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J Clin Microbiol. 2016 May;54(5):1304-13. doi: 10.1128/JCM.03195-15. Epub 2016 Mar 2.

Genomic Epidemiology and Molecular Resistance Mechanisms of Azithromycin-Resistant Neisseria gonorrhoeae in Canada from 1997 to 2014.

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Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
Science Technology Cores and Services Division, National Microbiology Laboratory, Public Health Agency of Canada, and Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Laboratoire de Santé Publique du Québec, Ste-Anne-de-Bellevue, Québec, Canada.
Public Health Ontario Laboratories, Toronto, Ontario, Canada.
British Columbia Centres for Disease Control Public Health Microbiology & Reference Laboratory, Vancouver, British Columbia, Canada.
Provincial Laboratory for Public Health, Edmonton, Alberta, Canada.
Saskatchewan Disease Control Laboratory, Regina, Saskatchewan, Canada.
Cadham Provincial Laboratory, Winnipeg, Manitoba, Canada.
Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, Ottawa, Ontario, Canada.
First Nations and Inuit Health Branch, Health Canada, Ottawa, Ontario, Canada.
Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada


The emergence of Neisseria gonorrhoeae strains with decreased susceptibility to cephalosporins and azithromycin (AZM) resistance (AZM(r)) represents a public health threat of untreatable gonorrhea infections. Genomic epidemiology through whole-genome sequencing was used to describe the emergence, dissemination, and spread of AZM(r) strains. The genomes of 213 AZM(r) and 23 AZM-susceptible N. gonorrhoeae isolates collected in Canada from 1989 to 2014 were sequenced. Core single nucleotide polymorphism (SNP) phylogenomic analysis resolved 246 isolates into 13 lineages. High-level AZM(r) (MICs ≥ 256 μg/ml) was found in 5 phylogenetically diverse isolates, all of which possessed the A2059G mutation (Escherichia coli numbering) in all four 23S rRNA alleles. One isolate with high-level AZM(r) collected in 2009 concurrently had decreased susceptibility to ceftriaxone (MIC = 0.125 μg/ml). An increase in the number of 23S rRNA alleles with the C2611T mutations (E. coli numbering) conferred low to moderate levels of AZM(r) (MICs = 2 to 4 and 8 to 32 μg/ml, respectively). Low-level AZM(r) was also associated with mtrR promoter mutations, including the -35A deletion and the presence of Neisseria meningitidis-like sequences. Geographic and temporal phylogenetic clustering indicates that emergent AZM(r) strains arise independently and can then rapidly expand clonally in a region through local sexual networks.

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