Male Urethritis in Emergency Medicine Medication

In the emergency department, single-dose antibiotic therapy for urethritis is administered to cover both gonococcal urethritis (GCU) and nongonococcal urethritis (NGU), since results of NAAT testing may not be immediately available, and compliance with outpatient treatment and follow-up may be uncertain. Consider presumptive treatment for T vaginalis, or base treatment on evidence of this organism on urine microscopy.

Therapy for GCU

The antimicrobial options in the treatment of GCU include ceftriaxone 125 mg IM single dose or cefixime 400 mg PO single dose. Alternative choices include a single-dose cephalosporin, such as ceftizoxime 500 mg IM or cefoxitin 2 g IM with probenecid 1 g PO, or cefotaxime 500 mg IM, or single-dose spectinomycin 2 g IM (reserved for patients with allergies to cephalosporins and not currently available in the United States). Single-dose azithromycin 2 g PO is also an alternative, but it may cause gastrointestinal distress and has theoretical concern for emerging resistance.

Quinolone resistance is increasing worldwide and is common in Asia, the Pacific, Europe, and the Middle East as well as in some parts of the United States.^[16] Quinolone-resistant GCU is also more prevalent in men who have sex with men. Because of increasing resistance, quinolones (eg, ciprofloxacin 500 mg PO single dose, levofloxacin 250 mg PO single dose, or ofloxacin 400 mg PO single dose) are not currently recommended by the Centers for Disease Control and Prevention (CDC) for routine or alternative regimens.^{[11, 12, 17]}

The recommendation was based on analysis of new data from the CDC's Gonococcal Isolate Surveillance Project (GISP). The data from GISP showed the proportion of gonorrhea cases in heterosexual men that were fluoroquinolone-resistant (QRNG) reached 6.7%, an 11-fold increase from 0.6% in 2001. The data were published in the April 13, 2007, issue of the Morbidity and Mortality Weekly Report.^[17] This limits treatment of gonorrhea to drugs in the cephalosporin class (eg, ceftriaxone 125 mg IM once as a single dose).

Fluoroquinolones may be an alternative treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented. For more information see, the CDC's Antibiotic-Resistant Gonorrhea Web site; CDC Updated Gonococcal Treatment Recommendations (April 2007); or Medscape Medical News on CDC Issues - New Treatment Recommendations for Gonorrhea.

Therapy for NGU

A single dose of azithromycin 1 g orally or doxycycline 100 mg orally twice daily for 7 days has been recommended for treatment of NGU by the CDC.^{[11, 12]} Doxycycline may have a higher clearance rate for Chlamydia than azithromycin^[18] ; however, azithromycin is more effective than doxycycline for M genitalium^{[19, 20, 18]} and U urealyticum infections. Single-dose azithromycin may induce resistance in M genitalium^[21] but also ensures compliance and may successfully treat cases of NGU in which test results are negative for Chlamydia, Mycoplasma, and Ureaplasma species.^{[22, 23]}

Alternative regimens include 10 days of moxifloxacin 400 mg daily (which may be more effective than azithromycin for M genitalium),^{[24, 25, 26]} 7 days of erythromycin base 500 mg 4 times daily, erythromycin ethylsuccinate 800 mg 4 times daily, ofloxacin 300 mg twice daily, or levofloxacin 500 mg once daily.^{[11, 12]} Minocycline or tetracycline are reasonable alternatives to doxycycline. Ciprofloxacin is ineffective against chlamydial infection. Combinations of probenecid with penicillin, amoxicillin, or ampicillin are no longer used because of resistance.

Therapy for T vaginalis

Consider empiric treatment for T vaginalis (although this organism may be present in as few as 2.5% of urethritis cases),^[5] or base treatment on presence of this organism on urine microscopy, with single treatment of metronidazole or tinidazole 2 g orally.

Antibiotic therapy with 2 g metronidazole or tinidazole is also recommended for sexual partners of individuals with documented Trichomonas, even if asymptomatic.

Therapy for recurrent or persistent urethritis

Recurrent symptoms may be related to reexposure (especially if sexual partner not also treated), noncompliance, chronic nonbacterial prostatitis, or infection with T vaginalis, M genitalium, or U urealyticum.

A single dose of metronidazole 2 g orally, or tinidazole 2 g orally, should be used (especially if not given initially) for suspected Trichomonas.

M genitalium can be a common cause of persistent urethritis, especially after doxycycline therapy,^[27] but also after azithromycin therapy. Therefore, a single-dose azithromycin 1 g is recommended^{[19, 28]} if the patient did not previously receive azithromycin (or cannot afford quinolones). Moxifloxacin 400 mg daily for 10 days is recommended if the patient previously received azithromycin.^{[24, 25, 26, 28]}

Prolonged (14-28 d) therapy with erythromycin has not been demonstrated to be of value.

Class Summary

Single-dose therapy to cover GCU and chlamydia includes azithromycin 2 g PO (limited by gastrointestinal intolerance) or azithromycin 1 g PO plus a cephalosporin.

Cefixime (Suprax)

Arrests bacterial cell wall synthesis and inhibits bacterial growth by binding to one or more penicillin-binding proteins.

Ceftriaxone (Rocephin)

Used because of increasing prevalence of penicillinase-producing N gonorrhoeae. Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms; arrests bacterial growth by binding to one or more penicillin-binding proteins.

Spectinomycin (Trobicin)

Structurally different from related aminoglycosides, inhibits protein synthesis in bacterial cells. Site of action is 30S ribosomal subunit. Used as alternative antimicrobial in treatment of urethral, endocervical, or rectal gonococcal infections in patients who cannot take cephalosporins or fluoroquinolones. Same regimen of this medication administered to pregnant women who are allergic to cephalosporins.

Azithromycin (Zithromax)

Used to treat mild to moderately severe infections caused by susceptible strains of microorganisms. Indicated for chlamydia and gonorrheal infections of genital tract.

Doxycycline (Dory, Bio-Tab)

Used in treatment of rectal syphilis. Inhibits protein synthesis and bacterial growth by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Tetracycline (Sumycin)

Treats susceptible bacterial infections of both gram-positive and gram-negative organisms as well as mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Minocycline (Dynacin, Minocin)

Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to susceptible chlamydial, rickettsial, and mycoplasmal infections.

Erythromycin (E-Mycin, Eryc, Ery-Tab)

Indicated for treatment of infections caused by susceptible strains of microorganisms, including Staphylococcus aureus. Inhibits RNA-dependent protein synthesis, possibly by stimulating dissociation of peptidyl tRNA from ribosomes, thus inhibiting bacterial growth. Twice-a-day dosing not recommended when doses greater than 1 g/d are administered.

Metronidazole (Flagyl)

Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Usually used in combination with other antimicrobial agents except when used for Clostridium difficile enterocolitis in which monotherapy is appropriate. Active against various anaerobic bacteria and protozoa. Appears to be absorbed into cells, and intermediate-metabolized compounds that are formed bind DNA and inhibit protein synthesis, causing cell death.

Class Summary

The quinolone class antibiotics are no longer considered effective against GCU due to increasing resistance. However, these antibiotics are useful for NGU as initial alternative to or when refractory to initial treatment with azithromycin.

Moxifloxacin (Avelox)

Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription. Useful for refractory NGU secondary to Mycoplasma genitalium infection.

Ofloxacin (Floxin)

Treats GU only. Penetrates prostate well and is effective against N gonorrhea and C trachomatis. A derivative of pyridine carboxylic acid with broad-spectrum bactericidal effect. Useful for the treatment of NGU.

Levofloxacin (Levaquin)

For pseudomonal infections and infections due to multidrug resistant gram-negative organisms as well as atypical infections such as Chlamydia, Mycoplasma and Ureaplasma species.