April 30, 2004
The 26 QRNG isolates in 2003 were obtained from 24 patients, of whom 22 were male and two were female partners of men identified with QRNG; seven (29%) were STD clinic patients. Of the 22 male QRNG patients, four (18%) reported having sex exclusively with women, one reported having sex with men and women, and 17 (77%) reported having sex exclusively with men. None of the patients with QRNG was identified as a result of treatment failure.
Medical records were reviewed for all 111 male gonorrhea patients who had diagnosis by culture at STD clinics in the state. Of these, seven (6.3%) had QRNG identified, with 11.1% (six of 54) QRNG prevalence among MSM and 1.8% (one of 55) among heterosexual men. A total of 14 female patients had gonorrhea diagnosed at STD clinics; none had QRNG.
Since 1987, the Massachusetts Department of Public Health has recommended use of ceftriaxone rather than fluoroquinolones for treatment of uncomplicated gonococcal infections. When local increases in QRNG were identified in late 2002, the health department issued a clinical advisory to health-care providers throughout the state, alerting them to the increase and advising that fluoroquinolones were not recommended for gonorrhea treatment unless antimicrobial susceptibility testing excluded fluoroquinolone resistance.** Beginning in June 2003, any health-care provider who reported a patient who had been treated with a fluoroquinolone was sent a notice recommending that a test of cure be performed unless susceptibility testing was performed initially to rule out QRNG.
Medical record reviews were performed at six of the STD clinics. During January-July 2003, a total of 394 gonococcal isolates from 369 patients at these six clinics were tested for antimicrobial susceptibility; QRNG was identified in 5% (18 of 369) of the patients. Seventeen (94%) of the 18 patients with QRNG were male, and 13 (77%) reported being MSM. QRNG prevalence among patients for whom sexual behavior was documented was 12.5% (14 of 112) among MSM, 1.6% (three of 183) among heterosexual men, and 2.4% (one of 42) among women.
Fourteen of the 17 patients with QRNG for whom gonorrhea treatment history was available had been treated with ceftriaxone. New York City STD clinic treatment protocols specify that gonorrhea be treated with ceftriaxone and that fluoroquinolones only be used if culture is performed so the patient can be recalled if QRNG is identified.
S. Ratelle, T. Bertrand and W. Dumas are with the Massachusetts Dept of Public Health. K. Macomber and D. Ganoczy are with the Michigan Dept of Community Health. J. Schillinger, S. Manning, J. Reddy and S. Blank are with the New York City Dept of Health and Mental Hygiene. S. Wang, H. Weinstock, J. Newhall, K. Workowski and S. Berman are with the Division of STD Prevention, National Center for HIV, STD, and TB Prevention, CDC.
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.4, 8 For those infections acquired where QRNG is not endemic, before determining treatment, clinicians should obtain travel histories from patients and information on the sex 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 at www.cdc.gov/std/gisp.
For patients with gonorrhea who are MSM or who provide a history suggesting acquisition of infection in an area with high QRNG prevalence, CDC recommends ceftriaxone 125 mg intramuscularly or cefixime 400 mg orally (not currently available in the United States9); 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.4, 10 If Chlamydia trachomatis is not ruled out, each regimen should be followed with either azithromycin 1.0 g orally (single dose) or doxycycline 100 mg orally twice daily for 7 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, Ltd. (Baltimore, Maryland) 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. CDC will provide additional information about the availability of cefixime and efficacy of other oral agents for treating gonorrhea as it becomes available (www.cdc.gov/std/treatment/cefixime.htm).
Clinicians must 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, antimicrobial susceptibility testing should be performed. Only culture of N. gonorrhoeae can be used to determine antimicrobial susceptibility. Health departments without the capacity to perform culture and antimicrobial susceptibility testing should develop those capabilities locally or partner with laboratories outside their jurisdictions. 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. Through their state and local health departments, clinicians and laboratorians should report treatment failures or resistant gonococcal isolates to CDC, telephone 404-639-2059.
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. Therefore, as part of effective gonorrhea-control programs, health departments should evaluate their current QRNG surveillance activities and consider plans to monitor for the presence of QRNG among heterosexual populations with gonorrhea. If prevalence increases nationally among heterosexuals, guidance from CDC will be forthcoming. Local and state treatment recommendations, technical information, surveillance data, references, and other links related to gonococcal resistance are available at www.cdc.gov/std/gisp.
* Defined by the National Committee on Clinical Laboratory Standards as N. gonorrhoeae resistant to ciprofloxacin (minimum inhibitory concentration [MIC] >1.0 µg/mL by agar dilution or disk diffusion zone size <27 mm) or ofloxacin (MIC >2.0 µg/mL or disk diffusion zone size <24 mm).