Treatment failure with 2 g of azithromycin (extended-release formulation) in gonorrhoea in Japan caused by the international multidrug-resistant ST1407 strain of Neisseria gonorrhoeae.
OBJECTIVE
Antimicrobial resistance in Neisseria gonorrhoeae is a major public health concern globally. We report the first verified treatment failure of gonorrhoea with 2 g of azithromycin (extended-release formulation) in Japan and characteristics of the corresponding N. gonorrhoeae isolates.


METHODS
Pre- and post-treatment isolates (n = 4) were investigated by Etest for antimicrobial susceptibility. The isolates were examined for molecular epidemiology by multilocus sequence typing (MLST), N. gonorrhoeae multi-antigen sequence typing (NG-MAST) and multiple-locus variable-number tandem repeat analysis (MLVA), and for the presence of azithromycin resistance determinants (23S rRNA gene mutations, erm genes and mtrR mutations).


RESULTS
All isolates were resistant to azithromycin (MIC 4 mg/L) and ciprofloxacin, but remained susceptible to cefixime, ceftriaxone and spectinomycin. All isolates were assigned to MLST ST1901 and NG-MAST ST1407 and three of four isolates possessed MLVA profile 8-3-21-16-1. All isolates contained the previously described C2599T mutation (N. gonorrhoeae numbering) in all four 23S rRNA alleles and the previously described single-nucleotide (A) deletion in the mtrR promoter region.


CONCLUSIONS
This verified treatment failure occurred in a patient infected with an MLST ST1901/NG-MAST ST1407 strain of N. gonorrhoeae. While this international strain commonly shows resistance or decreased susceptibility to multiple antimicrobials, including extended-spectrum cephalosporins, the strain reported here remained fully susceptible to the latter antimicrobials. Hence, two subtypes of azithromycin-resistant gonococcal MLST ST1901/NG-MAST ST1407 appear to have evolved and to be circulating in Japan. Azithromycin should not be recommended as a single antimicrobial for first-line empirical treatment of gonorrhoea.
National Institute of Infectious Diseases, Tokyo, Japan.
Tomoko
T
Morita-Ishihara
WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
Magnus
M
Unemo
Sonezaki Furubayashi Clinic, Osaka, Japan.
Kei-Ichi
K
Furubayashi
Osaka Prefectural Institute of Public Health, Osaka, Japan.
Takuya
T
Kawahata
National Institute of Infectious Diseases, Tokyo, Japan.
Ken
K
Shimuta
National Institute of Infectious Diseases, Tokyo, Japan.
Shu-Ichi
S
Nakayama
National Institute of Infectious Diseases, Tokyo, Japan ohnishi7@nih.go.jp.
Makoto
M
Ohnishi
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017963:Azithromycin / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics*; D015373:Bacterial Typing Techniques; D020682:Cefixime / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005260:Female; D006069:Gonorrhea / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007564:Japan; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D011401:Promoter Regions, Genetic; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D000198:Spectinomycin / Q000494:pharmacology; D017211:Treatment Failure
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012338:RNA, Ribosomal, 23S; D012097:Repressor Proteins; C087450:mtrR protein, Neisseria gonorrhoeae; D002939:Ciprofloxacin; D002443:Ceftriaxone; D017963:Azithromycin; D000198:Spectinomycin; D020682:Cefixime
23S rRNA; N. gonorrhoeae; N. gonorrhoeae multi-antigen sequence typing; NG-MAST; antimicrobial resistance; test of cure