Effect of nikkomycin Z and 50% human serum on the killing activity of high-concentration caspofungin against Candida species using time-kill methodology

Caspofungin and nikkomycin Z (NIK) efficacy alone and in combination were tested against seven Candida species showing or not showing paradoxical growth (PG) against caspofungin in time-kill test in RPMI-1640. Selected isolates against caspofungin and NIK were also tested in 50% serum. PG was always eliminated by NIK as well as by serum. In the serum, 1 and 16 μg/ml caspofungin yielded 0.14-4.0 and 0.34-4.0 log CFU decreases from the starting inocula for C. albicans, C. glabrata, C. tropicalis, and C. dubliniensis, respectively. CFU decrease (0.10-2.08 log) at 16 μg/ml, but not at lower caspofungin concentration was noted against C. parapsilosis, C. orthopsilosis, and C. metapsilosis. One C. parapsilosis isolate was not inhibited even by 16 μg/ml caspofungin. Caspofungin against C. albicans, C. glabrata, C. tropicalis, and C. dubliniensis maintained its activity in serum at even 1 μg/ml concentration. PG seems to an in vitro phenomenon, without clinical relevance.