To our knowledge, P. marneffei has never been described as a CNS pathogen. P. marneffei was isolated from the meninges of 1 patient in a review of 155 published penicilliosis cases and from 3 of 20 CSF specimens in a case series of 80 patients with penicilliosis from Thailand. However, the clinical features of those patients were not provided. The patients in this case series had CNS symptoms consistent with a CNS infection, and P. marneffei was the single pathogen isolated from CSF samples from 20 of 21 patients. It is not possible to exclude the involvement of M. tuberculosis by CSF and sputum microscopy and of other opportunistic viral pathogens not tested in this case series; therefore, it remains uncertain whether the CNS syndrome in these patients can be wholly attributed to P. marneffei. Concurrent growth of C. neoformans and P. marneffei has been observed from blood and CSF samples of HIV‐infected patients at our hospital, as occurred for patient 11 in this case series. P. marneffei grows much slower (at least 24–48 h later) than C. neoformans from clinical specimens, and neither has been observed to have competitive cultural advantages over the other. Unlike M. tuberculosis, cryptococcus is unlikely to have been missed, although cryptococcal antigen tests, if they were clinically available, would have been more informative. Selected members of the other 225 Penicillium species are known to cause CNS disease. Penicillium commune was isolated from multiple brain and lung autopsy specimens from a patient with acute leukemia who was receiving antibiotics and steroids. Penicillium chrysogenum was isolated from CSF and brain biopsy samples of 2 nonimmunocompromised individuals with CNS symptoms. An unidentified Penicillium species was isolated from multiple brain lesions of a patient with chronic liver disease at autopsy. These reports demonstrate the neurotropic potential of invasive Penicillium species, and P. marneffei, the most invasive of Penicillium species, is likely not an exception.
CNS infections are medical emergencies, and early empirical therapy can prevent irreversible neuronal damage and save lives. In HIV‐infected patients with CD4 count <100 cells/μL who present with a subacute febrile syndrome, including changes in mental status, and who live or have traveled to endemic regions, disease due to P. marneffei should be considered, along with viral encephalitis, tuberculosis, and cryptococcal meningoencephalitis. Given the long culture incubation time and high disease mortality, heightened clinical suspicion and prompt empirical treatment with a CNS‐penetrating antifungal drug, such as amphotericin B, are critical in the management of these patients.