Candida infections in surgical patients. Dose requirements and toxicity of amphotericin B

Abstract

The natural history of candidiasis in general surgical patients has been poorly documented, and the toxicity of amphotericin B is widely heralded. For these reasons therapy for candidiasis is frequently withheld in situations where antimicrobial treatment seems indicated on clinical grounds. The clinical courses of 47 general surgical patients who received amphotericin therapy for presumed Candida infection were reviewed. Nineteen patients had had solid tumors, but 12 were either localized or resected tumors. Only nine patients had received prior cancer themotherapy. Twenty-one patients were treated for fungemic disease, 10 for Candida in peritonitis fluid, and 16 for apparent colonization associated with fever and organ failure syndromes. Pre-existing renal or other organ failure was the primary determinant of survival with 4/22 survivors (18%) in patients with renal failure compared with 17/25 (78%) survivors in patients without such organ failure. In patients with serum creatinine values less than 2.5 mg/dl, amphotericin therapy was associated with a transient 30% fall in creatinine clearance and a proportionate rise in serum creatinine. Dose response curves were determined and revealed substantial sterilization of cultures in both fungemic and nonfungemic patients receiving greater than or equal to 6 mg/kg. This was confirmed by autopsy material. We suggest that in this acutely ill patient popoulation uncontrolled infection is the primary determinant of organ failure. Short-term limited dosing with amphotericin B (6-8 mg/kg total dose) in conjunction with appraisal of clinical response is adequate therapy for most presumed Candida infections. Long-term high dose therapy, such as that recommended in immuodepressed patients, is not a routine necessity.