Antifungal activity of HWA-138 and amphotericin B in experimental systemic candidiasis.

Abstract

HWA-138, a pentoxifylline analog, has been shown to increase yeast urinary clearance and to reduce yeast counts in the kidneys of rats infected with Candida albicans. Furthermore, HWA-138 has also been shown to prevent amphotericin B-induced acute renal failure in rats. We report here on the effects of HWA-138 alone and in combination with amphotericin B in the treatment of systemic candidiasis in mice. When single doses of HWA-138 were administered intravenously (10, 25, or 50 mg/kg of body weight) into infected mice, no significant improvement in survival was observed. In infected mice treated intravenously with multiple doses of HWA-138 (10, 25, or 50 mg/kg once daily for 5 consecutive days), a significant increase in survival time was seen only in animals also receiving 25 mg of HWA-138 per kg (14 +/- 3 days test versus 9 +/- 1 days control; P less than 0.05). The coadministration of subtherapeutic doses of amphotericin B and HWA-138 resulted in increased survival time. Combination therapy with amphotericin B (0.1-mg/kg single dose) and HWA-138 (10-, 25-, or 50-mg/kg multiple doses) resulted in a significant increase in survival time over controls (19 +/- 4, 19 +/- 5, and 21 +/- 9 days, respectively, versus 9 +/- 3 days; P less than 0.05). Combination therapy with amphotericin B (0.2-mg/kg single dose) and HWA-138 (10-, 25-, or 50-mg/kg multiple doses) also resulted in a significant increase in survival time over controls (24 +/- 6, 24 +/- 6, and 24 +/- 6, respectively, versus 9 +/- 3 days; P less than 0.05). Combination therapy with amphotericin B (0.2-mg/kg single dose) and HWA-138 (10-, 25-, or 50-mg/kg multiple doses) also resulted in a significant increase in survival time over controls (24 +/- 6, 24 +/- 6, and 24 +/- 6, respectively, versus 9 +/- 3 days; P < 0.05). Variance analysis of these findings indicate synergistic activity between amphotericin B and HWA-138 in the treatment of experimental candidiasis in mice.

• Authors: K M Wasan, K Vadiei, D R Luke, A Keyhani, R A White, T J McQueen, R Mehta, G Lopez-Berestein
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 35 Issue 10 Pg. 2046-8 (Oct 1991) ISSN: 0066-4804 [Print] United States
• PMID: 1759826 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antifungal Agents
• 1-(5-hydroxy-5-methylhexyl)-3-methylxanthine
• Amphotericin B
• Pentoxifylline

Topics

• Amphotericin B (therapeutic use)
• Animals
• Antifungal Agents (therapeutic use)
• Candidiasis (drug therapy)
• Drug Synergism
• Mice
• Mice, Inbred ICR
• Pentoxifylline (analogs & derivatives, therapeutic use)