Comparative effects of micafungin, caspofungin, and anidulafungin against a difficult-to-treat fungal opportunistic pathogen, Candida glabrata.
The aim of this study was to compare the in vitro and in vivo activities of micafungin, caspofungin, and anidulafungin against Candida glabrata. The MICs against 28 clinical isolates showed that the overall susceptibilities to caspofungin and to micafungin were not statistically different in the absence of human serum, whereas the isolates were less susceptible to micafungin than to caspofungin in its presence. Minimum fungicidal concentrations, as well as time-kill experiments, showed that caspofungin was more active than anidulafungin, while micafungin was superior to either caspofungin or anidulafungin without serum; its addition rendered caspofungin and micafungin equally effective. A murine model of systemic candidiasis against a C. glabrata-susceptible isolate was performed to study the effects of all three echinocandins, and kidney burden counts showed that caspofungin, micafungin, and anidulafungin were active starting from 0.25, 1, and 5 mg/kg of body weight/day, respectively. Two echinocandin-resistant strains of C. glabrata were selected: C. glabrata 30, a laboratory strain harboring the mutation Fks2p-P667T, and C. glabrata 51, a clinical isolate harboring the mutation Fks2p-D666G. Micafungin activity was shown to be as effective as or more effective than that of caspofungin or anidulafungin in terms of MICs. In vivo studies against these resistant strains showed that micafungin was active starting from 1 mg/kg/day, while caspofungin was effective only when administrated at higher doses of 5 or 10 mg/kg/day. Although a trend toward colony reduction was observed with the highest doses of anidulafungin, a significant statistical difference was never reached.
Department of Biomedical Sciences and Public Health, Clinic Infectious Disease, Università Politecnica delle Marche, Ancona, Italy. e.spreghini@univpm.it
Elisabetta
E
Spreghini
Fiorenza
F
Orlando
Maurizio
M
Sanguinetti
Brunella
B
Posteraro
Daniele
D
Giannini
Esther
E
Manso
Francesco
F
Barchiesi
D000077612:Anidulafungin; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D041221:Candida glabrata / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D000077336:Caspofungin; D004195:Disease Models, Animal; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D000077551:Micafungin; D051379:Mice; D008826:Microbial Sensitivity Tests; D009154:Mutation
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077612:Anidulafungin; D000077336:Caspofungin; D000077551:Micafungin