Neuroinvasive Bacillus cereus Infection in Immunocompromised Hosts: Epidemiologic Investigation of 5 Patients With Acute Myeloid Leukemia

Abstract

Background: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia.

Methods: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates.

Results: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year.

Conclusions: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen.

Keywords: Bacillus cereus; acute myeloid leukemia; immunocompromised; infection control investigation; neuroinvasive infection.

Figure 1.

Identification of neuroinvasive Bacillus cereus infections. The figure describes the methods for identifying neuroinvasive B cereus infections. Cases were defined as patients with a diagnosis of acute leukemia, positive microbiologic cultures (blood or cerebrospinal fluid) for B cereus ≥48 hours after admission, and correlating central nervous system radiographic findings. After 3 index cases were identified, all patients with microbiologic cultures positive for Bacillus species were assessed (n = 48). Cases of patients with a diagnosis of acute leukemia and a positive culture with B cereus during the risk period were extensively reviewed (n = 13), including 5 that exhibited correlating abnormal central nervous system radiographic findings consistent with neuroinvasive disease.

Figure 2.

Timeline of neuroinvasive Bacillus cereus infections. The figure demonstrates the timing of neuroinvasive B cereus infections, including first and recurrent fever, diagnosis of B cereus bacteremia, and recovery of neutrophils after intensive cytotoxic induction chemotherapy. ANC, absolute neutrophil count.

Figure 3.

Empiric antimicrobial strategy for prevention of neuroinvasive Bacillus cereus infections in patients with acute myeloid leukemia. The figure displays the empiric antimicrobial strategy that was initiated at our institution among patients with acute myeloid leukemia for the prevention of neuroinvasive B cereus infection. The strategy was elected to maximize antimicrobial stewardship by ensuring time-limited courses of empiric fluoroquinolone therapy and prompt discontinuation if blood cultures remained negative and there was no evidence of neuroinvasive B cereus infection. Fluoroquinolone therapy was selected given optimal central nervous system penetration and borderline elevated minimum inhibitory concentrations to vancomycin for the organisms isolated at our institution. AML, acute myeloid leukemia.