氟喹诺酮药物浓度对金黄色葡萄球菌耐药突变株选择的影响  

Effect of fluoroquinolone concentration on the selection of resistant mutants of Staphylococcus aureus

作　　者：崔俊昌[1] 刘又宁[1] 王睿[2] 梁蓓蓓[2] 

机构地区：[1]解放军总医院呼吸科,北京100853 [2]解放军总医院临床药理研究室,北京100853

出　　处：《中国感染与化疗杂志》2006年第5期309-312,共4页Chinese Journal of Infection and Chemotherapy

基　　金：国家自然科学基金资助项目(30370615)。

摘　　要：目的了解氟喹诺酮药物浓度对金葡菌耐药突变株选择的影响。方法将金葡菌ATCC 25923接种于不同浓度环丙沙星及加替沙星琼脂平皿上,根据不同药物浓度平皿上生长的菌落数．计算菌落生长比例。对不同药物浓度筛选出的耐药突变株进行编码拓扑异构酶ⅣC亚单位基因par C(grl A)和促旋酶A亚单位基因gyr A喹诺酮耐药决定区的PCR扩增和测序,并测定外排泵抑制剂利血平对环丙沙星和加替沙星MIC的影响。结果药物浓度对平皿中生长的菌落数有明显影响。环丙沙星在低、中浓度主要选择出主动外排泵介导的非靶位耐药突变株,高浓度选择出Grl A变异的耐药突变株,以Ser-80→Phe为主。加替沙星低浓度选择出非靶位及靶位变异菌株,而中、高浓度均选择出Grl A变异株,也以Ser-80→Phe为主。结论氟喹诺酮药物浓度对金葡菌耐药突变株菌落数以及耐药位点的选择都有明显影响。Objective To study the effect of fluoroquinolone concentration on the selection of resistant mutants of S. aureus. Methods The S. aureus strain ATCC 25923 was enriched in broth and the cells were plated on Mueller-Hinton agar plates containing ciprofloxacin or gatifloxacin. Colonies on each plate were counted and the recovery of input cells was calculated. Quinolone resistance-determining region （QRDR） mutations of parC （grlA） and gyrA of resistant mutants were identified by PCR amplification and gene sequencing. The effect of efflux-pump inhibitor reserpine on MICs of gatifloxacin and ciprofloxacin for resistant mutants was determined by agar dilution method. Results Fluoroquinolone concentration had strong influence on the recovery of resistant colonies and the selection of resistant allele. The colonies selected at low and medium concentration of ciprofloxacin were largely non-target mutants,and at high concentration, Ser-80→Phe GrlA mutants dominated. Non-target and GrlA mutants were selected by gatifloxacin at low concentration, and Ser-80→Phe GrlA mutants were selected mainly at medium and high concentration. Conclusions Fluoroquinolone concentration has strong influence on the recovery of resistant colonies and the resistant allele selection. In clinical practice, the selection of resistant mutants could be prevented by choosing higher drug doses that one can tolerate.

关 键 词：氟喹诺酮 金黄色葡萄球菌 耐药 防耐药变异浓度 

分 类 号：R96[医药卫生—药理学]