Format

Send to

Choose Destination
J Antimicrob Chemother. 2006 Jun;57(6):1235-9. Epub 2006 Apr 20.

Activity of newer triazoles against Histoplasma capsulatum from patients with AIDS who failed fluconazole.

Author information

1
MiraVista Diagnostics/MiraBella Technologies, 4444 Decatur Boulevard, Indianapolis, IN 46241, USA. jwheat@miravistalabs.com

Abstract

OBJECTIVES:

To determine the activity of newer triazoles against strains of Histoplasma capsulatum resistant to fluconazole.

METHODS:

Susceptibility testing was performed on 17 paired pre- and post-treatment H. capsulatum isolates from patients with AIDS who failed fluconazole.

RESULTS:

The median MICs of fluconazole, voriconazole, and posaconazole and ravuconazole for the pre-treatment isolates were 1 mg/L, 0.015 mg/L and <0.007 mg/L, respectively. A 4-fold or greater increase in the MIC of fluconazole and voriconazole was observed in 12 and 7 of the post-treatment isolates, respectively; the median fold increases in MIC were 8 and 2.1, respectively. No MIC increases were observed for posaconazole and ravuconazole. One pair of isolates exhibiting reduced susceptibility was examined in more detail. A single amino acid substitution (at tyrosine 136) was identified in the active site of the CYP51 protein from the post-treatment isolate, which is presumed to be responsible for reduced susceptibility to voriconazole and fluconazole, analogous to recent observations in Candida albicans.

CONCLUSIONS:

These findings support careful monitoring for relapse in patients receiving voriconazole treatment for histoplasmosis, particularly in those who were previously treated with fluconazole.

PMID:
16627592
DOI:
10.1093/jac/dkl133
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center