Background: Exserohilum (E.) rostratum was the primary fungal species implicated in the nationwide outbreak of contaminated steroid injections. This species is a rare cause of human infections, and little is known regarding optimal therapy. Despite prolonged voriconazole (VOR) therapy with or without amphotericin B (AMB), clinical failures have been seen. In addition, it has been suggested that the steroid component of the injection may have stimulated growth, leading to enhanced virulence.Methods: We studied 6 clinical isolates of E. rostratum from the outbreak with respect to in vitro antifungal susceptibility, including antifungal combinations, as well as the effect of methylprednisolone (MTP) on growth. CLSI microbroth dilution methodology M38-A2 was used, adapted for checkerboard dilution testing for 2 antifungal drugs. MICs and minimum effective concentration (MEC) - for caspofungin (CAS) only - were read at 48 hours. All isolates were tested to VOR; 3 isolates were tested with combinations of VOR with AMB, CAS or flucytosine (5FC). The fractional inhibitory concentration (FIC) index was calculated for each combination; FIC 4 = antagonism. The effects of MTP on growth was studied with 2 methods: 1) 3 isolates of E. rostratumwere grown on agar plates containing 0, 1, 10, 100, and 1000 μg/ml MTP and colony diameter was assessed at 48 hours; 2) microbroth dilution testing was performed with voriconazole and the addition of MTP at 0, 1, 10, 100, and 1000 μg/ml. Results: The VOR MIC of all isolates was 2 μg/ml. The mean MIC of AMB was 2.7 and of 5FC was >64 μg/ml ; the MEC of CAS was 4 μg/ml. The mean FIC index for VOR+AMB was 0.51, VOR+CAS was 1.0, and VOR+5FC was 2. There was no antagonism observed. MTP did not affect the MIC of VOR in microbroth dilution, though in agar media, only the 1000 μg/ml plate showed a 25% mean reduction of colony diameter at 48 hours. Conclusions: The interpretation of the VOR MIC for E. rostratum is not established; its clinical significance is unclear. No synergy or antagonism was observed when VOR was used with AMB, CAS or 5FC, though an additive effect could not be excluded. MTP did not enhance growth of E. rostratum in either agar or broth media; 1000 μg/ml inhibited growth on agar media alone. Alternative strategies to treat this fungal infection should be explored.
Full conference title:
53rd Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC, 53rd (2013)