title: In vivo efficacy of anidulafungin and caspofungin against Candida glabrata and association with in vitro potency in the presence of sera.
abstract: In vitro studies have demonstrated that anidulafungin has greater potency than caspofungin against Candida glabrata. However, data from in vivo studies demonstrating that it has superior efficacy are lacking. The objective of this study was to compare the activities of anidulafungin and caspofungin against C. glabrata in a murine model of disseminated candidiasis. Two clinical C. glabrata isolates were used, including one with reduced caspofungin susceptibility. MICs were determined by broth microdilution in the presence and absence of sera. For the animal studies, mice were immunosuppressed with 5-fluorouracil one day prior to intravenous inoculation. Treatment with anidulafungin and caspofungin (0, 0.5, 1, 5, and 10 mg/kg of body weight per day) was begun 24 h later and was continued through day 7 postinoculation. The CFU were enumerated from kidney tissue. According to the standard microdilution methodology, anidulafungin had superior in vitro activity. However, this enhanced potency was attenuated by the addition of mouse and human sera. Caspofungin reduced the kidney fungal burden at lower doses compared to that achieved with anidulafungin in mice infected with the isolate with the lower MIC. Against the strain with the elevated caspofungin MIC, both anidulafungin and caspofungin were effective in reducing the kidney fungal burden at the higher doses studied. Despite the greater in vitro activity of anidulafungin in the absence of sera, both echinocandins were similarly effective in reducing the fungal burden in kidney tissue. The superior in vitro activity of anidulafungin did not confer enhanced in vivo efficacy against C. glabrata.
authors.affiliation: UTHSCSA, PERC, MSC 6220, San Antonio, TX 78229, USA. wiederholdn@uthscsa.edu
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Wiederhold
authors.forename: Laura K
authors.initials: LK
authors.lastname: Najvar
authors.forename: Rosie
authors.initials: R
authors.lastname: Bocanegra
authors.forename: Destiny
authors.initials: D
authors.lastname: Molina
authors.forename: Marcos
authors.initials: M
authors.lastname: Olivo
authors.forename: John R
authors.initials: JR
authors.lastname: Graybill
mesh_terms: D000077612:Anidulafungin; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy; D000077336:Caspofungin; D054714:Echinocandins; D055666:Lipopeptides; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000494:pharmacology*; D044967:Serum / Q000502:physiology*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D000077612:Anidulafungin; D000077336:Caspofungin