Université Paris Est Créteil, Dynamyc, Créteil, France.
Université Tunis EL Manar, Faculté de médecine de Tunis, Tunis, Tunisie.
Front Cell Infect Microbiol. 2023 Jan 17;12:1038342. doi: 10.3389/fcimb.2022.1038342. eCollection 2022.
Azole resistance in (Af) has become a widespread threat and a major concern for optimal management of patients with invasive aspergillosis (IA). Combination of echinocandins with azoles is an attractive alternative option for the treatment of IA due to azole-resistant Af strains. The aim of this study was to evaluate the and combination of caspofungin (CAS) with either voriconazole (VRZ) or posaconazole (PSZ). interactions were assessed by two methods, and an animal model of IA in was used for evaluation. Assessment of efficacy was based on larvae mortality. Groups of 10 larvae were infected by 3 clinical strains of Af (azole susceptible, AfS; PSZ resistant, AfR1; VRZ and PSZ resistant strain, AfR2). , combination of CAS and azoles was indifferent against AfS, and AfR2, and a synergy was found for AfR1. When compared to VRZ monotherapy, the combination of VRZ at 4 µg/larva with CAS at 4 µg/larva improved survival of AfR2-infected larvae (p=0.0066). Combination of PSZ at 4µg/larva with CAS at 4 µg/larva improved survival of AfR1-infected larvae compared to CAS (p=0.0002) and PSZ (0.0024) monotherapy. Antagonism was never observed. In conclusion, the combination of caspofungin with azoles is a promising alternative for the treatment of azole resistant strains of Af.
（Af）中的唑类耐药性已成为侵袭性曲霉病（IA）患者最佳管理的广泛威胁和主要关注点。由于唑类耐药 Af 菌株，将棘白菌素与唑类药物联合使用是治疗 IA 的一种有吸引力的替代选择。本研究旨在评估棘白菌素（CAS）与伏立康唑（VRZ）或泊沙康唑（PSZ）联合使用的疗效和相互作用。通过两种方法评估相互作用，并使用 Af 所致 IA 的动物模型进行体外评估。疗效评估基于幼虫死亡率。将 10 只幼虫分为 10 组，通过 3 株临床 Af 菌株（唑类敏感，AfS；PSZ 耐药，AfR1；VRZ 和 PSZ 耐药株，AfR2）感染。结果表明，CAS 与唑类药物联合使用对 AfS 和 AfR2 无差异，而对 AfR1 则有协同作用。与 VRZ 单药治疗相比，VRZ 4μg/幼虫与 CAS 4μg/幼虫联合治疗可提高 AfR2 感染幼虫的存活率（p=0.0066）。与 CAS（p=0.0002）和 PSZ（0.0024）单药治疗相比，PSZ 4μg/幼虫与 CAS 4μg/幼虫联合治疗可提高 AfR1 感染幼虫的存活率。从未观察到拮抗作用。总之，棘白菌素与唑类药物联合使用是治疗唑类耐药 Af 菌株的一种有前途的替代方法。
