The Brief Case: Cryptococcus gattii Meningitis with Ventriculitis.

A39-year-old previously healthy man was transferred to Emory University Hospital Midtown, Atlanta, GA, USA, from Savannah, GA, USA, with a 1-month history of progressive headaches, drowsiness, blurred vision, and photosensitivity. Magnetic resonance imaging (MRI) revealed a noncommunicating obstructive hydrocephalus at the level of the third ventricle. Endoscopic ventriculostomy was attempted but could not be completed because of marked adhesions, scar tissue, and nodularity throughout the ependymal surfaces of the lateral ventricles. An external ventricular drainage catheter was placed, and a cerebrospinal fluid (CSF) sample was obtained. The CSF was bloody, with a normal glucose level of 40 mg/dl (normal range, 40 to 70 mg/dl), a corresponding serum glucose level of 100 mg/dl (normal range, 65 to 110 mg/dl), and an elevated CSF protein level of 148 mg/dl (normal range, 15 to 45 mg/dl). The CSF white blood cell count was elevated at 25 cells/ l (normal range, 0 to 5 cells/ l) with predominantly polymorphonuclear neutrophils (PMNs) (67%). A CSF Gram stain showed few PMNs but no organisms. A CSF cryptococcal latex agglutination antigen test (Meridian Bioscience Inc., Cincinnati, OH, USA) was negative, but a serum cryptococcal antigen titer performed a few days later was 32. Blood cultures taken at that time showed no growth, but bacterial and fungal cultures of the CSF grew a few cream-colored, mucoid colonies in 3 days (Fig. 1A). Direct microscopic examination of the colonies revealed round yeast cells that tested germ tube negative (Fig. 1B). The organism was able to hydrolyze urea, and a caffeic acid disk test was positive for melanin production, consistent with Cryptococcus neoformans, but upon growth, a blue coloration was produced on L-canavanine– glycine– bromothymol blue (CGB) agar (Centers for Disease Control and Prevention [CDC], Atlanta, GA, USA), distinguishing the isolate as Cryptococcus gattii (Fig. 1C). The identification was confirmed as C. gattii biotype VGI at the CDC by multilocus sequence typing, with 100% identity to the reference isolate across 4,141 nucleotides. The patient had recently pressure washed houses along the Georgia coast without wearing a mask. He was presumed to have acquired the C. gattii infection from organisms aerosolized through the action of pressurized wash water. An enzyme-linked immunosorbent assay (ELISA) for HIV type 1 and 2 antibodies and p24 antigen was negative. The patient was started on a combined treatment of amphotericin B lipid complex (5 mg/kg of body weight/day) and fluconazole (400 mg/day). Multiple negative cultures were achieved, but CSF protein remained high ( 300 mg/dl), and repeated MRI showed worsening ventriculitis. Flucytosine (100 mg/kg/day) and steroids (dexamethasone, 6 mg/day) were added to the treatment regimen, which adequately decreased the protein level, and a ventriculoperitoneal shunt was placed. The patient was confused and agitated throughout his hospital course but spoke fluently and was alert, oriented, and responsive to verbal commands at the time of discharge on hospital day 40. After discharge, the patient was maintained on oral fluconazole (400 mg daily) and remained shunt dependent. He required three shunt revisions over the next 4 months following an intra-abdominal infection with coagulase-negative Staphylococcus and two episodes of shunt malfunction. The patient expired 9 months after initial hospitalization due to a probable shunt blockage.