VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection

Teclegiorgis Gebremariam; Nathan P Wiederhold; Annette W Fothergill; Edward P Garvey; William J Hoekstra; Robert J Schotzinger; Thomas F Patterson; Scott G Filler; Ashraf S Ibrahim

doi:10.1128/AAC.01437-15

VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection

Antimicrob Agents Chemother. 2015 Dec;59(12):7815-7. doi: 10.1128/AAC.01437-15. Epub 2015 Sep 14.

Authors

Teclegiorgis Gebremariam¹, Nathan P Wiederhold², Annette W Fothergill², Edward P Garvey³, William J Hoekstra³, Robert J Schotzinger³, Thomas F Patterson⁴, Scott G Filler⁵, Ashraf S Ibrahim⁶

Affiliations

¹ The Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center and St. John's Cardiovascular Research Center, Torrance, California, USA.
² University of Texas Health Sciences at San Antonio, San Antonio, Texas, USA.
³ Viamet Pharmaceuticals, Inc., Durham, North Carolina, USA.
⁴ University of Texas Health Sciences at San Antonio, San Antonio, Texas, USA South Texas Veterans Health Care System, San Antonio, Texas, USA.
⁵ The Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center and St. John's Cardiovascular Research Center, Torrance, California, USA David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
⁶ The Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center and St. John's Cardiovascular Research Center, Torrance, California, USA David Geffen School of Medicine at UCLA, Los Angeles, California, USA [email protected].

Abstract

We studied the efficacy of the investigational drug VT-1161 against mucormycosis. VT-1161 had more potent in vitro activity against Rhizopus arrhizus var. arrhizus than against R. arrhizus var. delemar. VT-1161 treatment demonstrated dose-dependent plasma drug levels with prolonged survival time and lowered tissue fungal burden in immunosuppressed mice infected with R. arrhizus var. arrhizus and was as effective as high-dose liposomal amphotericin B treatment. These results support further development of VT-1161 against mucormycosis.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Amphotericin B / pharmacology
Animals
Antifungal Agents / blood
Antifungal Agents / pharmacokinetics
Antifungal Agents / pharmacology*
Immunocompromised Host*
Male
Mice
Mice, Inbred ICR
Microbial Sensitivity Tests
Mucormycosis / drug therapy*
Mucormycosis / immunology*
Mucormycosis / microbiology
Mucormycosis / mortality
Pyridines / blood
Pyridines / pharmacokinetics
Pyridines / pharmacology*
Rhizopus / drug effects*
Rhizopus / growth & development
Species Specificity
Survival Analysis
Tetrazoles / blood
Tetrazoles / pharmacokinetics
Tetrazoles / pharmacology*

Substances

Antifungal Agents
Pyridines
Tetrazoles
VT-1161
liposomal amphotericin B
Amphotericin B

Abstract

Publication types

MeSH terms

Substances

Grants and funding