Terbinafine inhibits Cryptococcus neoformans growth and modulates fungal morphology
Mem. Inst. Oswaldo Cruz
; 107(5): 582-590, Aug. 2012. ilus, tab
Article
in English
| LILACS
| ID: lil-643742
Responsible library:
BR1.1
ABSTRACT
Cryptococcus neoformans is an encapsulated fungus that causes cryptococcosis. Central nervous system infection is the most common clinical presentation followed by pulmonary, skin and eye manifestations. Cryptococcosis is primarily treated with amphotericin B (AMB), fluconazole (FLC) and itraconazole (ITC). In the present work, we evaluated the in vitro effect of terbinafine (TRB), an antifungal not commonly used to treat cryptococcosis. We specifically examined the effects of TRB, either alone or in conjunction with AMB, FLC and ITC, on clinical C. neoformans isolates, including some isolates resistant to AMB and ITC. Broth microdilution assays showed that TRB was the most effective drug in vitro. Antifungal combinations demonstrated synergism of TRB with AMB, FLC and ITC. The drug concentrations used for the combination formulations were as much as 32 and 16-fold lower than the minimum inhibitory concentration (MIC) values of FLC and AMB alone, respectively. In addition, calcofluor white staining revealed the presence of true septa in hyphae structures that were generated after drug treatment. Ultrastructural analyses demonstrated several alterations in response to drug treatment, such as cell wall alterations, plasma membrane detachment, presence of several cytoplasmic vacuoles and mitochondrial swelling. Therefore, we believe that the use of TRB alone or in combination with AMB and azoles should be explored as an alternative treatment for cryptococcosis patients who do not respond to standard therapies.
Full text:
Available
Collection:
International databases
Database:
LILACS
Main subject:
Fluconazole
/
Amphotericin B
/
Itraconazole
/
Cryptococcus neoformans
/
Antifungal Agents
/
Naphthalenes
Limits:
Humans
Language:
English
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
Tropical Medicine
/
Parasitology
Year:
2012
Document type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
Universidade Federal do Rio de Janeiro/BR