Activity of Isavuconazole, Amphotericin B, and Micafungin Alone and in Combination against Exserohilum rostratum

P. W. Moradi, V. Petraitis, R. Petraitiene, G. E. Strauss, D. H. Larone, Y. Zhao, A. W. Forthergill, M. Ghannoum, M. Simitsopoulou, E. Roilides, D. P. Kontoyiannis, D. S. Perlin, T. J. Walsh

Author address: 

Exserohilum Meningitis Study Consortium, New York, NY


Background: E. rostratum has been identified as causing a recent nationwide outbrake of meningitis related to contaminated vials of methylprednisolone. Little is known about effective antifungal monotherapy or combination therapy against E. rostratum meningitis (ERM). Isavuconazole (ISA) is a novel triazole that may have a role alone or in combination for treatment of ERM. We therefore studied the in vitro activity of ISA alone and in combination with other antifungal agents against E. rostratum.Methods: CLSI (M38-A2) broth microdilution methodology was used to determine MICs for ISA, micafungin (MFG), and amphotericin B (AMB) against 5 isolates of E. rostratum in triplicate. Minimum fungicidal concentrations (MFCs) were determined by plating wells with optical clearance. Two-drug combinations were studied in 96-well plates by checkerboard methods in duplicate: ISA (0.0625 - 32 μg/mL), MFG (0.5 - 32 μg/mL), and AMB (0.125 - 8 μg/mL). Plates were inoculated with of 0.25-5"¢104CFU/mL of E. rostratum. After 48-h of incubation at 37°C, OD measurements were recorded at 530 nm. Bliss independence drug interaction (BIDI) analysis was performed and fractional inhibitory concentration indices (FICI) were calculated. The effect of antifungal agents on hyphal structure was evaluated by light microscopy. Results: Hyphal truncation and distortion were observed with ISA at 0.125 μg/mL. More severe but structurally similar effects were observed with AMB at 0.125 μg/mL. Conclusion: ISA was active in vitro against E. rostratum at concentrations of 0.5 - 4 μg/mL. MFCs exceeded MICs for all antifungal agents against all isolates. AMB was the most active antifungal agent and induced the most structural damage in vitro. All interactions with ISA were independent by BIDI and additive by FICI.

abstract No: 


Full conference title: 

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC, 53rd (2013)