IN-VITRO ACTIVITY OF A NEW TRIAZOLE ANTIFUNGAL AGENT, SCH-56592, AGAINST CLINICAL ISOLATES OF FILAMENTOUS FUNGI

Sch 56592 is a new triazole derivative that possesses potent, broad-sp ectrum antifungal activity. We evaluated the in vitro activity of Sch 56592 compared with that of itraconazole, amphotericin B and 5-fluoroc ytosine against 51 clinical isolates of filamentous fungi, including A spergillus flavus (10), A. fumigatus (12), Fusarium spp. (13), Rhizopu s spp. (6), Pseudallescheria boydii (5), and one isolate each of Acrem onium spp., A. niger, A. tel reus, Paecilomyces spp., and Trichoderma spp. In vitro susceptibility testing was performed using the microdilu tion broth method outlined in the NCCLS 27-A document. Sch 56592 was h ighly active against A. flavus (MIC90, 0.25 mu g/ml), A. fumigatus (MI C90, 0.12 mu g/ml), P. boydii (MIC50, 1 mu ml) and Rhizopus spp (MIC50 , 1 mu g/ml). By comparison with itraconazole, Sch 56592 was four- to eight-fold more active against isolates of Aspergillus and both compou nds showed equipotent in vitro activity against P. boydii and Rhizopus spp. Sch 56592 was four- to 16-fold more active than amphotericin B a gainst Aspergillus spp, and P. boydii and both antifungal drugs displa yed similar activity against Rhizopus spp. Overall, Sch 56592 showed g ood in vitro activity against all isolates tested (MIC, less than or e qual to 2 mu g/ml) except isolates of Fusarium (MIC range, 1->4 mu g/m l). On the basis of these data Sch 56592 has promising activity agains t Aspergillus spp. and other species of filamentous fungi that are lik ely to be encountered clinically. Additional in vitro and in vivo stud ies are warranted.