The use of ketoconazole in prophylaxis of Candida sepsis

Candida sepsis has become an increasing problem in ICU patients with up to 50 per cent mortality rate. Ketoconazole, an oral antifungal agent, was used prophylactically in guinea pigs to see if this would prevent Candida sepsis. Absorption of ketoconazole has been stated to increase in an acid environment. Thirty-six guinea pigs were divided into three equal groups: group I received 1 cc normal saline, p.o.; group II received 10 mg/kg ketoconazole dissolved in 1 ml Maalox (Rorer Consumer; Fort Washington, PA); group III received 10 mg/kg ketoconazole in 1 ml in HCl, all given daily. Each animal received 10(8) colony forming units intravenously. The viability of the innoculum was confirmed by culture both pre- and postinjection. Each animal was observed daily for weight and ocular and skin lesions. Half of the animals were sacrificed on day seven and the remaining were sacrificed on day 14. Cultures, complete blood count (CBC), ketoconazole levels, and specimen histology were obtained. There was no difference between groups as to weight, leukocyte counts, skin or ocular lesions, or ketoconazole levels. Histologic analysis and quantitative cultures revealed little Candida invasion. In conclusion, Candida sepsis cannot be induced in healthy guinea pigs. The blood levels of ketoconazole were not affected by pH.