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Fluconazole Therapy for Coccidioidal Meningitis

John N. Galgiani, MD; Antonino Catanzaro, MD; Gretchen A. Cloud, MS; Jean Higgs, RN; Barry A. Friedman, MD; Robert A. Larsen, MD; John R. Graybill, MD, NIAID-Mycoses Study Group.
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From the Veterans Affairs Medical Center, University of Arizona College of Medicine, and Tucson Medical Center, Tucson, Arizona; University of California at San Diego, San Diego, California; University of Alabama at Birmingham, Birmingham, Alabama; University of Southern California, Los Angeles, California; Audie Murphy Memorial Veterans Affairs Medical Center and University of Texas at San Antonio, San Antonio, Texas. Requests for Reprints: John N. Galgiani, MD, Medical Service (111), Veterans Affairs Medical Center, Tucson, AZ 87523. Acknowledgments: The authors thank all of the physicians who referred their patients to our study and who provided access to their records. These included Drs. Harvey W. Buchsbaum, Howard J. Cohen, Richard D. DeFelice, W. Paul Diefenbach, Richard Ellison, Richard Fetchick, Josh Fierer, Jeffrey Gitt, Venu Gopal, Ronald O. Hadden, Robert H. Hamilton, Jerry Hutchinson, Peter C. Kelly, Enrique L. Labadie, Thomas Miller, Gary N. Reese, William A. Sibley, Jerry D. Smilack, Michael S. Smith, Kurt B. Stevenson, Robert Van Scoy, Elizabeth E. Wack, Randall C. Walker. The authors also thank Kathy Delgado for assistance in manuscript preparation. Grant Support: In part by contract NO1-AI-15082 from the National Institute of Allergy and Infectious Diseases, the U.S. Department of Veterans Affairs, and Pfizer Pharmaceuticals, Inc.

Copyright 2004 by the American College of Physicians

Ann Intern Med. 1993;119(1):28-35. doi:10.7326/0003-4819-119-1-199307010-00005
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Objective: To determine the efficacy and safety of fluconazole treatment of coccidioidal meningitis.

Design: Uncontrolled clinical trial.

Setting: Four university-based treatment centers in California, Arizona, and Texas. Most therapy was conducted without hospitalization.

Patients: Fifty consecutive patients with active coccidioidal meningitis, of which 47 (94%) were evaluable. Twenty-five patients had received no previous treatment for their meningitis, and nine had coinfection with human immunodeficiency virus (HIV).

Intervention: Fluconazole was administered in an oral dose of 400 mg once per day for up to 4 years (median, 37 months) in responding patients. Concurrent therapy with another antifungal agent was prohibited.

Measurements: Predefined assessment of infection-related abnormalities was done at the time of enrollment and was repeated at least every 4 months during treatment. Elimination of 40% or more of baseline abnormalities was considered a response.

Results: Thirty-seven of 47 (79%; 95% CI, 61% to 90%) evaluable patients responded to treatment. Response rates were similar for patients with and without previous therapy, for patients with and without concomitant HIV infection, and for patients with and without pre-existing hydrocephalus. Most improvement occurred within 4 to 8 months after starting treatment. Patient symptoms resolved more quickly than did cerebrospinal fluid abnormalities. In 15 of 20 responding patients followed for 20 months or more, residual low-level cerebrospinal fluid abnormalities remained throughout therapy. No patient discontinued therapy because of drug-related side effects, although confusion developed in two patients that resolved when the dose of fluconazole was reduced.

Conclusion: Fluconazole therapy is often effective in suppressing coccidioidal meningitis.


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Figure 1.
Kaplan-Meier estimates of the likelihood of achieving a response with fluconazole as either initial or retreatment therapy during the first 20 months of therapy.P

No difference in the rate of response was noted between patients treated for the first time and those who had relapsed from previous therapies. > 0.2.

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Figure 2.
Changes in the scores for different components of assessment during the course of therapy.

All components decreased with treatment. Symptoms showed the earliest change, whereas cerebrospinal fluid abnormalities improved more slowly. CSF = cerebrospinal fluid.

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Figure 3.
Changes in cerebrospinal fluid leukocyte counts in responding patients during fluconazole therapy.

Although most patients' cerebrospinal fluid leukocyte counts normalized, several did not, even after 20 months of treatment. CSF = cerebrospinal fluid.

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