Antimicrobial Resistance and Molecular Typing of Neisseria gonorrhoeae Isolates in Kyoto and Osaka, Japan, 2010 to 2012: Intensified Surveillance after Identification of the First Strain (H041) with High-Level Ceftriaxone Resistance

Abstract

In 2009, the first high-level ceftriaxone-resistant Neisseria gonorrhoeae strain (H041) was isolated in Kyoto, Japan. The present study describes an intensified surveillance (antimicrobial resistance and molecular typing) of Neisseria gonorrhoeae isolates in Kyoto and its neighboring prefecture Osaka, Japan, in 2010 to 2012, which was initiated after the identification of H041. From April 2010 to March 2012, 193 N. gonorrhoeae isolates were collected and the MICs (g/ml) to six antimicrobials, including ceftriaxone, were determined. All isolates showed susceptibility to ceftriaxone and cefixime (MIC values, <0.5 g/ml), and spectinomycin. The rates of resistance (intermediate susceptibility) to azithromycin, penicillin G, and ciprofloxacin were 3.6% (19.7%), 24.4% (71.0%), and 78.2% (0.5%), respectively. Multilocus sequence typing (MLST) showed that 40.9%, 19.2%, and 17.1% of isolates belonged to ST1901, ST7359, and ST7363, respectively. Furthermore, N. gonorrhoeae multiantigen sequence typing (NG-MAST) revealed that 12 (63%) of the 19 isolates with decreased susceptibility to ceftriaxone (MIC > 0.064 g/ml) were of ST1407. NG-MAST ST1407 was also the most prevalent ST (16.1%; 31 of 193 isolates). In those NG-MAST ST1407 strains, several mosaic type penA alleles were found, including SF-A type (penicillin binding protein 2 allele XXXIV) and its derivatives. These were confirmed using transformation of the penA mosaic alleles as critical determinants for enhanced cefixime and ceftriaxone MICs. The intensified surveillance in Kyoto and Osaka, Japan, did not identify any dissemination of the highlevel ceftriaxone-resistant N. gonorrhoeae strain H041, suggesting that H041 might have caused only a sporadic case and has not spread further.

Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics

“…Cu(gtsm) showed robust activity against several antibiotic-resistant isolates of N. gonorrhoeae (Table 3), including the MDR strains F89 (29) and H041 (30), which are resistant to ␤-lactams (except carbapenems), fluoroquinolones, macrolides, tetracycline, chloramphenicol, trimethoprim-sulfamethoxazole, chloramphenicol, and nitrofurantoin. The MICs for these isolates were comparable to that for the drug-susceptible strain 1291 ( Table 3), suggesting that the antibacterial activity of Cu(gtsm) was not diminished by enzymes and transporters that confer resistance to other antibiotics.…”

Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates with Decreased Cephalosporin Susceptibility Collected in Canada between 1989 and 2013

“…The penA mosaic XXXIV allele was first reported in the United States in 2008 (52)(53)(54)(55) and has spread worldwide. In 2009, an isolate was identified in Japan (H041) with a novel penA mosaic allele, NG-MAST type ST4220, and CRO and CFM MICs of 2 and 8 g/ml, respectively (9).…”

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

“…Since ceftriaxone is the last option for first-line empirical monotherapy of gonorrhea, the emergence of XDR gonococci might initiate an era of gonorrhea that is untreatable using antimicrobial monotherapy. Fortunately for now, however, based on the intensified surveillance undertaken in Kyoto and Osaka (2010 to 2012) after identification of the first XDR strain (H041), this strain has not spread further within the local community (162), which might indicate a lowered biological fitness.…”