Vanhoffelen Eliane, Van Win Tine, Van Braeckel Eva, Reséndiz-Sharpe Agustin, Cammue Bruno P A, Lagrou Katrien, Thevissen Karin, Vande Velde Greetje
Department of Imaging and Pathology, Biomedical MRI Unit, KU Leuven, Leuven, Belgium.
Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
Front Cell Infect Microbiol. 2025 Apr 25;15:1550457. doi: 10.3389/fcimb.2025.1550457. eCollection 2025.
Solid organ transplant recipients on immunosuppressants such as tacrolimus are at increased risk of developing pulmonary aspergillosis, a severe to deadly complication with limited treatment options, especially against azole-resistant strains. This study investigates the antifungal interaction between posaconazole and tacrolimus, prompted by a case where a liver transplant recipient on tacrolimus experienced unexpected eradication of chronic colonization following posaconazole prophylaxis.
We compared the combined antifungal activity of posaconazole and tacrolimus against azole-sensitive and resistant against planktonic isolates and biofilm formation and in larvae, to evaluate the potential benefit over posaconazole monotherapy.
The posaconazole-tacrolimus combination demonstrated a 4-fold increase in efficacy against azole-resistant isolates and a 30-fold increase against an azole-sensitive strain, in contrast to voriconazole. Moreover, this combination enhanced antifungal activity by 4- to 15-fold against biofilm formation of azole-sensitive strains, though no synergy was observed against azole-resistant biofilms. studies in confirmed a 2- to 7-fold decrease in fungal burden of both azole-sensitive and azole-resistant strains when combining posaconazole with tacrolimus, relative to posaconazole alone.
and findings confirm that posaconazole may offer therapeutic benefits for treating infections in patients receiving tacrolimus. These results warrant further confirmation in mice and exploration of their clinical implications.
接受他克莫司等免疫抑制剂治疗的实体器官移植受者发生肺曲霉病的风险增加，肺曲霉病是一种严重至致命的并发症，治疗选择有限，尤其是针对唑类耐药菌株。本研究受一例接受他克莫司治疗的肝移植受者在接受泊沙康唑预防后慢性定植意外清除的病例启发，调查了泊沙康唑与他克莫司之间的抗真菌相互作用。
我们比较了泊沙康唑和他克莫司联合对唑类敏感和耐药的浮游菌分离株及生物膜形成的抗真菌活性，以及在幼虫中的抗真菌活性，以评估相对于泊沙康唑单药治疗的潜在益处。
与伏立康唑相比，泊沙康唑 - 他克莫司联合用药对唑类耐药分离株的疗效提高了4倍，对唑类敏感菌株的疗效提高了30倍。此外，该联合用药对唑类敏感菌株生物膜形成的抗真菌活性增强了4至15倍，尽管对唑类耐药生物膜未观察到协同作用。在幼虫中的研究证实，与单独使用泊沙康唑相比，泊沙康唑与他克莫司联合使用时，唑类敏感和耐药菌株的真菌负荷均降低了2至7倍。
本研究结果证实，泊沙康唑可能为治疗接受他克莫司治疗患者的曲霉感染提供治疗益处。这些结果有待在小鼠中进一步证实并探索其临床意义。
