NAJVAR LK, SUN QN, BOCANEGRA R, LOEBENBERG D, GRAYBILL JR; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. J-1616.

The Univ. TX Health Sci. Ctr. at San Antonio, San Antonio, TX

BACKGROUND: Zygomycosis is an uncommon but highly aggressive fungal infection affecting patients with diabetes, neutropenia, burns or iron overload. Diagnosis is difficult and treatment is often ineffective. We evaluated POSA against 3 Mucor spp. isolates in a neutropenic mouse model. METHODS: The day before infection, Balb/c Nu/+ mice were rendered neutropenic with 5-fluorouracil at 150 mg/kg intravenously (IV) and cyclophosphamide at 200 mg/kg intraperitoneally (IP). Mice were infected IV with 5x10[4]-8x10[5] conidia/mouse of Mucor ramosissimus #98-1763, #95-2650 or Mucor circinelloides #00-1194. MICs using the NCCLS M38-P method for POSA, itraconazole (ITRA), and amphotericin B (AMB) at 48 hrs were 0.125, 0.25, 0.25 microg/ml (#98-1763), 0.25 microg/ml for all 3 drugs (#95-2650), and 8, 8, 0.25microg/ml (#00-1194), respectively. Therapy began the day after infection and continued through day 7 with POSA @5, 15, or 30 mg/kg BID orally, ITRA @30 mg/kg TID orally or AMB @1 mg/kg IP daily. Controls received water. In additional survival studies using #95-2650 and #00-1194, POSA was begun one day before infection. Mice were observed through day 15 for all survival studies. For tissue burden studies mice were treated days 1-7 and were terminated on day 8. Fungal burdens in spleens and kidneys were measured by serial quantitative counts. Statistical analysis used Log rank tests (survival) and Mann Whitney U tests (tissue burden), with p<0.05 for significance. RESULTS: POSA @15 and 30 mg/kg BID significantly prolonged survival and reduced fungal burden counts for all 3 isolates despite wide differences in MICs. Initiation of POSA before or after infection gave similar results. AMB prolonged survival and reduced fungal burden. ITRA was ineffective. CONCLUSIONS: These studies support clinical evaluation of POSA in zygomycosis.

Publication Types:

• Meeting Abstracts

Keywords:

• Amphotericin B
• Animals
• Humans
• Itraconazole
• Mice
• Microbial Sensitivity Tests
• Mycoses
• Neutropenia
• Triazoles
• Zygomycosis
• posaconazole
• therapy

Other ID:

• GWAIDS0029171

UI: 102268803

From Meeting Abstracts