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Please cite this article as: Chan K-S, Lee W-Y, Yu W-L, Coexisting Cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis, ...

Accepted Manuscript Coexisting Cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis Khee-Siang Chan, Wen-Ying Lee, Wen-Liang Yu, M.D. PII:

S1684-1182(16)00008-6

DOI:

10.1016/j.jmii.2015.12.007

Reference:

JMII 732

To appear in:

Journal of Microbiology, Immunology and Infection

Received Date: 30 June 2015 Revised Date:

31 October 2015

Accepted Date: 14 December 2015

Please cite this article as: Chan K-S, Lee W-Y, Yu W-L, Coexisting Cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis, Journal of Microbiology, Immunology and Infection (2016), doi: 10.1016/j.jmii.2015.12.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

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Review Article Coexisting Cytomegalovirus infection in immunocompetent patients

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with Clostridium difficile colitis

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Khee-Siang Chan a, Wen-Ying Lee b, c, Wen-Liang Yu a, d,*

RI PT

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a

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b

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c

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d

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Running Title: Coexisting Cytomegalovirus and Clostridium difficile Colitis

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Keywords: Clostridium difficile, C. difficile infection, colitis, cytomegalovirus,

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immunocompetent

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*Corresponding author: Wen-Liang Yu, M.D., Department of Medical Research, Chi

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Mei Medical Center, No. 901 Zhonghua Road, Yongkang District, 710 Tainan City,

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Taiwan. Tel: +886-6- 281-2811 ext 52606, Fax: +886-6- 283-3351, E-mail address:

SC

Department of Pathology, Chi Mei Medical Center, Tainan City, Taiwan

M AN U

Department of Pathology, Taipei Medical University, Taipei City, Taiwan

EP

TE D

Department of Medicine, Taipei Medical University, Taipei, Taiwan

AC C

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Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan

[email protected] (W.-L Yu)

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Abstract

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Cytomegalovirus (CMV) colitis usually occurs in the immunocompromised patients

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with human immunodeficiency virus infection, organ transplantation, and malignancy

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receiving chemotherapy or ulcerative colitis receiving immunosuppressive agents.

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However, CMV colitis is increasingly recognized in the immunocompetent hosts.

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Notably, CMV colitis coexisting with Clostridium difficile infection (CDI) in

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apparently healthy individuals has been published in recent years, which could result

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in high morbidity and mortality. CMV colitis is a rare but possible differential

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diagnosis in the immunocompetent patients with abdominal pain, watery or especially

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bloody diarrhea, which could be refractory to standard treatment for CDI. As a

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characteristic of CDI, however, pseudomembranous colitis may be only caused by

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CMV infection. Real-time CMV-PCR for blood and stool samples may be a useful

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and noninvasive diagnostic strategy to identify CMV infection when treatment of CDI

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eventually fails to show significant benefits. Quantitative CMV-PCR in mucosal

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biopsies may increase the diagnostic yield of traditional histopathology. CMV colitis is potentially life-threatening if severe complications occur, such as sepsis secondary to colitis, massive colorectal bleeding, toxic megacolon and colonic perforation, so

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that may necessity preemptive antiviral treatment for those who are positive for

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CMV-PCR in blood and/or stool samples while pending histological diagnosis. 2

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Background

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Cytomegalovirus (CMV) is a highly prevalent and globally distributed virus. CMV

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infection in healthy adults is usually asymptomatic or causes a mildly infectious

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mononucleosis-like syndrome. CMV then usually becomes dormant until reactivation

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in the patients with severely immunocompromised status, who may potentially

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develop invasive CMV disease with a wide range of manifestations, most commonly

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colorectal infection with hemorrhagic ulceration. Coexistent two entities- CMV colitis

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and Clostridium difficile colitis have usually been reported among the

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immunocompromised patients, who have human immunodeficiency virus (HIV)

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infection, organ transplantation, hematologic malignancy, solitary organ cancer, or

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inflammatory bowel disease receiving immunosuppressive agents.1-9 For example,

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Florescu et al. reviewed 9 patients who developed C. difficile and CMV colitis, among

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them, 8 patients were immunocompromised: 4 transplant recipients, 2 oncology

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patients, 1 patient with advanced acquired immunodeficiency syndrome, and 1 on an

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immunosuppressive regimen for severe ulcerative colitis.8 Besides, CMV colitis can

mimic or present as pseudomembranous colitis in the immunocompromised patients.10-14

CMV gastrointestinal disease rarely occurs in the immunocompetent patients and could resolve completely without the use of antiviral drugs, if the immunity is 3

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obtained.15 In addition, CMV colitis is increasingly recognized in the apparently

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immunocompetent patients in some immunomodulating conditions, such as elderly,

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pregnancy, chronic renal failure, coronary artery disease, ischemic heart disease,

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congestive heart failure, diabetes mellitus, steroid use, blood transfusion and

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prolonged stay in the intensive care units (ICU).15-28 However, CMV colitis in these

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patients has often been neglected by clinical physicians.28 Therefore, this review

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article will mainly focus on the English literature of CMV colitis coexisting、

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following or followed by Clostridium difficile colitis among previously healthy or

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apparently immunocompetent adult patients. We will also review those of CMV

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colitis presenting as a sole cause of pseudomembranous colitis without CDI.

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Epidemiology of CMV Colitis in the immunocompetent patients

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One systemic review identified only 91 immunocompetent patients with

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gastrointestinal CMV infections for the period of 1950-2007.25 Another literature

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review from 1980 to 2003 identified 44 immunocompetent patients with CMV colitis.

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Among them, spontaneous remission occurred in 31.8%, mostly individuals

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