Survival of a case of Bacillus cereus meningitis with brain abscess presenting as immune reconstitution syndrome after febrile neutropenia – a case report and literature review-

Bacillus cereus is a Gram positive, aerobic facultative, spore-forming, rod-shaped bacterium. It is motile, catalase positive and ubiquitous, found in air, soil, water, and food [1]. Because of the ubiquitous distribution of B. cereus in food products, the bacterium is ingested in small numbers and becomes part of the transitory human intestinal flora [2]. Traditionally, the detection of Bacillus species in sterile samples has been regarded as contamination. However, the organism has the potential to cause severe infectious diseases in immunocompromised hosts [1]. Herein, we report a case of B. cereus meningitis with brain abscess, arising in the setting of neutropenia, and presenting as immune reconstitution syndrome after bone marrow recovery.

On day 3, disorientation, slurred speech, and confusion appeared. Slight nuchal rigidity was observed, and the neck flexion test was positive. Although meningitis was suggested, lumbar puncture was not performed because of severe thrombocytopenia (21,000/μL). Instead, linezolid (1200 mg/day), vancomycin (targeted trough of 20 mg/dL), and acyclovir (30 mg/kg/day) were administered in addition to high dose meropenem (6 g/day).

On day 5, she was transferred to the intensive care unit because of shock. At this time, lumbar puncture yielded the following results: opening pressure: 18 cmH₂O; cells: 43/mm³ (mononuclear cells dominant, with no abnormal cells); glucose: 31 mg/dL; protein: 155 mg/dL; negative for HSV-DNA, VZV-DNA, CMV-DNA, HHV-6 DNA, Cryptococcus-Antigen and WT-1 (Wilms Tumor-1). Cerebrospinal fluid (CSF) culture was negative, but B. cereus PCR was positive, leading to the diagnosis as B. cereus meningitis.

With inotropic agents, deep sedation, and antimicrobials, she recovered and became afebrile. On day 19, however, her fever, meningism and consciousness level dramatically worsened despite recovery of bone marrow function. The CSF findings revealed markedly increased cells (2040 cells/mm³), and decreased glucose level (12 mg/dL). The CSF culture and PCR for B. cereus were both negative, and other diseases were excluded by the aforementioned examinations. Therefore, in concert with the increased leukocytes in peripheral blood and CSF, it was suggestive of immune reconstitution syndrome after B. cereus meningitis. The gadolinium enhanced magnetic resonance imaging (MRI) performed on day 15 had already detected meningeal thickening and several ring enhancement lesions. Glucocorticoid administration was not used to treat immune reconstitution syndrome. Meropenem, vancomycin, and linezolid were continued for 26, 40, and 45 days, respectively. They were stopped after CSF and MRI findings were confirmed to be normalized. On day 90, she was discharged to her home without any sequela, and her AML remains in remission for 5 years.

Central nervous system infections caused by B. cereus can be classified as three diseases: 1) postsurgical meningitis, ventriculitis or brain abscess, which can occur several days after a surgical procedure and often affects devices [3]; 2) neonatal meningitis or encephalitis occurring in premature neonates at 7 days of age (median, range 1–49 days) [4]; 3) necrotizing meningitis or hemorrhage in cases of severe neutropenia, predominantly affecting patients with leukemia (Table 1) [3‐14].

While postsurgical infections typically resolve in spite of marked CSF pleocytosis, in the order of 10⁵ cells/mm³, the latter two infection types have very poor prognoses with mortality rate greater than 75%. Notably, in many cases of these two malicious diseases, CSF cell counts are usually less than 10² cells/mm³.

Fourteen cases of neutropenia-associated B. cereus meningitis have been reported so far (Table 2). All but one case had hematological malignancies (AML: 6, acute lymphoblastic leukemia: 7, myelodysplastic syndrome: 1, aplastic anemia: 1) and all had severe neutropenia of less than 500/μL at the onset of disease. Moreover, 79% had less than 100/μL blood leukocytes, suggesting a role for severe neutropenia in the pathogenesis of this disease. The cases demonstrated mild or absent CSF pleocytosis, which is considered to be a result of both the severely immunodeficient state of the patient and the character of B. cereus infection in itself, which causes little inflammatory reaction [15].

Second, we were able to closely track the CSF and MRI findings with the recovery of hematopoiesis. The patient’s meningitis symptoms were improving until day 19, when neutrophils rapidly increased. With the recovery of neutrophil count, a dramatic worsening of fever, consciousness and meningism was demonstrated. This could be considered as a type of immune reconstitution syndrome, though the term originally denoted the recovery of cellular immunity from AIDS or other immunosuppressive states. As shown in Fig. 1, we serially observed parameters of cellular immunity as well as neutrophil count. Interestingly, the severity of meningitis symptoms clearly synchronized with the blood neutrophil count, and the correlation is even more dramatic for CSF cells, CSF soluble interleukin-2 receptor (sIL-2R), and CSF adenosine deaminase (ADA). On day 19, the vast majority of CSF cells were polymorphonuclear cells (neutrophils). Later, CSF, sIL-2R and ADA increased, indicating that a typical inflammation cascade was ongoing. As differential diagnosis, other infections or an intracranial recurrence of AML were considered, but negative culture, cytology and clinical course were indicative of B. cereus meningitis. Therefore, we continued the antibiotics and the symptoms gradually improved.