Evaluation of L-743,872 (872) in the treatment of murine histoplasmosis.
Program Abstr Intersci Conf Antimicrob Agents Chemother. 1996 Sep 15-18;:107 (abstract no. F43). Unique Identifier : AIDSLINE MED/98927663 Najvar L; Graybill J; Montalbo E; Barchiesi F; Luther M; University of Texas Health Science Center, San Antonio, TX.
Abstract:
Balb/c Nu/+ mice were infected intravenously with clinical isolate #93-255 of Histoplasma capsulatum at 5x10(6) CFU/mouse. The MIC's for 872 were read at 7 days to account for the slow growth of the organism and were performed by the NCCLS method. The MIC was 0.25 mcg/ml. Treatment was initiated 24 hours after infection intraperitoneally (IP) with 872 given at 0.01, 0.05, 0.1, 0.25, 0.5, 5, 10 mg/kg once daily or 5 mg/kg twice daily. 872 was prepared daily in sterile water. Controls received sterile water IP. Therapy was continued through day 7 and mice were then followed through day 30 for survival. For tissue burden studies treatment was the same but mice were sacrificed on day 8. Livers and spleens were removed, weighed, homogenized and fungal burden was measured by serial quantitative counts. Prolongation of survival was measured by Logrank and Wilcoxon tests. Dunnett's One-tailed T test was used to measure the reduction of colony counts in the liver and spleens. 872 prolonged survival at a dose as low as 0.05 mg/kg/day. Similar results were obtained in the tissue burden studies. In conclusion 872 has proven to be a potent drug in the murine model of histoplasmosis and warrants clinical development.
Keywords: *Antibiotics, Peptide/THERAPEUTIC USE *Antifungal Agents/THERAPEUTIC USE *Histoplasmosis/DRUG THERAPY 980430
M9841211
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