耐利福平金黄色葡萄球菌突变株体内选择的临床研究

Clinical studies on the selective enrichment of rifampicin-resistant S.aureus mutants in vivo

目的对耐药突变选择窗(MSW)和金黄色葡萄球菌耐药突变株体内选择的关系进行初步研究。方法选择前鼻腔携带金黄色葡萄球菌的结核患者为实验组,观察含利福平(RFP)联合化疗方案治疗前及治疗2、4、5周后金黄色葡萄球菌对RFP敏感性的变化,对获得性RFP耐药患者治疗前后分离的菌株进行分子分型。以前鼻腔携带金黄色葡萄球菌的糖尿病患者为对照组。结果实验组58例患者治疗后有5例前鼻腔携带的金黄色葡萄球菌获得RFP耐药,脉冲场凝胶电泳和蛋白A分子分型结果表明这5例患者携带的菌株不同,但同一患者治疗前后分离的菌株同源。对照组39例患者中无耐药菌株出现。结论耐利福平的金黄色葡萄球菌突变株的选择性富集是在MSW内完成的。

Objective To study the correlation between mutant selection window （MSW） and selective enrichment of Staphylococcus aureus resistant mutants in vivo. Methods Tuberculosis patients colonized with S. aureus in anterior nares were selected as experimental group. The susceptibility of S. aureus to rifampicin was determined at the beginning of and 2,4 and 5 weeks after the anti-tuberculosis therapy with rifarnpicin-contalning regimens. S. aureus isolates developing acquired resistance were examined by molecular strain typing. Diabetes patients colonized with S. aureus served as an untreated control. Results The S. aureus isolated from 5 patients acquired rifampiein resistance in 58 tuberculosis patients. It was determined by pulsed-field gel electrophoresis and protein A repeat sequence the strains of S. aureus were different, but the isolates obtained from the same patient before and after acquisition of resistance were the same strains. No resistance was acquired in 39 untreated control patients, which differed statistically from treated patients. Conclusion The selective enrichrnent of rifampicirrresistant S. aureus mutants occurred when rifampicin concentration was in the mutant selection window.