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

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

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 Talaromyces marneffei

摘要

摘要:
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 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 index，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。

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 concentration index (FICI).
Results The combination of AmB and CLA showed the highest synergy rate (18/20, 90%), and the geometric mean of , IC₁₀₀of AmB decreased from 2.297 μg/mL to 0.536 μg/mL after the combination (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%, respectively). 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.

HTML全文

参考文献(21)

施引文献

资源附件(0)