SEARCH

SEARCH BY CITATION

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.

image

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.

Download figure to PowerPoint

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

  1. Top of page
  2. Conflict of interest
  3. References

None declared.

References

  1. Top of page
  2. Conflict of interest
  3. References
  • 1
    Tanaka M, Nakayama H, Haraoka M et al. Antimicrobial resistance of Neisseria gonorrhoeae and high prevalence of ciprofloxacin-resistant isolates in Japan, 1993 to 1998. J. Clin. Microbiol. 2000; 38: 5215.
  • 2
    Tanaka M, Nakayama H, Tunoe H et al. A remarkable reduction in the susceptibility of Neisseria gonorrhoeae isolates to cephems and the selection of antibiotic regimens for the single-dose treatment of gonococcal infection in Japan. J. Infect. Chemother. 2002; 8: 816.
  • 3
    Tanaka M, Koga Y, Nakayama H et al. Antibiotic-resistant phenotypes and genotypes of Neisseria gonorrhoeae Isolates in Japan: identification of strain clusters with multidrug-resistant phenotypes. Sex. Transm. Dis. 2011; 38: 8715.
  • 4
    Eastick K. Gonococcal antibiotic surveillance in Scotland (GASS): prevalence, patterns and trends in 2009. HPS Wkly Rep. 2010; 44:33942. [Cited 30 Aug 2011.] Available from URL: http://www.documents.hps.scot.nhs.uk/ewr/pdf2010/1034.pdf
  • 5
    Golparian D, Hellmark B, Fredlund H et al. Emergence, spread and characteristics of Neisseria gonorrhoeae isolates with in vitro decreased susceptibility and resistance to extended-spectrum cephalosporins in Sweden. Sex. Transm. Infect. 2010; 86: 45460.
  • 6
    Florindo C, Pereira R, Boura M et al. Genotypes and antimicrobial-resistant phenotypes of Neisseria gonorrhoeae in Portugal (2004–2009). Sex. Transm. Infect. 2010; 86: 44953.
  • 7
    Tapsall JW, Ray S, Limnios A. Characteristics and population dynamics of mosaic penA allele-containing Neisseria gonorrhoeae isolates collected in Sydney, Australia, in 2007–2008. Antimicrob. Agents Chemother. 2010; 54: 5546.
  • 8
    Martin IM, Ison CA, Aanensen DM et al. Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J. Infect. Dis. 2004; 189: 1497505.
  • 9
    Unemo M, Golparian D, Hestner A. Ceftriaxone treatment failure of pharyngeal gonorrhoea verified by international recommendations, Sweden, July 2010. Euro. Surveill. 2011; 16: pii: 19792. [Cited 30 Aug 2011.] Available from URL: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19792.
  • 10
    Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. Gonococcal Infections. MMWR Morb. Mortal. Wkly Rep. 2010; 59 (No. RR-12): 4955.