Molecular epidemiology and mechanisms of resistance of azithromycin-resistant Neisseria gonorrhoeae isolated in France during 2013-14.
The objective of this study was to determine the prevalence and mechanisms of azithromycin resistance of Neisseria gonorrhoeae French isolates from 2013 to 2014.



N. gonorrhoeae samples isolated in a network of laboratories were tested for susceptibility to azithromycin between April 2013 and March 2014. Fifty-four isolates that were non-susceptible to azithromycin and 18 susceptible isolates were characterized for molecular mechanisms of resistance by PCR/sequencing and genotyped using N. gonorrhoeae multiantigen sequence typing (NG-MAST).



Among the 970 N. gonorrhoeae isolates, 54 (5.56%) were non-susceptible to azithromycin, 9 (1%) were resistant and 45 (4.6%) showed intermediate resistance. Azithromycin-non-susceptible isolates harboured a C2599T mutation in the rrl gene encoding the 23S rRNA alleles (5.5%), a C substitution in the mtrR promoter (5.5%), an A deletion in the mtrR promoter (53.7%) and mutations in the L4 ribosomal protein (14.8%) and in the MtrR repressor (25.9%). No isolates showed an L22 mutation or carried an erm, ere, mef(A)/(E) or mphA gene. Thirty different STs were highlighted using the NG-MAST technique. The predominant genogroups non-susceptible to azithromycin were G21 (31%), G1407 (20%) and G2400 (15%). Genogroup G2400 (15%) was revealed to be a novel cluster prevalent in the south of France and resistant to azithromycin, ciprofloxacin and tetracycline.



Our study highlights that the prevalence of resistance of N. gonorrhoeae to azithromycin in France is low and essentially due to multiple genetic mutations. Its dissemination occurs through three major genogroups including a novel one in France (G2400).
APHP, Lariboisière-Fernand Widal Hospital, Laboratory of Bacteriology and Associated Laboratory for the National Reference Centre for Gonococci, F-75010 Paris, France Department of Tropical and Infectious Diseases, CHI, Villeneuve Saint Georges, France.
Anna
A
Belkacem
APHP, Lariboisière-Fernand Widal Hospital, Laboratory of Bacteriology and Associated Laboratory for the National Reference Centre for Gonococci, F-75010 Paris, France INSERM, IAME, UMR 1137, F-75018 Paris, France University Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
Hervé
H
Jacquier
Alfred Fournier Institute, National Reference Centre for Gonococci, F-75014 Paris, France.
Agathe
A
Goubard
APHP, Lariboisière-Fernand Widal Hospital, Laboratory of Bacteriology and Associated Laboratory for the National Reference Centre for Gonococci, F-75010 Paris, France INSERM, IAME, UMR 1137, F-75018 Paris, France University Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
Faiza
F
Mougari
French Institute for Public Health Surveillance (InVS), Department of Infectious Diseases, Saint-Maurice, France.
Guy
G
La Ruche
Department of Tropical and Infectious Diseases, CHI, Villeneuve Saint Georges, France.
Olivier
O
Patey
APHP, Lariboisière-Fernand Widal Hospital, Laboratory of Bacteriology and Associated Laboratory for the National Reference Centre for Gonococci, F-75010 Paris, France INSERM, IAME, UMR 1137, F-75018 Paris, France University Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
Maïté
M
Micaëlo
French Institute for Public Health Surveillance (InVS), Department of Infectious Diseases, Saint-Maurice, France.
Caroline
C
Semaille
APHP, Lariboisière-Fernand Widal Hospital, Laboratory of Bacteriology and Associated Laboratory for the National Reference Centre for Gonococci, F-75010 Paris, France INSERM, IAME, UMR 1137, F-75018 Paris, France University Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
Emmanuelle
E
Cambau
APHP, Lariboisière-Fernand Widal Hospital, Laboratory of Bacteriology and Associated Laboratory for the National Reference Centre for Gonococci, F-75010 Paris, France INSERM, IAME, UMR 1137, F-75018 Paris, France University Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France beatrice.bercot@aphp.fr.
Béatrice
B
Bercot
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D016000:Cluster Analysis; D024881:Drug Resistance, Bacterial; D005260:Female; D005602:France / Q000453:epidemiology; D005838:Genotype; D006069:Gonorrhea / Q000453:epidemiology* / Q000382:microbiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D015995:Prevalence; D017422:Sequence Analysis, DNA; D055815:Young Adult
D000900:Anti-Bacterial Agents; D017963:Azithromycin