Previous in vivo studies have reported
caspofungin dose escalation to be effective against Candida glabrata with reduced susceptibility. We hypothesized that higher doses of
caspofungin would be effective against
invasive candidiasis caused by the more virulent species Candida albicans, including isolates resistant to this
echinocandin. Immunocompetent mice were inoculated with one of three C. albicans isolates, including one susceptible and two resistant isolates with different FKS1 hot spot 1 point mutations. Mice received daily
caspofungin treatment for 7 days and were then followed off
therapy for 2 weeks to assess survival. Kidney tissue and blood were collected, and fungal burden and serum (1 → 3)-β-D-glucan were measured. Significant differences in virulence were observed among the three C. albicans isolates, which translated into differences in responses to
caspofungin. The most virulent of the resistant isolates studied (isolate 43001; Fks1p F641S) did not respond to
caspofungin doses of up to 10 mg/kg of
body weight, as there were no differences in survival (survival range, 0 to 12% with treatment), tissue burden, or (1 → 3)-β-D-glucan concentration compared to those for untreated controls. Higher doses of
caspofungin did improve survival against the second resistant isolate (53264; Fks1p S645P) that demonstrated reduced virulence (5 and 10 mg/kg; 80% survival). In contrast,
caspofungin doses as low as 1 mg/kg improved survival (85 to 95%) and reduced tissue burden and (1 → 3)-β-D-glucan concentration against the susceptible isolate (ATCC 90028). These data suggest that
caspofungin dose escalation for
invasive candidiasis may not be consistently effective against resistant C. albicans isolates, and this may be associated with the virulence of the strain.