Emergence of multidrug-resistant Neisseria gonorrhoeae strains circulating worldwide


Masatoshi Tanaka M.D., Ph.D., Department of Urology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. Email: matanaka@cis.fukuoka-u.ac.jp

Neisseria gonorrhoeae is a common organism, which causes sexually transmitted infections. It has been rapidly acquiring resistance to a variety of antibiotics, such as penicillin, tetracycline, ciprofloxacin and oral cephalosporin, in Japan.1,2 To select an adequate antibiotic for the management of gonococcal infection, it is important to trace the spread of antibiotic-resistant N. gonorrhoeae by using strain characterization methods, such as auxotyping, serovar and antibiogram. By using these conventional strain-characterization methods, it was found that gonococcal isolates resistant to antibiotics seemed to be transmitted in a relatively narrow domestic region in Japan through sexual intercourse with female commercial sex workers. However, current investigations using molecular typing methods, of which the discriminatory power is stronger than conventional techniques, have shown that antibiotic-resistant gonococcal strains are circulating worldwide.3–7N. gonorrhoeae multi-antigen sequence typing (NG-MAST) is one of the most advantageous methods, because it generates a simple numerical sequence type (ST) based on the combined sequences of the por and tbpB genes.8

We carried out NG-MAST on 239 gonococcal isolates in Fukuoka, Japan, in 2008.3 The most prevalent ST were ST2958 (20.5%), followed by ST4018 (7.5%), ST1407 (6.7%) and ST4487 (5.9%) (Fig. 1). Antibiotic susceptibility tests showed that ST2958 and ST1407 were characterized by a multidrug-resistant phenotype, whereas ST4018 and ST4487 presented a susceptible phenotype. The resistance rates in the ST2958 strains for penicillin (minimum inhibitory concentration [MIC] ≥ 2 mg/L), tetracycline (MIC ≥ 2 mg/L) and ciprofloxacin (MIC ≥ 1 mg/L) were 28.6%, 40.8% and 98.0%, respectively. The rates of decreased susceptibility of the ST2958 strains to ceftriaxone (MIC ranging from 0.06 to 0.5 mg/L) and cefixime (MIC ranging from 0.06 to 0.5 mg/L) were 22.4% and 85.7%, respectively. The ST1407 strains showed a very similar antibiogram of a multidrug-resistant phenotype to the ST2958 strains.

Figure 1.

The distribution of Neiserria gonorrhoeae multi-antigen sequence typing (NG-MAST) sequence types of N. gonorrhoeae isolates (n = 239). The others were represented by 1 or 2 isolates each.

Interestingly, ST1407 was first identified in Scotland in 2007 and accounted for 15.4% of all typed isolates in Scotland in 2009.4 Furthermore, ST1407 was recently identified as one of the frequent isolates in several countries including Sweden,5 Portugal6 and Australia,7 and it showed a multidrug-resistant phenotype. The strains belonging to ST1407 in other countries and those in Japan have very similar phenotypes with regard to resistance to multiple antibiotics. These data suggest that ST1407 is circulating worldwide.

ST2958, which also has a multidrug-resistant phenotype, was the most prevalent strain in Fukuoka, Japan, but has not been found elsewhere so far. Therefore, ST2958 might be an original strain in Japan. In 2010, one gonococcal strain of ST2958 was isolated from a pharyngeal infection in a man in Sweden, and it showed resistance to a single dose of 250 mg ceftriaxone.9 Four days earlier, the man had had protected vaginal intercourse and unprotected oral sex with a casual female partner in Japan. The ST2958 strain isolated in Sweden also showed a multidrug resistance phenotype (ceftriaxone MIC 0.125 or 0.25 mg/L, cefixime MIC 0.5 mg/L, ampicillin MIC 2 mg/L, ciprofloxacin MIC > 32 mg/L). These data provide a warning of the potential future dissemination of the multidrug-resistant N. gonorrhoeae strains of ST1407 and ST2958 into other regions beyond the limited areas.

According to the Centers for Disease Control and Prevention (CDC) guideline10 for uncomplicated gonococcal infections in the genitourinary tract and pharynx, a 250-mg dose of ceftriaxone is now used as a first-line regimen in many countries. However, I would like to strongly recommend a high 1000 mg dose of ceftriaxone, which is a first-line regimen in the Japanese guideline, owing to the increasingly wide geographic dissemination of multidrug-resistant N. gonorrhoeae strains with decreased susceptibility to cephalosporins in vitro3–7 and a case report of treatment failure of ceftriaxone 250 mg against pharyngeal infection.9

Conflict of interest

None declared.