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Posaconazole enhances the activity of amphotericin B against Aspergillus hyphae in vitro

Susanne Perkhofer1, Helene Lugger, Manfred P Dierich

  • 1Department of Hygiene, Microbiology and Social Medicine, Medical University Innsbruck, Fritz-Pregl Str. 3, A-6020 Innsbruck, Austria. Susanne.Perkhofer@i-med.ac.at

Antimicrobial Agents and Chemotherapy
|November 23, 2006
PubMed

Insights

Posaconazole-amphotericin B combinations show greater synergy against Aspergillus hyphae than voriconazole-amphotericin B. This combination is more effective against hyphae than conidia, suggesting targeted antifungal strategies.

Area of Science:

  • Mycology
  • Antimicrobial Resistance
  • Infectious Diseases

Background:

  • Aspergillus species are opportunistic fungal pathogens causing invasive aspergillosis.
  • Azole antifungals like posaconazole and voriconazole are crucial for treating invasive aspergillosis.
  • Amphotericin B remains a cornerstone therapy, often used in combination regimens.

Purpose of the Study:

  • To evaluate the in vitro synergistic activity of posaconazole and voriconazole, alone and in combination with amphotericin B.
  • To compare the efficacy of these combinations against different morphological forms (conidia and hyphae) of Aspergillus isolates.

Main Methods:

  • Determination of Minimum Inhibitory Concentrations (MICs) and Fractional Inhibitory Concentrations (FICs).
  • Testing of posaconazole (POS), voriconazole (VRZ), and amphotericin B (AMB) individually and in combination.
  • Evaluation against 100 clinical isolates of Aspergillus, assessing activity against both conidia and hyphae.

Main Results:

  • Posaconazole-amphotericin B (POS-AMB) demonstrated significant synergistic activity against Aspergillus hyphae in 75% of isolates.
  • Voriconazole-amphotericin B (VRZ-AMB) showed synergistic activity against hyphae in 37% of isolates.
  • POS-AMB exhibited significantly greater synergistic activity against hyphae compared to conidia (12% synergy).

Conclusions:

  • The combination of posaconazole and amphotericin B offers superior synergistic antifungal activity against Aspergillus hyphae in vitro.
  • These findings suggest that combination therapy, particularly POS-AMB, may be a promising strategy for targeting the hyphal form of Aspergillus.
  • Further clinical investigation is warranted to confirm the therapeutic benefit of POS-AMB in invasive aspergillosis.

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