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

1. 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. This is the second reported case of B. cereus typhlitis.

2. 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/[micro]L 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. The 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 collection--findings consistent with typhlitis. Labs revealed an ANC of less than 500 cells/[micro]L. 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. The 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/[micro]L. Complete clinical remission of the AML was ultimately achieved following 2 rounds of consolidation chemotherapy.

3. Discussion

Typhlitis, also known as neutropenic enterocolitis (or, rarely, ileocecal syndrome) is the most common cause of fever and 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].

The 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. The 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). The 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, 9-12]. 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].

The 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. These conclusions are summarized in Table 2.

https://doi.org/10.1155/2018/7510715

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Authors' Contributions

All authors have participated significantly in writing of this manuscript and approve of its content. The final manuscript has been seen and approved by all authors.

References

[1] B. D. Badgwell, J. N. Cormier, C. J. Wray et al., "Challenges in surgical management of abdominal pain in the neutropenic cancer patient," Annals of Surgery, vol. 248, no. 1, pp. 104-109, 2008.

[2] G. D. Rifkin, "Neutropenic enterocolitis and Clostridium septicum infection in patients with agranulocytosis," Archives of Internal Medicine, vol. 140, no. 6, pp. 834-835, 1980.

[3] J. A. Katz, M. L. Wagner, M. V. Gresik, D. H. Mahoney, and D. J. Fernbach, "Typhlitis: an 18-year experience and postmortem review," Cancer, vol. 65, no. 4, pp. 1041-1047, 1990.

[4] M. Gorschluter, U. Mey, J. Strehl et al., "Neutropenic enterocolitis in adults: systematic analysis of evidence quality," European Journal ofHaematology, vol. 75, no. 1, pp. 1-13,2005.

[5] Y. Uchino, N. Iriyama, K. Matsumoto et al., "A case series of Bacillus cereus septicemia in patients with hematological disease," Internal Medicine, vol. 51, no. 19, pp. 2733-2738, 2012.

[6] J. Frankard, R. Li, F. Taccone et al., "Bacillus cereus pneumonia in a patient with acute lymphoblastic leukemia," European Journal of Clinical Microbiology & Infectious Diseases, vol. 23, no. 9, pp. 725-728, 2004.

[7] E. F. Marley, N. K. Saini, C. Venkatraman, and J. M. Orenstein, "Fatal Bacillus cereus meningoencephalitis in an adult with acute myelogenous leukemia," Southern Medical Journal, vol. 88, no. 9, pp. 969-972, 1995.

[8] J. Le Scanff, I. Mohammedi, A. Thiebaut, O. Martin, L. Argaud, and D. Robert, "Necrotizing gastritis due to Bacillus cereus in an immunocompromised patient," Infection, vol. 34, no. 2, pp. 98-99, 2006.

[9] D. Inoue, Y. Nagai, M. Mori et al., "Fulminant sepsis caused by Bacillus cereus in patients with hematologic malignancies: analysis of its prognosis and risk factors," Leukemia & Lymphoma, vol. 51, no. 5, pp. 860-869, 2010.

[10] A. S. Ginsburg, L. G. Salazar, L. D. True, and M. L. Disis, "Fatal Bacillus cereus sepsis following resolving neutropenic enterocolitis during the treatment of acute leukemia," American Journal of Hematology, vol. 72, no. 3, pp. 204-208, 2003.

[11] M. O. Musa, M. Al Douri, S. Khan, T. Shafi, A. Al Humaidh, and A. M. Al Rasheed, "Fulminant septicaemic syndrome of Bacillus cereus: three case reports," Journal of Infection, vol. 39, no. 2, pp. 154-156, 1999.

[12] N. Akiyama, K. Mitani, Y. Tanaka et al., "Fulminant septicemic syndrome of Bacillus cereus in a leukemic patient," Internal Medicine, vol. 36, no. 3, pp. 221-226, 1997.

James D. Denham (iD), (1) Sowmya Nanjappa (iD), (1,2) and John N. Greene (iD) (1,2)

(1) Morsani College of Medicine, University of South Florida, Tampa, FL, USA

(2) H. Lee Moffitt Cancer Center, Tampa, FL, USA

Correspondence should be addressed to James D. Denham; jdenham@health.usf.edu

Received 13 December 2017; Accepted 18 February 2018; Published 11 March 2018

Academic Editor: Gernot Walder
Table 1: Summary of literature review findings.

Reference
Number            Author                        Summary

[5]           Uchino et al.        This article reports 13 cases of
                                   septicemia caused by B. cereus.
                                 Uchino et al. report a case fatality
                                    rate of 25% and found that the
                                 presence of liver and CNS involvement
                                    portended a poorer prognosis.
                                 Clindamycin resistance was found to
                                 be high in this series (76.9%), and
                                   Uchino et al. recommend against
                                 using clindamycin and carbapenems in
                                  the empiric treatment of B. cereus
                                              infections.
[6]          Frankard et al.        This article reports a case of
                                 pneumonia caused by B. cereus in the
                                context of a neutropenic patient with
                                  ALL. This patient was treated with
                                    VCN and demonstrated clinical
                                  improvement. She was readmitted 3
                                     weeks later with a recurrent
                                 pneumonia due to Streptococcus spp.,
                                  and she expired due to this later
                                              infection.
[7]           Marley et al.         Marley et al. report a case of
                                  meningoencephalitis occurring in a
                                     patient undergoing induction
                                  chemotherapy for AML. The patient
                                   became febrile with an ANC of 20/
                                 [mm.sup.3]. Over several hours, the
                                     patient experienced a rapid
                                 deterioration of mentation, and a CT
                                   scan revealed multiple enhancing
                                  lesions in the brain. The patient
                                 died 12 hours following the onset of
                                    neurological symptoms. Autopsy
                                  additionally found multiple liver
                                              abscesses.
[8]          Le Scanff et al.     Le Scanff et al. report a case of
                                  necrotizing gastritis in a female
                                  patient with AML 63 days following
                                  induction chemotherapy initiation.
                                     The patient developed severe
                                     epigastric pain and massive
                                  hematemesis leading to hemodynamic
                                    instability; blood and gastric
                                 mucosal cultures revealed B. cereus.
                                     This patient was successfully
                                   treated with combination of VCN
                                             and imipenem.
[9]            Inoue et al.      This substantial article reports 23
                                 cases of B. cereus bacteremia in HM
                                 patients, with 12 of these patients
                                   developing a frank sepsis. Inoue
                                    reports a case fatality rate of
                                  25% for B. cereus sepsis. Further,
                                   independent risk-factor analysis
                                     concluded that a low ANC, CV
                                  catheterization, and CNS symptoms
                                  were all significantly associated
                                       with a poorer prognosis.
[10]         Ginsburg et al.     Ginsburg et al. report a fatal case
                                 of B. cereus sepsis that arose in a
                                 22-year-old male following induction
                                  chemotherapy for AML. On hospital
                                day 5, the patient became febrile and
                                  neutropenic and a CTscan revealed
                                 findings consistent with colitis, but
                                 stool C. difficile testing remained
                                  negative. His symptoms resolved by
                                  hospital day 14 with metronidazole
                                 and imipenem. However, 6 days later,
                                 he developed diffuse abdominal pain
                                    and blood cultures revealed B.
                                    cereus. VCN and ampicillin were
                                     added, but a new CTrevealed
                                  pancolitis and multiple hypodense
                                  lesions in the liver. The patient
                                expired on the thirty-fourth hospital
                                 day. Autopsy confirmed the presence
                                      of B. cereus in the liver
                                            microabscesses.
[11]           Musa et al.           This 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.
[12]          Akiyama et al.       Akiyama et al. report a case of
                                   fatal B. cereus septicemia in a
                                     64-year-old patient with AML
                                  undergoing induction chemotherapy.
                                    Autopsy revealed a necrotizing
                                  infection in the leptomeninges of
                                    the brain and spinal cord and
                                    numerous microabscesses of the
                                 liver. B. cereus was present within
                                            these lesions.

CNS = central nervous system; ALL = acute lymphoblastic leukemia;

VCN= vancomycin; AML= acute myelogenous leukemia. ANC= absolute
neutrophil count. CT =computed tomography. HM= hematologic
malignancy. CV= central venous. C. difficile = Clostridium
difficile.

Table 2: Conclusions for Bacillus cereus infection in
neutropenic hematologic malignancy patients.

                                    Reference
             Conclusion               Number

1        Neutropenia is the           [5-12]
        primary risk factor
         for infection, as
      opposed to intoxication,
           with B. cereus
2         B. cereus has a          [5, 7, 9-12]
        predilection for the
         CNS and the liver;
       involvement of either
         of these two organ
         systems portends a
           poor prognosis
3        The case fatality            [5, 9]
         rate for B. cereus
           sepsis appears
              to be 25%
4      The most commonly used         [5-10]
       definitive therapy for
        B. cereus infection
      appears to be vancomycin
     with or without carbapenem

CNS = central nervous system.
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Title Annotation:Case Report
Author:Denham, James D.; Nanjappa, Sowmya; Greene, John N.
Publication:Case Reports in Infectious Diseases
Date:Jan 1, 2018
Words:2099
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