Bacillus cereus Typhlitis in a Patient with Acute Myelogenous Leukemia: A Case Report and Review of the Literature

Bacillus cereus is a Gram-positive rod that is now recognized as a rare cause of frank disease in the neutropenic hematologic malignancy patient. Because this pathogen is rarely isolated in clinical specimens, no large studies exist to guide the management of these acutely ill patients. Individual case reports and case series exist in the literature describing various clinical manifestations of B. cereus in the neutropenic patient including bacteremia/septicemia, pneumonia, meningitis/encephalitis, hepatic abscesses, and gastritis. In this report, we describe a case of typhlitis caused by B. cereus in a 74-year-old female with recently diagnosed acute myelogenous leukemia (AML), and we summarize the available English language literature to draw tentative conclusions regarding the clinical manifestations of this organism.


Background
Bacillus cereus is a Gram-positive, spore-forming rod that classically causes food poisoning via plasmid-encoded toxins. Life-threatening infections with B. cereus have been reported in patients with hematologic malignancies, primarily as these patients experience neutropenia following the initiation of induction chemotherapy. Here, we report a case of B. cereus colitis/typhlitis in a neutropenic patient with acute myelogenous leukemia (AML), and we summarize the literature regarding the infectious manifestations of B. cereus in patients with hematologic malignancies. is is the second reported case of B. cereus typhlitis.

Case Report
A 74-year-old Caucasian female with a 2-month history of pancytopenia and a preliminary diagnosis of myelodysplastic syndrome (MDS) presented to our tertiary cancer treatment facility for further evaluation. A repeat bone marrow biopsy was performed and demonstrated 26% blasts, and the patient was formally diagnosed with acute myelogenous leukemia (AML). One month later, the patient was admitted to our facility for induction "7 + 3" chemotherapy with sorafenib. On admission, the patient was found to have mild pancytopenia with an absolute neutrophil count (ANC) between 500 and 1,000 cells/μL but had no specific complaints and an unremarkable physical examination.
Following initiation of chemotherapy, antimicrobial prophylaxis with ciprofloxacin, acyclovir, and micafungin was begun, and nebulized amphotericin B was added because computed tomography (CT) scan of the chest demonstrated several ground-glass infiltrates with no pulmonary symptoms. e ground-glass infiltrates remained stable on follow-up CT scan. Mild hemoptysis developed and empiric cefepime was begun in place of oral ciprofloxacin on the 8th day of neutropenia due to fever. She remained stable and well appearing until the 10th day of neutropenia when nonbloody diarrhea without abdominal pain developed. Clostridium difficile stool polymerase chain reaction (PCR) analysis was negative. Loperamide was administered to help reduce the diarrhea.
Diarrhea persisted despite escalating doses of loperamide, and on the 13th day of neutropenia, right upper quadrant abdominal pain developed and metronidazole 500 mg twice daily was initiated. CT scan of the abdomen and pelvis revealed cecal wall thickening associated with fat stranding and right paracolic gutter fluid collectionfindings consistent with typhlitis. Labs revealed an ANC of less than 500 cells/μL. Stool cultures obtained the following day revealed a preponderance of Bacillus cereus with the absence of usual enteric flora. Physical examination then demonstrated dull periumbilical pain upon palpation and a sharper pain in the right lower quadrant of the abdomen. Metronidazole was changed to clindamycin 450 mg thrice daily. During the next several days, the abdominal pain and diarrhea resolved. e patient's later hospital course was complicated by vancomycin-resistant Enterococcus (VRE) bacteremia that developed after 21 days of neutropenia and was treated with central venous catheter removal and linezolid 600 mg twice per day. She would finish the 2-week linezolid course outpatient; she was discharged afebrile after 30 hospital days with an ANC of 3.28 cells/μL. Complete clinical remission of the AML was ultimately achieved following 2 rounds of consolidation chemotherapy.

Discussion
Typhlitis, also known as neutropenic enterocolitis (or, rarely, ileocecal syndrome) is the most common cause of fever and is case series describes 3 patients, 2 with AML and 1 with ALL, who develop septicemia due to B. cereus. All 3 patients died despite treatment with amikacin. Additionally, all 3 patients developed a similar syndrome of abnormal posturing and clinical signs of brain stem death. 1 patient in this case series was found to have elevated liver enzymes and serum bilirubin perimortem.

Case Reports in Infectious Diseases
abdominal tenderness in the neutropenic patient [1]. Historically, Clostridium septicum was pointed to as a common etiologic agent of typhlitis [2]. It is known, however, that the microbiologic etiology of this disease is broad and diverse, with an 18-year study in leukemic children finding that 84% and 16% of cases being caused by bacteria and fungi, respectively [3]. Currently, there exist no high-quality casecontrol, cohort, or randomized controlled trials to guide clinicians in the best management of typhlitis [4]. e isolation of B. cereus from clinical specimens was historically considered contamination. However, it is now clear from the literature that B. cereus can cause a wide spectrum of disease in the neutropenic patient. Our patient, a 74-year-old female undergoing induction chemotherapy for AML, was found to have typhlitis with stool culture confirming the presence of B. cereus in the colon with a notable absence of the usual enteric flora. e initiation of clindamycin led to a rapid improvement in our patient's symptoms. Our patient's blood cultures remained sterile during the episode of typhlitis.
On review of the literature, we found a handful of reports describing the various clinical manifestations of B. cereus (Table 1). e most common manifestation was sepsis. As reported by Uchino et al., patients who develop central nervous system (CNS) symptoms or who have bacterial involvement of the liver tend to have a worse prognosis [5,9]. Indeed, from our review, it is clear that while B. cereus bacteremia can result in the seeding of almost any organ, B. cereus seems to preferentially seed the brain/meninges and the liver [5,7,[9][10][11][12]. CNS involvement is most commonly multifocal and leads to a rapid deterioration in mental status and frequently leads to development of a comatose state. Liver involvement is often asymptomatic but can manifest on CT scan as multiple subcentimeter, hypodense lesions. Pathologic analysis of the liver at autopsy reveals microabscesses with large Gram-positive rods present within the lesions [10,12]. e management of the neutropenic patient with cultures positive for B. cereus presents a clinical dilemma as no large studies exist to guide the management of these critically ill patients. From our review of the available English language literature, some tentative conclusions may be drawn regarding this organism in the context of the neutropenic hematologic malignancy patient. ese conclusions are summarized in Table 2.
Case Reports in Infectious Diseases 3