Correlation of the in Vitro Antifungal Drug Susceptibility with the in Vivo Activity of Fluconazole in a Murine Model of Cerebral Infection Caused by Cryptococcus Gattii

Overview

Journal Eur J Clin Microbiol Infect Dis

Publisher Springer

Specialties Infectious Diseases
Microbiology

Date 2010 Aug 31

PMID 20803047

Citations 5

Authors

F E S Mendes

L V N Oliveira

E S Faria

D G Alvarenga

M R Pinto

C P Taborda

B M Soares

P S Cisalpino

D A Santos

Affiliations

Soon will be listed here.

Abstract

Forty Cryptococcus gattii strains were submitted to antifungal susceptibility testing with fluconazole, itraconazole, amphotericin B and terbinafine. The minimum inhibitory concentration (MIC) ranges were 0.5-64.0 for fluconazole, <0.015-0.25 for itraconazole, 0.015-0.5 for amphotericin B and 0.062-2.0 for terbinafine. A bioassay for the quantitation of fluconazole in murine brain tissue was developed. Swiss mice received daily injections of the antifungal, and their brains were withdrawn at different times over the 14-day study period. The drug concentrations varied from 12.98 to 44.60 μg/mL. This assay was used to evaluate the therapy with fluconazole in a model of infection caused by C. gattii. Swiss mice were infected intracranially and treated with fluconazole for 7, 10 or 14 days. The treatment reduced the fungal burden, but an increase in fungal growth was observed on day 14. The MIC for fluconazole against sequential isolates was 16 μg/mL, except for the isolates obtained from animals treated for 14 days (MIC = 64 μg/mL). The quantitation of cytokines revealed a predominance of IFN-γ and IL-12 in the non-treated group and elevation of IL-4 and IL-10 in the treated group. Our data revealed the possibility of acquired resistance during the antifungal drug therapy.

Citing Articles

Treatment with pCramoll Alone and in Combination with Fluconazole Provides Therapeutic Benefits in Infected Mice.

Jandu J, Costa M, Santos J, Andrade F, Magalhaes T, Silva M Front Cell Infect Microbiol. 2017; 7:211.

PMID: 28596945 PMC: 5442327. DOI: 10.3389/fcimb.2017.00211.

Management of Cryptococcus gattii meningoencephalitis.

Franco-Paredes C, Womack T, Bohlmeyer T, Sellers B, Hays A, Patel K Lancet Infect Dis. 2014; 15(3):348-55.

PMID: 25467646 PMC: 4481715. DOI: 10.1016/S1473-3099(14)70945-4.

Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to distinct behaviors in murine Cryptococcosis.

Santos J, Assuncao Holanda R, Frases S, Bravim M, Araujo G, Campi Santos P PLoS One. 2014; 9(11):e112669.

PMID: 25392951 PMC: 4231059. DOI: 10.1371/journal.pone.0112669.

Dynamic interaction between fluconazole and amphotericin B against Cryptococcus gattii.

Santos J, Gouveia L, Taylor E, Resende-Stoianoff M, Pianetti G, Cesar I Antimicrob Agents Chemother. 2012; 56(5):2553-8.

PMID: 22290956 PMC: 3346628. DOI: 10.1128/AAC.06098-11.

Cryptococcus gattii: a resurgent fungal pathogen.

Chaturvedi V, Chaturvedi S Trends Microbiol. 2011; 19(11):564-71.

PMID: 21880492 PMC: 3205261. DOI: 10.1016/j.tim.2011.07.010.

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