In vivo studies with a Candida tropicalis isolate exhibiting paradoxical growth in vitro in the presence of high concentration of caspofungin
2010
Bayegan, Sedigh, University of Debrecen, Debrecen, Hungary | Majoros, Laszlo, University of Debrecen, Debrecen, Hungary | Kardos, Gabor, University of Debrecen, Debrecen, Hungary | Kemeny-Geke, Adam, University of Debrecen, Debrecen, Hungary | Miszti, Cecilia, University of Debrecen, Debrecen, Hungary | Kovacs, Renato, University of Debrecen, Debrecen, Hungary | Gesztelyi, Rudolf, University of Debrecen, Debrecen, Hungary
We investigated the activity of caspofungin against a Candida tropicalis clinical isolate showing paradoxical growth in vitro. BALB/c mice immunosuppressed by cyclophosphamide were infected intraperitoneally using 10∨7 CFU/mouse. Caspofungin was administered intraperitoneally once daily for 5 days or as a single dose using the following doses: 0.12, 0.25, 1, 2, 3, 5, and 15 mg/kg. The single dose of caspofungin was effective only at 5 and 15 mg/kg concentrations (100% survival). Five-day caspofungin treatment led to 100% survival at doses of 1 mg/kg or higher. Caspofungin treatment significantly decreased the number of viable yeasts in the peritoneal lavage samples as well as in the infected abscesses at doses 1, 3, 5, and 15 mg/kg caspofungin as compared to the untreated control (P less than 0.001 in all cases), and even to the group treated with 0.12 mg/kg caspofungin (P less than 0.05 in all cases). At 2 mg/kg caspofungin dose, sterilization of the internal organs was reproducibly incomplete, suggesting that the role of paradoxical growth in the late clinical failure cannot be excluded.
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