Paradoxical growth effect of caspofungin on Candida spp. sessile cells not only at high drug concentrations

According to the available literature, echinocandins display high anti-Candida spp. activity. Paradoxical growth (PG) of Candida spp. planktonic cells promoted by echinocandins is widely reported. Here we report on the ability of Candida spp. sessile cells to display PG when they are exposed to caspofungin in vitro, even at relatively low drug concentrations. Clinical significance of PG during echinocandin therapy of candidiasis remains uncertain. We assessed in vitro susceptibilities of Candida spp. sessile cells to caspofungin and analyzed the frequency of PG. The minimum inhibitory concentrations of caspofungin for sessile cells (SMICs) were determined for 70 clinical Candida spp. isolates (29 Candida albicans, 26 Candida parapsilosis, and 15 Candida glabrata isolates) and were defined as the lowest drug concentrations that resulted in at least 50% reduction in metabolic activity. PG was defined as a resurgence of growth (>50% of that in the drug-free growth control well) at drug concentrations above the MIC. The caspofungin SMICs ranged from ≤0.015 to >256 µg ml^-1. We observed PG in 26.9-93.1% of isolates tested, depending on the Candida species and age of sessile cells. Antibiofilm activity of caspofungin is species-specific, and strongly strain-depending among C. albicans and C. parapsilosis isolates. Interestingly, PG was present also at relatively low caspofungin concentrations.