Antifungal susceptibility challenges in dimorphic fungus Histoplasma capsulatum: Correlation of mold and yeast form of 23 molecularly identified strains

Shallu Kathuria1*. Pradeep K Singh1, Jacques F Meis2,3 and Anuradha Chowdhary1

Author address: 

'Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India; department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands; 3Department of Medical Micro

Abstract: 

Histoplasma capsulatum, dimorphic fungus and an etiologic agent of histoplasmosis, causes an array of diseases ranging from acute pulmonary to disseminated infection. Despite recent increase in the H. capsulatum reports from India, the data on antifungal susceptibility of molecularly characterized H. capsulatum is not available from this part of the world. Herein, we present the in vitro antifungal susceptibility profile of 8 antifungal agents against 23 molecularly identified clinical H. capsulatum strains. We also evaluated the correlation between MICs of yeast and mold forms of H. capsulatum for better interpretation of susceptibility profile. Twenty one strains of H. capsulatum originating from chronic pulmonary (n=l 1) and systemic disseminated (n=7) histoplasmosis patients along with 2 reference strains, were investigated for antifungal susceptibility by microbroth dilution using modified CLSIM38-A2. The isolates were cultured from blood, BAL, FNAB, bone-marrow and lymph-node aspirates. The isolates were confirmed by ITS and D1/D2 sequencing. They yeast conversion was observed on BHI agar. Antifungal susceptibility profiles of the mold (M) and yeast (Y) form of H. capsulatum revealed lowest geometric mean MICs to itraconazole (M:0.043 ng/ml; Y:0.032 |ig/ml) followed by posaconazole (M:0.05|xg/ml; Y:0.045 ng/ml), isavuconazole (M:0.055 p.g/ml,Y:0.046 (ig/ml), voriconazole (M:0.102 fig/ml, Y:0.12p.g/ml), amphotericin B (M:0.11 p.g/ml, Y:0.08 jig/ml) and caspofungin (M:0.094 (ig/ml, Y:0.102 (ig/ml). Statistically significant difference was observed in MICs of yeast and mold form for fluconazole while both the forms showed high MICs to flucytosine The study reports for the first time from India, the antifungal susceptibility profile of large number ofH. capsulatum, tissue and saprobic form. Posaconazole and isavuconazole exhibited promising activity. Furthermore, the cumbersome technique of yeast conversion for susceptibility testing is not mandatory, as the MICs were almost similar of both the forms. Acknowlegement: This work was financially supported by Indian Council of Medical Research (5/3/3/26/2010-ECD-I), New Delhi 9830;Corresponding author [email protected]
2014

abstract No: 

OP-007

Full conference title: 

Society for Indian Human and Animal Mycologists 2014
    • SIHAM