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J Antimicrob Chemother. 2014 Aug;69(8):2086-90. doi: 10.1093/jac/dku118. Epub 2014 Apr 28.

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.

Author information

1
National Institute of Infectious Diseases, Tokyo, Japan.
2
WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
3
Sonezaki Furubayashi Clinic, Osaka, Japan.
4
Osaka Prefectural Institute of Public Health, Osaka, Japan.
5
National Institute of Infectious Diseases, Tokyo, Japan ohnishi7@nih.go.jp.

Abstract

OBJECTIVES:

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.

KEYWORDS:

23S rRNA; N. gonorrhoeae; N. gonorrhoeae multi-antigen sequence typing; NG-MAST; antimicrobial resistance; test of cure

PMID:
24777907
DOI:
10.1093/jac/dku118
[Indexed for MEDLINE]

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