Clinical Correlations of in vitro Susceptibility Testing of the Combination of Amphotericin B and Fluconazole in AIDS-Associated Cryptococcal Meningitis

ALEJANDRO SANCHEZ, MD1, ANNEMARIE BROUWER, MD2, ANNA KARINA CELAYA, MPH3, NANCY CHANG1, MADELINE BAUER, PhD1, THOMAS A. HARRISON, MD2, ROBERT LARSEN, MD1;

Author address: 

1USC Sch of Med, Los Angeles, CA, 2St. George’s Hospital Medical School, London, United Kingdom, 3UCLA-King Drew Medical Center, Los Angeles, CA.

Abstract: 

Background: Combining amphotericin B and fluconazole in the treatment of cryptococcal meningitis is appealing. Susceptibility testing of Cryptococcus neoformans to this combination would facilitate the assessment of response to treatment. Methods: The number of cfu/mL of CSF was measured at baseline and at two weeks defining the patient response. Isolates from 10 of 16 subjects receiving the combination of amphotericin B and fluconazole were tested. 2 untested isolates died and 4 subjects did not have quantitative cerebrospinal (CSF) cultures conducted. Susceptibility of the subjects’ C. neoformans isolate used a macrobroth dilution method modified to employ an inoculum that corresponded to the number of organisms/mL found in the baseline CSF sample. In vitro responses were determined by counting the number of living organisms remaining after 48 hours. Results: Among the 10 subjects’ the in vitro response to amphotericin B at 1.5 mg/L predicted a sterile CSF sample at two weeks in 2 (20%) and in each such the CSF sample at two weeks was sterile. For these individuals there was no demonstrable benefit to the addition of fluconazole. For the remaining 8 subjects the measured in vivo microbial response was better than the predicted in vitro response. The median improvement between the in vitro predicted response and the observed patient response was 2.0 log10 cfu/mL. Conclusions: Comparing the predicted in vitro response to amphotericin B alone, the combination of amphotericin B and fluconazole appears to have benefited those with meningitis caused by C. neoformans. In no individual did the combination appear to reduce the expected therapeutic response to amphotericin B. This combination of antifungal drugs holds promise and should be evaluated in larger numbers of subjects.
2006

abstract No: 

561

Full conference title: 

Infectious Diseases Society of America, 44th Annual Meeting
    • IDSA 44th