Changes in cell wall synthesis and ultrastructure during paradoxical growth effect of caspofungin on four different Candida species.

Paradoxical effect of caspofungin: reduced activity against Candida albicans at high drug concentrations.

Resistance problems with caspofungin, an echinocandin inhibitor of fungal cell wall glucan synthesis, have been rare. We noted paradoxical turbid growth of Candida albicans isolates in broth in some high (supra-MIC) concentrations. Among isolates submitted for susceptibility testing and screened at drug concentrations up to 12.5 microg/ml, the frequency was 16%. Analysis of the turbid growth in...

Paradoxical effect of caspofungin against Candida bloodstream isolates is mediated by multiple pathways but eliminated in human serum.

Paradoxical growth of Candida in vitro at echinocandin concentrations exceeding the MIC is well described, but the clinical relevance is unknown. We assessed echinocandin paradoxical effects against Candida bloodstream isolates (BSI) in the presence or absence of human serum and investigated regulatory mechanisms. As determined by broth microdilution, a paradoxical effect was evident for 60% (1...

PARADOXICAL GROWTH TO CASPOFUNGIN IN Candida albicans IS 1 ASSOCIATED WITH MULTIPLE CELL WALL REARRANGEMENTS AND 2 DECREASED

Elevated chitin content reduces the susceptibility of Candida species to caspofungin.

The echinocandin antifungal drugs inhibit synthesis of the major fungal cell wall polysaccharide β(1,3)-glucan. Echinocandins have good efficacy against Candida albicans but reduced activity against other Candida species, in particular Candida parapsilosis and Candida guilliermondii. Treatment of Candida albicans with a sub-MIC level of caspofungin has been reported to cause a compensatory incr...

Paradoxical effect to caspofungin in Candida species does not confer survival advantage in a Drosophila model of candidiasis

The paradoxical growth (PG) to echinocandins has been observed in vitro in Candida and Aspergillus species. Its mechanisms are incompletely understood, although activation of calcineurin and chitin biosynthesis pathways have been implicated. Importantly, the in vivo relevance of PG is not well defined as there is paucity of both animal model and clinical data on the implications of this phenome...