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Activity of sertraline against Cryptococcus neoformans: in vitro and in vivo assays
Rogelio de J Treviño-Rangel1, Hiram Villanueva-Lozano2, Pedro Hernández-Rodríguez2
1Department of Microbiology, School of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
Abstract:
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.
Insights
Sertraline shows promising antifungal activity against Cryptococcus species in laboratory and animal models. This selective serotonin reuptake inhibitor may offer a new treatment option for cryptococcal meningitis, especially in HIV/AIDS patients.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Cryptococcus neoformans causes meningitis, particularly in HIV/AIDS populations.
- Current antifungals like amphotericin B and fluconazole are standard treatments.
- Sertraline's potential as an antifungal agent is under investigation with varied results.
Purpose of the Study:
- To evaluate the in vitro antifungal effects of sertraline against Cryptococcus species.
- To assess the in vivo efficacy of sertraline in a murine model of cryptococcal meningoencephalitis.
Main Methods:
- In vitro susceptibility testing of 153 Cryptococcus spp. strains against fluconazole, amphotericin B, voriconazole, and sertraline.
- In vivo study in mice with cryptococcal meningoencephalitis, evaluating fungal burden, antigenaemia, and histopathology.
- Therapeutic efficacy assessed using amphotericin B, fluconazole, and varying doses of sertraline.
Main Results:
- All tested Cryptococcus strains were susceptible to the evaluated antifungals.
- Sertraline demonstrated growth inhibition at clinically relevant concentrations in vitro.
- A sertraline dose of 15 mg/kg significantly reduced fungal burden in mouse brains and spleens, comparable to fluconazole.
Conclusions:
- Sertraline exhibits significant in vitro and in vivo anti-cryptococcal activity.
- Sertraline presents a potential novel therapeutic alternative for managing meningeal cryptococcosis.
- Further clinical studies are warranted to confirm sertraline's efficacy in patients.
