Candida infections of the central nervous system
- Carol A Kauffman, MD
Carol A Kauffman, MD
- Section Editor — Fungal Infections
- Professor of Internal Medicine
- University of Michigan Medical School
- Veterans Affairs Ann Arbor Healthcare System
Candida infections of the central nervous system (CNS) most often involve the meninges. However, intracranial abscesses can occur either as an isolated phenomenon or associated with meningitis [1,2]. The abscesses are usually small microabscesses, multiple, and associated with disseminated infection in immunocompromised hosts .
Candida meningitis can occur as a manifestation of disseminated candidiasis, which most often occurs in premature neonates [4-6], in the presence of ventricular drainage devices [7-10], and as isolated chronic meningitis [3,11,12]. In addition to hematogenous spread [4,5,13], Candida can enter the CNS at the time of craniotomy  or through a ventricular shunt [7-10].
The clinical features, diagnosis, and treatment of Candida meningitis will be reviewed here. An overview of Candida infections is presented separately. Candidemia and invasive candidiasis are also discussed separately. (See "Overview of Candida infections" and "Epidemiology and pathogenesis of candidemia in adults" and "Clinical manifestations and diagnosis of candidemia and invasive candidiasis in adults" and "Treatment of candidemia and invasive candidiasis in adults" and "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis" and "Candidemia and invasive candidiasis in children: Management" and "Epidemiology and risk factors for Candida infection in neonates" and "Treatment of Candida infection in neonates".)
As with Candida infections at most other sites, patients who develop central nervous system infections are usually immunocompromised . In addition to occurring in premature neonates and after neurosurgery [4,5,7-10,14], the risk is also in increased HIV-infected patients  and in those with leukemia . (See "Epidemiology and pathogenesis of candidemia in adults", section on 'Risk factors' and "Epidemiology and risk factors for Candida infection in neonates" and "Candidemia and invasive candidiasis in children: Clinical manifestations and diagnosis", section on 'Risk factors'.)
Candida central nervous system (CNS) infections are almost always due to C. albicans [3,4] but can occur with other species, such as C. parapsilosis and C. tropicalis [9,13]. C. glabrata is a rare cause of CNS infection [4,9]. (See "Epidemiology and pathogenesis of candidemia in adults", section on 'Epidemiology'.)
- Mattiuzzi G, Giles FJ. Management of intracranial fungal infections in patients with haematological malignancies. Br J Haematol 2005; 131:287.
- Fennelly AM, Slenker AK, Murphy LC, et al. Candida cerebral abscesses: a case report and review of the literature. Med Mycol 2013; 51:779.
- Sánchez-Portocarrero J, Pérez-Cecilia E, Corral O, et al. The central nervous system and infection by Candida species. Diagn Microbiol Infect Dis 2000; 37:169.
- Fernandez M, Moylett EH, Noyola DE, Baker CJ. Candidal meningitis in neonates: a 10-year review. Clin Infect Dis 2000; 31:458.
- Lee BE, Cheung PY, Robinson JL, et al. Comparative study of mortality and morbidity in premature infants (birth weight, < 1,250 g) with candidemia or candidal meningitis. Clin Infect Dis 1998; 27:559.
- Cohen-Wolkowiez M, Smith PB, Mangum B, et al. Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures. J Perinatol 2007; 27:97.
- Nguyen MH, Yu VL. Meningitis caused by Candida species: an emerging problem in neurosurgical patients. Clin Infect Dis 1995; 21:323.
- Sánchez-Portocarrero J, Martín-Rabadán P, Saldaña CJ, Pérez-Cecilia E. Candida cerebrospinal fluid shunt infection. Report of two new cases and review of the literature. Diagn Microbiol Infect Dis 1994; 20:33.
- Chiou CC, Wong TT, Lin HH, et al. Fungal infection of ventriculoperitoneal shunts in children. Clin Infect Dis 1994; 19:1049.
- Cruciani M, Di Perri G, Molesini M, et al. Use of fluconazole in the treatment of Candida albicans hydrocephalus shunt infection. Eur J Clin Microbiol Infect Dis 1992; 11:957.
- Voice RA, Bradley SF, Sangeorzan JA, Kauffman CA. Chronic candidal meningitis: an uncommon manifestation of candidiasis. Clin Infect Dis 1994; 19:60.
- Casado JL, Quereda C, Oliva J, et al. Candidal meningitis in HIV-infected patients: analysis of 14 cases. Clin Infect Dis 1997; 25:673.
- McCullers JA, Vargas SL, Flynn PM, et al. Candidal meningitis in children with cancer. Clin Infect Dis 2000; 31:451.
- O'Brien D, Stevens NT, Lim CH, et al. Candida infection of the central nervous system following neurosurgery: a 12-year review. Acta Neurochir (Wien) 2011; 153:1347.
- Lipton SA, Hickey WF, Morris JH, Loscalzo J. Candidal infection in the central nervous system. Am J Med 1984; 76:101.
- O'Brien D, Cotter M, Lim CH, et al. Candida parapsilosis meningitis associated with Gliadel (BCNU) wafer implants. Br J Neurosurg 2011; 25:289.
- Pepper J, Zrinzo L, Mirza B, et al. The risk of hardware infection in deep brain stimulation surgery is greater at impulse generator replacement than at the primary procedure. Stereotact Funct Neurosurg 2013; 91:56.
- Glick JA, Graham RS, Voils SA. Candida meningitis post Gliadel wafer placement successfully treated with intrathecal and intravenous amphotericin B. Ann Pharmacother 2010; 44:215.
- Lyons JL, Erkkinen MG, Vodopivec I. Cerebrospinal fluid (1,3)-β-D-glucan in isolated Candida meningitis. Clin Infect Dis 2015; 60:161.
- Pendlebury WW, Perl DP, Munoz DG. Multiple microabscesses in the central nervous system: a clinicopathologic study. J Neuropathol Exp Neurol 1989; 48:290.
- Lai PH, Lin SM, Pan HB, Yang CF. Disseminated miliary cerebral candidiasis. AJNR Am J Neuroradiol 1997; 18:1303.
- Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 62:e1.
- Groll AH, Giri N, Petraitis V, et al. Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system. J Infect Dis 2000; 182:274.
- Slavoski LA, Tunkel AR. Therapy of fungal meningitis. Clin Neuropharmacol 1995; 18:95.
- van den Anker JN, van Popele NM, Sauer PJ. Antifungal agents in neonatal systemic candidiasis. Antimicrob Agents Chemother 1995; 39:1391.
- Benjamin DK Jr, Stoll BJ, Fanaroff AA, et al. Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics 2006; 117:84.
- Johnson LB, Kauffman CA. Voriconazole: a new triazole antifungal agent. Clin Infect Dis 2003; 36:630.
- Epelbaum S, Laurent C, Morin G, et al. Failure of fluconazole treatment in Candida meningitis. J Pediatr 1993; 123:168.
- Torres HA, Hachem RY, Chemaly RF, et al. Posaconazole: a broad-spectrum triazole antifungal. Lancet Infect Dis 2005; 5:775.
- Deresinski SC, Stevens DA. Caspofungin. Clin Infect Dis 2003; 36:1445.
- Prabhu RM, Orenstein R. Failure of caspofungin to treat brain abscesses secondary to Candida albicans prosthetic valve endocarditis. Clin Infect Dis 2004; 39:1253.
- Hope WW, Mickiene D, Petraitis V, et al. The pharmacokinetics and pharmacodynamics of micafungin in experimental hematogenous Candida meningoencephalitis: implications for echinocandin therapy in neonates. J Infect Dis 2008; 197:163.
- Warn PA, Livermore J, Howard S, et al. Anidulafungin for neonatal hematogenous Candida meningoencephalitis: identification of candidate regimens for humans using a translational pharmacological approach. Antimicrob Agents Chemother 2012; 56:708.
- CLINICAL FEATURES
- Premature neonates
- CNS shunts and other devices
- Chronic meningitis
- CSF analysis
- Antifungal therapy
- - Duration
- Removal of CNS devices
- SUMMARY AND RECOMMENDATIONS
- Epidemiology and clinical features