Identification of Patients with Acute AIDS-Associated Cryptococcal Meningitis Who Can Be Effectively Treated with Fluconazole: The Role of Antifungal Susceptibility Testing

No method currently exists to predict which patients with acute AIDS-associated cryptococcal meningitis can be effectively treated with fluconazole. The objective of this study was to determine the relationship of cryptococcal susceptibility to fluconazole, along with clinical variables, to the risk...

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Bibliographic Details
Published in:	Clinical infectious diseases Vol. 22; no. 2; pp. 322 - 328
Main Authors:	Witt, Mallory D., Lewis, Roger J., Larsen, Robert A., Milefchik, Eric N., Leal, Mary Ann E., Haubrich, Richard H., Richie, John A., Edwards, John E., Ghannoum, Mahmoud A.
Format:	Journal Article
Language:	English
Published:	Chicago, IL The University of Chicago Press 01-02-1996 University of Chicago Press
Subjects:	Adult AIDS AIDS-Related Opportunistic Infections - drug therapy AIDS-Related Opportunistic Infections - microbiology AIDS/HIV Antibiotics. Antiinfectious agents. Antiparasitic agents Antifungal agents Antifungal Agents - pharmacology Antifungal Agents - therapeutic use Antifungals Biological and medical sciences Blood Clinical Articles Clinical Trials as Topic Cryptococcal meningitis Cryptococcus Cryptococcus neoformans - drug effects Female Fluconazole - pharmacology Fluconazole - therapeutic use Flucytosine - therapeutic use Fungal infections Health outcomes Humans Logistic Models Logistic regression Male Medical sciences Medical treatment failures Meningitis, Cryptococcal - drug therapy Meningitis, Cryptococcal - microbiology Microbial Sensitivity Tests Modeling Multivariate Analysis Pharmacology. Drug treatments Regression analysis Treatment Failure Human Immunopathology Nervous system diseases Mycosis Drug susceptibility test Acute Cryptococcosis AIDS Immune deficiency Infection Antifungal agent Chemotherapy Sensitivity Treatment Viral disease Central nervous system disease Minimum inhibitory concentration Triazole derivatives Meningitis
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Summary:	No method currently exists to predict which patients with acute AIDS-associated cryptococcal meningitis can be effectively treated with fluconazole. The objective of this study was to determine the relationship of cryptococcal susceptibility to fluconazole, along with clinical variables, to the risk of treatment failure for patients with acute AIDS-associated cryptococcal meningitis. Results of in vitro fluconazole susceptibility testing of cryptococcal isolates and data from two clinical trials were analyzed. Susceptibility to fluconazole was determined by means of both microtiter and macrobroth (M27-P) dilution methods. Treatment was defined as successful if the patient was alive at 10 weeks and if a cerebrospinal fluid culture was sterile at that time. Seventy-six patients receiving fluconazole ± flucytosine were included; therapy failed for 19. Patients whose therapy failed were more likely to have a positive blood and urine culture and a higher titer in serum and cerebrospinal fluid of cryptococcal antigen, and the MIC of fluconazole against their isolates (as determined by the microtiter method) was more likely to be higher; they were less likely to have received flucytosine. Logistic regression modeling revealed that a negative blood culture, a low MIC of fluconazole (per the microtiter method), and treatment with flucytosine were factors independently associated with successful treatment.
Bibliography:	ark:/67375/HXZ-QQTVQX0H-3 Reprints or correspondence: Dr. Mallory D. Witt, Division of Allergy and Immunology, N-24, Harbor-UCLA Medical Center, Box 449, 1000 West Carson Street, Torrance, California 90509. istex:1E40A3104A5CDA9418EB4732CF8AA8AE90E361C2 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	1058-4838 1537-6591
DOI:	10.1093/clinids/22.2.322