Fatal Bacillus cereus meningitis without inflammatory reaction in cerebral spinal fluid after bone marrow transplantation.

Abstract

Patients undergoing bone marrow transplantation (BMT) are susceptible to meningitis caused by uncommon pathogens because of the severe immunosuppression due to the BMT procedure or its complications, such as graft-versus-host disease. We report a case of Bacilluscereus meningitis after BMT for severe aplastic anemia. This is the first report of meningitis by B. cereus in a patient who underwent BMT. A 16-year-old female patient, with severe aplastic anemia, underwent related allogeneic BMT. The conditioning regimen was cyclophosphamide (200 mg/kg intravenously, divided over 4 days) and graft-versus-host disease immunoprophylaxis with cyclosporine and methotrexate, in accordance with the Seattle protocol. On day 14, the patient was neutropenic (white blood cell count 90 μL with granulocytes) and had a fever (39.2°C) associated with nuchal rigidity, altered level of consciousness, and repeated episodes of tonic-clonic generalized seizures. She became comatose, eye-opening only as a response to painful stimulus, with bilateral papilledema and anisocoric pupils, generalized hyperreflexia, and bilateral extensor-plantar responses. Brain computed tomography scan was normal. Cerebral spinal fluid (CSF) with 4 cells/mm3 (70% lymphocytes, 30% monocytes) showed the following: CSF glucose, 77 mg/dL; glucose CSF to blood ratio, 0.32; CSF total proteins, 250 mg/dL. Veneral Disease Research Laboratory test was negative; immunologic reaction (IFI, ELISA) for Cysticercus cellulosae (IgG) and toxoplasmosis (IgG and IgM) results were negative. Gram stain smear of CSF showed a great quantity (++/1–10 CFU/OIF) of spore-forming gram-positive bacilli. Direct mycologic examination (Indian ink, Giemsa, Grocott, periodic acid-Schiff) and cultures for fungus were negative. Blood and CSF culture after 24 hr showed Bacillus sp. The patient was treated with ceftazidime and imipenem with no success. Brain death was diagnosed 2 days after the onset. Complete identification of the etiologic agent from CSF and blood by biochemical standard methods showed Bacilluscereus to be sensitive to amikacin, imipenem, and vancomycin and resistant to ceftazidime. Bacillus genera include a group of more than 60 bacteria species characterized as being ubiquitous, aerobic, or facultative anaerobic gram-positive bacillus, endospore-forming and flagellated, with B. anthracis being an exception. Frequently, the species of this genus are dismissed as saprophytic contaminants or normal flora. However, B. cereus, which previously had been recognized as a causative pathogen only in food intoxications, has now become associated with several local and systemic opportunistic infections (1–5). At major risk for meningitis by Bacilluscereus are neonates, intravenous drug users, immunologically compromised patients, and those with indwelling lines, shunts, or artificial prothesis (1–5). In this case there was no criteria for sepsis before the onset of meningitis; the positive blood culture was obtained at the same time as the CSF culture and could have been a bacteremia. The patient did not have a catheter-mediated infection and catheter culture was negative. There were no food poisoning-like symptoms before the onset of meningitis. The lack of inflammatory response in the CSF, in this case, may be explained by the combination of the severely immunodeficient condition of the patient and the character of B. cereus infection itself, which causes minimal inflammatory reaction (2,3). Although in the case of postsurgical B. cereus meningitis in an immunocompetent patient, there is an increased number of cells in the CSF (1). The course of the meningitis is usually fulminant, evolving to death in intervals of 10 to 48 hr after the initial neurologic manifestations (2). Although Bacillus cereus is a rare etiologic agent in meningitis, its isolation from CSF specimens must be carefully evaluated, especially in immunocompromised patients and those submitted to neurosurgical procedures. Because of a rapidly fatal clinical course, early suspicion of this syndrome is important for determining appropriate treatment. Sérgio Monteiro de Almeida Hélio A. G. Teive Ivar Brandi Samir Kanaan Nabhan Lineu Cesar Werneck Marco A. Bittencourt Carlos R. Medeiros Ricardo Pasquini Helena Homem de Mello