Differential fungicidal activities of amphotericin B and voriconazole against Aspergillus species determined by microbroth methodology

Joseph Meletiadis, Charalampos Antachopoulos, Theodouli Stergiopoulou, Spyros Pournaras, Emmanuel Roilides, Thomas J. Walsh

Research output: Contribution to journalArticle

Abstract

Antifungal agents may differ in their fungicidal activities against Aspergillus spp. In order to compare the fungicidal activities of voriconazole and amphotericin B against 40 isolates of Aspergillus fumigatus, A. flavus, and A. terreus, we developed a new microbroth colorimetric method for assessing fungicidal activities and determining minimal fungicidal concentrations (MFCs). This methodology follows the antifungal susceptibility testing reference method M-38A for MIC determination. After drug removal and addition of fresh medium, growth of viable conidia adhering to the bottoms of the microtitration wells was assessed by a colorimetric assay of metabolic activity after 24 h of incubation. The new method was faster (six times), reproducible (92 to 97%), and in agreement with culture-based MFCs (91 to 100%). Differential fungicidal activities of voriconazole and amphotericin B were found among the three Aspergillus species, with A. fumigatus and A. flavus having the lowest (1 and 2 mg/liter, respectively) and A. terreus the highest (>16 mg/liter) median amphotericin B MFCs; A. flavus had a lower median voriconazole MFC (4 mg/liter) than the other species (>8 mg/liter; P <0.05). Amphotericin B was fungicidal (MFC/MIC ≤ 4) against all A. fumigatus and A. flavus isolates but no A. terreus isolates, whereas voriconazole was fungicidal against 82% of A. flavus isolates and fungistatic (MFC/MIC > 4) against 94% of A. fumigatus and 84% of A. terreus isolates. The new methodology revealed a concentration- dependent sigmoid pattern of fungicidal effects, indicating that fungicidal activity is not an all-or-nothing phenomenon and that some degree of fungicidal action can be found even for agents considered fungistatic based on the MFC/MIC ratio.

Original languageEnglish (US)
Pages (from-to)3329-3337
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume51
Issue number9
DOIs
StatePublished - Sep 2007
Externally publishedYes

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Aspergillus fumigatus
Amphotericin B
Aspergillus
Fungal Spores
Antifungal Agents
Sigmoid Colon
Growth
Pharmaceutical Preparations
Voriconazole

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Differential fungicidal activities of amphotericin B and voriconazole against Aspergillus species determined by microbroth methodology. / Meletiadis, Joseph; Antachopoulos, Charalampos; Stergiopoulou, Theodouli; Pournaras, Spyros; Roilides, Emmanuel; Walsh, Thomas J.

In: Antimicrobial Agents and Chemotherapy, Vol. 51, No. 9, 09.2007, p. 3329-3337.

Research output: Contribution to journalArticle

Meletiadis, Joseph ; Antachopoulos, Charalampos ; Stergiopoulou, Theodouli ; Pournaras, Spyros ; Roilides, Emmanuel ; Walsh, Thomas J. / Differential fungicidal activities of amphotericin B and voriconazole against Aspergillus species determined by microbroth methodology. In: Antimicrobial Agents and Chemotherapy. 2007 ; Vol. 51, No. 9. pp. 3329-3337.
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