Optimal therapy of cryptococcosis in patients with the acquired immunodeficiency syndrome

Although amphotericin B (AB) is the primary therapeutic agent for cryptococcosis complicating the acquired immunodeficiency syndrome (AIDS), the total dose administered is extremely variable, and the end point of therapy has not been well defined. Since these patients require life-long suppressive therapy following the primary therapy, the definition of treatment "end point" becomes crucial. To delineate more effective treatment approaches, we reviewed the medical records of 48 patients with cryptococcosis complicating AIDS. Fever (81%) and headache (77%) were the predominant symptoms. A clinical response to AB (defervescence and resolution of symptoms) was noted in 46% of the febrile patients. The cumulative AB dose administered to the time of clinical response was variable (0.1-1.76 g), but was noted early in the majority of the patients (less than 0.4 g). Repeat fungal cultures from the initial positive site for Cryptococcus neoformans (CN), obtained after observation of the clinical response, were negative in 7/7 patients. Nosocomial bacterial infections were quite common and often complicated intravenous AB therapy. Bacteremias were documented in 10/14 febrile episodes occurring during AB therapy in the 22 patients with an initial clinical response. Bacteremias were identified in 6/21 patients who failed to defervesce with AB therapy. Staphylococcus aureus (N = 9) and Salmonella species (N = 2) were the most common pathogens causing bacteremia. An algorithm for the treatment of cryptococcosis complicating AIDS may shorten the duration of primary intravenous AB therapy. This might reduce secondary infectious complications and the costs of hospitalization.