临床分离金黄色葡萄球菌对大环内酯类抗生素耐药性及耐药基因的分析  

Macrolide-resistant Phenotypes and Genotypes of Staphylococcus Aureus Isolated from Clinical Samples

作　　者：姚健[1,2] 邵雷[2] 刘鹏宇[2] 陈代杰[2] 张玉彬[1] 

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009 [2]中国医药工业研究总院上海医药工业研究院,创新药物与制药工艺国家重点实验室,上海201203

出　　处：《药物生物技术》2016年第4期291-295,共5页Pharmaceutical Biotechnology

基　　金：国家“重大新药创制”科技重大专项(No.2013ZX09301302,No.2014ZX09507009-025);上海市自然科学基金(No.16ZR1435400)

摘　　要：文章研究了上海华山医院临床分离的金黄色葡萄球菌菌株对大环内酯类抗生素的耐药性及耐药基因的分布情况。通过MIC法对临床标本分离的27株金黄色葡萄球菌对大环内酯类抗生素药敏性进行检测,并通过PCR扩增分析其中14株菌携带的大环内酯类抗生素耐药基因。结果表明27株金黄色葡萄球菌对4种大环内酯类抗生素:红霉素、螺旋霉素I、阿奇霉素和克拉霉素的耐药率分别为74.1%,48.1%,74.1%和74.1%;对林可酰胺类抗生素林可霉素的耐药率为77.8%;对酮内酯类抗生素泰立霉素的耐药率为77.8%。分析了其中14株临床菌的23rRNA序列保守碱基位点的突变和所携带的大环内酯类抗生素耐药基因情况。结果表明这14株临床菌的23rRNA序列保守碱基位点均没有发生突变。根据耐药基因PCR检测结果,发现这14种临床菌株中,有6株ermA阳性菌和和3株ermC阳性菌,但是并没有发现ermB的阳性菌株;ermA和ermC的检出率分别是42.86%和21.43%;耐药基因ermA存在于MRSA菌株中,其阳性率85.71%;而耐药基因ermC则出现在MSSA菌株中,其阳性率42.86%。另外,耐药基因msr A在14株临床分离菌株的检出率是92.86%,但没有发现它和大环内酯抗生素的药物敏感性存在相关性。27株临床分离菌株对除螺旋霉素I外的其它5种大环内酯-林可酰胺类抗生素耐药率均大于70%。耐药基因ermA和ermC是金黄色葡萄球耐药的主要原因。To investigate macrolide antibiotics sensitivity and distribution of related resistance gene of Staphylococcus aureus isolated from Shanghai Huashan Hospital clinical,the drug sensitivity of 27 strains Staphylococcus aureus isolated from Shanghai Huashan Hospital clinical specimens to macrolide antibiotics by MIC method were tested. The macrolide antibiotics related resistance gene of14 strains among them were detected by PCR. The resistance rate of Staphylococcus aureus specimens was 74. 1% for Erythromycin,Azithromycin and Clarithromycin; 48. 1% for Spiramycin; 77. 8% for Clindamycin and telithromycin. There is no mutation at specific adenine residue of 23 S rRNA,which produces macrolide resistance due to modification of the drug target. According to the result of PCR test it found ermA and ermC positive strains,but not a ermB positive strain. The detection rate of ermA and ermC was 42. 86%and 21. 43%,respectively. 85. 71% of MRSA isolates contain the gene ermA and 42. 86% of MSSA isolates contain the gene ermC.MRSA is often multi-drug resistant strain,which is macrolide antibiotics resistant due to the presence of ermA. While the probability MSSA carrying the gene ermC may be more random. In addition,detection rate of gene msr A in 14 clinical isolates is 92. 86%,but it isnot found that it has any correlation with drug sensitivity of macrolide antibiotics. The resistance rates of 27 clinical isolates to other5 macrolide-lincosamide antibiotics except spiramycin I were over 70%. The ermA and ermC maybe the main reason for macrolide antibiotic resisitance of Staphylococcus aureus in Hospital of Shanghai.

关 键 词：金黄色葡萄球菌 大环内酯类抗生素 耐药性 甲基化酶 23rRNA序列保守碱基位点 多药耐药外排泵 

分 类 号：R378.11[医药卫生—病原生物学]