In vivo evaluation of the antifungal activity of sertraline against Aspergillus fumigatus

• Published in: Journal of antimicrobial chemotherapy 2019-03, Vol.74 (3), p.663-666
• Main Authors: Treviño-Rangel, Rogelio de J, Villanueva-Lozano, Hiram, Méndez-Galomo, Karen S, Solís-Villegas, Elia M, Becerril-García, Miguel A, Montoya, Alexandra M, Robledo-Leal, Efrén R, González, Gloria M
• Format: Article
• Language: English
• Subjects: Animals; Antifungal Agents - administration & dosage; Antifungal Agents - pharmacology; Aspergillosis - drug therapy; Aspergillosis - microbiology; Aspergillus fumigatus - drug effects; Colony Count, Microbial; Disease Models, Animal; Histocytochemistry; Lepidoptera; Lung - microbiology; Lung - pathology; Male; Mannans - analysis; Mice, Inbred BALB C; Sertraline - administration & dosage; Sertraline - pharmacology; Survival Analysis; Treatment Outcome
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dky455

Abstract Background Invasive pulmonary aspergillosis is a life-threatening fungal disease principally caused by the ubiquitous mould Aspergillus fumigatus. This clinical entity is a major cause of morbidity and mortality (principally, but not restricted to, immunocompromised individuals). A few recent reports suggest in vitro fungicidal activity of sertraline against Aspergillus spp., but this activity has not yet been investigated in vivo. Objectives To evaluate the antifungal activity of sertraline in two in vivo models of aspergillosis. Methods The antifungal activity of sertraline as monotherapy at three different doses (3, 10 and 15 mg/kg) was evaluated in Galleria mellonella and in a murine model of invasive pulmonary aspergillosis. Therapeutic efficacy parameters determined were larval survival and health index score for G. mellonella, whereas pulmonary fungal burden, galactomannan and lung histopathology were assessed in the murine model. Results Sertraline treatments improved larval survival and health index score, especially at doses of 10 and 15 mg/kg. Moreover, 10 mg/kg sertraline was able to reduce pulmonary fungal burden with an efficacy comparable with that of 3 mg/kg amphotericin B and 10 mg/kg voriconazole. Conclusions To the best of our knowledge, this is the first in vivo study that evaluates the antifungal activity of sertraline against A. fumigatus, showing a possible promising option for the adjuvant treatment of pulmonary aspergillosis.