Markouli

After reading the publication entitled “Infections in Myelodysplastic Syndrome in Relation to Stage and Therapy” (Mediterr J Hematol Infect Dis. 2018; 10(1): e2018039) that was published in your journal, we would like to congratulate the authors for this interesting review article and make some contributions specifically concerning Bacillus cereus infections in patients with hematological malignancies.
Bacillus cereus is a spore-building, Gram-positive rod that may cause three distinct syndromes: food intoxication, localized infection, or bacteremia with potential hematogenous complications (e.g., liver and cerebral abscesses).[2,3] Furthermore, patients with hematological diseases are at greater risk for invasive B. cereus infections.[2] Herein, we present an interesting case of fulminant B. cereus septicemia in a patient with myelodysplastic syndrome (MDS).
Α 74-year-old woman was diagnosed with MDS upon assessment of severe pancytopenia. Bone marrow (BM) examination revealed a blast percentage of 12% compatible with MDS with excess blasts 2 (MDS-EB-2) per the 2016 World Health Organization (WHO) classification,[4] whereas the BM cytogenetic analysis was normal (46, XX). She was started on treatment with 5-azacytidine at a dose of 75 mg/m²/day subcutaneously (IV) for 7 days in 28-day cycles. On day 20 of Cycle 2, while the patient was neutropenic (0.5x10⁹/L), she developed a fever of 39°C accompanied by chills, fatigue, and fainting. Her physical examination and initial chest X-ray did not reveal any specific findings. Computed tomography (CT) scan of the brain, conducted to investigate fainting, did not suggest central nervous system (CNS) involvement. Within one hour from the febrile episode, IV piperacillin/tazobactam at a dose of 4,5 g q6h was started along with filgrastim at a dose of 300 mcg daily. The patient reported diarrhea within the next 20 hours, and stool cultures were obtained. By that time, gram-positive, rod-shaped bacteria were isolated from both blood cultures, and vancomycin was added to the regimen. B. cereus was identified in the blood but was not isolated from the stool. Her central venous catheter was considered to be the source of her infection. The patient remained febrile for an additional 3 days after B. cereus isolation. A transthoracic echocardiogram did not reveal findings compatible with B. cereus endocarditis. Two days later, the fever subsided, and clinical improvement was noted within four days, as diarrhea and fatigue ameliorated.
In our case, a 74-year-old patient with MDS was diagnosed with isolated B. cereus bacteremia while on cycle 2 of chemotherapy. Studies have shown that immunocompromised patients with isolated B. cereus bacteremia usually follow a more benign course compared to organ-involved cases, having a more severe clinical presentation and life-threatening course.[3] In this context, we gathered reported cases of B. cereus bacteremia with contemporary manifestations from various organ systems in patients with hematological malignancies (Supplementary file 1).
Concerning general patient characteristics, 30 out of 73 patients were female (41%) and 31 were male (42.4%), while sex was not mentioned in 12 cases. Most patients were middle-aged, with the median age of 36 and the interquartile range being 45 years. Concerning risk factors for infection, all patients were neutropenic, and 45 had a diagnosis of acute leukemia (61.6%). Among patients with acute leukemia, 66.6% had acute myeloid leukemia (AML). The percentage of patients with intravascular catheters, an important risk factor since B. cereus can adhere to foreign bodies by producing biofilms,[3] was 76.7%. Notably, 56.1% of these patients had concurrent gastrointestinal symptoms, such as abdominal pain and diarrhea. However, CNS involvement was the most common manifestation (80.8% of patients). Other common symptoms included fever in 46.5% and headache in 23.1% of patients. Although the issue of ICU hospitalization was not mentioned in all cases, it was reported in 10.1% of patients. The death occurred in 34.2% of patients, and 92% of these deaths occurred within 30 days of symptom onset. Of note, 76.7% of patients received vancomycin, and 26.7% of those died, whereas 61.1% of patients who did not receive vancomycin died.
This outcome is in line with the well-studied susceptibility pattern of B. cereus, which is characterized by susceptibility to vancomycin but is resistant to penicillins and cephalosporins.[5] The presence of a CVC in most patients, which can be a source of infection similarly to our case, highlights the importance of early central catheter removal within 72 hours from the onset of B. cereus bacteremia, as previously recommended.[3] In addition, catheter infection may be associated with a worse outcome with frequent neurologic complications. Regardless of the presence of a central catheter, B. cereus infections should be included in the differential diagnosis of neutropenic patients with hematologic malignancies who have recently received chemotherapy and present with neurological symptoms.
Inappropriate antibiotic treatment is predictive of higher mortality rates in patients with bacteremia compared to appropriate therapy.[6] It is, therefore, crucial to select the right antimicrobial agents for empirical treatment according to the antimicrobial susceptibility of the pathogen. In the presence of CNS disease, abscess drainage in large and accessible abscesses should also be encouraged.[7] Most B. cereus isolates produce beta-lactamases and are resistant to penicillins and cephalosporins. Therefore, vancomycin should be included in empirical treatment regimens.[8] Alternative agents having in vitro activity against Bacillus spp include aminoglycosides, carbapenems, and fluoroquinolones.[9] However, reports of carbapenem resistance have recently been reported, and carbapenems are no longer considered appropriate as an empiric treatment.[10]
In conclusion, B. cereus should always be taken into consideration as a potential threat for patients with hematological malignancies, and a low threshold for prompt diagnosis and treatment should be placed.

Bacillus Cereus in Hematological Malignancies