1450. Methylprednisolone (MP) Enhances the Growth of Exserohilum rostratum in Vitro and Increases Death in a Fly Model
Session: Poster Abstract Session: Fungal Infections
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C

Background: Contaminated vials of methylprednisolone with the dematiaceous mold Exserohilum rostratum (E. rostratum) resulted in a fatal multistate outbreak of central nervous system infection in the USA in immunocompetent hosts. As fungi might possess steroid receptors that could affect their growth and/or virulence in the presence of corticosteroids, we hypothesized that MP enhances the growth and/or virulence of E.rostratum.

Methods: E.rostratum isolate was grown on potato dextrose agar plates (PDA) at 37oC for 5 days to obtain macroconidia. To assess growth rate, 10 3 conidia/ml of E. rostratum were added to 300ml of RPMI broth in a 96-well plates that were incubated in a plate reader at 37oC for 2 days, in the presence of different MP concentrations (0, 0.160 ,0.320 mg/ml). In addition, we inoculated by injection wild type (WT) flies with 106 conidia/ml of E. rostratum, pre-exposed or not to high MP dose MP (0.320 mg/ml) for 7 days. Survival rates were recorded for 7 days after infection. The in vitro experiments were performed in triplicate whereas the in vivo experiments were performed in duplicate on different days.

Results: Compared to control (no MP), the growth of E. rostratum in the presence of a high concentration (0.320 mg/ml) of MP was significantly enhanced (p=0.0067) whereas 0.160 mg/ml of MP did not have a significant effect on E. rostratum growth (p=0.0821) (Graph 1). Similarly, we observed an increase in death in flies infected with E. rostratum spores pre-exposed to 0.320 mg/ml of MP, compared to flies infected with non-exposed to MP spores (p=0.0002) (Graph 2)

Conclusion: High concentration of MP significantly increases the growth of E. rostratum in vitro and increases death in an immunocompetent fly model.

Peguy Saad, MD, Infectious Diseases, Baylor College of Medicine, Houston, TX; Infectious Diseases, MD Anderson Cancer Center, houston, TX, Nathaniel Albert, BS, MD Anderson Cancer Center, Houston, TX, David Perlin, PhD, PHRI-University of Medicine and Dentistry of New Jersey, Newark, NJ, Fazal Shirazi, PhD, Infectious Diseases, MD Anderson Cancer Center, Houston, TX, Dimitrios Farmakiotis, MD, Baylor College of Medicine, Houston, TX, Emmanuel Roilides, PhD, NCI, NIH, Bethesda, MD, Thomas Walsh, MD, FIDSA, Transplantation-Oncology, Weill Cornell Medical College of Cornell University, New York City, NY and Dimitrios Kontoyiannis, MD, ScD, FIDSA, The University of Texas M.D. Anderson Cancer Center, Houston, TX

Disclosures:

P. Saad, None

N. Albert, None

D. Perlin, None

F. Shirazi, None

D. Farmakiotis, None

E. Roilides, None

T. Walsh, iCo: Consultant, Consulting fee
Draius: Consultant, Consulting fee
Trius Therapeutics: Consultant, Consulting fee
Astellas Pharma US: Consultant, Consulting fee and Research grant
Sigma Tau Pharmaceuticals: Consultant, Consulting fee
Novartis: Consultant, Consulting fee and Research grant
Methylgene: Consultant, Consulting fee
Merck: Grant Investigator, Research grant

D. Kontoyiannis, Merck: Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research grant and Speaker honorarium
Gilead: Speaker's Bureau, Speaker honorarium
Astellas: Investigator, Research grant
T2 biosystems: Investigator, Research grant

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