Treviño-Rangel Rogelio de J, Villanueva-Lozano Hiram, Hernández-Rodríguez Pedro, Martínez-Reséndez Michel F, García-Juárez Jaime, Rodríguez-Rocha Humberto, González Gloria M
Department of Microbiology, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
Department of Internal Medicine, Infectology Service, University Hospital "Dr. José E. González", Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
Med Mycol. 2016 Mar;54(3):280-6. doi: 10.1093/mmy/myv109. Epub 2015 Dec 24.
Cryptococcus neoformans infection is an important cause of meningitis in HIV/AIDS endemic regions. Antifungals for its management include amphotericin B, flucytosine, and fluconazole. Recently, treatment of this mycosis with sertraline has been studied with variable clinical outcomes. The aim of the study was to assess the in vitro antifungal effect of sertraline against clinical isolates of Cryptococcus spp. as well as its in vivo activity in a murine model of cryptococcal meningoencephalitis. The in vitro susceptibility to fluconazole, amphotericin B, voriconazole and sertraline of 153 Cryptococcus spp. strains were evaluated according to CLSI procedures. Fungal tissue burden, serum antigenaemia and histopathology, together with the therapeutic efficacy of amphotericin B (3 mg/kg), fluconazole (15 mg/kg), and sertraline (3, 10, and 15 mg/kg) were evaluated in mice intracranially inoculated with one isolate of Cryptococcus neoformans. All strains were susceptible to the antifungals studied and exhibited growth inhibition with sertraline at clinically relevant concentrations. Sertraline at a dose of 15 mg/kg reduced the fungal burden in the brain and spleen with an efficacy comparable to that of fluconazole. In conclusion, sertraline exhibited an excellent in vitro-in vivo anti-cryptococcal activity, representing a possible new alternative for the clinical management of meningeal cryptococcosis.
新型隐球菌感染是艾滋病毒/艾滋病流行地区脑膜炎的重要病因。用于治疗的抗真菌药物包括两性霉素B、氟胞嘧啶和氟康唑。最近，已经对舍曲林治疗这种真菌病进行了研究，临床结果各不相同。本研究的目的是评估舍曲林对新型隐球菌临床分离株的体外抗真菌作用及其在隐球菌性脑膜脑炎小鼠模型中的体内活性。根据临床和实验室标准研究所（CLSI）的程序，评估了153株新型隐球菌菌株对氟康唑, 两性霉素B, 伏立康唑和舍曲林的体外敏感性。在颅内接种一株新型隐球菌的小鼠中，评估了真菌组织负荷、血清抗原血症和组织病理学，以及两性霉素B（3mg/kg）、氟康唑（15mg/kg）和舍曲林（3、10和15mg/kg）的治疗效果。所有菌株对所研究的抗真菌药物均敏感，并且在临床相关浓度下舍曲林可抑制其生长。15mg/kg剂量的舍曲林可降低脑和脾中的真菌负荷，其疗效与氟康唑相当。总之，舍曲林表现出优异的体外-体内抗隐球菌活性，是脑膜隐球菌病临床治疗的一种可能的新选择。
