克拉霉素联合抗真菌药物作用于马尔尼菲篮状菌的体外药敏研究OA
In vitro susceptibility study of clarithromycin combined with antifungal agents against Talaro-myces marneffei
目的:评估克拉霉素(clarithromycin,CLA)与4种抗真菌药物对马尔尼菲篮状菌(Talaromyces marneffei,TM)的体外联合效应,并比较不同判读标准对联合药敏结果的影响,为临床治疗TM和非结核分枝杆菌(nontuberculous mycobacteria,NTM)合并感染提供理论依据.方法:采用棋盘格法,对20株TM(19株临床株+1株标准株)进行CLA与两性霉素B(amphotericin B,AmB)、氟康唑(fluconazole,FLC)、伊曲康唑(itraconazole,ITC)、伏立康唑(voriconazole,VOC)的联合药敏实验.唑类药物分别采用50%抑制浓度(IC50)与完全抑制浓度(IC100)两种判读标准,使用部分抑制浓度指数(fractional inhibitory concentration in-dex,FICI)判定联合效应.结果:AmB+CLA协同率最高(18/20,90%),联合后AmB的IC100几何均数从2.297 μg/mL降至0.536 μg/mL(P＜0.001).ITC+CLA在两种判读标准下均表现稳定(协同率45%～65%,相加率35%～55%).FLC和VOC联合CLA的效应高度依赖判读标准:IC50判读时以无关作用为主(100%和85%),IC100判读时转变为相加作用为主(85%和75%).所有组合均未观察到拮抗作用.结论:AmB+CLA协同效应最强,提示其可能作为重症合并感染联合治疗的潜在优选方案;ITC联合CLA效应稳定,提示其具有适用于口服序贯治疗的潜力;FLC和VOC联合CLA需达到完全抑制浓度方能体现联合优势.判读标准的选择可显著影响唑类药物联合药敏的定性结论.
Objective:To evaluate the in vitro combined effects of clarithromycin(CLA)with 4 antifungal agents against Talaromyces marneffei(TM),and to compare the impacts of different interpretive criteria on the combined susceptibility results,thereby providing a theoretical basis for the clinical treatment of co-infection caused by TM and nontuberculous mycobacteria(NTM).Methods:The checkerboard microdilution method was adopted to perform the combination susceptibility testing of CLA with amphotericin B(AmB),fluconazole(FLC),itraconazole(ITC)and voriconazole(VOC)against 20 TM strains(19 clinical isolates+1 reference strain).For azoles,2 interpretive criteria were respectively adopted:half-maximal inhibitory concentration(IC50)and complete-inhibitory concentration(IC100),and the combined effects were assessed using fractional inhibitory con-centration index(FICI).Results:The combination of AmB and CLA showed the highest synergy rate(18/20,90%),and the geometric mean of IC100 of AmB decreased from 2.297 μg/mL to 0.536 μg/mL after the combina-tion(P＜0.001).The combination of ITC and CLA showed consistent activity under both interpretive criteria,with synergy rates of 45%-65%and additive rates of 35%-55%.The synergistic effects of the FLC-CLA and VOC-CLA combinations were highly dependent on the interpretive criteria:indifferent interactions predominated at IC50(100%and 85%,respectively),whereas additive interactions predominated at IC100(85%and 75%,respec-tively).No antagonism was observed for any combination.Conclusion:The combination of AmB and CLA exhibits the strongest synergistic effect,suggesting its potential as a preferred option for combined therapy in severe co-infections.The combination of ITC and CLA exhibits a stable synergistic effect,suggesting its potential for oral sequential therapy.The synergistic effects of the FLC-CLA and VOC-CLA combinations can only be observed at IC100.The choice of interpretive criteria significantly affects the qualitative outcomes of azole-combination susceptibility testing.
覃乾峰;潘开素;黄澜;黄啟华;廖柳维;向中兰;周真;廖万清;曹存巍
广西医科大学第一附属医院皮肤性病科,南宁 530021||广西真菌病防治研究重点实验室,南宁 530021广西医科大学第一附属医院皮肤性病科,南宁 530021||广西真菌病防治研究重点实验室,南宁 530021||防城港市万清皮肤病与真菌病防控研究院,防城港 538000广西医科大学第一附属医院皮肤性病科,南宁 530021||广西真菌病防治研究重点实验室,南宁 530021广西医科大学第一附属医院皮肤性病科,南宁 530021||广西真菌病防治研究重点实验室,南宁 530021广西医科大学第一附属医院皮肤性病科,南宁 530021||广西真菌病防治研究重点实验室,南宁 530021广西真菌病防治研究重点实验室,南宁 530021广西医科大学第一附属医院皮肤性病科,南宁 530021||广西真菌病防治研究重点实验室,南宁 530021海军军医大学第二附属医院皮肤科,上海 200003广西医科大学第一附属医院皮肤性病科,南宁 530021||广西真菌病防治研究重点实验室,南宁 530021||防城港市万清皮肤病与真菌病防控研究院,防城港 538000
医药卫生
马尔尼菲篮状菌克拉霉素联合药敏抗真菌药物非结核分枝杆菌体外研究协同效应棋盘格法
Talaromyces marneffeiclarithromycincombination susceptibility testingantifungal agentsnontu-berculous mycobacteriain vitro studysynergistic effectscheckerboard microdilution method
《广西医科大学学报》 2026 (4)
488-496,9
国家自然科学区域联合基金(U25A2088)广西重点研发计划资助项目(桂科AB24010134)
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