Phase-dependent antifungal activity against Aspergillus fumigatus developing multicellular filamentous biofilms

Eilidh Mowat, Sue Lang, Craig Williams, Elaine McCulloch, Brian L. Jones, Gordon Ramage

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: Aspergillus fumigatus undergoes morphological transition throughout its growth and development. These changes have direct implications for the effectiveness of antifungal treatment. Here we report the in vitro antifungal activity of voriconazole, amphotericin B and caspofungin against three specific phases of multicellular development of A. fumigatus.

METHODS: A. fumigatus conidia were propagated for 8, 12 and 24 h prior to antifungal challenge. The resultant activity of the three agents tested was determined using an XTT reduction assay to assess both endpoint and time-kill susceptibility profiles.

RESULTS: Endpoint susceptibility testing demonstrated a time-dependent decrease in efficacy for all three antifungal agents as the complexity of the A. fumigatus hyphal structure developed. Overall, amphotericin B exhibited the best spectrum of activity at each phase of growth, but was comparable to voriconazole against germinated conidial growth (8 h). Later, both voriconazole and caspofungin were ineffective against complex mycelial structures (12 and 24 h). Time-kill studies demonstrated that amphotericin B was significantly more efficacious at reducing A. fumigatus metabolism than both voriconazole and caspofungin for all three growth phases examined, most notably after 1 h of drug exposure (P < 0.001).

CONCLUSIONS: Overall, the data presented demonstrate that treatment of actively growing A. fumigatus cells with antifungal agents is more efficacious than treating mature structures in vitro. Amphotericin B was consistently more effective against each phase and displayed rapid effects, and therefore may be a suitable option for managing patient groups at risk from aspergillosis infections.

Original languageEnglish
Pages (from-to)1281-4
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Volume62
Issue number6
DOIs
Publication statusPublished - Dec 2008
Externally publishedYes

Fingerprint

Aspergillus fumigatus
Biofilms
caspofungin
Amphotericin B
Antifungal Agents
Growth
Aspergillosis
Fungal Spores
Growth and Development
Voriconazole
Infection
Pharmaceutical Preparations

Keywords

  • Amphotericin B
  • Antifungal Agents
  • Aspergillus fumigatus
  • Biofilms
  • Echinocandins
  • Formazans
  • Humans
  • Lipopeptides
  • Microbial Sensitivity Tests
  • Microbial Viability
  • Mycelium
  • Oxidation-Reduction
  • Pyrimidines
  • Spores, Fungal
  • Triazoles
  • Voriconazole
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Mowat, Eilidh ; Lang, Sue ; Williams, Craig ; McCulloch, Elaine ; Jones, Brian L. ; Ramage, Gordon. / Phase-dependent antifungal activity against Aspergillus fumigatus developing multicellular filamentous biofilms. In: Journal of Antimicrobial Chemotherapy. 2008 ; Vol. 62, No. 6. pp. 1281-4.
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abstract = "OBJECTIVES: Aspergillus fumigatus undergoes morphological transition throughout its growth and development. These changes have direct implications for the effectiveness of antifungal treatment. Here we report the in vitro antifungal activity of voriconazole, amphotericin B and caspofungin against three specific phases of multicellular development of A. fumigatus.METHODS: A. fumigatus conidia were propagated for 8, 12 and 24 h prior to antifungal challenge. The resultant activity of the three agents tested was determined using an XTT reduction assay to assess both endpoint and time-kill susceptibility profiles.RESULTS: Endpoint susceptibility testing demonstrated a time-dependent decrease in efficacy for all three antifungal agents as the complexity of the A. fumigatus hyphal structure developed. Overall, amphotericin B exhibited the best spectrum of activity at each phase of growth, but was comparable to voriconazole against germinated conidial growth (8 h). Later, both voriconazole and caspofungin were ineffective against complex mycelial structures (12 and 24 h). Time-kill studies demonstrated that amphotericin B was significantly more efficacious at reducing A. fumigatus metabolism than both voriconazole and caspofungin for all three growth phases examined, most notably after 1 h of drug exposure (P < 0.001).CONCLUSIONS: Overall, the data presented demonstrate that treatment of actively growing A. fumigatus cells with antifungal agents is more efficacious than treating mature structures in vitro. Amphotericin B was consistently more effective against each phase and displayed rapid effects, and therefore may be a suitable option for managing patient groups at risk from aspergillosis infections.",
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Phase-dependent antifungal activity against Aspergillus fumigatus developing multicellular filamentous biofilms. / Mowat, Eilidh; Lang, Sue; Williams, Craig; McCulloch, Elaine; Jones, Brian L. ; Ramage, Gordon.

In: Journal of Antimicrobial Chemotherapy, Vol. 62, No. 6, 12.2008, p. 1281-4.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase-dependent antifungal activity against Aspergillus fumigatus developing multicellular filamentous biofilms

AU - Mowat, Eilidh

AU - Lang, Sue

AU - Williams, Craig

AU - McCulloch, Elaine

AU - Jones, Brian L.

AU - Ramage, Gordon

PY - 2008/12

Y1 - 2008/12

N2 - OBJECTIVES: Aspergillus fumigatus undergoes morphological transition throughout its growth and development. These changes have direct implications for the effectiveness of antifungal treatment. Here we report the in vitro antifungal activity of voriconazole, amphotericin B and caspofungin against three specific phases of multicellular development of A. fumigatus.METHODS: A. fumigatus conidia were propagated for 8, 12 and 24 h prior to antifungal challenge. The resultant activity of the three agents tested was determined using an XTT reduction assay to assess both endpoint and time-kill susceptibility profiles.RESULTS: Endpoint susceptibility testing demonstrated a time-dependent decrease in efficacy for all three antifungal agents as the complexity of the A. fumigatus hyphal structure developed. Overall, amphotericin B exhibited the best spectrum of activity at each phase of growth, but was comparable to voriconazole against germinated conidial growth (8 h). Later, both voriconazole and caspofungin were ineffective against complex mycelial structures (12 and 24 h). Time-kill studies demonstrated that amphotericin B was significantly more efficacious at reducing A. fumigatus metabolism than both voriconazole and caspofungin for all three growth phases examined, most notably after 1 h of drug exposure (P < 0.001).CONCLUSIONS: Overall, the data presented demonstrate that treatment of actively growing A. fumigatus cells with antifungal agents is more efficacious than treating mature structures in vitro. Amphotericin B was consistently more effective against each phase and displayed rapid effects, and therefore may be a suitable option for managing patient groups at risk from aspergillosis infections.

AB - OBJECTIVES: Aspergillus fumigatus undergoes morphological transition throughout its growth and development. These changes have direct implications for the effectiveness of antifungal treatment. Here we report the in vitro antifungal activity of voriconazole, amphotericin B and caspofungin against three specific phases of multicellular development of A. fumigatus.METHODS: A. fumigatus conidia were propagated for 8, 12 and 24 h prior to antifungal challenge. The resultant activity of the three agents tested was determined using an XTT reduction assay to assess both endpoint and time-kill susceptibility profiles.RESULTS: Endpoint susceptibility testing demonstrated a time-dependent decrease in efficacy for all three antifungal agents as the complexity of the A. fumigatus hyphal structure developed. Overall, amphotericin B exhibited the best spectrum of activity at each phase of growth, but was comparable to voriconazole against germinated conidial growth (8 h). Later, both voriconazole and caspofungin were ineffective against complex mycelial structures (12 and 24 h). Time-kill studies demonstrated that amphotericin B was significantly more efficacious at reducing A. fumigatus metabolism than both voriconazole and caspofungin for all three growth phases examined, most notably after 1 h of drug exposure (P < 0.001).CONCLUSIONS: Overall, the data presented demonstrate that treatment of actively growing A. fumigatus cells with antifungal agents is more efficacious than treating mature structures in vitro. Amphotericin B was consistently more effective against each phase and displayed rapid effects, and therefore may be a suitable option for managing patient groups at risk from aspergillosis infections.

KW - Amphotericin B

KW - Antifungal Agents

KW - Aspergillus fumigatus

KW - Biofilms

KW - Echinocandins

KW - Formazans

KW - Humans

KW - Lipopeptides

KW - Microbial Sensitivity Tests

KW - Microbial Viability

KW - Mycelium

KW - Oxidation-Reduction

KW - Pyrimidines

KW - Spores, Fungal

KW - Triazoles

KW - Voriconazole

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/jac/dkn402

DO - 10.1093/jac/dkn402

M3 - Article

VL - 62

SP - 1281

EP - 1284

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 6

ER -