Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans. Academic Article uri icon

Overview

MeSH

  • Animals
  • Area Under Curve
  • Candidiasis, Oral
  • Drug Resistance, Fungal
  • Esophageal Diseases
  • Female
  • Half-Life
  • Immunosuppression
  • Rabbits

MeSH Major

  • Antifungal Agents
  • Candida albicans
  • Candidiasis
  • Cycloleucine
  • Enzyme Inhibitors
  • Fluconazole
  • Isoleucine-tRNA Ligase

abstract

  • PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring beta-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 microg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P

publication date

  • October 2004

has subject area

  • Animals
  • Antifungal Agents
  • Area Under Curve
  • Candida albicans
  • Candidiasis
  • Candidiasis, Oral
  • Cycloleucine
  • Drug Resistance, Fungal
  • Enzyme Inhibitors
  • Esophageal Diseases
  • Female
  • Fluconazole
  • Half-Life
  • Immunosuppression
  • Isoleucine-tRNA Ligase
  • Rabbits

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC521932

Digital Object Identifier (DOI)

  • 10.1128/AAC.48.10.3959-3967.2004

PubMed ID

  • 15388459

Additional Document Info

start page

  • 3959

end page

  • 3967

volume

  • 48

number

  • 10