Approach
The goals of treatment are to alleviate acute symptoms and prevent transmission.
Initial treatment considerations
For symptomatic people with confirmed urethritis (mucopurulent discharge, Gram stain with ≥2 polymorphonuclear leukocytes [PMNs] per high power field, positive leukocyte esterase test on urine, or ≥10 PMNs per high power field on urine sediment), presumptive treatment for both gonococcal (GU) and nongonococcal urethritis (NGU) should be given pending test results.[1][29][32][42][43] Patients should abstain from sex during treatment. If urethritis cannot be confirmed, treatment should be deferred, unless the patient is considered at high risk for infection and unlikely to return for follow-up.
For all patients with urethritis, every effort should be made to ensure that the patient's sex partners from the preceding 60 days are evaluated and treated with a recommended regimen.
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Expedited partner therapy should be considered for heterosexual patients with chlamydia or gonorrhea infection where it cannot be ensured that all of a patient’s sex partners from the prior 60 days will be evaluated and treated.[1] This is the practice of delivering medications or prescriptions to the partner through the patient without the partner being examined by a healthcare provider.[1] Laws governing expedited partner therapy vary by state. Patients should contact their local health department to determine the legality of this practice in their area.[1][44][45][46] These programs are controversial because, while effective for reducing transmission of gonorrhea and chlamydial urethritis, they omit the opportunity to provide in-person contact, counseling, detection of other sexually transmitted infections, or detection of antibiotic allergies.[47]
Urethritis may facilitate HIV transmission. Treatment is the same in people with HIV as in people without HIV.[1]
Initial Gram stain suggestive of gonorrhea
The Centers for Disease Control and Prevention (CDC) has reviewed the recommendations for the treatment of gonorrhea on the basis of increasing concern about antimicrobial stewardship, in particular the impact of antimicrobial use on the microbiome and changes in azithromycin susceptibility for gonorrhea and other organisms. Therefore, the CDC now recommends ceftriaxone monotherapy for the treatment of Neisseria gonorrhoeae as it remains highly susceptible to ceftriaxone, azithromycin resistance is increasing, and prudent use of antimicrobial agents supports limiting their use.[1]
Treatment with 7 days of oral doxycycline is recommended when chlamydial infection has not been excluded.[1]
If ceftriaxone is not available, oral cefixime is a suitable alternative agent.[1]
In patients who have a cephalosporin allergy, intramuscular gentamicin in a single dose plus a high dose of azithromycin may be considered; however, gastrointestinal adverse effects may limit the use of these regimens.[1]
Intramuscular ceftriaxone monotherapy is the recommended first-line regimen in pregnant women, preferably given under direct observation. A single dose of azithromycin may be added to treat chlamydia, if chlamydial infection has not been excluded.[1] Consultation with an infectious disease specialist is recommended if the patient has a cephalosporin allergy or there are any other considerations that preclude treatment with these regimens.[1][Figure caption and citation for the preceding image starts]: Gram stain of urethral exudate showing gram-negative diplococci and polymorphonuclear leukocytesAdapted from Public Health Image Library, CDC; Jacobs N, 1974 [Citation ends].
Initial Gram stain not suggestive of gonorrhea
These patients are initially treated for NGU alone. Presumptive treatment with doxycycline is recommended, as this drug is highly effective for C trachomatis and has some activity against M genitalium.[1] Azithromycin should be considered as a secondary treatment option due to increasing reports of treatment failure and macrolide antimicrobial resistance with M genitalium.[29][48] A multi-day azithromycin dosing regimen may protect against inducing M genitaliumresistance.[1]
Erythromycin and levofloxacin are no longer recommended for the treatment of NGU due to gastrointestinal adverse effects and inferior efficacy, respectively.[1]
Pregnant women should be treated with azithromycin first-line.[1] Amoxicillin is an alternative treatment if chlamydial infection is detected.[1] Doxycycline and fluoroquinolones are not recommended in pregnancy. Consultation with an infectious disease specialist is recommended if the patient has any considerations that preclude treatment with these regimens.
When results of any nucleic acid amplification test (NAAT) and/or culture testing are available, the choice of antibiotic is based on the local epidemiology of specific infections and antimicrobial sensitivity patterns. If a NAAT is positive for gonorrhea, a culture should be performed before antigonococcal treatment is added.[29]
Follow-up
The CDC recommends that a test of cure is not needed for people who receive a diagnosis of uncomplicated urogenital gonorrhea who are treated with any of the recommended or alternative regimens.[1] Men who are given a specific diagnosis of chlamydia, gonorrhea, or trichomonas should be retested 3 months after treatment, as rates of reinfection are reported to be high, regardless of whether their sex partners were treated.
Pregnant women should be retested to ensure cure, preferably with a NAAT such as ligase chain reaction or polymerase chain reaction of urethral discharge and/or urine sediment. Chlamydia test of cure is recommended 4 weeks after treatment, with a retest at 3 months. Retest for gonorrhea is recommended at 3 months.[1]
Recurrent or persistent urethritis
Objective signs of urethritis should be confirmed. Without objective evidence of urethritis, prolonged or repeated courses of antimicrobials have little benefit. Patients should then be (re)evaluated for noninfectious causes of urethritis (e.g., trauma, instrumentation, foreign body insertion, chemical irritation including spermicides).
If the patient did not reliably complete the initial treatment or was re-exposed by an untreated partner, he/she may be retreated with the same regimen initially used.
Treatment failure should be considered in the following patients:[1]
Patients whose symptoms do not resolve in 3 to 5 days after appropriate treatment and who report no sexual contact during the post-treatment period
Patients with a positive test of cure (i.e., positive culture >72 hours or NAAT >7 days after receiving recommended treatment) and who report no sexual contact during the post-treatment period.
Patients with gonococcal urethritis and suspected treatment failure should have relevant clinical specimens for culture and antimicrobial susceptibility testing and an infectious disease specialist consulted.[1]
In areas where Trichomonas vaginalis is prevalent, men who have sex with women and have persistent or recurrent urethritis should be presumptively treated with metronidazole or tinidazole.[1] If T vaginalis is unlikely, and M genitalium is detected on testing, resistance testing directs appropriate therapy.[1][28] If M genitalium is macrolide resistant or resistance testing for M genitalium is unavailable, patients should be presumptively treated with doxycycline to decrease bacterial load, followed by moxifloxacin to clear the infection.[1] Antibiotic regimens may vary according to local protocols; consult local guidance. Patients with persistent or recurrent NGU after presumptive treatment for M genitalium or T vaginalis should be referred to a specialist for treatment.[1]
Systemic fluoroquinolone antibiotics, such as moxifloxacin, may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to, tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[49]
Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability).
Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.
Treatment failures should prompt consultation with an infectious disease specialist and be reported to the CDC through the local or state health department within 24 hours of diagnosis.[1]
As a last step for refractory cases, rare causes such as herpetic urethritis should be ruled out.
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