Caballero Unai, Eraso Elena, Quindós Guillermo, Jauregizar Nerea
Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain.
Department of Immunology, Microbiology and Parasitology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain.
Pharmaceutics. 2021 Aug 25;13(9):1333. doi: 10.3390/pharmaceutics13091333.
Treatment of invasive infections caused by is challenging due to the limited therapeutic options. The combination of antifungal drugs may be an interesting and feasible approach to be investigated. The aim of this study was to examine the in vitro activity of amphotericin B in combination with anidulafungin or caspofungin against . In vitro static time-kill curve experiments were conducted for 48 h with different combinations of amphotericin B with anidulafungin or caspofungin against six blood isolates of . The antifungal activity of 0.5 mg/L of amphotericin B was limited against the six isolates of . Similarly, echinocandins alone had a negligible effect, even at the highest tested concentrations. By contrast, 1 mg/L of amphotericin B showed fungistatic activity. Synergy was rapidly achieved (8 h) with 0.5 mg/L of amphotericin B plus 2 mg/L of anidulafungin or caspofungin. These combinations lead to a sustained fungistatic effect, and the fungicidal endpoint was reached against some isolates. Additionally, ≥0.5 mg/L of either of the two echinocandins with 1 mg/L of amphotericin B resulted in fungicidal effect against all isolates. In conclusion, combinations of amphotericin B with anidulafungin or caspofungin provided greater killing with a lower dose requirement for amphotericin B compared to monotherapy, with synergistic and/or fungicidal outcomes.
由于治疗选择有限，治疗由[病原体名称未给出]引起的侵袭性感染具有挑战性。抗真菌药物联合使用可能是一种值得研究的有趣且可行的方法。本研究的目的是检测两性霉素B与阿尼芬净或卡泊芬净联合使用对[病原体名称未给出]的体外活性。用两性霉素B与阿尼芬净或卡泊芬净的不同组合对[病原体名称未给出]的六株血液分离株进行了48小时的体外静态时间杀菌曲线实验。0.5mg/L的两性霉素B对这六株[病原体名称未给出]分离株的抗真菌活性有限。同样，即使在最高测试浓度下，单独使用棘白菌素的效果也可忽略不计。相比之下，1mg/L的两性霉素B表现出抑菌活性。0.5mg/L的两性霉素B加2mg/L的阿尼芬净或卡泊芬净能迅速实现协同作用（8小时）。这些组合导致持续的抑菌效果，并且对一些[病原体名称未给出]分离株达到了杀菌终点。此外，两种棘白菌素中任一种≥0.5mg/L与1mg/L的两性霉素B联合使用对所有[病原体名称未给出]分离株均产生杀菌作用。总之，与单一疗法相比，两性霉素B与阿尼芬净或卡泊芬净联合使用能以更低的两性霉素B剂量需求实现更大的杀菌效果，并产生协同和/或杀菌结果。
