Unraveling drug penetration of echinocandin antifungals at the site of infection in an intra-abdominal abscess model

Yanan Zhao, Brendan Prideaux, Yoji Nagasaki, Min Hee Lee, Pei Yu Chen, Landry Blanc, Hsinpin Ho, Cornelius J. Clancy, Minh Hong Nguyen, Véronique Dartois, David S. Perlin

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Intra-abdominal candidiasis (IAC) is a prominent invasive fungal infection associated with high mortality. Prompt antifungal therapy and source control are crucial for successful treatment. Echinocandin antifungal drugs are first-line agents; however, their clinical effectiveness is highly variable, with known potential for breakthrough resistance, and little is known about drug exposure at the site of infection. Using matrix-assisted desorption ionization mass spectrometry imaging technology, we investigated the spatial and quantitative distribution in tissue lesions for two echinocandin drugs, micafungin and CD101, in a clinically relevant IAC mouse model. Drug accumulation within lesions was observed with both drugs at their humanized therapeutic doses. CD101, but not micafungin, accumulated in lesions at levels above the mutant prevention concentration of the infecting strain. These findings indicate that current echinocandin drugs are limited by penetration at the site of infection and have implications for clinical outcomes and emergence of resistance in patients with IAC.

Original languageEnglish (US)
JournalAntimicrobial agents and chemotherapy
Volume61
Issue number10
DOIs
StatePublished - 2017

Keywords

  • Drug penetration
  • Echinocandin
  • Intra-abdominal candidiasis
  • Matrix-assisted desorption ionization (MALDI) mass spectrometry imaging

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Zhao, Y., Prideaux, B., Nagasaki, Y., Lee, M. H., Chen, P. Y., Blanc, L., Ho, H., Clancy, C. J., Nguyen, M. H., Dartois, V., & Perlin, D. S. (2017). Unraveling drug penetration of echinocandin antifungals at the site of infection in an intra-abdominal abscess model. Antimicrobial agents and chemotherapy, 61(10). https://doi.org/10.1128/AAC.01009-17