Comment on Callado et al: “Syphilis Treatment: Systematic Review and Meta-analysis Investigating Nonpenicillin Therapeutic Strategies”

In the United States, gonorrhea is the second most commonly reported notifiable disease, with 339,593 cases documented in 2005. Since 1993, fluoroquinolones (i.e., ciprofloxacin, ofloxacin, or levofloxacin) have been used frequently in the treatment of gonorrhea because of their high efficacy, ready availability, and convenience as a single-dose, oral therapy. However, prevalence of fluoroquinolone resistance in Neisseria gonorrhoeae has been increasing and is becoming widespread in the United States, necessitating changes in treatment regimens. Beginning in 2000, fluoroquinolones were no longer recommended for gonorrhea treatment in persons who acquired their infections in Asia or the Pacific Islands (including Hawaii); in 2002, this recommendation was extended to California. In 2004, CDC recommended that fluoroquinolones not be used in the United States to treat gonorrhea in men who have sex with men (MSM). This report, based on data from the Gonococcal Isolate Surveillance Project (GISP), summarizes data on fluoroquinolone-resistant N. gonorrhoeae (QRNG) in heterosexual males and in MSM throughout the United States. This report also updates CDC's Sexually Transmitted Diseases Treatment Guidelines, 2006 regarding the treatment of infections caused by N. gonorrhoeae. On the basis of the most recent evidence, CDC no longer recommends the use of fluoroquinolones for the treatment of gonococcal infections and associated conditions such as pelvic inflammatory disease (PID). Consequently, only one class of drugs, the cephalosporins, is still recommended and available for the treatment of gonorrhea.

The incidence of syphilis has been increasing in the United States since reaching a nadir in 2000. Several clinical trials have demonstrated that treatment with oral azithromycin may be useful for syphilis control. After reports of azithromycin treatment failures in San Francisco, we investigated the clinical and epidemiologic characteristics of patients with syphilis due to azithromycin-resistant Treponema pallidum infection. We reviewed city-wide case reports and conducted molecular screening for patients seen at the San Francisco metropolitan STD clinic (San Francisco City Clinic) to identify patients who did not respond to azithromycin treatment for syphilis or who were infected with azithromycin-resistant T. pallidum. We conducted an epidemiologic investigation and retrospective case-control study to identify risk factors for acquiring syphilis due to azithromycin-resistant T. pallidum. From January 2000 through December 2004, molecular screening of 124 samples identified 46 azithromycin-resistant T. pallidum isolates and 72 wild-type T. pallidum isolates. Six instances of treatment failure were identified through record review. In total, we identified 52 case patients (one of whom had 2 episodes) and 72 control patients. All case patients were male and either gay or bisexual, and 31% (16 of 52) were infected with human immunodeficiency virus. Investigation of patient-partner links and a retrospective case-control study did not reveal a sexual network or demographic differences between cases and controls. However, 7 case patients had recently used azithromycin, compared with 1 control patient. Surveillance data demonstrated that azithromycin-resistant T. pallidum prevalence increased from 0% in 2000 to 56% in 2004 among syphilis cases observed at the San Francisco City Clinic. Azithromycin-resistant T. pallidum is widespread in San Francisco. We recommend against using azithromycin for the management of syphilis in communities where macrolide-resistant T. pallidum is present and recommend active surveillance for resistance in sites where azithromycin is used.