广西医科大学学报2026，Vol.43Issue(4)：488-496,9.DOI:10.16190/j.cnki.45-1211/r.2026.04.005
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
In vitro susceptibility study of clarithromycin combined with antifungal agents against Talaro-myces marneffei
摘要
Abstract
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.关键词
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Key words
Talaromyces marneffei/clarithromycin/combination susceptibility testing/antifungal agents/nontu-berculous mycobacteria/in vitro study/synergistic effects/checkerboard microdilution method分类
医药卫生引用本文复制引用
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..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[J].广西医科大学学报,2026,43(4):488-496,9.基金项目
国家自然科学区域联合基金(U25A2088) （U25A2088）
广西重点研发计划资助项目(桂科AB24010134) （桂科AB24010134）
