In vivo studies with a Candida tropicalis isolate exhibiting paradoxical growth in vitro in the presence of high concentration of caspofungin.
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<0.001 in all cases), and even to the group treated with 0.12 mg/kg caspofungin (P<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.
Bayegan
Sedigh
S
Department of Medical Microbiology, Medical and Health Science Center, University of Debrecen, Debrecen, H-4032, Hungary.
Majoros
Laszlo
L
Kardos
Gabor
G
Kemény-Beke
Adam
A
Miszti
Cecilia
C
Kovacs
Renato
R
Gesztelyi
Rudolf
R
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D001202:Ascitic Fluid / Q000382:microbiology; D041022:Candida tropicalis / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D000077336:Caspofungin; D015169:Colony Count, Microbial; D054714:Echinocandins / Q000008:administration & dosage*; D005260:Female; D016867:Immunocompromised Host; D007274:Injections, Intraperitoneal; D055666:Lipopeptides; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D016019:Survival Analysis
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin