Sa, a mould of environmental flora, is increasingly encountered as a pathogen in invasive mycoses in immunocompromised hosts, possibly as a result of improved prophylaxis and therapy of yeasts. Sa is regarded as difficult to treat, owing to resistance to current antifungals. M is an investigational echinocandin antifungal, acting to inhibit 1,3-beta-glucan, an essential cell wall polysaccharide. In the course of studies of 166 various isolates from ongoing clinical trials (ICAAC ’02, #M-1520), Sa susceptibility to M was noted with a few isolates. The present study explored Sa susceptibility to M. Ten clinical Sa isolates were tested by broth macrodilution (Diagn. Microbiol. Infect. Dis. 29:103, 1997), with in-run susceptible C. kefyr controls, and an MEC (min. effective conc., corresponding to 80% inhibition of growth) determined. The MEC distribution was 0.25 µg/ml (3 isolates), 0.5 (1), 1 (3), and 2 (3). Of note, even 2 µg/ml is a clinically relevant M concentration. Six isolates were concurrently tested vs. amphotericin B (AmB), with an MEC distribution of 0.5 (1), 4 (2), 8 (1), and >8 (2), confirming a general impression of resistance. Of note, concurrent testing in RPMI-1640 (NCCLS method M38P) gave the same results, though tests done in Yeast Nitrogen Broth gave consistently lower AmB values. Classical MIC, and MFC (>96% kill), results gave values >8 µg/ml for both drugs; in YNB with AmB, values were lower in 3-4/6 isolates. A lack of activity by conventional agents against Sa led to the study and licensing of voriconazole against the genus. The present data suggest whereas M not quite as active in vitro, vs. Sa, as M is vs. Candida and Aspergillus, this echinocandin also has Sa activity. If in vivo-in vitro correlations support our observations, M activity may be encouraging news in treating infections caused by this difficult pathogen.
Full conference title:
The 15 th Congress of the International Society for Human and Animal Mycology
- ISHAM 15th (2003)