Increases in Fluoroquinolone-Resistant Neisseria Gonorrhoeae

The Centers for Disease Control and Prevention (CDC) has released revised recommendations for gonorrhea treatment based on an increase in fluoroquinolone-resistant Neisseria gonorrhoeae . “Increases in Fluoroquinolone-Resistant Neisseria gonorrhoeae Among Men Who Have Sex with Men—United States, 2003, and Revised Recommendations for Gonorrhea Treatment, 2004” appears in the April 30, 2004, issue of Morbidity and Mortality Weekly Report and is available online at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5316a1.htm.

In the United States, an estimated 700,000 to 800,000 persons are infected with N. gonorrhoeae annually. Since 1993, the CDC has recommended use of fluoroquinolones (i.e., ciprofloxacin, ofloxacin, or levofloxacin) for gonorrhea treatment. Fluoroquinolones are used frequently to treat gonorrhea in the United States because they are inexpensive and easy to administer and their continued use might decrease the use of cephalosporins and delay the development of cephalosporin resistance.

However, local and national data suggest that the prevalence of fluoroquinolone-resistant N. gonorrhoeae (QRNG) among men who have sex with men infected with gonorrhea is close to or exceeds 5 percent. While this level of resistance often is used as the level at which a therapeutic regimen should be changed, other factors, including prevalence of gonorrhea, availability of antimicrobial susceptibility data, and cost of various diagnostic and treatment options, might result in higher or lower thresholds for change. In the absence of anti-microbial susceptibility testing or tests of cure, fluoroquinolones should no longer be used to treat proven or suspected gonococcal infections in men who have sex with men.

Fluoroquinolones also should not be used to treat patients whose gonorrhea was acquired in Asia, the Pacific Islands (including Hawaii), California, and other areas, such as England and Wales, with increased QRNG prevalence. For those infections acquired where QRNG is not endemic, before determining treatment, physicians should obtain travel histories from patients and information on the gender of sex partners from male patients with proven or suspected gonorrhea. A list of places that should be included in a relevant travel history is available online at http://www.cdc.gov/std/gisp.

For male patients with gonorrhea who have sex with men or who provide a history suggesting acquisition of infection in an area with high QRNG prevalence, the CDC recommends ceftriaxone, 125 mg intramuscularly, or cefixime, 400 mg orally (which is not available in the United States); spectinomycin, 2 g intramuscularly, is an alternative. Spectinomycin may be used for urogenital and anorectal gonorrhea but is not sufficiently effective to treat pharyngeal gonorrhea. If Chlamydia trachomatis is not ruled out, each regimen should be followed with either azithromycin, 1 g orally (single dose), or doxycycline, 100 mg orally twice daily for seven days, to treat possible co-infection with chlamydia.

The limited availability of a recommended oral treatment regimen for gonorrhea poses practical problems for treating QRNG. Besides the fluoroquinolones, cefixime, whose manufacture was discontinued in 2002, is the only CDC-recommended oral agent for treating gonorrhea. Although Lupin received Food and Drug Administration approval to manufacture and market cefixime in February 2004, the 400-mg tablets to treat gonorrhea are not yet available; the suspension (100 mg/5 mL) is available. The health departments of California and Washington state have suggested alternative oral treatments (e.g., cefpodoxime, 400 mg) that have not yet been evaluated adequately. The CDC will provide additional information about the availability of cefixime and efficacy of other oral agents for treating gonorrhea as it becomes available (http://www.cdc.gov/std/treatment/cefixime.htm).

The CDC advises physicians to be vigilant in identifying treatment failures when fluoroquinolones are used, advise their patients about the importance of follow-up if symptoms persist, and be prepared to evaluate such cases by culture. In cases of persistent gonococcal infection after treatment with fluoroquinolones, anti-microbial susceptibility testing should be performed. Only culture of N. gonorrhoeae can be used to determine antimicrobial susceptibility. The antimicrobial susceptibility testing panel should, at a minimum, include a fluoroquinolone, ceftriaxone, spectinomycin, azithromycin, and any other drugs in local use for gonorrhea treatment. Arrangements for antimicrobial susceptibility testing can be made by contacting state and local health departments.

Given the apparent low prevalence of QRNG among heterosexuals, a national change in treatment in that group is not recommended at this time. However, QRNG prevalence among heterosexuals is likely to increase over time and already might be high enough in some areas to warrant new local treatment recommendations. For example, increased prevalence of QRNG among heterosexuals has been identified in several counties in Michigan, where recommendations have been made to avoid using fluoroquinolones among all persons infected with gonorrhea. Because gonococcal infections, especially in women, frequently are asymptomatic, monitoring for symptomatic treatment failures alone does not provide a reliable indication of emerging antimicrobial resistance. If prevalence increases nationally among heterosexuals, guidance from the CDC will be forthcoming. Local and state treatment recommendations, technical information, surveillance data, references, and other links related to gonococcal resistance are available at http://www.cdc.gov/std/gisp.