Experimental Candida albicans endocarditis: characterization of the disease and response to therapy

Abstract

Endocarditis caused by Candida albicans was induced in rabbits after insertion of a catheter across the aortic valve. The mean survival time of 34 rabbits was 26 days. Only 7% of temperature recordings taken were elevated. Candida was recovered from only 9% of blood cultures taken. Precipitating and agglutinating serum antibody was detected after 12 days of infection. Antibody titers rose progressively until death in rabbits with endocarditis, whereas titers peaked early and subsequently decreased in animals that received an intravenous injection of C. albicans without precatheterization. Three groups of rabbits were treated for 6 days with amphotericin B, 5-fluorocytosine, or the two durgs in combination. Amphotericin B alone reduced the mean titer of organisms from log10 8.79 +/- 1.46 to log 10 3.1 +/- 1.9 colony-forming units/g. 5-Fluorocytosine was less effective (mean titer after 6 days of therapy was log10 7.4 +/- 0.33 colony-forming units/g). The addition of 5-fluorocytosine to amphotericin B did not increase the rate at which Candida cells were eradicated from the vegetations. These in vivo results corrleated with the failure to demonstrate an increased rate of fungicidal activity in vitro with the two drugs.

Adherence of Candida albicans to a fibrin-platelet matrix formed in vitro

“…Endocarditis caused by C. albicans has been studed by using a rabbit model which mimics the disease in humans in a number of ways (1,11). In the rabbit model, catheterization via the carotid artery traumatizes the endocardium of the aortic valve.…”

“…Rabbits were subsequently boosted with six additional intravenous injections over a 2-week period. Charcoal agglutination titers (11) from boosted animals were 1:256. Normal serum was collected from nonimmunized rabbits.…”

“…In a study of 87 patients with Candida endocarditis, only 20% recovered (13). The major reason for this low recovery rate is that early diagnosis is difficult because the classic signs and symptoms of an infection are not always present (11,13).…”

“…The pathogenesis of the disease has been studied with a rabbit model (1,11). The infection was established in rabbits precatheterized via the carotid artery.…”

ADP-like platelet aggregation activity generated by viridans streptococci incubated with exogenous ATP

“…In contrast, exogenous ATPases have been described on bacteriophage (5), yeasts 14, and the intracellular parasite, Chlamydia psittaci (8). Interestingly, some of these microorganisms have been associated with platelet activation and aggregation events (17,19) and endocarditis (15).…”