OLSON JA, SMITH PJ, ADLER-MOORE JP; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. M-993.

California State Polytechnic University, Pomona, CA.

BACKGROUND: Systemic aspergillosis in IS patients is difficult to treat and often requires prolonged therapy with high drug doses. To determine if efficacy would be enhanced or decreased by combining different antifungal drugs, AmBi monotherapy was compared with sequential combination therapy of AmBi with Itra or Cn in a murine IS systemic aspergillosis model. METHODS: Mice (n = 7/treatment group) were immunosuppressed IP with cyclophosphamide (100 mg/kg) every third day beginning on day -3, challenged IV day 0 with 1-2 X 10ex4 Aspergillus fumigatus conidia and monitored for survival for 25 days. Daily monotherapy (mono) was given d1-3 or d1-6 with 5 mg/kg AmBi IV, 2.5 mg/kg Cn IV or 100 mg/kg Itra PO. Combination therapy was as follows: AmBi d1-3 followed by Itra or Cn on d4-6; Itra or Cn d1-3 followed by AmBi on d4-6; AmBi with Itra or Cn d1-6. Control mice were given saline IV d1-6. RESULTS: Control mice died by day 9. Three days of mono with AmBi, Cn or Itra provided little or no protection (survival = 0-14%) while 6 days of AmBi mono (survival = 57%, p<0.001) or Itra mono (survival = 71%, p<0.001) was protective; Cn for 6 days produced only 28% survival. Sequential treatments of AmBi/Cn or Cn/AmBi (57% survival, p<0.001) as well as AmBi d1-3 followed by Itra d4-6 (71% survival, p<0.001) were also effective. In contrast, if Itra was given first or AmBi and Itra were given together, there was reduced protection (43% and 28% survival, respectively). Some reduction in efficacy was also seen when AmBi and Cn were given together for 6 days (43% survival). CONCLUSIONS: Sequential therapy with AmBi/Cn or Cn/AmBi was comparable to extended therapy with AmBi alone. Since antagonism was observed when AmBi was administered with Itra or following Itra treatment, AmBi should be used prior to Itra therapy in this murine aspergillosis model.

Publication Types:

• Meeting Abstracts

Keywords:

• AmBisome
• Amphotericin B
• Animals
• Antifungal Agents
• Aspergillosis
• Aspergillus fumigatus
• Central Nervous System
• Central Nervous System Fungal Infections
• Humans
• Itraconazole
• Mice
• Muridae
• Peptides, Cyclic
• caspofungin
• therapy

Other ID:

• GWAIDS0025267

UI: 102264891

From Meeting Abstracts