July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Association of fungal species, in vitro susceptibility, and in vivo antifungal agent efficacy for isolates sampled from equine fungal keratitis
Author Affiliations & Notes
  • Megan Cullen
    Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, United States
  • Megan Jacob
    Department of Population Health and Pathobiology, North Carolina State University, Raleigh, North Carolina, United States
  • Vicki Cornish
    College of Agriculture and Life Sciences, North Carolina State University, Raleigh, North Carolina, United States
  • Ian VanderSchel
    College of Agriculture and Life Sciences, North Carolina State University, Raleigh, North Carolina, United States
  • Henry Van T Cotter
    College of Agriculture and Life Sciences, North Carolina State University, Raleigh, North Carolina, United States
  • Marc A Cubeta
    College of Agriculture and Life Sciences, North Carolina State University, Raleigh, North Carolina, United States
  • Ignazio Carbone
    College of Agriculture and Life Sciences, North Carolina State University, Raleigh, North Carolina, United States
  • Brian C Gilger
    Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, United States
  • Footnotes
    Commercial Relationships   Megan Cullen, None; Megan Jacob, None; Vicki Cornish, None; Ian VanderSchel, None; Henry Cotter, None; Marc Cubeta, None; Ignazio Carbone, None; Brian Gilger, None
  • Footnotes
    Support  NIH 5T32AI052080-15
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2097. doi:https://doi.org/
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      Megan Cullen, Megan Jacob, Vicki Cornish, Ian VanderSchel, Henry Van T Cotter, Marc A Cubeta, Ignazio Carbone, Brian C Gilger; Association of fungal species, in vitro susceptibility, and in vivo antifungal agent efficacy for isolates sampled from equine fungal keratitis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2097. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Equine fungal keratitis (EFK) is often treated empirically without the benefit of susceptibility testing. The purpose of this study was to compare in vitro drug susceptibility to in vivo efficacy of antifungal agents in the Galleria model against four species commonly isolated from EFK.

Methods : Isolates of Aspergillus flavus (n=15), Aspergillus fumigatus (n=3), Fusarium falciforme (n=9), and Fusarium keratoplasticum (n=1), obtained from clinical cases of EFK, were identified using multi-locus sequence typing. Minimum inhibitory concentration (MIC) assays were performed in duplicate on each isolate against fluconazole (FLC), voriconazole (VRC), thiabendazole (THB), terbinafine (TRB), and natamycin (NAT) based on CLSI guidelines. In vivo anti-fungal efficacy of VRC, TRB, and NAT was assessed in a representative sample of isolates of each species using a Galleria mellonella (GM) model. Antifungals were tested at concentrations 4x the therapeutic dose to establish safety in GM. Larvae were injected with conidial suspensions at concentrations known to produce >70% mortality within 7 days. Treated GM were administered a clinically relevant dose of an antifungal agent 2 hours after conidial injection. Survival curves between treatment groups, untreated larvae (conidial control), and uninfected larvae (injected control) were compared on day 7.

Results : Significant (p=<0.001) species-related differences were noted when comparing MIC results of VRC, TRB, THB, and NAT against A. flavus, A. fumigatus, and F. falciforme (Figure 1). VRC had a lower MIC relative to NAT. Using the GM model, F. falciforme exhibited the most sensitivity to NAT in vivo (100% survival on day 7), followed by TRB (60% survival), while only 50% of VRC-injected larvae survived.

Conclusions : Accurate species identification of fungi is important for guiding treatment. MIC results did not always correlate to in vivo efficacy, and knowledge of in vivo response for given species and antifungal agent may help improve clinical interpretation of culture and sensitivity results.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Antifungal agents in different boxes have significantly different MIC's (ANOVA, 2-factor. P<0.001 for fungus-antifungal agent interaction. Mean separation: Tukey with α= 0.05). Antifungal names are positioned at log2 MIC value closest to their mean for that fungal species.

Antifungal agents in different boxes have significantly different MIC's (ANOVA, 2-factor. P<0.001 for fungus-antifungal agent interaction. Mean separation: Tukey with α= 0.05). Antifungal names are positioned at log2 MIC value closest to their mean for that fungal species.

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