IBRAHIM AS, AVANESIAN V, LEE H, EDWARDS JE; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. M-192.

Research and Education Institute, Harbor-UCLA Medical Center, Torrance, CA

BACKGROUND:The treatment of mucormycosis with AmB is associated with substantial toxicity and mortality in patients with uncontrolled diabetes. Because AmBisome is less nephrotoxic than AmB, it can be used at higher doses for the treatment of mucormycosis. We used the mouse model of hematogenously disseminated mucormycosis to compare the efficacy of AmB to AmBisome. METHODS: To compare the efficacy of the two drugs, streptozotocin-induced diabetic Balb/C mice were infected with 5 X 10[2] or 10[4] spores of Rhizopus oryzae via the tail vein. 24h post infection, mice were treated i.v. with 0.5 mg/kg/AmB 2X/d, or 2.5 mg/kg/AmBisome 2X/d for a period of 4d. To determine drug toxicity, uninfected mice were treated i.v. with the same doses of AmB or AmBisome used in treatment. The survival of mice within each group was recorded over a period of 14d. RESULTS: AmB was more toxic to diabetic mice than AmBisome. Due to this toxicity, drug doses of both drugs were divided in half and given twice daily. At 5 X 10[2], 20% of untreated infected mice survived the infection, whereas AmB treated mice and those treated with AmBisome had 80% and 90% survival, respectively. At a higher inoculum of 10[4], there was no statistical difference between the median survival time of untreated mice (2.5 days) and those treated with AmB (3.5 days) or AmBisome (2.5 days). CONCLUSIONS: AmBisome is less toxic than AmB in a diabetic mouse model. We have shown that AmBisome is as effective as AmB in prolonging the survival of infected mice. More severe infection was not responsive to either drug. Further investigations are warranted with AmBisome to study its effectiveness in the treatment of hematogenously disseminated mucormycosis at higher challenge doses.

Publication Types:

• Meeting Abstracts

Keywords:

• AmBisome
• Amphotericin B
• Animals
• Fat Emulsions, Intravenous
• Humans
• Mice
• Mice, Inbred BALB C
• Mucormycosis
• Muridae
• Rhizopus
• Streptozocin
• drug therapy
• therapy

Other ID:

• GWAIDS0027062

UI: 102266686

From Meeting Abstracts