5-Fluorocytosine in the Treatment of Experimental Candidiasis in Immunosuppressed Mice

Abstract

A model infection with Candida albicans was established in mice. The animals were pretreated for 1 week with azathioprine, given dexamethasone, and then infected intravenously with Candida . Mortality for the group given Candida infection alone was 20%, 38% when azathioprine was added, and 50% when dexamethasone and azathioprine were given with infection. The titers of Candida in most mice were 10 6 per gram of kidney. The rest of the mice were killed at 30 days. At this time, 16% had no evidence of Candida in the kidneys, but 40% of the mice had titers of 10 6 or more. Mice treated with 5-fluorocytosine had a mortality of less than 4% in 30 days. Five percent of the treated mice killed at 30 days had titers of Candida of 10 6 . Therefore, 5-fluorocytosine increases survival in the presence of continued therapy with azathioprine with or without pretreatment with dexamethasone. The survival is associated with decreased titers of Candida in the kidneys.

Studies on bredinin. I. Isolation, characterization and biological properties.

“…The failute to protect against systemic candidiasis in mice with bredinin depends probably on not only its weak activity but the immunosuppressive activity; as a good example, azathioprine has been used as a subsidiary agent against infection in experimental mycosis. 13) Many clinically severe diseases such as collagen diseases, blood autoimmune diseases, specific autoimmune diseases located in a particular organ and organ transplantation are all thought to participate in cellular immunity. These diseases have been subjected to immunosuppressive therapy with antimetabolites, alkylating agents, antibiotics, corticosteroids, plant alkaloids or anti-lymphocyte globulin4)…”

Experimental and Clinical Studies of 5-Fluorocytosine Activity in <i>Candida </i>Ocular Infections

“…In vitro, experimental and clinical studies on the susceptibility to 5-FC of Candida species involved in various diseases, such as endo carditis, meningitis, septicemia or urinary infections, have been reported [8,13,15,18,22,23,25]. However, to the best of our knowledge, no experimental study has been published concerning the activity of 5-FC in ocular Candida infections (except for a case report of an intraocular Candida infection treated with 5-FC and an editorial note on the possi bility of treating ocular infections with this substance [6,16]).…”