阿奇霉素耐药及头孢曲松低敏淋球菌基因分型与多态性研究

摘要

目的 分析广州地区阿奇霉素耐药及广谱头孢菌素低敏淋球菌基因分型和基因多态性特征.方法 检测阿奇霉素(AZM)和头孢曲松(CRO)最小抑菌浓度(MIC).检测AZM耐药(AZM-R)淋球菌23S rRNA、多重可传递耐药调节(mtrR)基因和青霉素结合蛋白2(PBP2)编码基因(penA)突变类型.采用淋球菌多抗原序列分型法(NG-MAST)检测菌株基因型.结果 共检测淋球菌485株,包括AZM-R菌株(MIC≥1 mg/L)77株(15.9%),其中AZM低度耐药(AZM-LLR,MIC=1 mg/L)菌株33株(6.8%)、AZM中度耐药(AZM-MLR,MIC≥2 mg/L)菌株44株(9.1%).AZM-MLR菌株中CRO低敏(MIC≥0.125 mg/L)菌株19株(占43.2%),构成比高于AZM-LLR菌株中的CRO低敏株(18.2%,P<0.05).各类菌株间23S rRNA、mtrR、penA基因突变或联合突变检出率比较差异无统计学意义(P>0.05).AZM-LLR与CRO低敏菌株,以及AZM-MLR与CRO低敏菌株间各类突变检出率比较差异无统计学意义(P>0.05).未检出A2059G突变及AZM高度耐药株(MIC≥256 mg/L).77株AZM-R菌株经NG-MAST检测,检出67株序列类型,其中30株有异常.多数序列类型表现为单一表型.结论 该地区出现的AZM耐药及CRO低敏淋球菌值得持续监测和进一步研究,以明确其耐药机制.%Objective To analyze the characteristics of genotyping and gene polymorphism of Neisseria gonorrhoeae(N.go) with azithromycin(AZM)-resistance(AZM-R) and decreased susceptibility to ceftriaxone(CROD).Methods The minimum inhibitory concentration(MIC) of AZM and CRO were determined.AZM-R isolates were detected for mutations in 23S rRNA,mtrR and penA genes.Genotypes were analyzed by using N.go multi-antigen sequence typing(NG-MAST).Results All total of 485 isolates of N.go were detected.77(15.9%) strains were AZM-R(MIC≥1 mg/L),including 33(6.8%) isolates of AZM low-level resistant(AZM-LLR,MIC=1 mg/L) strains and 44(9.1%) isolates of AZM middle-level resistant(AZM-MLR,MIC≥2 mg/L) strains.There were more CROD(MIC≥0.125 mg/L) strains in AZM-MLR isolates(43.2%),compared with those in AZM-LLR isolates(18.2%,P<0.05).The detected rates of 23S rRNA,mtrR,penA single or combined mutations were without significant differences between AZM-LLR isolates and AZM-MLR isolates(P>0.05).Similar results were found between combined AZM-LLR/CROD isolates and combined AZM-MLR/CROD isolates(P>0.05).No mutation of A2059G and AZM high-level resistant(AZM-HLR,MIC≥256 mg/L) isolate were found.Among 77 AZM-R isolates,67 sequence types(ST) were identified by NG-MAST,of which 30 types were novel.Most ST were represented by a single isolate.Conclusion AZM-R and CROD isolates,presented in this area,might be deserved continuous surveillance to identify the mechanism of concurrent resistance.