Increasing resistance to azithromycin of Neisseria gonorrhoeae in eastern Chinese cities: mechanisms and genetic diversity of resistant Nanjing isolates [PublishAheadOfPrint]

Azithromycin resistance (AZM-R) of Neisseria gonorrhoeae is emerging as a clinical and public health challenge. We determined molecular characteristics of recent AZM-R Nanjing gonococcal isolates and tracked the emergence of AZM-R isolates in eastern Chinese cities in recent years. 384 N. gonorrhoeae isolates from Nanjing collected from 2013 to 2014 were tested for susceptibility to AZM and six additional antibiotics; all AZM-R strains were characterized genetically for resistance determinants by sequencing and were genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST). Among the 384 isolates, 124 (32.3%) were AZM-R. High-level resistance (MIC ≥ 256 mg/L) was present in 10.4% (40/384) of isolates, all of which possessed the A2143G mutation in all four 23S rRNA alleles. Low-to-mid resistance (MIC 1 to 64 mg/L) was present in 21.9% (84/384) of isolates, 59.5% of which possessed the C2599T mutation in all four 23S rRNA alleles. The 124 AZM-R isolates were distributed into 71 different NG-MAST STs. ST1866 was the most prevalent type in high-level AZM-R (HL-AZM-R) isolates (45% [18/40]). This study together with previous reports revealed that the prevalence of AZM-R in N. gonorrhoeae isolates in certain eastern Chinese cities has risen more than 4-fold (7% to 32%) from 2008 to 2014. The principle mechanisms of AZM resistance in recent Nanjing isolates were: A2143G mutations (high-level resistance) and C2599T mutations (low-to-mid resistance) in the 23S rRNA alleles. Characterization of NG-MAST STs and phylogenetic analysis indicated genetic diversity of N. gonorrhoeae in Nanjing; however, ST1866 was the dominant genotype associated with HL-AZM-R isolates.

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