The Combined Use of Itraconazole and Flucytosine in the Treatment of Chronic Candida Cystitis in a Bottlenose Dolphin (Tursiops truncates)
IAAAM 1995
Thomas H. Reidarson, DVM; Jim McBain, DVM
Sea World of California, San Diego, CA

An eight year old female bottlenose dolphin had a persistent inflammatory disease which became apparent about two months after the death of her three-day-old calf. Four months into the disease course, which was poorly responsive to antibiotic therapy, she developed multiple coalescing raised red masses in her oral commissures. Cultures of oral lesions revealed heavy growth of Candida albicans. One month later hematuria developed. Urine cultures revealed the same yeast, candida albicans.

Oral itraconazole therapy was started at a dose of 2.5 mg/kg BID which resulted in peak blood and urine levels of 5.4-7.9 mcg/ml and 4.4 mcg/ml respectively. Twenty-four hour minimum inhibitory concentrations for itraconazole from one of the isolates of C. albicans ranged from 0.030-0.035 mcg/ml. Despite the use of what appeared to be a therapeutic dose of itraconazole, candiduria persisted. In fact, during two months of therapy the number of yeasts increased and branching hyphae was noted. During the same time the dolphin's BUN and creatinine levels steadily climbed and her clinical condition worsened.

Two hundred cc sterile water containing 20 mg of amphotericin B was infused into the urinary bladder and retained for 20 minutes before draining. After five daily treatments, the dose was increased to 140 mg in 200 cc water for two additional treatments due to the persistence of yeasts. At the end of seven days of therapy cystoscopy revealed a severe cystitis, and candiduria was still present.

Failure of the urinary bladder irrigations and the deteriorating clinical status of the dolphin led to the suspicion that a retrograde invasion of the ureters and kidneys by C. albicans had occurred. The irrigations were stopped and oral flucytosine was added to the itraconazole therapy at a dose of 20 mg/kg TID. Peak blood and urine levels of flucytosine were 20.5 mcg/ml and > 160 mcg/ml respectively. Within four days of instituting therapy the animal's appetite began to improve and the numbers of yeasts markedly decreased. By one month no yeasts were observed or cultured. After seven months of combination therapy and three months of no therapy, the animal remains asymptomatic.

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Thomas H. Reidarson, DVM
Sea World of California
San Diego, CA, USA


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