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Comparison of fluconazole (Flu), amphotericin B(AmB), 5-fluoro-cytosine (5FC), and the combination of flu and 5FC for the treatment of Candida albicans endocarditis, endophthalmitis, and renal disease in rabbits.

Louie A, Liu W, Miller D, Madu C, Liu Q, Drusano G, Miller M; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1996 Sep 15-18; 30 (abstract no. B48).

Albany Medical College, Albany, NY.

Purpose: To compare the efficacy of Flu, AmB, and 5FC monotherapies with the combination of Flu and 5FC in a rabbit model of C. albicans endocarditis, endophthalmitis, and pyelonephritis. The dose of Flu used was that which resulted in an area-under-the-concentration-curve in rabbits that are seen in humans who receive Flu at 1600 mg/day--the highest dose that does not cause CNS toxicity in man. Methods: To establish aortic valve endocarditis, endophthalmitis and pyelonephritis, New Zealand White rabbits were injected IV with 2 x 10(7) CFUs of C. albicans strain ATCC 36082 at 48 hr after a catheter was inserted across the aortic valve orifice. Therapy with Flu 85.2 mg/kg/day (given as two doses per day), AmB 1 mg/kg QD, 5FC 50 mg/kg QD or the combination of Flu and 5FC (at the doses indicated) were administered IV begin 24 hr after C. albicans injection. Quantitative cultures of heart valve vegetations, the choroid-retina, vitreous, and kidney were conducted after 1, 5, 14 and 21 days of therapy. Results: All untreated controls died within 18 days. The relative decrease in CFUs/g in the vitreous was greater for Flu than AmB recipients at day 5 (p is less than 0.05) but was similar thereafter; no difference in choroidal CFUs was noted between groups at any time. Fungal densities in kidneys of AmB recipients were lower at day 5 of therapy when compared with other therapies (p is less than 0.05) but were similar at days 14 and 21. While fungal counts in cardiac valves of Flu recipients were similar to controls on day 5 of therapy and did not change from days 1 to 21, AmB therapy significantly decreased valvular CFUs at days 5, 14 and 21 (p is less than 0.05). 5FC plus Flu gave similar results as Flu monotherapy at all sites except for valves where it was better than Flu alone (p is less than 0.05).

Publication Types:
  • Meeting Abstracts
Keywords:
  • Amphotericin B
  • Animals
  • Antigens, Fungal
  • Body Fluids
  • Candida albicans
  • Endocarditis
  • Endophthalmitis
  • Fluconazole
  • Flucytosine
  • Humans
  • Kidney
  • Kidney Function Tests
  • Male
  • Pyelonephritis
  • Rabbits
  • immunology
  • therapy
Other ID:
  • 98927595
UI: 102234769

From Meeting Abstracts




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