Galactomannan Is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis

Antimicrob Agents Chemother. 2019 Dec 20;64(1):e01966-19. doi: 10.1128/AAC.01966-19. Print 2019 Dec 20.

Abstract

Galactomannan (GM) detection in biological samples has been shown to predict therapeutic response by azoles and polyenes. In a murine invasive pulmonary aspergillosis model, fosmanogepix or posaconazole treatment resulted in an ∼6- to 7-log reduction in conidial equivalents (CE)/g lung tissue after 96 h versus placebo. Changes in GM levels in BAL fluid and serum mirrored reductions in lung CE, with significant decreases seen after 96 h or 72 h for fosmanogepix or posaconazole, respectively (P < 0.02).

Keywords: 1-aminobenzotriazole; APX001; APX001A; Aspergillus; Aspergillus fumigatus; Gwt1; antifungal; antifungal agents; fosmanogepix; galactomannan; infection model; manogepix; murine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / therapeutic use*
  • Aspergillosis / drug therapy
  • Aspergillosis / metabolism
  • Aspergillus fumigatus / drug effects
  • Aspergillus fumigatus / pathogenicity
  • Biomarkers / metabolism*
  • Galactose / analogs & derivatives
  • Immunocompromised Host
  • Invasive Pulmonary Aspergillosis / drug therapy*
  • Invasive Pulmonary Aspergillosis / metabolism*
  • Lung / microbiology
  • Male
  • Mannans / metabolism*
  • Mice
  • Microbial Sensitivity Tests
  • Triazoles / therapeutic use

Substances

  • Antifungal Agents
  • Biomarkers
  • Mannans
  • Triazoles
  • galactomannan
  • posaconazole
  • Galactose