Kimberly A. Workowski, MD; Stuart M. Berman, MD, ScM; John M. Douglas, MD
Prevention and control of gonorrhea is an important public health concern due to the high burden of disease, the recent increase in reported infection rates, and the reproductive and economic consequences of infection. Effective antibiotic treatment is one essential component of an integrated approach to gonorrhea control. Over the past 60 years, however, development of resistance in Neisseria gonorrhoeae to multiple antimicrobial classes challenges this component of gonorrhea control. An integrated, comprehensive prevention strategy should include enhancement of national and international surveillance systems to monitor antimicrobial resistance and new strategies to maximize the benefit and prolong the utility of antimicrobials, including combination regimens, implementation of screening recommendations for individuals at high risk for infection, and the assurance of prompt and effective treatment for infected persons and their sexual partners. Progress in controlling the epidemic and avoiding a resurgence as treatment options wane will require careful attention to all components of a comprehensive prevention strategy.
QRNG = quinolone-resistant Neisseria gonorrhoeae; MSM = men who have sex with men.
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Department of Urology, Graduate School of Medicine, Gifu University
May 11, 2008
Emerging Antimicrobial Resistance in Neisseria gonorrhoeae
Workowski and colleagues report the emerging antimicrobial resistance in Neisseria gonorrhoeae and the urgent need of an integrated, comprehensive approach to control gonorrhea (1). In particular, we agree with them in the importance of enhancement of national and international surveillance systems to monitor antimicrobial resistance. In Japan, nationwide surveillance of antimicrobial resistance of N. gonorrhoeae has not been conduced, and high priority has not been placed on funding for such surveillance. Antimicrobial resistance of N. gonorrhoeae has not been controlled in an efficient or timely manner to prolong the efficacy of existing antibiotics. As a consequence, effective oral regimens for treatment of gonorrhea have been lost.
In Japan, treatment failures with fluoroquinolones were first reported in 1994. Since the late 1990s, there has been an increase in clinical strains with decreased susceptibility to fluoroquinolones (2). In 1999, fluoroquinolones were excluded from recommendations and guidelines for treatment of gonococcal infections. As alternatives to fluoroquinolones, oral cephalosporins were commonly used. Since 2001, however, a decrease in susceptibility of clinical strains to them has also been observed (2). Such strains have a mosaic penicillin-binding protein 2 (PBP 2) composed of fragments of PBP 2 from Neisseria cinerea and Neisseria perflava (3). This mosaic PBP 2 is significantly associated with decreased susceptibility to oral cephalosporins. The emergence and spread of such strains forced exclusion of cefixime from the 2006 recommendations and guidelines. In Japan, a single oral 1-g dose of azithromycin is used for treatment of non-gonococcal urethritis but is not registered for treatment of gonorrhea. However, decreased susceptibility of clinical strains to azithromycin has been observed (4). Higher doses of azithromycin are not and will not be recommended. No longer are there oral regimens for treatment of gonorrhea in Japan. For spectinomycin and ceftriaxone, resistance is rare. Strains with the mosaic PBP 2 are still sensitive to ceftriaxone. Ceftriaxone is also effective against gonococcal pharyngeal infection. In Japan, therefore, ceftriaxone is the only agent recommended as the first-choice treatment for gonococcal infections.
In conclusion, global spread of N. gonorrhoeae strains against which oral regimens are not effective is a matter of serious concern, and emergence of N. gonorrhoeae strains with resistance to injectable agents is disastrous. As Workowski and colleagues describe (1), ideally, a coherent global surveillance system, which can generate the high-quality data on which decisions for treatment change are based, rather than regional surveillances in isolation, should be established before the disease becomes untreatable.
Takashi Deguchi, MD and Mitsuru Yasuda, MD Graduate School of Medicine, Gifu University Gifu, Japan Shin-ichi Maeda, MD Toyota Memorial Hospital, Toyota, Japan.
Potential Financial Conflicts of Interest: None disclosed.
1. Workowski KA, Berman SM, Douglas JM. Emerging antimicrobial resistance in Neisseria gonorrhoeae: urgent need to strengthen prevention strategies. Ann Intern Med. 2008;148:606-13. [PMID: 18413622]
2. Ito M, Yasuda M, Yokoi S, Ito S-I, Takahashi Y, Ishihara S, et al. Remarkable increase in Central Japan in 2001-2002 of Neisseria gonorrhoeae isolates with decreased susceptibility to penicillin, tetracycline, oral cephalosporins, and fluoroquinolones. Antimicrob Agents Chemother. 2004;48:3185-7. [PMID: 15273147]
3. Ito M, Deguchi T, Mizutani K-S, Yasuda M, Yokoi S, Ito S-I, et al. Emergence and spread of Neisseria gonorrhoeae clinical isolates harboring mosaic-like structure of penicillin-binding protein 2 in central Japan. Antimicrob Agents Chemother. 2005;49:137-43. [PMID: 15616287]
4. Yasuda M, Hagiwara N, Ishihara S, Maeda S, Deguchi T. Remarkable increase of Neisseria gonorrhoeae with decreased susceptibility to cefixime and azithromycin. [Abstract]. Presented in the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, California 27 September-30, 2006: Abstract L2-1230.
Workowski KA, Berman SM, Douglas JM. Emerging Antimicrobial Resistance in Neisseria gonorrhoeae: Urgent Need to Strengthen Prevention Strategies. Ann Intern Med. 2008;148:606-613. doi: 10.7326/0003-4819-148-8-200804150-00005
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Published: Ann Intern Med. 2008;148(8):606-613.
Infectious Disease, Sexually Transmitted Infections.
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