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Combined antifungal therapy in a murine infection by Candida glabrata

Marçal Mariné1, Carolina Serena, F Javier Pastor

  • 1Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Carrer Sant Llorenç 21, 43201, Reus, Spain.

The Journal of Antimicrobial Chemotherapy
|October 3, 2006
PubMed
Abstract

Insights

New antifungal drug combinations were tested for disseminated Candida glabrata infections. Micafungin plus amphotericin B showed the most promise in reducing fungal burden and improving survival in a murine model.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Pharmacology

Background:

  • Disseminated Candida glabrata infections pose a significant therapeutic challenge.
  • Current antifungal treatments are often ineffective for non-responsive cases.

Purpose of the Study:

  • To evaluate novel antifungal drug combinations for treating disseminated C. glabrata infections.
  • To identify effective treatment strategies for drug-resistant fungal infections.

Main Methods:

  • A murine model of neutropenia was established using cyclophosphamide and 5-fluorouracil.
  • Mice were infected with Candida glabrata, and the efficacy of drug combinations (micafungin with amphotericin B, fluconazole, or flucytosine; amphotericin B with fluconazole) was assessed.
  • Survival rates and fungal tissue burden in organs were measured.

Main Results:

  • Micafungin combined with amphotericin B demonstrated the greatest efficacy in reducing fungal tissue burden.
  • Specific combinations of micafungin and amphotericin B prolonged survival and showed synergistic effects in reducing fungal load in the spleen and kidney.
  • Amphotericin B at 1.5 mg/kg combined with varying doses of micafungin effectively reduced tissue burden.

Conclusions:

  • Amphotericin B in combination with micafungin is a promising therapeutic strategy for disseminated C. glabrata infections.
  • Combination therapy offers improved outcomes compared to monotherapy for resistant fungal infections.

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