Background:: PLD-118 is a novel antifungal of the beta-amino acid class, primarily active against Candida spp., including azole-resistant strains. We compared the in vitro activity of PLD-118 with amphotericin B and fluconazole on C. parapsilosis, C. glabrata, C. tropicalis, C. krusei and C. guilliermondii strains. Both MIC values were measured and time-kill curves were performed. Methods: The method was microtitre plate dilution assay previously described (41st ICAAC). Test medium was YNG, inoculum size: 50-100 cfu/well and the optical density was measured after 24 and 48 hours of incubation at 37°C. For all substances tested, the inhibitory concentrations (IC) inhibiting the normal fungi growth to the extent of 50%, 80% and 90% were measured. The time-kill studies were performed using the methodology adapted to the method used for MIC determinations for PLD-118 (inoculum size, medium composition, pH of the medium). Results: We compared different end points for MIC determination for all antifungal substances tested. PLD 118 had the best in vitro activity on C. glabrata and C. krusei isolates (MIC after 24-48 hours were within 0.25-8 µg/ml range). Time-kill studies performed on those two Candida species with amphotericin B, fluconazole and PLD 118 showed that methodology tailored for PLD 118 could be used for standard antifungals as well. Conclusions: We have defined conditions where in vitro activity of PLD 118 by both MIC and time-kill could be measured in reproducible way for various Candida non-albicans species. Due to the interesting activity on these strains in vitro, further in vivo efficacy studies are warranted.
Full conference title:
42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 42nd