In Vitro Susceptibility of Filamentous Fungal Isolates From a Corneal Ulcer Clinical Trial

Abstract

Purpose To describe the minimum inhibitory concentration (MIC) of fungal isolates to natamycin and voriconazole, and to compare these MICs to previous ocular susceptibility studies. Design Experimental laboratory study using isolates from a randomized clinical trial. Methods The Mycotic Ulcer Treatment Trial I was a randomized, double-masked, multicenter trial comparing topical natamycin and voriconazole for fungal keratitis treatment. Susceptibility testing to natamycin and voriconazole were performed according to Clinical and Laboratory Standards Institute methods. The relationship between organism and MIC was assessed. A literature review was performed to compare results to previous ocular susceptibility studies. Results Of the 323 patients enrolled in the trial, MICs were available for 221 (68%). Fusarium (N=126) and Aspergillus species (N=52) were the most commonly isolated organisms. MICs to natamycin and voriconazole were significantly different across all genera (P<0.001). The MIC median (MIC50) and 90th percentile (MIC90) for natamycin were equal to or higher than voriconazole for all organisms, except Curvularia species. Compared to other organisms, Fusarium species isolates had the highest MICs to voriconazole and A. flavus isolates had the highest MICs to natamycin. Our results were similar to previous reports except the voriconazole MIC90 against Aspergillus species was 2-fold higher and the natamycin MIC90 against A. fumigatus was 4-fold higher in our study. Conclusion In this large susceptibility study, Fusarium isolates were least susceptible to voriconazole and A. flavus isolates were least susceptible to natamycin when compared to other filamentous fungi. In the future, susceptibility testing may help guide therapy if performed in a timely manner.

In vitro susceptibility of filamentous fungi from mycotic keratitis to azole drugs

“…were resistant to VRC and hence higher concentration of drug is required for the effective treatment. However, there are studies that have suggested that VRC may have a broader antifungal spectrum [19,20]. Similar to our findings, Lalitha et al [17] and Iqbal et al [31] stated that Fusarium spp.…”

Contribution of ATPase copper transporters in animal but not plant virulence of the crossover pathogen Aspergillus flavus

“…However, a prominent fungal exception to this rarity is A. flavus which not only causes toxic seed diseases but also is a common agent of keratitis as well as a frequent pathogen of immunosuppressed patients [26,38]. This fungus is common in agricultural soils and hard to eliminate from that environment due to formation of resistant overwintering structures called sclerotia.…”

In vitro synergy of natamycin and voriconazole against clinical isolates of Fusarium, Candida, Aspergillus and Curvularia spp

“…Although several fungi were sensitive to natamycin, the authors concluded that the treatment outcome was poor in late stages 20. In another in vitro study by Lalitha et al 21 MIC of both natamycin and voriconazole in mycotic ulcer treatment for filamentous fungi have been described. The authors concluded that Fusarium isolates were least susceptible to voriconazole, and Aspergillus flavus isolates were least susceptible to natamycin 21.…”