2002/Vol. 51/No.RR-6
Sexually Transmitted Diseases
Treatment Guidelines 2002

Management of Male Patients Who Have Urethritis

Urethritis is caused by an infection characterized by urethral discharge of mucopurulent or purulent material and sometimes by dysuria or urethral pruritis. Asymptomatic infections are common. The principal bacterial pathogens of proven clinical importance in men who have urethritis are N. gonorrhoeae and C. trachomatis. Testing to determine the specific etiology is recommended because both chlamydia and gonorrhea are conditions that are reportable to state health departments, and a specific diagnosis may enhance partner notification and improve compliance with treatment, especially in the exposed partner. If diagnostic tools (e.g., a Gram stain and microscope) are unavailable, patients should be treated for both infections. The additional antibiotic exposure and expense of treating a person who has nongonococcal urethritis (NGU) for both infections also should encourage the health-care provider to make a specific diagnosis. Nucleic acid amplification tests enable detection of N. gonorrhoeae and C. trachomatis on all specimens. These tests are more sensitive than traditional culture techniques for C. trachomatis and are the preferred method for the detection of this organism.

Etiology

NGU is diagnosed if Gram-negative intracellular diplococci cannot be identified on urethral smears. C. trachomatis is a frequent cause (i.e., 15%--55% of cases); however, the prevalence differs by age group, with lower prevalence of this organism among older men. The proportion of NGU cases caused by chlamydia has been declining gradually. Complications of NGU among men infected with C. trachomatis include epididymitis and Reiter's syndrome. Documentation of chlamydia infection is important because of the need for partner referral for evaluation and treatment.

The etiology of most cases of nonchlamydial NGU is unknown. Ureaplasma urealyticum and Mycoplasma genitalium have been implicated as causes of NGU in some studies. Specific diagnostic tests for these organisms are not indicated, because the detection of these organisms is often difficult and would not alter therapy.

T. vaginalis and HSV sometimes cause NGU. Diagnostic and treatment procedures for these organisms are reserved for situations in which these infections are suspected (e.g., contact with trichomoniasis and genital lesions suggestive of genital herpes) or when NGU is not responsive to therapy.

Confirmed Urethritis

Clinicians should document that urethritis is present. Urethritis can be documented on the basis of any of the following signs.

Mucopurulent or purulent discharge. Gram stain of urethral secretions demonstrating >5 WBCs per oil immersion field. The Gram stain is the preferred rapid diagnostic test for evaluating urethritis. It is highly sensitive and specific for documenting both urethritis and the presence or absence of gonococcal infection. Gonococcal infection is established by documenting the presence of WBCs containing intracellular Gram-negative diplococci. Positive leukocyte esterase test on first-void urine or microscopic examination of first-void urine demonstrating >10 WBCs per high power field.

If none of these criteria is present, then treatment should be deferred, and the patient should be tested for N. gonorrhoeae and C. trachomatis and followed closely if test results are negative. If the results demonstrate infection with either N. gonorrhoeae or C. trachomatis, the appropriate treatment should be given and sex partners referred for evaluation and treatment.

Empiric treatment of symptoms without documentation of urethritis is recommended only for patients at high risk for infection who are unlikely to return for a follow-up evaluation. Such patients should be treated for gonorrhea and chlamydia. Partners of patients treated empirically should be evaluated and treated.

Management of Patients Who Have Nongonococcal Urethritis

Diagnosis

All patients who have urethritis should be evaluated for the presence of gonococcal and chlamydial infection. Testing for chlamydia is strongly recommended because of the increased utility and availability of highly sensitive and specific testing methods, and because a specific diagnosis may enhance partner notification and improve compliance with treatment, especially in the exposed partner.

Treatment

Treatment should be initiated as soon as possible after diagnosis. Single-dose regimens have the advantage of improved compliance and of DOT. To improve compliance, the medication should be provided in the clinic or health-care provider's office.

Recommended Regimens   Azithromycin 1 g orally in a single dose         OR Doxycycline 100 mg orally twice a day for 7 days.   Alternative Regimens   Erythromycin base 500 mg orally four times a day for 7 days,         OR Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days,        OR Ofloxacin 300 mg twice a day for 7 days,        OR Levofloxacin 500 mg once daily for 7 days.

Follow-Up for Patients Who Have Urethritis

Patients should be instructed to return for evaluation if symptoms persist or recur after completion of therapy. Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, are not a sufficient basis for re-treatment. Patients should be instructed to abstain from sexual intercourse until 7 days after therapy is initiated.

Partner Referral

Patients should refer for evaluation and treatment all sex partners within the preceding 60 days. Because a specific diagnosis may facilitate partner referral, testing for gonorrhea and chlamydia is encouraged.

Recurrent and Persistent Urethritis

Objective signs of urethritis should be present before initiation of antimicrobial therapy. Effective regimens have not been identified for treating patients who do not have objective signs of urethritis but who have persistent symptoms after treatment. Patients who have persistent or recurrent urethritis should be re-treated with the initial regimen if they did not comply with the treatment regimen or if they were reexposed to an untreated sex partner. Otherwise, a culture of an intra-urethral swab specimen and a first-void urine specimen for T. vaginalis should be performed. Some cases of recurrent urethritis following doxycycline treatment may be caused by tetracycline-resistant U. urealyticum. Urologic examinations usually do not reveal a specific etiology. If the patient was compliant with the initial regimen and re-exposure can be excluded, the following regimen is recommended.

Recommended Regimens   Metronidazole 2 g orally in a single dose        PLUS Erythromycin base 500 mg orally four times a day for 7 days       OR Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days.

Special Considerations

HIV Infection

Gonococcal urethritis, chlamydial urethritis, and nongoncoccal, nonchlamydial urethritis may facilitate HIV transmission. Patients who have NGU and also are infected with HIV should receive the same treatment regimen as those who are HIV-negative.

Management of Patients Who Have Mucopurulent Cervicitis (MPC)

MPC is characterized by a purulent or mucopurulent endocervical exudate visible in the endocervical canal or in an endocervical swab specimen. Some specialists also diagnose MPC on the basis of easily induced cervical bleeding. Although some specialists consider an increased number of polymorphonuclear leukocytes on endocervical Gram stain as being useful in the diagnosis of MPC, this criterion has not been standardized, has a low positive-predictive value (PPV), and is not available in some settings. MPC often is asymptomatic, but some women have an abnormal vaginal discharge and vaginal bleeding (e.g., after sexual intercourse). MPC can be caused by C. trachomatis or N. gonorrhoeae; however, in most cases neither organism can be isolated. MPC can persist despite repeated courses of antimicrobial therapy. Because relapse or reinfection with C. trachomatis or N. gonorrhoeae usually does not occur in persons with persistent cases of MPC, other non-microbiologic determinants (e.g., inflammation in the zone of ectopy) might be involved.

Patients who have MPC should be tested for C. trachomatis and for N. gonorrhoeae with the most sensitive and specific test available. However, MPC is not a sensitive predictor of infection with these organisms; most women who have C. trachomatis or N. gonorrhoeae do not have MPC.

Treatment

The results of sensitive tests for C. trachomatis or N. gonorrhoeae (e.g., culture or nucleic acid amplification tests) should determine the need for treatment, unless the likelihood of infection with either organism is high or the patient is unlikely to return for treatment. Empiric treatment should be considered for a patient who is suspected of having gonorrhea and/or chlamydia if a) the prevalences of these infections are high in the patient population and b) the patient might be difficult to locate for treatment. If relapse and reinfection have been excluded, management options of persistent MPC are undefined. For such persons, additional antimicrobial therapy may be of minimal benefit.

Follow-Up

Follow-up should be conducted as recommended for the infections for which a woman is being treated. If symptoms persist, women should be instructed to return for reevaluation and to abstain from sexual intercourse, even if they have completed the prescribed therapy.

Management of Sex Partners

Management of sex partners of women treated for MPC should be appropriate for the identified or suspected STD. Partners should be notified, examined, and treated for the STD identified or suspected in the index patient.

Because a microbiologic test of cure usually is not recommended, patients and their sex partners should abstain from sexual intercourse until therapy is completed (i.e., 7 days after a single-dose regimen or after completion of a 7-day regimen).

Special Considerations

HIV Infection

Patients who have MPC and also are infected with HIV should receive the same treatment regimen as those who are HIV-negative.

Chlamydial Infections

In the United States, chlamydial genital infection occurs frequently among sexually active adolescents and young adults. Asymptomatic infection is common among both men and women. Sexually active adolescent women should be screened for chlamydial infection at least annually, even if symptoms are not present. Annual screening of all sexually active women aged 20--25 years is also recommended, as is screening of older women with risk factors (e.g., those who have a new sex partner and those with multiple sex partners). An appropriate sexual risk assessment should always be conducted and may indicate more frequent screening for some women.

Chlamydial Infections in Adolescents and Adults

Several important sequelae can result from C. trachomatis infection in women; the most serious of these include pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. Some women who have apparently uncomplicated cervical infection already have subclinical upper-reproductive--tract infection. A recent investigation of patients in a health maintenance organization demonstrated that screening and treatment of cervical infection can reduce the likelihood of PID.

Treatment

Treating infected patients prevents transmission to sex partners. In addition, treatment of chlamydia in pregnant women usually prevents transmission of C. trachomatis to infants during birth. Treatment of sex partners helps to prevent reinfection of the index patient and infection of other partners.

Coinfection with C. trachomatis often occurs among patients who have gonococcal infection; therefore, presumptive treatment of such patients for chlamydia is appropriate (see Gonococcal Infection, Dual Therapy for Gonococcal and Chlamydial Infections). The following recommended treatment regimens and alternative regimens cure infection and usually relieve symptoms.

Recommended Regimens   Azithromycin 1 g orally in a single dose      OR Doxycycline 100 mg orally twice a day for 7 days.   Alternative Regimens   Erythromycin base 500 mg orally four times a day for 7 days,      OR Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days,      OR Ofloxacin 300 mg orally twice a day for 7 days,      OR Levofloxacin 500 mg orally for 7 days.

The results of clinical trials indicate that azithromycin and doxycycline are equally efficacious (46,47). These investigations were conducted primarily in populations in which follow-up was encouraged and adherence to a 7-day regimen was good. Azithromycin should always be available to health-care providers to treat patients for whom compliance is in question.

In populations that have erratic health-care-seeking behavior, poor compliance with treatment, or unpredictable follow-up, azithromycin may be more cost-effective because it enables the provision of single-dose DOT. Doxycycline costs less than azithromycin, and it has been used extensively for a longer period. Erythromycin is less efficacious than either azithromycin or doxycycline, and gastrointestinal side effects frequently discourage patients from complying with this regimen. Ofloxacin is similar in efficacy to doxycycline and azithromycin, but it is more expensive to use and offers no advantage with regard to the dosage regimen. Levofloxacin has not been evaluated for treatment of C. trachomatis infection in clinical trials, but because its pharmacology and in vitro microbiologic activity are similar to that of ofloxacin, levofloxacin may be substituted in doses of 500 mg once a day for 7 days. Other quinolones either are not reliably effective against chlamydial infection or have not been adequately evaluated.

To maximize compliance with recommended therapies, medications for chlamydial infections should be dispensed on site, and the first dose should be directly observed. To minimize further transmission of infection, patients treated for chlamydia should be instructed to abstain from sexual intercourse for 7 days after single-dose therapy or until completion of a 7-day regimen. To minimize the risk for reinfection, patients also should be instructed to abstain from sexual intercourse until all of their sex partners are treated.

Follow-Up

Patients do not need to be retested for chlamydia after completing treatment with doxycycline or azithromycin unless symptoms persist or reinfection is suspected. A test of cure may be considered 3 weeks after completion of treatment with erythromycin. The validity of chlamydial culture testing at <3 weeks after completion of therapy to identify patients who did not respond to therapy has not been established. False-negative results can occur resulting from infections involving small numbers of chlamydial organisms. In addition, nonculture tests conducted at <3 weeks after completion of therapy for patients who were treated successfully could yield false-positive results because of continued excretion of dead organisms.

A high prevalence of C. trachomatis infection is found in women who have had chlamydial infection in the preceding several months. Most post-treatment infections result from reinfection, often occurring because patient's sex partners were not treated or because the patient resumed sex among a network of persons with a high prevalence of infection. Repeat infection confers an elevated risk of PID and other complications when compared with initial infection. Therefore, recently infected women are a high priority for repeat testing for C. trachomatis. For these reasons, clinicians and health-care agencies should consider advising all women with chlamydial infection to be rescreened 3--4 months after treatment. Some specialists believe rescreening is an especially high priority for adolescents. Providers are also strongly encouraged to rescreen all women treated for chlamydial infection whenever they next present for care within the following 12 months, regardless of whether the patient believes that her sex partners were treated.

Rescreening is distinct from early retesting to detect therapeutic failure (test-of-cure). Except in pregnant women, test-of-cure is not recommended for persons treated with the recommended regimens, unless therapeutic compliance is in question.

Management of Sex Partners

Patients should be instructed to refer their sex partners for evaluation, testing, and treatment. The following recommendations on exposure intervals are based on limited evaluation. Sex partners should be evaluated, tested, and treated if they had sexual contact with the patient during the 60 days preceding onset of symptoms in the patient or diagnosis of chlamydia. The most recent sex partner should be evaluated and treated even if the time of the last sexual contact was >60 days before symptom onset or diagnosis.

Patients should be instructed to abstain from sexual intercourse until they and their sex partners have completed treatment. Abstinence should be continued until 7 days after a single-dose regimen or after completion of a 7-day regimen. Timely treatment of sex partners is essential for decreasing the risk for reinfecting the index patient.

Special Considerations

Pregnancy. Doxycycline and ofloxacin are contraindicated in pregnant women. However, clinical experience and preliminary data suggest that azithromycin is safe and effective (48,49). Repeat testing (preferably by culture) 3 weeks after completion of therapy with the following regimens is recommended for all pregnant women, because these regimens may not be highly efficacious and the frequent side effects of erythromycin might discourage patient compliance with this regimen.

Recommended Regimens   Erythromycin base 500 mg orally four times a day for 7 days      OR Amoxicillin 500 mg orally three times daily for 7 days.   Alternative Regimens   Erythromycin base 250 mg orally four times a day for 14 days,      OR Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days,      OR Erythromycin ethylsuccinate 400 mg orally four times a day for 14 days,      OR Azithromycin 1 g orally, single dose.

NOTE: Erythromycin estolate is contraindicated during pregnancy because of drug-related hepatotoxicity.

HIV Infection. Patients who have chlamydial infection and also are infected with HIV should receive the same treatment regimen as those who are HIV-negative.

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