title: Influence of fungicidal activity against Candida tropicalis on the efficacy of micafungin and liposomal amphotericin B in a neutropenic murine lethal infection model.
abstract: OBJECTIVE
  To investigate the correlation between in vitro killing activity and in vivo efficacy of micafungin (MCFG) and liposomal amphotericin B (L-AMB) against Candida tropicalis in a neutropenic murine lethal infection model.
  
  
  METHODS
  Candida albicans (one strain) and C. tropicalis (three strains) were tested in time-kill studies. Cyclophosphamide-treated mice were inoculated intravenously with each strain. One day after inoculation, antifungals were administered intravenously once daily for 1 or 3 days.
  
  
  RESULTS
  MCFG exhibited fungicidal activity against C. albicans ATCC 90029 and C. tropicalis SP-20142, and fungistatic activity against C. tropicalis ATCC 42678 and SP-20047. The ED(50)s (dosage that results in 50% survival) of MCFG for C. tropicalis ATCC 42678 and SP-20047 (4.1-50 mg/kg) were higher than those for other strains (1.6-12 mg/kg). A 1-day course of MCFG was not effective against C. tropicalis ATCC 42678 and SP-20047 at the clinical dose (5 mg/kg), which achieved an AUC level almost equal to that of 100 mg in humans, whereas a 3-day course of 5 mg/kg MCFG was efficacious against all strains. In contrast, L-AMB showed fungicidal activity against all strains tested and the ED(50)s of L-AMB were 0.08-0.65 mg/kg. In both treatment regimens, the minimum effective doses of L-AMB (≤0.5 mg/kg) were less than the clinical dosage (≤5 mg/kg).
  
  
  CONCLUSIONS
  The in vivo efficacy of MCFG and L-AMB showed a correlation with the in vitro killing activity. At the clinical dose, L-AMB exerted anti-C. tropicalis activity within a shorter treatment period than MCFG.
authors: Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan. koji-takemoto@ds-pharma.co.jp
authors: Koji
authors: K
authors: Takemoto
authors: Tatsuo
authors: T
authors: Nakayama
authors: Katsunori
authors: K
authors: Kanazawa
authors: Yutaka
authors: Y
authors: Ueda
mesh_terms: D000666:Amphotericin B / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D019540:Area Under Curve; D041022:Candida tropicalis / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D004195:Disease Models, Animal; D054714:Echinocandins / Q000493:pharmacokinetics / Q000494:pharmacology*; D055666:Lipopeptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D000077551:Micafungin; D051379:Mice; D008826:Microbial Sensitivity Tests; D009503:Neutropenia / Q000150:complications*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; C068538:liposomal amphotericin B; D000666:Amphotericin B; D000077551:Micafungin