Correlation between in vitro and in vivo antifungal activities in experimental fluconazole-resistant oropharyngeal and esophageal candidiasis. Academic Article uri icon

Overview

MeSH

  • Animals
  • Child
  • Colony Count, Microbial
  • Disease Models, Animal
  • Drug Resistance, Microbial
  • Duodenum
  • Female
  • Humans
  • Immunosuppression
  • Mouth
  • Rabbits
  • Stomach

MeSH Major

  • Candidiasis
  • Candidiasis, Oral
  • Esophageal Diseases
  • Fluconazole
  • Microbial Sensitivity Tests
  • Pharyngeal Diseases

abstract

  • Oropharyngeal and esophageal candidiasis (OPEC) is a frequent opportunistic mycosis in immunocompromised patients. Azole-resistant OPEC is a refractory form of this infection occurring particularly in human immunodeficiency virus (HIV)-infected patients. The procedures developed by the Antifungal Subcommittee of the National Committee for Clinical Laboratory Standards (NCCLS) are an important advance in standardization of in vitro antifungal susceptibility methodology. In order to further understand the relationship between NCCLS methodology and antifungal therapeutic response, we studied the potential correlation between in vitro susceptibility to fluconazole and in vivo response in a rabbit model of fluconazole-resistant OPEC. MICs of fluconazole were determined by NCCLS methods. Three fluconazole-susceptible (FS) (MIC, /=64 microgram/ml) isolates of Candida albicans from prospectively monitored HIV-infected children with OPEC were studied. FR isolates were recovered from children with severe OPEC refractory to fluconazole, and FS isolates were recovered from those with mucosal candidiasis responsive to fluconazole. Fluconazole at 2 mg/kg of body weight/day was administered to infected animals for 7 days. The concentrations of fluconazole in plasma were maintained above the MICs for FS isolates throughout the dosing interval. Fluconazole concentrations in the esophagus were greater than or equal to those in plasma. Rabbits infected with FS isolates and treated with fluconazole had significant reductions in oral mucosal quantitative cultures (P < 0.001) and tissue burden of C. albicans in tongue, soft palate, and esophagus (P < 0.001). In comparison, rabbits infected with FR isolates were unresponsive to fluconazole and had no reduction in oral mucosal quantitative cultures or tissue burden of C. albicans versus untreated controls. We conclude that there is a strong correlation between in vitro fluconazole susceptibility by NCCLS methods and in vivo response to fluconazole therapy of OPEC due to C. albicans.

publication date

  • June 2000

has subject area

  • Animals
  • Candidiasis
  • Candidiasis, Oral
  • Child
  • Colony Count, Microbial
  • Disease Models, Animal
  • Drug Resistance, Microbial
  • Duodenum
  • Esophageal Diseases
  • Female
  • Fluconazole
  • Humans
  • Immunosuppression
  • Microbial Sensitivity Tests
  • Mouth
  • Pharyngeal Diseases
  • Rabbits
  • Stomach

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC86806

PubMed ID

  • 10835005

Additional Document Info

start page

  • 2369

end page

  • 2373

volume

  • 38

number

  • 6