This patient has urethritis due to Chlamydia trachomatis and should be treated with azithromycin. Azithromycin, a macrolide antibiotic, is the preferred treatment of urethritis and cervicitis due to C. trachomatis because it can be given as single-dose therapy. The patient should be screened for other sexually transmitted infections and encouraged to refer his sexual partner for evaluation and treatment. Doxycycline is also effective against chlamydia; however, a 7-day regimen is required. The single-dose therapy of azithromycin is preferred to enhance adherence.

Penicillins have activity against C. trachomatis but have far lower cure rates than do azithromycin, doxycycline, or the fluoroquinolones ofloxacin or levofloxacin. Because of the lower cure rate, a test of cure is indicated when these agents are used.

Cefixime, an oral third-generation cephalosporin, has no activity against C. trachomatis, although it is an alternative for the treatment of Neisseria gonorrhoeae infections if ceftriaxone is unavailable. It would provide adequate antimicrobial coverage for treatment of urinary tract infection; however, this patient's colony count of Escherichia coli in the urine culture is insignificant and does not warrant therapy.

Dual treatment with ceftriaxone plus azithromycin for N. gonorrhoeae and C. trachomatis would be appropriate if empiric therapy were given before availability of the nucleic acid amplification test results. If only N. gonorrhoeae is diagnosed, dual therapy with ceftriaxone and azithromycin is recommended because of the high incidence of concomitant infection with C. trachomatis. Dual therapy also offers potential increased efficacy for treating gonorrhea in men, considering increasing minimum inhibitor concentrations for cephalosporins among gonorrhea isolates.