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Fluconazole Therapy in Coccidioidal Meningitis Maintained With Intrathecal Amphotericin B

Fluconazole Therapy in Coccidioidal Meningitis Maintained With Intrathecal Amphotericin B Abstract Background: Meningitis follows approximately 0.15% to 0.75% of cases of extrapulmonary coccidioidomycosis. Successful treatment of coccidioidal meningitis (CM) has generally required intrathecal therapy with amphotericin B, which often causes significant toxic effects and discomfort to the patient. Prior to fluconazole, azoles had not been efficacious in CM either because of toxicity at elevated doses or because of poor cerebrospinal fluid distribution. Fluconazole however, has been found to have both good cerebrospinal fluid penetration and a favorable side effect profile. Methods: We studied 11 patients with CM who were maintained with amphotericin B and were then switched to oral fluconazole therapy alone at a dosage of 400 mg/d for a period of up to 19 months. The patients were evaluated clinically for evidence of deterioration measured by need for hospitalization, development of extrameningeal disease during the study period, need to reinstitute intrathecal amphotericin B therapy because of worsening disease, cerebrospinal fluid leukocyte count, protein level, and serologic tests for complement-fixing antibody. Results: Three patients required hospitalization during the study, two patients for reasons unrelated to CM. No patient developed extrameningeal disease or required discontinuation of fluconazole therapy because of deteriorating disease. Patients at exit reported no symptoms related to meningitis or adverse effects related to fluconazole therapy. There was no deterioration in general health or neurologic status. Conclusions: Our study demonstrates that conversion from amphotericin B to fluconazole was associated with a stable disease course of CM for up to 19 months. Further studies delineating both optimal dosage and characteristics of patients likely to respond to fluconazole therapy alone are needed.(Arch Intern Med. 1995;155:1665-1668) References 1. Tressler CB, Sugar AM. Fungal meningitis. Infect Dis Clin North Am . 1990;4: 789-803. 2. Shetter AG, Fischer DW, Flom RA. Computed tomography in cases of coccidioidal meningitis with clinical correlation. West J Med . 1985;142:782-786. 3. Vincent T, Galgiani JN, Huppert M, Salkin D. The natural history of coccidioidal meningitis: VA—Armed Forces Cooperative Studies 1955-58. Clin Infect Dis . 1993;16:247-254.Crossref 4. Winn WA. The use of amphotericin B in the treatment of coccidioidal disease. Am J Med . 1959;27:617-635.Crossref 5. Sobel RA, Ellis WG, Nielsen SL, Davis RL. Central nervous system coccidioidomycosis: a clinicopathologic study of treatment with and without amphotericin B. Hum Pathol . 1984;15:980-995.Crossref 6. Drutz DJ. Amphotericin B in the treatment of coccidioidomycosis. Drugs . 1983; 26:337-346.Crossref 7. Craven PC, Graybill JR, Jorgenson JH, Dismukes WE, Levine BE. High-dose ketoconazole for treatment of fungal infections of the central nervous system. Ann Intern Med . 1983;98:160-167.Crossref 8. Buchsbaum HW, Fuhs JJ, Friedman BA. Coccidioidal meningitis treated with high-dose ketoconazole. In: Einstein HE, Catanzaro A, eds. Coccidioidomycosis: Proceedings of the Fourth International Conference . Washington, DC: National Foundation for Infectious Disease; 1984:438-443. 9. Tucker RM, Denning DW, Dupont B, Stevens DA. Itraconazole therapy for chronic coccidioidal meningitis. Ann Intern Med . 1990;112:108-112.Crossref 10. Deresinski SC, Galgiani JN, Stevens DA. Miconazole treatment of human coccidioidomycosis: status report. In: Ajello L, ed. Coccidioidomycosis: Current Clinical and Diagnostic Status . Miami, Fla: Symposia Specialists; 1977:267-292. 11. Tucker RM, Williams PL, Arathoon EG, et al. Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis. Antimicrob Agents Chemother . 1988;32:369-373.Crossref 12. Galgiani JN, Catanzaro A, Cloud G. Fluconazole therapy for coccidioidal meningitis. Ann Intern Med . 1993;119:28-35.Crossref 13. Classen DC, Burke JP, Smith CB. Treatment of coccidioidal meningitis with fluconazole. J Infect Dis . 1988;158:903-904.Crossref 14. Tucker RM, Galgiani JN, Denning DW, et al. Treatment of coccidioidal meningitis with fluconazole. Rev Infect Dis . 1990;12( (suppl 3) ):5380-5389.Crossref 15. Lee BE, Feinberg M, Abraham JJ, Murthy ARK. Congenital malformations in an infant born to a woman treated with fluconazole. Pediatr Infect Dis J . 1992; 11:1062-1064.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Fluconazole Therapy in Coccidioidal Meningitis Maintained With Intrathecal Amphotericin B

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References (15)

Publisher
American Medical Association
Copyright
Copyright © 1995 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1995.00430150157016
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Abstract

Abstract Background: Meningitis follows approximately 0.15% to 0.75% of cases of extrapulmonary coccidioidomycosis. Successful treatment of coccidioidal meningitis (CM) has generally required intrathecal therapy with amphotericin B, which often causes significant toxic effects and discomfort to the patient. Prior to fluconazole, azoles had not been efficacious in CM either because of toxicity at elevated doses or because of poor cerebrospinal fluid distribution. Fluconazole however, has been found to have both good cerebrospinal fluid penetration and a favorable side effect profile. Methods: We studied 11 patients with CM who were maintained with amphotericin B and were then switched to oral fluconazole therapy alone at a dosage of 400 mg/d for a period of up to 19 months. The patients were evaluated clinically for evidence of deterioration measured by need for hospitalization, development of extrameningeal disease during the study period, need to reinstitute intrathecal amphotericin B therapy because of worsening disease, cerebrospinal fluid leukocyte count, protein level, and serologic tests for complement-fixing antibody. Results: Three patients required hospitalization during the study, two patients for reasons unrelated to CM. No patient developed extrameningeal disease or required discontinuation of fluconazole therapy because of deteriorating disease. Patients at exit reported no symptoms related to meningitis or adverse effects related to fluconazole therapy. There was no deterioration in general health or neurologic status. Conclusions: Our study demonstrates that conversion from amphotericin B to fluconazole was associated with a stable disease course of CM for up to 19 months. Further studies delineating both optimal dosage and characteristics of patients likely to respond to fluconazole therapy alone are needed.(Arch Intern Med. 1995;155:1665-1668) References 1. Tressler CB, Sugar AM. Fungal meningitis. Infect Dis Clin North Am . 1990;4: 789-803. 2. Shetter AG, Fischer DW, Flom RA. Computed tomography in cases of coccidioidal meningitis with clinical correlation. West J Med . 1985;142:782-786. 3. Vincent T, Galgiani JN, Huppert M, Salkin D. The natural history of coccidioidal meningitis: VA—Armed Forces Cooperative Studies 1955-58. Clin Infect Dis . 1993;16:247-254.Crossref 4. Winn WA. The use of amphotericin B in the treatment of coccidioidal disease. Am J Med . 1959;27:617-635.Crossref 5. Sobel RA, Ellis WG, Nielsen SL, Davis RL. Central nervous system coccidioidomycosis: a clinicopathologic study of treatment with and without amphotericin B. Hum Pathol . 1984;15:980-995.Crossref 6. Drutz DJ. Amphotericin B in the treatment of coccidioidomycosis. Drugs . 1983; 26:337-346.Crossref 7. Craven PC, Graybill JR, Jorgenson JH, Dismukes WE, Levine BE. High-dose ketoconazole for treatment of fungal infections of the central nervous system. Ann Intern Med . 1983;98:160-167.Crossref 8. Buchsbaum HW, Fuhs JJ, Friedman BA. Coccidioidal meningitis treated with high-dose ketoconazole. In: Einstein HE, Catanzaro A, eds. Coccidioidomycosis: Proceedings of the Fourth International Conference . Washington, DC: National Foundation for Infectious Disease; 1984:438-443. 9. Tucker RM, Denning DW, Dupont B, Stevens DA. Itraconazole therapy for chronic coccidioidal meningitis. Ann Intern Med . 1990;112:108-112.Crossref 10. Deresinski SC, Galgiani JN, Stevens DA. Miconazole treatment of human coccidioidomycosis: status report. In: Ajello L, ed. Coccidioidomycosis: Current Clinical and Diagnostic Status . Miami, Fla: Symposia Specialists; 1977:267-292. 11. Tucker RM, Williams PL, Arathoon EG, et al. Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis. Antimicrob Agents Chemother . 1988;32:369-373.Crossref 12. Galgiani JN, Catanzaro A, Cloud G. Fluconazole therapy for coccidioidal meningitis. Ann Intern Med . 1993;119:28-35.Crossref 13. Classen DC, Burke JP, Smith CB. Treatment of coccidioidal meningitis with fluconazole. J Infect Dis . 1988;158:903-904.Crossref 14. Tucker RM, Galgiani JN, Denning DW, et al. Treatment of coccidioidal meningitis with fluconazole. Rev Infect Dis . 1990;12( (suppl 3) ):5380-5389.Crossref 15. Lee BE, Feinberg M, Abraham JJ, Murthy ARK. Congenital malformations in an infant born to a woman treated with fluconazole. Pediatr Infect Dis J . 1992; 11:1062-1064.Crossref

Journal

Archives of Internal Medicine – American Medical Association

Published: Aug 7, 1995

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