Evaluation of aminocandin and caspofungin against Candida glabrata including isolates with reduced caspofungin susceptibility.
BACKGROUND
Aminocandin is an investigational echinocandin with excellent activity against Candida species, including Candida albicans and Candida tropicalis. However, few data are available for this agent versus Candida glabrata. We compared the in vitro potency and in vivo efficacy of aminocandin and caspofungin against clinical isolates of C. glabrata including those with reduced caspofungin susceptibility (MIC > 2 mg/L).


METHODS
In vitro activity was assessed using microdilution broth susceptibility testing. Three isolates, one with a low and two with elevated caspofungin MICs, were chosen and mice were infected with C. glabrata followed by a single dose of aminocandin or caspofungin (0.5-100 mg/kg), or daily doses of caspofungin (0.07-14.3 mg/kg) begun 1 day after inoculation. Reduction in fungal burden, assessed in kidney tissue on day 8 post-inoculation, was the marker of antifungal response.


RESULTS
Aminocandin was more potent than caspofungin against each isolate with reduced caspofungin susceptibility. Mice infected with the caspofungin-susceptible isolate had significant decreases in tissue burden with low doses of either drug. Higher single doses of aminocandin (> or = 10 mg/kg) were required to reduce fungal burden against the two isolates with elevated caspofungin MICs. Single dose administration of caspofungin was ineffective against one of these isolates, and higher daily doses were required to reduce fungal burden.


CONCLUSIONS
These studies suggest that aminocandin has the potential for extended interval dosing in the treatment of C. glabrata infections caused by susceptible isolates. However, higher doses may be required against isolates with reduced caspofungin susceptibility.
Brzankalski
Gabriela E
GE
Division of Infectious Diseases, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Najvar
Laura K
LK
Wiederhold
Nathan P
NP
Bocanegra
Rosie
R
Fothergill
Annette W
AW
Rinaldi
Michael G
MG
Pattterson
Thomas F
TF
Graybill
John R
JR
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D041221:Candida glabrata / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D000077336:Caspofungin; D015169:Colony Count, Microbial; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D007668:Kidney / Q000382:microbiology; D055666:Lipopeptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; C476911:aminocandin; D000077336:Caspofungin