摘要目的 探讨体外以浓度梯级倍增的氟康唑诱导不同来源阿萨希毛孢子菌(T.asahii)获得耐药子代,并观察它们的耐药稳定性.方法 保存的11株T.asahii中筛选出的氟康唑MIC值较低的临床分离株CBS2479及环境分离株CBS8904,在含氟康唑浓度梯级倍增的PDA固体培养基中分别传代培养,每次转种前均用E-test法测定氟康唑对其MIC值,直至其＞256 μg/ml;选用氟康唑MIC值＞256 μg/ml的耐药菌株CBS2479R/CBS8904R分别在不含氟康唑的PDA培养基中连续传代培养,并监测每代菌株MIC值,观察其耐药稳定性.结果 氟康唑MIC值分别为0.25 μg/ml及1.5 μg/ml的T.asahiiCBS2479/CBS8904均被成功地诱导为氟康唑MIC值＞256 μg/ml的耐药子代菌株CBS2479R/CBS8904R;将其在不含氟康唑PDA培养基中连续传代18d,CBS2479R氟康唑MIC值未见下降;CBS8904R氟康唑MIC值逐渐下降,至第18天时降为64 μg/ml.结论 氟康唑在体外能诱导不同来源的T.asahii均对其产生耐药性,不同来源的T.asahii其耐药子代的稳定性不同.

abstractsObjective To induce fluconazole resistance in T.asahii by culture in medium containing increasing concentrations of fluconazole,and to evaluate the stability of the induced resistance.Methods Two T.asahii strains with a highest sensitivity to fluoconazole,including a clinical isolate CBS2479 (minumum inhibitory concentration (MIC) =0.25 μg/ml) and an environmental isolate CBS8904 (MIC =1.5 μg/ml),were selected from 11 T.asahii strains stored in the laboratory of the Department of Dermatology,General Hospital of Beijing Military Region.Both strains were respectively and serially subcultured in potato dextrose agar (PDA) medium containing growing concentrations of fluconazole (from 0.5 MIC to 256 μg/ml).E-test was performed to evaluate the susceptibility of T.asahii to fluconazole after each passage.To evaluate the stability of fluconazole resistance,the T.asahii isolates with induced resistance (MIC ＞ 256 μg/ml) were serially subcultured in drug-free PDA medium,and drug susceptibility assay was performed after each subculture.Results After serial culture in PDA medium containing fluconazole,high level of fluconazole resistance (MIC ＞ 256 μg/ml) developed in both of the fluconazole-susceptible T.asahii strains CBS2479 and CBS8904.The MIC value of fluconazole remained unchanged in the fluconazole-resistant strain CBS2479R,but gradually decreased to 64 μg/ml in the other resistant strain CBS8904R after 18-day culture in fluconazole-free PDA medium.Conclusions Fluconazole resistance can be induced in T.asahii strains from different origins by serial culture in medium containing growing concentrations of fluconazole,and the stability of the induced fluconazole resistance varies between strains of different origins.