CLINICAL CORRELATIONS OF IN VITRO SUSCEPTIBILITY OF AMPHOTERICIN B PLUS FLUCYTOSINE IN AIDS-ASSOCIATED CRYPTOCOCCAL MENINGITIS.

Abstract

Purpose of the Study Cryptococcal meningitis is often treated with a combination of amphotericin B and flucytosine (5-FC). Susceptibility of Cryptococcus neoformans to these drugs has not been correlated with outcome. In one large trial, there appeared to be little clinical benefit from the addition of 5-FC to amphotericin B. We have previously used isolates from patients treated with amphotericin B alone to determine the equivalent concentration of amphotericin B at which the in vitro response has the strongest association with the quantitative patient response after 14 days of treatment with amphotericin given at 0.7 mg/kg/d. We now report our evaluation of in vitro susceptibility in patients who received the combination of amphotericin B plus 5-FC. Methods Used Sixteen patients entered in a trial conducted in Thailand were treated with amphotericin B at 0.7 mg/kg combined with 5-FC at 100 mg/kg daily for 14 days. Patient response was measured by the numbers of C. neoformans per mL of cerebrospinal fluid on day 14. Summary of Results When comparing the predicted response to amphotericin B alone based on in vitro susceptibility testing, the patient response when 5-FC is added to the treatment regimen is better than the predicted response to amphotericin B alone in a large portion of persons with cryptococcal meningitis. Conclusions In vitro susceptibility testing can provide clinicians with important information for use in considering the value of adding 5-FC to amphotericin B.