Ceftriaxone-Resistant Neisseria gonorrhoeae, Japan

To the Editor: Spread of multi-drug-resistant Neisseria gonorrhoeae is a major public health concern. Effective antimicrobial therapy is a key element in gonorrhea control. However , N. gonorrhoeae has developed resistance to multiple classes of anti-microbial drugs, including β-lactams, tetracyclines, and fl uoroquinolones (1–3). Even an extended-spectrum oral cephalosporin-resistant, cefi xime-resistant N. gonorrhoeae has emerged, and cefi xime has now been withdrawn from use in Japan. Best practice treatment is limited to injectable extended spectrum cephalosporins, such as ceftriaxone and spectinomycin. The emergence of ceftriaxone-resistant N. gonorrhoeae threatens effective disease control. We identifi ed a novel ceftriax-one-resistant N. gonorrhoeae isolated from a 31-year-old female commercial sex worker; MIC of ceftriaxone for this isolate was high (2 μg/mL). The woman visited a clinic in Kyoto for a routine examination for sexually transmitted infections in January 2009. Although she had no obvious symptoms or signs, a throat sample collected on her fi rst visit yielded a positive result for N. gonorrhoeae by the strand displacement amplifi cation test but a vagi-nal sample taken at the same time was negative. After 2 weeks, another throat sample was positive for N. gonorrhoe-ae when cultured on Thayer-Martin medium, and the patient subsequently received 1 g ceftriaxone intravenously. Her pharyngeal sample was also N. gonorrhoeae positive by strand displacement amplifi cation test on the third visit 2 weeks later, and further ceftriaxone treatment was prescribed. However, a culture for test of cure was not conducted because reinfection was considered. A negative result was finally obtained in April 2009. The culture showed positive reactions in oxidase and catalase tests. Gram staining showed gram-negative diplococci. The ID-test HN-20 Rapid system (Nissui, Tokyo, Japan) classi-fi ed the bacterium as N. gonorrhoeae. Susceptibility was determined by the agar dilution method (4). For this strain, named H041, MIC of ceftriaxone was high (2 μg/mL), and the strain was highly resistant to penicillin G (4 μg/ mL), cefi xime (8 μg/mL), and levofl ox-acin (32 μg/mL). However, it demonstrated susceptibility to spectinomycin (16 μg/mL) and reduced susceptibility to azithromycin (0.5 μg/mL). To characterize the ceftriaxone-resistant N. gonorrhoeae H041, mul-tilocus sequence typing characterized the strain as ST7363 (5), which is the predominant sequence type (ST) among cefi xime-resistant clones (6). N. gonorrhoea multiantigen sequence typing (NG-MAST) was also performed (7). The NG-MAST strategy uses 2 genes, por and tbpB, for porin and a transferrin-binding protein, respectively. NG-MAST indicated that the strain H041 was …