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Is It Ever Safe To Stop Azole Therapy for Coccidioides immitis Meningitis?

Daniel H. Dewsnup, DO, MS; John N. Galgiani, MD; J. Richard Graybill, MD; Manuel Diaz, MD; Adrian Rendon, MD; Gretchen A. Cloud, MS; and David A. Stevens, MD
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From Santa Clara Valley Medical Center and The California Institute for Medical Research, San Jose, California; Stanford University School of Medicine, Standford, California; The National Institute of Allergy and Infectious Diseases Mycoses Study Group, Bethesda, Maryland; Veterans Affairs Medical Center and University of Arizona, Tucson, Arizona; Audie Murphy Memorial Veterans Hospital and University of Texas Health Science Center, San Antonio, Texas; Universidad Autonoma de Nuevo Leon and Hospital Universitario, Monterrey, Mexico; and University of Alabama, Birmingham, Alabama. Acknowledgments: The authors thank Thomas G. Evans, MD, Stephanie Eyherabide, RN, L. Thomas Fife, MD, Jean Higgs, RN, Bernard E. Levine, MD, John F. Rothrock, MD, Ziad Shehab, MD, Martha H. Tanner, MD, Judy Tenopir, Idelle Weisman, MD, and others who provided helpful information. Grant Support: In part by the National Institute of Allergy and Infectious Diseases (Contract N01-AI-15082); The Office of Veterans Affairs; Janssen Research Foundation, Titusville, New Jersey; Pfizer Central Research and Pfizer International, Groton, Connecticut and New York, New York; and the Bank of Stockton, Stockton, California. Requests for Reprints: David A. Stevens, MD, Department of Medicine, Santa Clara Valley Medical Center, 751 South Bascom Avenue, San Jose, CA 95128-2699. Current Author Addresses: Dr. Dewsnup: Infectious Disease/HIV Unit, California Medical Facility, PO Box 2000, Vacaville, CA 95696.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1996;124(3):305-310. doi:10.7326/0003-4819-124-3-199602010-00004
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Objective: To determine 1) whether patients with coccidioidal meningitis who had achieved remission with oral azole therapy were cured and 2) when oral azole therapy could be discontinued in these patients.

Design: Data were gathered on patients with coccidioidal meningitis who had successfully responded to azole therapy in previous clinical trials.

Setting: Referral centers, including university, county, and veterans' hospitals and clinics.

Patients: 18 patients in whom azole therapy for meningitis had been discontinued, usually because of a presumption of cure.

Main Outcome Measures: Clinical and cerebrospinal fluid relapse.

Results: 14 of 18 patients (78% [95% CI, 52% to 94%]) had relapse with disseminated disease after discontinuation of therapy, for a total of 1 nonmeningeal and 15 meningeal relapses to date. Relapse occurred both soon and late (range, 0.5 to 30 months) after therapy was discontinued. The characteristics of patients who did not have relapse, including the particular azole used, the duration of therapy, the reason therapy was discontinued, and the cerebrospinal fluid indices before discontinuation, were similar to the characteristics of patients who had relapse. Relapse had serious consequences in some patients; 3 patients died.

Conclusion: Our data suggest 1) that disease is only suppressed in patients with meningitis who achieve remission while receiving azole therapy and 2) that discontinuing azole therapy is unsafe. The alternative is lifelong treatment with azoles; this appears to be acceptable, because toxicity is uncommon with triazole therapy, even long-term triazole therapy.





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