AIDS-associated Cryptococcus laurentii meningoencephalitis resistant to amphotericin B, apparently prompted by a cured Cryptococcus neoformans disease

Abstract number: p734

Manfredi  R., Fulgaro  C., Legnani  G., Sabbatani  S.

Objective: 

Cryptococcus laurentii is a rare pathogen among immunocompromised patients (p), with <20 described episodes and only 1 report of possible association with C. neoformans. An exceedingly rare case of dual HIV-associated C. neoformans followed by C. laurentii meningoencephalitis is presented and discussed on the ground of the literature which reports only 2 cases of HIV-associated C. laurentii infection.

Case report: 

A 34-y-old man HIV-infected for 8 years was lost to follow-up until his admission due to fever and headache. Lumbar puncture led to microscopical recognition of cryptococci, with both culture examination and capsular antigen search confirming a C. neoformans meningoencephalitis, with yeasts testing susceptible to all antifungals; a moderately advanced immunodeficiency concurred (CD4+ count 151/mL). Liposomal amphotericin B (lAB) was promptly started at 3 mg/kg/day with immediate benefit, but our p self-discharged after 12 d, and did not undergo antimycotic-antiretroviral therapy, until a subsequent hospitalization occurred 14 weeks later, owing to the same signs-symptoms, associated to the isolation of C. neoformans from both CSF and blood, positive antigen search and a persisting sensitivity to all antifungals. Negative CSF–blood cultures were achieved after 28 days of lAB, but 5 weeks later a novel relapse of meningoencephalitis occurred despite HAART and a maintenance weekly lAB. An unexpected, isolated CSF C. laurentii infection was documented with a surprising resistance to AB, while all mycological searches for C. neoformans (CSF–blood–urine cultures, capsular antigenemia) proved negative. High-dose fluconazole was started and HAART continued: negative C. laurentii microscopy-culture CSF assays were obtained after 43 d, while a significant immune recovery concurred: CD4+ count 256 cells/mL.

Conclusions: 

Clinicians facing HIV-infected p should consider that cryptococcosis may still occur, especially when HIV disease is missed-neglected. A dual, subsequent infection by C. neoformans and C. laurentii is possible, although very infrequent event, so that the eradication of C. neoformans does not guarantee that another Cryptococcus spp. infection could occur subsequently, although an apparently effective therapy was used. Susceptibility studies are mandatory for C. laurentii, due to its unpredictable sensitivity profile. Further investigation is needed to establish whether antimycotic therapy directed against cryptococcosis my help select resistant C. laurentii strains.