Increasing Resistance to Azithromycin in Neisseria gonorrhoeae in Eastern Chinese Cities: Resistance Mechanisms and Genetic Diversity among Isolates from Nanjing.

Chuan Wan,Yang Li,Xiao-Hong Su,Sai Li,Peter A Rice,Bao-Xi Wang,Wen-Jing Le,Yu-Rong Liu

doi:10.1128/aac.02499-17

Abstract

ABSTRACTAzithromycin 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. A total of 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 multiantigen sequence typing (NG-MAST). Among the 384 isolates, 124 (32.3%) were AZM-R. High-level resistance (MIC, ≥256 mg/liter) 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-level resistance (MIC, 1 to 64 mg/liter) 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 in 71 different NG-MAST sequence types (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 >4-fold (7% to 32%) from 2008 to 2014. The principal mechanisms of AZM resistance in recent Nanjing isolates were A2143G mutations (high-level resistance) and C2599T mutations (low- to mid-level resistance) in the 23S rRNA alleles. Characterization of NG-MAST STs and phylogenetic analysis indicated the genetic diversity of N. gonorrhoeae in Nanjing; however, ST1866 was the dominant genotype associated with HL-AZM-R isolates.

Highlights

Azithromycin resistance (AZM-R) of Neisseria gonorrhoeae is emerging as a clinical and public health challenge
AZM is widely used in China to treat C. trachomatis infection, but it is not recommended for use as monotherapy to treat gonorrhea
Our results indicate that the prevalence of AZM-R N. gonorrhoeae in Nanjing has risen Ͼ4-fold, from 6.8% to 32.3%, in the 7-year period between 2008 and 2009 [33] to 2013–2014, exceeding the national average by ϳ1 3/4-fold in the latter period [36]

Summary

Introduction

Azithromycin resistance (AZM-R) of Neisseria gonorrhoeae is emerging as a clinical and public health challenge. High-level resistance (MIC, Ն256 mg/liter) 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-level resistance (MIC, 1 to 64 mg/liter) was present in 21.9% (84/384) of isolates, 59.5% of which possessed the C2599T mutation in all four 23S rRNA alleles. The emergence of decreased susceptibility or frank resistance of N. gonorrhoeae to ceftriaxone [3,4,5] (the last available agent used for first-line empirical monotherapy) has resulted in public health recommendations from Australia, Canada, Europe and the United States to use dual antimicrobial therapy consisting of a single dose of ceftriaxone (250 mg or 500 mg intramuscularly) and. The sporadic development of high-level AZM resistance (HL-AZM-R) [15,16,17,18,19,20,21,22] and numerous clinical failures [23,24,25,26,27] in many countries are of great concern and threaten the long-term efficacy of the currently recommended regimen

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Conclusion