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

研究成果: ジャーナルへの寄稿記事

19 引用 (Scopus)

抄録

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.

元の言語英語
ジャーナルAntimicrobial Agents and Chemotherapy
61
発行部数10
DOI
出版物ステータス出版済み - 1 1 2017

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Echinocandins
Abdominal Abscess
Candidiasis
Infection
Pharmaceutical Preparations
Tissue Distribution
Mass Spectrometry
Therapeutics
Technology
Mortality

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

これを引用

Unraveling drug penetration of echinocandin antifungals at the site of infection in an intra-abdominal abscess model. / Zhao, Yanan; Prideaux, Brendan; Nagasaki, Yoji; Lee, Min Hee; Chen, Pei Yu; Blanc, Landry; Ho, Hsinpin; Clancy, Cornelius J.; Nguyen, Minh Hong; Dartois, Véronique; Perlin, David S.

:: Antimicrobial Agents and Chemotherapy, 巻 61, 番号 10, 01.01.2017.

研究成果: ジャーナルへの寄稿記事

Zhao, Y, Prideaux, B, Nagasaki, Y, Lee, MH, Chen, PY, Blanc, L, Ho, H, Clancy, CJ, Nguyen, MH, Dartois, V & Perlin, DS 2017, 'Unraveling drug penetration of echinocandin antifungals at the site of infection in an intra-abdominal abscess model', Antimicrobial Agents and Chemotherapy, 巻. 61, 番号 10. https://doi.org/10.1128/AAC.01009-17
Zhao, Yanan ; Prideaux, Brendan ; Nagasaki, Yoji ; Lee, Min Hee ; Chen, Pei Yu ; Blanc, Landry ; Ho, Hsinpin ; Clancy, Cornelius J. ; Nguyen, Minh Hong ; Dartois, Véronique ; Perlin, David S. / Unraveling drug penetration of echinocandin antifungals at the site of infection in an intra-abdominal abscess model. :: Antimicrobial Agents and Chemotherapy. 2017 ; 巻 61, 番号 10.
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AU - Chen, Pei Yu

AU - Blanc, Landry

AU - Ho, Hsinpin

AU - Clancy, Cornelius J.

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