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目的测定大环内酯类药物对肺炎链球菌的防耐药突变浓度(mutant prevention concentration,MPC),扩增突变选择窗(mutant selection window,MSW)内筛选的耐药突变体的耐药基因,以了解肺炎链球菌对大环内酯类药物耐药的发生机制。方法肉汤法富集1010CFU/ml ATCC49619,采用平板二倍稀释法测定罗红霉素和阿奇霉素对ATCC49619的最低抑菌浓度(minimal inhibitory concentration,MIC)、MIC99、初测MPC(Provisional MPC,MPCpr)以及MPC。PCR法扩增不同药物筛选出的耐药突变株的耐药基因ermB和mefA并测序。结果罗红霉素和阿奇霉素对ATCC49619的MPC分别为0.80μg/ml和0.51μg/ml,细菌耐药选择指数(MPC/MIC99)为5.0和3.9。筛选出的耐药突变株中扩增出ermB耐药基因。结论通过调整药物剂量,可以限制对大环内酯类耐药的肺炎链球菌突变体的富集。肺炎链球菌对大环内酯类药物耐药机制可能与携带ermB基因有关。
OBJECTIVE: To determine the effect of macrolides on the susceptibility of Streptococcus pneumoniae to multidrug resistance (MPC), multidrug resistant (MDR) mutants in the mutant selection window (MSW) To understand the Streptococcus pneumoniae macrolide drug resistance mechanism. Methods The minimal inhibitory concentration (MIC), MIC99, MPC (Provisional MPC) and MPCpr of ATCC49619 and roxithromycin (ATCC49619) were determined by two-fold plate dilution method with 1010CFU / ml ATCC49619. . The resistance genes ermB and mefA of drug-resistant mutant strains screened by different drugs were amplified by PCR and sequenced. Results The MPC of roxithromycin and azithromycin against ATCC49619 were 0.80μg / ml and 0.51μg / ml, respectively. The MPC / MIC99 was 5.0 and 3.9, respectively. The selected drug-resistant mutant strains amplified ermB resistance gene. Conclusions Enrichment of macrolide-resistant Streptococcus pneumoniae mutants can be limited by adjusting the dose of the drug. Streptococcus pneumoniae macrolide resistance mechanisms may be related to carrying ermB gene.