Skip to main content

Management of Hospitalized Patients with Inflammatory Bowel Disease and CMV Infection or Clostridium Difficile Infection

  • Chapter
  • First Online:
Management of Inpatient Inflammatory Bowel Disease

Abstract

Patients with inflammatory bowel disease (IBD) are at increased risk of developing Clostridioides difficile (C. difficile) and cytomegalovirus (CMV) infection. Although symptoms in both conditions often overlap with those of IBD, it is essential to diagnose them quickly as they can both lead to adverse outcomes such as increased risk of colectomy or death. C. difficile should be ruled out in all patients hospitalized with a flare using a stool-based two-step testing algorithm. If C. difficile infection is present, oral vancomycin is the treatment of choice. Among patients with severe or steroid-refractory colitis, a sigmoidoscopy with biopsies to rule out CMV should be performed early in the hospital admission. Although the optimal diagnostic method for CMV is still unclear, histopathology with immunohistochemistry possibly combined with blood CMV DNA testing is preferred. CMV colitis should be treated with intravenous ganciclovir initially, which can then be transitioned to oral valganciclovir for a total of 2–3 weeks. The management of immunosuppressive therapy in the setting of superimposed C. difficile or CMV infection should be individualized, but both the underlying IBD and infection have to be aggressively treated.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Khanna S, Shin A, Kelly CP. Management of Clostridium difficile infection in inflammatory bowel disease: expert review from the clinical practice updates committee of the AGA Institute. Clin Gastroenterol Hepatol. 2017;15(2):166–74.

    Article  PubMed  Google Scholar 

  2. D’Aoust J, Battat R, Bessissow T. Management of inflammatory bowel disease with Clostridium difficile infection. World J Gastroenterol. 2017;23(27):4986–5003.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bossuyt P, Verhaegen J, Van Assche G, Rutgeerts P, Vermeire S. Increasing incidence of Clostridium difficile-associated diarrhea in inflammatory bowel disease. J Crohns Colitis. 2009;3(1):4–7.

    Article  PubMed  Google Scholar 

  4. McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1–e48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Baron SW, Ostrowsky BE, Nori P, Drory DY, Levi MH, Szymczak WA, et al. Screening of Clostridioides difficile carriers in an urban academic medical center: understanding implications of disease. Infect Control Hosp Epidemiol. 2020;41(2):149–53.

    PubMed  PubMed Central  Google Scholar 

  6. Ricciardi R, Ogilvie JW Jr, Roberts PL, Marcello PW, Concannon TW, Baxter NN. Epidemiology of Clostridium difficile colitis in hospitalized patients with inflammatory bowel diseases. Dis Colon Rectum. 2009;52(1):40–5.

    Article  PubMed  Google Scholar 

  7. Axelrad JE, Joelson A, Nobel YR, Lawlor G, Green PHR, Lichtiger S, et al. Enteric infection in relapse of inflammatory bowel disease: the utility of stool microbial PCR testing. Inflamm Bowel Dis. 2017;23(6):1034–9.

    Article  PubMed  Google Scholar 

  8. Balram B, Battat R, Al-Khoury A, D’Aoust J, Afif W, Bitton A, et al. Risk factors associated with Clostridium difficile infection in inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis. 2019;13(1):27–38.

    Article  PubMed  Google Scholar 

  9. Lei DK, Ollech JE, Andersen M, Weisshof R, Zmeter N, Sossenheimer P, et al. Long-duration Oral vancomycin to treat Clostridioides difficile in patients with inflammatory bowel disease is associated with a low rate of recurrence. Am J Gastroenterol. 2019;114(12):1904–8.

    Article  PubMed  Google Scholar 

  10. Chen XL, Deng J, Chen X, Wan SS, Wang Y, Cao Q. High incidence and morbidity of Clostridium difficile infection among hospitalized patients with inflammatory bowel disease: a prospective observational cohort study. J Dig Dis. 2019;20(9):460–6.

    Article  PubMed  Google Scholar 

  11. Ananthakrishnan AN, McGinley EL, Binion DG. Excess hospitalisation burden associated with Clostridium difficile in patients with inflammatory bowel disease. Gut. 2008;57(2):205–10.

    Article  CAS  PubMed  Google Scholar 

  12. Negrón ME, Rezaie A, Barkema HW, Rioux K, De Buck J, Checkley S, et al. Ulcerative colitis patients with Clostridium difficile are at increased risk of death, colectomy, and postoperative complications: a population-based inception cohort study. Am J Gastroenterol. 2016;111(5):691–704.

    Article  PubMed  Google Scholar 

  13. Razik R, Rumman A, Bahreini Z, McGeer A, Nguyen GC. Recurrence of Clostridium difficile infection in patients with inflammatory bowel disease: the RECIDIVISM study. Am J Gastroenterol. 2016;111(8):1141–6.

    Article  PubMed  Google Scholar 

  14. Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108(4):478–98.

    Article  CAS  PubMed  Google Scholar 

  15. Issa M, Ananthakrishnan AN, Binion DG. Clostridium difficile and inflammatory bowel disease. Inflamm Bowel Dis. 2008;14(10):1432–42.

    Article  PubMed  Google Scholar 

  16. Seppälä K, Hjelt L, Sipponen P. Colonoscopy in the diagnosis of antibiotic-associated colitis. A prospective study. Scand J Gastroenterol. 1981;16(4):465–8.

    Article  PubMed  Google Scholar 

  17. Ben-Horin S, Margalit M, Bossuyt P, Maul J, Shapira Y, Bojic D, et al. Prevalence and clinical impact of endoscopic pseudomembranes in patients with inflammatory bowel disease and Clostridium difficile infection. J Crohns Colitis. 2010;4(2):194–8.

    Article  PubMed  Google Scholar 

  18. Wang T, Matukas L, Streutker CJ. Histologic findings and clinical characteristics in acutely symptomatic ulcerative colitis patients with superimposed Clostridium difficile infection. Am J Clin Pathol. 2013;140(6):831–7.

    Article  PubMed  Google Scholar 

  19. Johnson S, Louie TJ, Gerding DN, Cornely OA, Chasan-Taber S, Fitts D, et al. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014;59(3):345–54.

    Article  CAS  PubMed  Google Scholar 

  20. Horton HA, Dezfoli S, Berel D, Hirsch J, Ippoliti A, McGovern D, et al. Antibiotics for treatment of Clostridium difficile infection in hospitalized patients with inflammatory bowel disease. Antimicrob Agents Chemother. 2014;58(9):5054–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019;114(3):384–413.

    Article  PubMed  Google Scholar 

  22. Fischer M, Sipe B, Cheng Y-W, Phelps E, Rogers N, Sagi S, et al. Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: a promising treatment approach. Gut Microbes. 2017;8(3):289–302.

    Article  CAS  PubMed  Google Scholar 

  23. Ianiro G, Masucci L, Quaranta G, Simonelli C, Lopetuso LR, Sanguinetti M, et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy plus vancomycin for the treatment of severe refractory Clostridium difficile infection—single versus multiple infusions. Aliment Pharmacol Ther. 2018;48(2):152–9.

    Article  CAS  PubMed  Google Scholar 

  24. Agrawal M, Aroniadis OC, Brandt LJ, Kelly C, Freeman S, Surawicz C, et al. The Long-term efficacy and safety of fecal microbiota transplant for recurrent, severe, and complicated Clostridium difficile infection in 146 elderly individuals. J Clin Gastroenterol. 2016;50(5):403–7.

    Article  PubMed  Google Scholar 

  25. Fischer M, Kao D, Kelly C, Kuchipudi A, Jafri S-M, Blumenkehl M, et al. Fecal microbiota transplantation is safe and efficacious for recurrent or refractory Clostridium difficile infection in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2016;22(10):2402–9.

    Article  PubMed  Google Scholar 

  26. Meighani A, Hart BR, Bourgi K, Miller N, John A, Ramesh M. Outcomes of fecal microbiota transplantation for Clostridium difficile infection in patients with inflammatory bowel disease. Dig Dis Sci. 2017;62(10):2870–5.

    Article  PubMed  Google Scholar 

  27. Hirten RP, Grinspan A, Fu S-C, Luo Y, Suarez-Farinas M, Rowland J, et al. Microbial engraftment and efficacy of fecal microbiota transplant for clostridium difficile in patients with and without inflammatory bowel disease. Inflamm Bowel Dis. 2019;25(6):969–79.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yanai H, Nguyen GC, Yun L, Lebwohl O, Navaneethan U, Stone CD, et al. Practice of gastroenterologists in treating flaring inflammatory bowel disease patients with clostridium difficile: antibiotics alone or combined antibiotics/immunomodulators? Inflamm Bowel Dis. 2010;17(7):1540–6.

    Article  PubMed  Google Scholar 

  29. Ben-Horin S, Margalit M, Bossuyt P, Maul J, Shapira Y, Bojic D, et al. Combination immunomodulator and antibiotic treatment in patients with inflammatory bowel disease and Clostridium difficile infection. Clin Gastroenterol Hepatol. 2009;7(9):981–7.

    Article  PubMed  Google Scholar 

  30. Ananthakrishnan AN, Guzman-Perez R, Gainer V, Cai T, Churchill S, Kohane I, et al. Predictors of severe outcomes associated with Clostridium difficile infection in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2012;35(7):789–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lukin DJ, Lawlor G, Hudesman DP, Durbin L, Axelrad JE, Passi M, et al. Escalation of immunosuppressive therapy for inflammatory bowel disease is not associated with adverse outcomes after infection with Clostridium difficile. Inflamm Bowel Dis. 2019;25(4):775–81.

    Article  PubMed  Google Scholar 

  32. Oh SJ, Lee CK, Kim Y-W, Jeong SJ, Park YM, Oh CH, et al. True cytomegalovirus colitis is a poor prognostic indicator in patients with ulcerative colitis flares: the 10-year experience of an academic referral inflammatory bowel disease center. Scand J Gastroenterol. 2019;54(8):976–83.

    Article  PubMed  Google Scholar 

  33. Pillet S, Pozzetto B, Roblin X. Cytomegalovirus and ulcerative colitis: place of antiviral therapy. World J Gastroenterol. 2016;22(6):2030–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Krech U. Complement-fixing antibodies against cytomegalovirus in different parts of the world. Bull World Health Organ. 1973;49(1):103–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Matsuoka K, Iwao Y, Mori T, Sakuraba A, Yajima T, Hisamatsu T, et al. Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol. 2007;102(2):331–7.

    Article  PubMed  Google Scholar 

  36. Sager K, Alam S, Bond A, Chinnappan L, Probert CS. Review article: cytomegalovirus and inflammatory bowel disease. Aliment Pharmacol Ther. 2015;41(8):725–33.

    Article  CAS  PubMed  Google Scholar 

  37. Criscuoli V, Casà A, Orlando A, Pecoraro G, Oliva L, Traina M, et al. Severe acute colitis associated with CMV: a prevalence study. Dig Liver Dis. 2004;36(12):818–20.

    Article  CAS  PubMed  Google Scholar 

  38. Roblin X, Pillet S, Berthelot P, Del Tedesco E, Phelip J-M, Chambonnière M-L, et al. Prevalence of cytomegalovirus infection in steroid-refractory Crohn’s disease. Inflamm Bowel Dis. 2012;18(7):E1396–E7.

    Article  PubMed  Google Scholar 

  39. Siegmund B. Cytomegalovirus infection associated with inflammatory bowel disease. Lancet Gastroenterol Hepatol. 2017;2(5):369–76.

    Article  PubMed  Google Scholar 

  40. Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, et al. Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials. Clin Infect Dis. 2017;64(1):87–91.

    Article  PubMed  Google Scholar 

  41. Delvincourt M, Lopez A, Pillet S, Bourrier A, Seksik P, Cosnes J, et al. The impact of cytomegalovirus reactivation and its treatment on the course of inflammatory bowel disease. Aliment Pharmacol Ther. 2014;39(7):712–20.

    Article  CAS  PubMed  Google Scholar 

  42. Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohn’s Colitis. 2014;8(6):443–68.

    Article  CAS  Google Scholar 

  43. Kandiel A, Lashner B. Cytomegalovirus colitis complicating inflammatory bowel disease. Am J Gastroenterol. 2006;101(12):2857–65.

    Article  CAS  PubMed  Google Scholar 

  44. Maher MM, Nassar MI. Acute cytomegalovirus infection is a risk factor in refractory and complicated inflammatory bowel disease. Dig Dis Sci. 2009;54(11):2456–62.

    Article  PubMed  Google Scholar 

  45. Kredel LI, Mundt P, van Riesen L, Jöhrens K, Hofmann J, Loddenkemper C, et al. Accuracy of diagnostic tests and a new algorithm for diagnosing cytomegalovirus colitis in inflammatory bowel diseases: a diagnostic study. Int J Color Dis. 2019;34(2):229–37.

    Article  Google Scholar 

  46. McCurdy JD, Jones A, Enders FT, Killian JM, Loftus EV Jr, Smyrk TC, et al. A model for identifying cytomegalovirus in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2015;13(1):131–7; quiz e7

    Article  PubMed  Google Scholar 

  47. Zagórowicz E, Bugajski M, Wieszczy P, Pietrzak A, Magdziak A, Mróz A. Cytomegalovirus infection in ulcerative colitis is related to severe inflammation and a high count of cytomegalovirus-positive cells in biopsy is a risk factor for colectomy. J Crohns Colitis. 2016;10(10):1205–11.

    Article  PubMed  Google Scholar 

  48. Römkens TEH, Bulte GJ, Nissen LHC, Drenth JPH. Cytomegalovirus in inflammatory bowel disease: a systematic review. World J Gastroenterol. 2016;22(3):1321–30.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Pillet S, Williet N, Pouvaret A, Del Tedesco E, Saint-Sardos P, Pozzetto B, et al. Distribution of cytomegalovirus DNA load in the inflamed colon of ulcerative colitis patients. Am J Gastroenterol. 2016;111(3):439–41.

    Article  CAS  PubMed  Google Scholar 

  50. Roblin X, Pillet S, Oussalah A, Berthelot P, Del Tedesco E, Phelip J-M, et al. Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis. Am J Gastroenterol. 2011;106(11):2001–8.

    Article  CAS  PubMed  Google Scholar 

  51. Long MD, Onyiah JC, Miller M, Herfarth HH. Cytomegalovirus viral load in the colon and risk of colectomy in hospitalized patients with inflammatory bowel diseases. Inflamm Bowel Dis. 2016;22(6):E21–E2.

    Article  PubMed  Google Scholar 

  52. Mavropoulou E, Ternes K, Mechie N-C, Bremer SCB, Kunsch S, Ellenrieder V, et al. Cytomegalovirus colitis in inflammatory bowel disease and after haematopoietic stem cell transplantation: diagnostic accuracy, predictors, risk factors and disease outcome. BMJ Open Gastroenterol. 2019;6(1):e000258.

    Article  PubMed  PubMed Central  Google Scholar 

  53. McCurdy JD, Enders FT, Jones A, Killian JM, Loftus EV Jr, Bruining DH, et al. Detection of cytomegalovirus in patients with inflammatory bowel disease: where to biopsy and how many biopsies? Inflamm Bowel Dis. 2015;21(12):2833–8.

    Article  PubMed  Google Scholar 

  54. Omiya M, Matsushita M, Tanaka T, Kawamata S, Okazaki K. The absence of large ulcer predicts latent cytomegalovirus infection in ulcerative colitis with positive mucosal viral assay. Intern Med. 2010;49(21):2277–82.

    Article  PubMed  Google Scholar 

  55. Suzuki H, Kato J, Kuriyama M, Hiraoka S, Kuwaki K, Yamamoto K. Specific endoscopic features of ulcerative colitis complicated by cytomegalovirus infection. World J Gastroenterol. 2010;16(10):1245–51.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Jones A, McCurdy JD, Loftus EV Jr, Bruining DH, Enders FT, Killian JM, et al. Effects of antiviral therapy for patients with inflammatory bowel disease and a positive intestinal biopsy for cytomegalovirus. Clin Gastroenterol Hepatol. 2015;13(5):949–55.

    Article  CAS  PubMed  Google Scholar 

  57. Kopylov U, Papamichael K, Katsanos K, Waterman M, Bar-Gil Shitrit A, Boysen T, et al. Impact of infliximab and cyclosporine on the risk of colectomy in hospitalized patients with ulcerative colitis complicated by cytomegalovirus-a multicenter retrospective study. Inflamm Bowel Dis. 2017;23(9):1605–13.

    Article  PubMed  Google Scholar 

  58. Kopylov U, Sasson G, Geyshis B, Oikawa MT, Barshack I, Eliakim R, et al. Cytomegalovirus positive ulcerative colitis: a single center experience and literature review. World J Gastrointest Pathophysiol. 2013;4(1):18–23.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Kim YS, Kim Y-H, Kim JS, Cheon JH, Ye BD, Jung S-A, et al. The prevalence and efficacy of ganciclovir on steroid-refractory ulcerative colitis with cytomegalovirus infection: a prospective multicenter study. J Clin Gastroenterol. 2012;46(1):51–6.

    Article  CAS  PubMed  Google Scholar 

  60. Shukla T, Singh S, Loftus EV Jr, Bruining DH, McCurdy JD. Antiviral therapy in steroid-refractory ulcerative colitis with cytomegalovirus: systematic review and meta-analysis. Inflamm Bowel Dis. 2015;21(11):2718–25.

    Article  PubMed  Google Scholar 

  61. Baradhi KM, Aure RL, El-Amm JM. High-dose valganciclovir treatment for resistant cytomegalovirus colitis due to UL97 and UL54 mutations. Transplant Proc. 2018;50(1):142–4.

    Article  CAS  PubMed  Google Scholar 

  62. Åsberg A, Humar A, Rollag H, Jardine AG, Mouas H, Pescovitz MD, et al. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2007;7(9):2106–13.

    Article  PubMed  Google Scholar 

  63. Ahmed I, Kassem W, Salam Y, Furnari M, Mehta T. Outcome of cytomegalovirus colitis in inflammatory bowel disease with different regimes of ganciclovir. Middle East J Dig Dis. 2018;10(4):219–27.

    Article  Google Scholar 

  64. Kim YS, Kim YH, Kim JS, Cheon JH, Ye BD, Jung SA, et al. The prevalence and efficacy of ganciclovir on steroid-refractory ulcerative colitis with cytomegalovirus infection: a prospective multicenter study. J Clin Gastroenterol. 2012;46(1):51–6.

    Article  CAS  PubMed  Google Scholar 

  65. D’Ovidio V, Vernia P, Gentile G, Capobianchi A, Marcheggiano A, Viscido A, et al. Cytomegalovirus infection in inflammatory bowel disease patients undergoing anti-TNFα therapy. J Clin Virol. 2008;43(2):180–3.

    Article  PubMed  Google Scholar 

Download references

Disclosure

The authors declared no financial conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jean-Paul Achkar .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

El Ouali, S., Achkar, JP. (2022). Management of Hospitalized Patients with Inflammatory Bowel Disease and CMV Infection or Clostridium Difficile Infection. In: Feuerstein, J.D., Cheifetz, A.S. (eds) Management of Inpatient Inflammatory Bowel Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-0716-1987-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-1987-2_8

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-0716-1986-5

  • Online ISBN: 978-1-0716-1987-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics