PLD-118: In Vitro Activity on Candida albicans Strains - Comparison with In Vivo Efficacy in Systemic Candidiasis Mouse Model.

A. HASENOHRL, N. MARSIC, K. ORESKOVIC

Author address: 

PLIVA d.d. Research Division, Zagreb, Croatia.

Abstract: 

Background: PLD-118 is a novel antifungal of the beta-amino acid class, active primarily in Candida spp. The in vitro activity could not be observed when NCCLS methodology is employed. When tested, using specially designed method, on C. albicans strains MIC values for PLD-118 were distributed over the wide range. We showed that in vivo activity in an mouse model could be used to monitor correlation with in vitro activity. Methods: C. albicans strains were checked for pathogenicity in BalbC mice. Strains capable for causing 100% mortality when 106 inoculum used were processed further. Systemic cadidiasis was induced by iv administration of fresh inoculum of chosen C. albicans strains and PLD-118 was given at 30 min postinfection, two times daily for 4 days at doses 1, 5 and 25 mg/kg/day. The method for in vitro activity assessment 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 strains tested, the inhibitory concentrations (IC) inhibiting the normal fungi growth to the extent of 50%, 80% and 90% were recorded. Results: We compared ED50 (mg/kg/day) and different end points for MIC determination for PLD-118 and fluconazole. MIC values for fluconazole (IC50 after 48 hours) ranged
2003

abstract No: 

F-1229

Full conference title: 

43rd Interscience Conference on Antimicrobial Agents
    • ICAAC 43rd