Management of Cryptococcus gattii meningoencephalitis

Abstract

Cryptococcosis is a fungal disease caused by Cryptococcus neoformans and Cryptococcus gattii. By inhalation and subsequent pulmonary infection, it may disseminate to the CNS and cause meningitis or meningoencephalitis. Most cases occur in immunosuppressed hosts, including patients with HIV/AIDS, patients receiving immunosuppressing drugs, and solid organ transplant recipients. However, cryptococcosis also occurs in individuals with apparently healthy immune systems. A growing number of cases are caused by C. gattii, with infections occurring in both immunosuppressed and immunocompetent individuals. In the majority of documented cases, treatment of C. gattii infection of the CNS requires aggressive management of raised intracranial pressure along with standard antifungal therapy. Early cerebrospinal fluid evacuation is often needed through placement of a percutaneous lumbar drain or ventriculostomy. Furthermore, pharmacological immunosuppression with a high dose of dexamethasone is sometimes needed to ameliorate a persistently increased inflammatory response and to reduce intracranial pressure. In this Grand Round, we present the case of an otherwise healthy adolescent female patient, who, despite aggressive management, succumbed to C. gattii meningoencephalitis. We also present a review of the existing literature and discuss optimum clinical management of meningoencephalitis caused by C. gattii.

Fluconazole Susceptibility in Cryptococcus gattii Is Dependent on the ABC Transporter Pdr11

“…The emergence of C. gattii as an important pathogen has resulted in numerous studies to define its epidemiology and clinical features, as well as the virulence components responsible for the lower treatment response rates than those observed with C. neoformans (21,(28)(29)(30)(31)(32). In some regions, C. gattii has been observed to exhibit reduced in vitro susceptibility to fluconazole and other triazole agents (33).…”

Cryptococcosis

“…For instance, in certain areas of the world, C gattii has been observed to cause cerebral cryptococcomas and/or obstructive hydrocephalus with or without large pulmonary mass lesions more frequently than C neoformans . 12,52,53 These patients with parenchymal brain involvement may have a high intracranial pressure and present with cranial neuropathies. In such patients, who have been observed to respond poorly to antifungal therapy, early neurosurgical intervention to control pressure or ensure a correct diagnosis and longer antifungal treatment courses may be required for a successful outcome.…”

“…93,133 In HIV-infected patients, initial induction treatment usually begins with combination therapy as described, followed by consolidation treatment with fluconazole (400–800 mg/d) for 8 weeks in patients who have demonstrated favorable response. Longer courses of both induction (eg, 6 weeks) and consolidation (or “eradication”) therapy have been suggested in C gattii meningoencephalitis, irrespective of host immune status, owing to the observed severity of neurologic disease in this group of patients, 11,52,53 but this is not certain and in general C gattii should be treated similarly to C neoformans . After consolidation, long-term suppression is commenced with oral fluconazole (200–400 mg/d).…”

“…97 Consideration of early neurosurgical consultation has been recommended in cases of meningoencephalitis owing to C gattii where CNS inflammation is often severe. 52,53 Medical treatments such as corticosteroids (unless IRIS suspected or in cases of severe C gattii infection), mannitol, and acetazolamide are generally not recommended. 52,53,129,167 If shunt placement is necessary, CSF sterilization is not required before insertion, which can be performed once appropriate antifungal therapy has been commenced.…”

“…In any patient in whom cryptococcemia is identified, symptoms are severe, or CSF examination reveals asymptomatic CNS involvement, treatment for cryptococcal meningitis is recommended. 93 The potential for severe pulmonary infection owing to C gattii should be appreciated when Cryptococcus is isolated from respiratory cultures in settings where this species is endemic 11,12,52,53,171 ; however, to date, there are no convincing data that species identification is required to optimally select antifungal therapy, and disease severity remains the critical factor in determining initial treatment. Cerebral cryptococcomas often can be managed with prolonged antifungal therapy without the need for surgical removal unless mass effect or other evidence of obstruction is identified.…”