P3.244 Genetic characteristics and molecular mechanisms of resistance of azithromycin-resistantneisseria gonorrhoeaeisolated in shenzhen, china during 2011–2015

Abstract

Introduction Most current guidelines now recommend Azithromycin (AZM) as a component of dual therapy for gonorrhoea in combination with third-generation cephalosporins. Here we investigated the prevalence, molecular mechanisms and genetic characteristics of azithromycin-resistant(AZM-R) N.gonorrhoeae isolates in Shenzhen area from 2011 to 2015. Methods A total of 788 N. gonorrhoeae isolates were collected.The agar dilution method and E-test were used to determine the minimum inhibitory concentration (MIC) of these strains to AZM. All AZM-R isolates(MIC ≥2 µg/ml) were screened for mutations in 23S rRNA, mtrR and erm genes and genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST). Results 50 (6.3%) AZM-R isolates were collected, including 21 with azithromycin high-level resistant (AZM-HLR, MIC ≥256 µg/ml) and 29 with azithromycin middle-level resistant (AZM-MLR, MIC between 2 to 16 µg/ml). There were 18 strains had mutations (A2143G) and 12 strains had mutations (C2611T) in the four copies of the 23S rRNA gene in the AZ-HLR and AZ-MLR group respectively. Analysis of the promoter and coding region of mtrR gene, significantly more AZM-HLR exhibited one pattern contained G45D and Y105H mutations compared with the AZM-MLR and AZ-S.Only one strains with positive PCR detection of ermB gene(MIC=2 µg/ml). Among all the isolates, 81 sequence types (STs) were identified by NG-MAST, of which 8 STs were more often in the AZ-R group. Some STs (ST3356 and ST1866) that were observed had been noted in a previous reports of emerging AZM-R N. gonorrhoeae in Nanjing, Chongqing and Guangzhou. No resistant strains cluster was observed by NJ phylogenetic tree. Conclusion AZM should not be recommended as a monotherapy for gonococcal in Shenzhen. The high–level and middle-level resistance to AZM in N. gonorrhoeae were mainly mediated by specific mutations A2059G and C2611T in 23S rRNA respectively. Repeated emergence of ST1866 and ST3356 may help us to better monitor and analyse the epidemiological characteristics of AZM-R N. gonorrhoeae strains. Support: Shenzhen Centre For Chronic Disease Control has been responsible for antimicrobial resistance surveillance program of N. gonorrhoeae in Shenzhen since 1992.