- John N Galgiani, MD
John N Galgiani, MD
- Professor of Medicine
- University of Arizona
Coccidioidomycosis is caused by the dimorphic fungi of the genus Coccidioides (C. immitis and C. posadasii), which are endemic in desert regions of the southwestern United States and Central and South America. (See "Primary coccidioidal infection", section on 'Epidemiology' and "Primary coccidioidal infection", section on 'Microbiology'.)
Coccidioidal meningitis will be reviewed here. Primary infection, extrapulmonary infection outside of the central nervous system, laboratory diagnosis, pulmonary sequelae, and infection in immunocompromised hosts are discussed separately. (See "Primary coccidioidal infection" and "Coccidioidomycosis: Laboratory diagnosis and screening" and "Manifestations and treatment of extrapulmonary coccidioidomycosis" and "Coccidioidomycosis in compromised hosts".)
Coccidioidomycosis has protean manifestations, and primary infection is frequently unrecognized. However, disseminated infection can occur. Meningitis is the most lethal complication of coccidioidomycosis, and thus it is crucial to recognize this serious complication. If untreated, meningitis is lethal for 95 percent of patients within two years . This contrasts sharply with most nonmeningeal infections, which are either self-limited respiratory syndromes or cause chronic focal morbidity within or beyond the lungs. (See "Primary coccidioidal infection" and "Coccidioidomycosis in compromised hosts".)
Precise statistics about the incidence of meningitis due to this fungus are not available. The Arizona Department of Health Services found that, in 2007, 8 percent of reported new coccidioidal infections were disseminated and, of these, 17 percent involved the central nervous system . Applying these statistics to the total number of 4900 reported cases in Arizona provides an annual estimate of about 60 cases in Arizona or 100 cases in the United States. Since it is estimated that there are more than 150,000 infections with Coccidioides spp annually, these estimates suggest that the proportion of patients with meningitis is less than 0.1 percent of all exposures.
The treatment of coccidioidal meningitis has evolved to include oral therapies that have largely supplanted the need to instill antifungal agents directly into the cerebrospinal fluid. Nonetheless, the management of coccidioidal meningitis remains difficult and often requires the orchestration of several medical subspecialties to optimize the clinical response.
- Vincent T, Galgiani JN, Huppert M, Salkin D. The natural history of coccidioidal meningitis: VA-Armed Forces cooperative studies, 1955-1958. Clin Infect Dis 1993; 16:247.
- Foley CG, Tsang CA, Christ C, Anderson SM. Impact of disseminated coccidioidomycosis in Arizona, 2007-2008. Presented at the Fifty-Fifth Annual Coccidioidomycosis Study Group, Davis, CA, April 2, 2011.
- Johnson RH, Einstein HE. Coccidioidal meningitis. Clin Infect Dis 2006; 42:103.
- Almoujahed MO, Johnson LB, Gehring R, Khatib R. Coccidioidal meningitis: incidental diagnosis 3 y after ventriculo-peritoneal shunt placement for hydrocephalus. Scand J Infect Dis 2002; 34:142.
- Ampel NM, Giblin A, Mourani JP, Galgiani JN. Factors and outcomes associated with the decision to treat primary pulmonary coccidioidomycosis. Clin Infect Dis 2009; 48:172.
- Lundergan LL, Kerrick SS, Galgiani JN. Coccidioidomycosis at a university outpatient clinic: A clinical description. In: Coccidioidomycosis. Proceedings of the Fourth International Conference, Einstein HE, Catanzaro A (Eds), National Foundation for Infectious Diseases, Washington 1985. p.47.
- Harrison HR, Galgiani JN, Reynolds AF Jr, et al. Amphotericin B and imidazole therapy for coccidioidal meningitis in children. Pediatr Infect Dis 1983; 2:216.
- Saitoh A, Homans J, Kovacs A. Fluconazole treatment of coccidioidal meningitis in children: two case reports and a review of the literature. Pediatr Infect Dis J 2000; 19:1204.
- Williams PL, Johnson R, Pappagianis D, et al. Vasculitic and encephalitic complications associated with Coccidioides immitis infection of the central nervous system in humans: report of 10 cases and review. Clin Infect Dis 1992; 14:673.
- Webb M, Ziauddin A, Okusa MD. Coccidioidomycosis meningitis and syndrome of inappropriate antidiuretic hormone. Am J Med Sci 2002; 324:155.
- Arsura EL, Johnson R, Penrose J, et al. Neuroimaging as a guide to predict outcomes for patients with coccidioidal meningitis. Clin Infect Dis 2005; 40:624.
- Erly WK, Bellon RJ, Seeger JF, Carmody RF. MR imaging of acute coccidioidal meningitis. AJNR Am J Neuroradiol 1999; 20:509.
- Komotar RJ, Clatterbuck RE. Coccidioidomycosis of the brain, mimicking en plaque meningioma. J Neurol Neurosurg Psychiatry 2003; 74:806.
- Bañuelos AF, Williams PL, Johnson RH, et al. Central nervous system abscesses due to Coccidioides species. Clin Infect Dis 1996; 22:240.
- Kassis C, Zaidi S, Kuberski T, et al. Role of Coccidioides Antigen Testing in the Cerebrospinal Fluid for the Diagnosis of Coccidioidal Meningitis. Clin Infect Dis 2015; 61:1521.
- Ismail Y, Arsura EL. Eosinophilic meningitis associated with coccidioidomycosis. West J Med 1993; 158:300.
- Lo Re V 3rd, Gluckman SJ. Eosinophilic meningitis. Am J Med 2003; 114:217.
- Pappagianis D, Saito M, Van Hoosear KH. Antibody in cerebrospinal fluid in non-meningitic coccidioidomycosis. Sabouraudia 1972; 10:173.
- Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clin Infect Dis 2016; 63:e112.
- Galgiani JN, Catanzaro A, Cloud GA, et al. Fluconazole therapy for coccidioidal meningitis. The NIAID-Mycoses Study Group. Ann Intern Med 1993; 119:28.
- Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. (Accessed on July 08, 2014).
- Tucker RM, Denning DW, Dupont B, Stevens DA. Itraconazole therapy for chronic coccidioidal meningitis. Ann Intern Med 1990; 112:108.
- Saubolle MA, McKellar PP, Sussland D. Epidemiologic, clinical, and diagnostic aspects of coccidioidomycosis. J Clin Microbiol 2007; 45:26.
- Lee BE, Feinberg M, Abraham JJ, Murthy AR. Congenital malformations in an infant born to a woman treated with fluconazole. Pediatr Infect Dis J 1992; 11:1062.
- Bercovitch RS, Catanzaro A, Schwartz BS, et al. Coccidioidomycosis during pregnancy: a review and recommendations for management. Clin Infect Dis 2011; 53:363.
- Dewsnup DH, Galgiani JN, Graybill JR, et al. Is it ever safe to stop azole therapy for Coccidioides immitis meningitis? Ann Intern Med 1996; 124:305.
- Clemons KV, Sobel RA, Williams PL, et al. Efficacy of intravenous liposomal amphotericin B (AmBisome) against coccidioidal meningitis in rabbits. Antimicrob Agents Chemother 2002; 46:2420.
- Capilla J, Clemons KV, Sobel RA, Stevens DA. Efficacy of amphotericin B lipid complex in a rabbit model of coccidioidal meningitis. J Antimicrob Chemother 2007; 60:673.
- Clemons KV, Capilla J, Sobel RA, et al. Comparative efficacies of lipid-complexed amphotericin B and liposomal amphotericin B against coccidioidal meningitis in rabbits. Antimicrob Agents Chemother 2009; 53:1858.
- Cortez KJ, Walsh TJ, Bennett JE. Successful treatment of coccidioidal meningitis with voriconazole. Clin Infect Dis 2003; 36:1619.
- Proia LA, Tenorio AR. Successful use of voriconazole for treatment of Coccidioides meningitis. Antimicrob Agents Chemother 2004; 48:2341.
- Kim MM, Vikram HR, Kusne S, et al. Treatment of refractory coccidioidomycosis with voriconazole or posaconazole. Clin Infect Dis 2011; 53:1060.
- Pascual A, Calandra T, Bolay S, et al. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis 2008; 46:201.
- Schein R, Homans J, Larsen RA, Neely M. Posaconazole for chronic refractory coccidioidal meningitis. Clin Infect Dis 2011; 53:1252.
- Stevens DA, Shatsky SA. Intrathecal amphotericin in the management of coccidioidal meningitis. Semin Respir Infect 2001; 16:263.
- Romeo JH, Rice LB, McQuarrie IG. Hydrocephalus in coccidioidal meningitis: case report and review of the literature. Neurosurgery 2000; 47:773.
- CLINICAL MANIFESTATIONS
- Signs and symptoms
- Imaging findings
- Initial approach to diagnosis
- Routine examination of CSF
- Approach when cultures and antibody tests are negative
- Specific diagnostic tests
- - Culture
- - CSF antibody testing
- - CSF coccidioidal antigen levels
- Antifungal therapy
- Management of increased intracranial pressure
- Monitoring treatment response
- SUMMARY AND RECOMMENDATIONS