肺炎链球菌对抗菌药物的耐药性调查及对大环内酯类抗生素耐药机制研究

Antimicrobial resistance of Streptococcus pneumoniae and mechanisms of resis-tance to macrolides

目的 :调查成都地区肺炎链球菌对抗菌药物的敏感性 ,研究成都地区肺炎链球菌对大环内酯类抗生素耐药机制。方法 :收集 2 0 0 1年 9月— 2 0 0 2年 9月成都地区临床分离的肺炎链球菌 ,测定其对 13种抗菌药物的耐药性及对大环内酯类抗生素的耐药表型 ;用聚合酶链反应 (PCR)扩增耐药基因ermB和mefA ,并对ermB和mefA进行基因序列分析。 结果 :82株肺炎链球菌中 13株对青霉素低度耐药 (占 15 .9% ) ,肺炎链球菌对大环内酯类抗生素和克林霉素表现出较高的耐药率 ,对红霉素和克林霉素耐药率分别为 80 .5 % (6 6 / 82 )和 6 8.3% (5 6 / 82 )。耐大环内酯类肺炎链球菌中 ,96 .4 %菌株表现为内在型耐药。标准菌株ATCC4 96 19及 16株红霉素敏感菌株均未检测到ermB基因及mefA基因 ;ermB基因和mefA基因分别在 6 2和 11株耐红霉素肺炎链球菌中检测到 ,其中 7株菌同时检测到ermB基因和mefA基因。所测ermB和mefA基因序列与基因库收录序列高度一致。结论 :成都地区临床分离的肺炎链球菌对青霉素耐药率较低 ,但对大环内酯类抗生素和克林霉素耐药却非常普遍。ermB基因介导的靶位改变是成都地区肺炎链球菌对大环内酯类抗生素的主要耐药机制。

Objective: To investigate the antimicrobial susceptibility of Streptococcus pneumoniae isolated in Chengdu from September 2001 to September 2002 and their mechanisms of resistance to macrolide. Methods:Antimicrobial susceptibility of S. pneumoniae was determined by agar dilution method. Phenotypes of macrolide-resistant S. pneumoniae were determined using double disk test with erythromycin and clindamycin disks. ermB and mefA genes were amplified by PCR and sequenced. Results:Among 82 strains of S. pneumoniae, 15.9% were intermediate to and no strain was resistant to penicillin. The resistance rates to erythromycin and clindamycin were 80.5% and 68.3%, respectively. Of 66 erythromycin-resistant strains, 96.4% were constitutive resistant. ermB was detected in 62 strains and mefA in 11 strains, both ermB and mefA genes were found in 7 strains. DNA sequencing demonstrated that the sequences of ermB and mefA genes were identical to the sequences deposited in GenBank. Conclusions:The resistance rate of S. pneumoniae to penicillin is low in Chengdu area, but the resistance rates to erythromycin and clindamycin are very high. Target modification by ErmB methylase is the predominant mechanism in macrolide-resistant S. pneumoniae in Chengdu.