Hostname: page-component-797576ffbb-gvrqt Total loading time: 0 Render date: 2023-12-06T20:02:08.227Z Has data issue: false Feature Flags: { "corePageComponentGetUserInfoFromSharedSession": true, "coreDisableEcommerce": false, "useRatesEcommerce": true } hasContentIssue false

Outcomes of Clostridium difficile Infection in Hospitalized Leukemia Patients: A Nationwide Analysis

Published online by Cambridge University Press:  24 March 2015

Ruihong Luo
Department of Internal Medicine, University of Nevada School of Medicine, Las Vegas, Nevada
Alan Greenberg
Infectious Disease Specialists, University Medical Center, Las Vegas, Nevada
Christian D. Stone*
Section of Gastroenterology and Hepatology, University of Nevada School of Medicine, Las Vegas, Nevada
Address all correspondence to Christian D. Stone, MD, MPH, Associate Professor of Medicine, Section of Gastroenterology and Hepatology, University of Nevada School of Medicine, 2040 W. Charleston Blvd, Suite 300, Las Vegas, NV 89102 (



The incidence of Clostridium difficile infection (CDI) has increased among hospitalized patients and is a common complication of leukemia. We investigated the risks for and outcomes of CDI in hospitalized leukemia patients.


Adults with a primary diagnosis of leukemia were extracted from the United States Nationwide Inpatient Sample database, 2005–2011. The primary outcomes of interest were CDI incidence, CDI-associated mortality, length of stay (LOS), and charges. In a secondary analysis, we sought to identify independent risk factors for CDI in leukemia patients. Logistic regression was used to derive odds ratios (ORs) adjusted for potential confounders.


A total of 1,243,107 leukemia hospitalizations were identified. Overall CDI incidence was 3.4% and increased from 3.0% to 3.5% during the 7-year study period. Leukemia patients had 2.6-fold higher risk for CDI than non-leukemia patients, adjusted for LOS. CDI was associated with a 20% increase in mortality of leukemia patients, as well as 2.6 times prolonged LOS and higher hospital charges. Multivariate analysis revealed that age >65 years (OR, 1.13), male gender (OR, 1.14), prolonged LOS, admission to teaching hospital (OR, 1.16), complications of sepsis (OR, 1.83), neutropenia (OR, 1.35), renal failure (OR, 1.18), and bone marrow or stem cell transplantation (OR, 1.27) were significantly associated with CDI occurrence.


Hospitalized leukemia patients have greater than twice the risk of CDI than non-leukemia patients. The incidence of CDI in this population increased 16.7% from 2005 to 2011. Development of CDI in leukemia patients was associated with increased mortality, longer LOS, and higher hospital charges.

Infect Control Hosp Epidemiol 2015;36(7):794–801

Original Articles
© 2015 by The Society for Healthcare Epidemiology of America. All rights reserved 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


1. Kelly, CP, LaMont, JT. Clostridium difficile—more difficult than ever. N Engl J Med 2008;359:19321940.Google Scholar
2. Kyne, L, Hamer, MB, Polavaram, R, Kelly, CP. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile . Clin Infect Dis 2002;34:346353.Google Scholar
3. Bignard, GE. Risk factors for Clostridium difficile infection. J Hosp Infect 1998;40:115.Google Scholar
4. Schalk, E, Bohr, UR, Konig, B, Scheinpflug, K, Mohren, M. Clostridium difficile associated diarrhea, a frequent complication in patients with acute myeloid leukemia. Ann Hematol 2010;89:914.Google Scholar
5. Cartoni, C, Dragoni, F, Micozzi, A, et al. Neutropenic enterocolitis in patients with acute leukemia: prognostic significance of bowel wall thickening detected by ultrasonography. J Clin Oncol 2001;19:756761.Google Scholar
6. Ballett, JG, Gerding, DN. Clinical recognition and diagnosis of Clostridium difficile infection. Clin Infect Dis 2008;46:S12S18.Google Scholar
7. Anand, A, Glatt, AE. Clostridium difficile infection associated with antineoplastic chemotherapy: a review. Clin Infect Dis 1993;17:109113.Google Scholar
8. Agency for Healthcare Research and Quality, Rockville, MD. Nationwide Inpatient Sample (NIS)-HCUP Coding Practices. Published 2008. Accessed January 29, 2015.Google Scholar
9. Spadao, F, Gerhardt, J, Guimaraes, T, et al. Incidence of diarrhea by Clostridium difficile in hematologic patients and hematopoietic stem cell transplantation patients: Risk factors for severe forms and death. Rev Inst Med Trop Sao Paulo 2014;56:325331.Google Scholar
10. Alonso, CD, Treadway, SB, Hanna, DB, et al. Epidemiology and outcomes of Clostridium difficile infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2012;54:10531063.Google Scholar
11. Loo, VG, Poirier, L, Miller, MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005;353:24422449.Google Scholar
12. Cohen, SH, Gerding, DN, Johnson, S, et al. Society for Healthcare Epidemiology of America; Infectious Diseases Society of America. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 2010;31:431455.Google Scholar
13. Dubberke, ER, Reske, KA, Yan, Y, Olsen, MA, McDonald, LC, Fraser, VJ. Clostridium difficile-associated disease in a setting of endemicity: identification of novel risk factors. Clin Infect Dis 2007;45:15431549.Google Scholar
14. Gafter-Gvili, A, Fraser, A, Paul, M, Leibovici, L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med 2005;142:979995.Google Scholar
15. Bucaneve, G, Micozzi, A, Menichetti, F, et al. Grouppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) Infection Program. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med 2005;353:977987.Google Scholar
16. Cullen, M, Steven, N, Billingham, L, et al. Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy +/- Antibiotic in a Number of Tumours (SIGNIFICANT) Trial Group. Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas. N Engl J Med 2005;353:988998.Google Scholar
17. Pepin, J, Saheb, N, Coulombe, MA, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis 2005;41:12541260.Google Scholar
18. McDonald, LC, Killgore, GE, Thompson, A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile . N Engl J Med 2005;353:24332441.Google Scholar
19. Dettenkofer, M, Ebner, W, Bertz, H, et al. Surveillance of nosocomial infections in adult recipients of allogeneic and autologous bone marrow and peripheral blood stem-cell transplantation. Bone Marrow Transpl 2003;31:795801.Google Scholar
20. Pant, C, Anderson, MP, O’Connor, JA, Marshall, CM, Deshpande, A, Sferra, TJ. Association of Clostridium difficile infection with outcomes of hospitalized solid organ transplant recipients: results from the 2009 Nationwide Inpatient Sample database. Transpl Infect Dis 2012;14:540547.Google Scholar
21. Ali, M, Anathakrishnan, AN, Ahmad, S, Kumar, N, Kumar, G, Saeian, K. Clostridium difficile infection in hospitalized liver transplant patients: a nationwide analysis. Liver Transpl 2012;18:972978.Google Scholar
22. Nguyen, GC, Kaplan, GG, Harris, ML, Brant, SR. A national survey of the prevalence and impact of Clostridium difficile infection among hospitalized inflammatory bowel disease patients. Am J Gastroenterol 2008;103:14431450.Google Scholar
23. Miller, M, Gravel, D, Mulvey, M, et al. Health care-associated Clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality. Clin Infect Dis 2010;50:194201.Google Scholar
24. He, M, Miyajima, F, Roberts, P, et al. Emergence and global spread of epidemic healthcare- associated Clostridium difficile. Nat Genet 2013;45:109113.Google Scholar
25. Apostolopoulou, E, Raftopoulos, V, Terzis, K, Elefsiniotis, I. Infection probability score: a predictor of Clostridium difficile-associated disease onset in patients with haematological malignancy. Eur J Oncol Nurs 2011;15:404409.Google Scholar
26. Rodemann, JF, Dubberke, ER, Reske, KA, Seo Da, H, Stone, CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol 2007;5:339344.Google Scholar
27. Bajaj, JS, Ananthakrishnan, AN, Hafeezullah, M, et al. Clostridium difficile is associated with poor outcomes in patients with cirrhosis: A national and tertiary center perspective. Am J Gastroenterol 2010;105:106113.Google Scholar
28. Micek, ST, Schramm, G, Morrow, L, et al. Clostridium difficile infection: a multicenter study of epidemiology and outcomes in mechanically ventilated patients. Crit Care Med 2013;41:19681975.Google Scholar
29. Mitchell, BG, Gardner, A, Barnett, AG, Hiller, JE, Graves, N. The prolongation of length of stay because of Clostridium difficile infection. Am J Infect Control 2014;42:164167.Google Scholar
30. Leung, S, Metzger, BS, Currie, BP. Incidence of Clostridium difficile infection in patients with acute leukemia and lymphoma after allogeneic hematopoietic stem cell transplantation. Infect Control Hosp Epidemiol 2010;31:313315.Google Scholar
31. McKinnell, JA, Miller, LG, Eells, SJ, Cui, E, Huang, SS. A systematic literature review and meta-analysis of factors associated with methicillin-resistant Staphylococcus aureus colonization at time of hospital or intensive care unit admission. Infect Control Hosp Epidemiol 2013;34:10771086.Google Scholar
32. Pant, C, Sferra, TJ, Deshpande, A, Minocha, A. Clinical approach to severe Clostridium difficile infection: update for the hospital practitioner. Eur J Intern Med 2011;22:561568.Google Scholar
33. Scheurer, DB, Hicks, LS, Cook, EF, Schnipper, JL. Accuracy of ICD-9 coding for Clostridium difficile infections: a retrospective cohort. Epidemiol Infect 2007;135:10101013.Google Scholar
34. Dubberke, ER, Reske, KA, McDonald, LC, Fraser, VJ. ICD-9 codes and surveillance for Clostridium difficile-associated disease. Emerg Infect Dis 2006;12:15761579.Google Scholar