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A prospective cohort study on hospital mortality due to Clostridium difficile infection

  • Clinical and Epidemiological Study
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Abstract

Purpose

Although an increase in burden of disease has frequently been reported for Clostridium difficile infection (CDI), specific data on the effect of CDI on a patient’s risk of death or overall hospital mortality are scarce. Therefore, we performed a prospective cohort study to analyse the effect of CDI on the risk of pre-discharge all-cause death in all inpatients with CDI compared to all inpatients without CDI during 2009 in a single hospital.

Methods

Clostridium difficile infection was defined as by the European Society of Clinical Microbiology and Infectious Diseases. Data were collected from the medical charts of CDI patients and from the hospital discharge data of non-CDI and CDI patients. The effect measures of CDI used to compute the risk of pre-discharge all-cause death were risk ratio, attributable risk, mortality fraction (%) and population attributable risk percentage. Co-morbidity was categorized using the Charlson co-morbidity score in which a value of ≤2 was defined as low co-morbidity and that of >2 as moderate/severe co-morbidity. A stratified analysis and a Poisson regression model were applied to adjust for the effects of the risk factors sex, age and severity of co-morbidity.

Results

A total of 185 hospitalized patients with CDI were compared to 38,644 other hospitalized patients without CDI admitted between 1 January 2009 and 31 December 2009. The mean age of the CDI and non-CDI patients was 74.3 (range 72.3–76.4) and 51.9 (range 51.6–52.1) years, respectively. Of the 185 CDI, 136 (73.5 %) and 49 (26.5 %) were categorized with low and high co-morbidity, respectively, versus 32,107 (83.4 %) and 6,352 (16.5 %), respectively, in non-CDI patients. Overall, 24 of the 185 CDI patients (13 %) versus 1,021 of the 38,459 non-CDI patients (2.7 %) died during their hospital stay, resulting in a relative risk of pre-discharge death of 4.89 [95 % confidence interval (CI) 3.35–7.13] for CDI patients, a CDI attributable risk of death of 10.3 per 100 patients and a CDI attributable fraction of 79.5 % (95 % CI 70.1–86 %). After adjustment for age, sex and co-morbidity the relative risk of pre-discharge death was 2.74 (95 % CI 1.82–4.10; p < 0.0001) for patients with CDI, and the proportion of hospital deaths due to CDI was 1.72 (95 % CI 1.22–2.05).

Conclusion

The results of this study lead to the conclusion that hospitalized patients with CDI are—independent of age, sex and co-morbidity severity—2.74-fold more likely to die during their hospital stay than all other hospitalized patients. The eradication of CDI in the hospital could have prevented 1.72 % of in-hospital deaths in our study population during the 1 year of the study.

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References

  1. Tedesco FJ, Barton RW, Alpers DH. Clindamycin-associated colitis: a prospective study. Ann Intern Med. 1974;81:429–33.

    PubMed  CAS  Google Scholar 

  2. Pepin J, Alary ME, Valiquette L, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591–7.

    Article  PubMed  CAS  Google Scholar 

  3. 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;41:1254–60.

    Article  PubMed  CAS  Google Scholar 

  4. Pepin J, Valiquette L, Alary ME, et al. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. Can Med Assoc J. 2004;171:466–72.

    Article  Google Scholar 

  5. Pepin J, Valiquette L, Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. Can Med Assoc J. 2005;173:1037–42.

    Article  Google Scholar 

  6. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005;353:2433–41.

    Article  PubMed  CAS  Google Scholar 

  7. Warny M, Pepin J, Fang A, et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet. 2005;366:1079–84.

    Article  PubMed  CAS  Google Scholar 

  8. Kuijper EJ, Coignard B, Tull P. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect. 2006;12:2–18.

    Article  PubMed  CAS  Google Scholar 

  9. Clements AC, Magalhaes RJ, Tatem AJ, et al. Clostridium difficile PCR ribotype 027: assessing the risks of further worldwide spread. Lancet Infect Dis. 2010;10:395–404.

    Article  PubMed  Google Scholar 

  10. Joseph R, Demeyer D, Vanrenterghem D, et al. First isolation of Clostridium difficile PCR ribotype 027, toxinotype III in Belgium. Euro Surveill. 2005;10:E051020.4.

    PubMed  Google Scholar 

  11. Cheknis AK, Sambol SP, Davidson DM, et al. Distribution of Clostridium difficile strains from a North American, European and Australian trial of treatment for C. difficile infections: 2005–2007. Anaerobe. 2009;15:230–3.

    Article  PubMed  Google Scholar 

  12. McFarland LV, Clarridge JE, Beneda HW, et al. Fluoroquinolone use and risk factors for Clostridium difficile-associated disease within a veteran’s administration health care system. Clin Infect Dis. 2007;45:1141–51.

    Article  PubMed  Google Scholar 

  13. Hubert B, Loo VG, Bourgault AM, et al. A portrait of the geographic dissemination of the Clostridium difficile North American pulsed-field type 1 strain and the epidemiology of C. difficile-associated disease in Quebec. Clin Infect Dis. 2007;44:238–44.

    Article  PubMed  CAS  Google Scholar 

  14. Vaishnavi C. Clinical spectrum and pathogenesis of Clostridium difficile associated diseases. Indian J Med Res. 2010;131:487–99.

    PubMed  Google Scholar 

  15. AGES, Prävention und kontrolle von Clostridium difficile, 2 Auflage, 2007, Vienna. Available at: http://www.ages.at/uploads/media/Clostridium_difficile_04.pdf. Accessed 14 Dec 2011.

  16. Pittet D, Donaldson L. Clean care is safer care: a worldwide priority. Lancet. 2005;366:1246–7.

    Article  PubMed  Google Scholar 

  17. Dubberke ER, Reske KA, Olsen MA, et al. Short- and long-term attributable costs of Clostridium difficile-associated disease in nonsurgical inpatients. Clin Infect Dis. 2008;46:497–504.

    Article  PubMed  Google Scholar 

  18. Paladino JA, Schentag JJ. The economics of Clostridium difficile-associated disease for providers and payers. Clin Infect Dis. 2008;46:505–6.

    Article  PubMed  Google Scholar 

  19. Zilberberg MD. Clostridium difficile-related hospitalizations among US adults, 2006. Emerg Infect Dis. 2009;15:122–4.

    Article  PubMed  Google Scholar 

  20. Bauer MP, Kuijper EJ, van Dissel JT. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect. 2009;15:1067–79.

    Article  PubMed  CAS  Google Scholar 

  21. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic co-morbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.

    Article  PubMed  CAS  Google Scholar 

  22. van den Berg RJ, Claas EC, Oyib DH, et al. Characterization of toxin A-negative, toxin B-positive Clostridium difficile isolates from outbreaks in different countries by amplified fragment length polymorphism and PCR ribotyping. J Clin Microbiol. 2004;42:1035–41.

    Article  PubMed  Google Scholar 

  23. Indra A, Schmid D, Huhulescu S, et al. Characterization of clinical Clostridium difficile isolates by PCR ribotyping and detection of toxin genes in Austria, 2006–2007. J Med Microbiol. 2008;57:702–8.

    Article  PubMed  CAS  Google Scholar 

  24. Zilberberg MD, Shorr AF, Kollef MH. Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, US, 2000–2005. Emerg Infect Dis. 2008;14:929–31.

    Article  PubMed  Google Scholar 

  25. Lyytikainen O, Turunen H, Sund R, et al. Hospitalizations and deaths associated with Clostridium difficile infection, Finland, 1996–2004. Emerg Infect Dis. 2009;15:761–5.

    Article  PubMed  Google Scholar 

  26. Indra A, Huhulescu S, Fiedler A, et al. Outbreak of Clostridium difficile 027 infection in Vienna, Austria 2008–2009. Euro Surveill. 2009;14(17):1–2.

    Google Scholar 

  27. Kenneally C, Rosini JM, Skrupky LP, et al. Analysis of 30-day mortality for Clostridium difficile-associated disease in the ICU setting. Chest. 2007;132:418–24.

    Article  PubMed  Google Scholar 

  28. Marra AR, Edmond MB, Wenzel RP, et al. Hospital-acquired Clostridium difficile-associated disease in the intensive care unit setting: epidemiology, clinical course and outcome. BMC Infect Dis. 2007;7:42.

    Article  PubMed  Google Scholar 

  29. 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;353:2442–9.

    Article  PubMed  CAS  Google Scholar 

  30. Zilberberg MD, Shorr AF, Micek ST, et al. Clostridium difficile-associated disease and mortality among the elderly critically ill. Crit Care Med. 2009;37:2583–9.

    Article  PubMed  Google Scholar 

  31. Curns AT, Steiner CA, Sejvar JJ, et al. Hospital charges attributable to a primary diagnosis of infectious diseases in older adults in the US, 1998–2004. J Am Geriatr Soc. 2008;56:969–75.

    Article  PubMed  Google Scholar 

  32. Yoshikawa TT. Antimicrobial resistance and aging: beginning of the end of the antibiotic era? J Am Geriatr Soc. 2002;50:S226–9.

    Article  PubMed  Google Scholar 

  33. Zilberberg MD, Shorr AF, Kollef MH. Growth and geographic variation in hospitalizations with resistant infections, US, 2000–2005. Emerg Infect Dis. 2008;14:1756–8.

    Article  PubMed  Google Scholar 

  34. Lozniewski A, Rabaud C, Dotto E, et al. Laboratory diagnosis of Clostridium difficile-associated diarrhea and colitis: usefulness of premier Cytoclone A + B enzyme immunoassay for combined detection of stool toxins and toxigenic C. difficile strains. J Clin Microbiol. 2001;39:1996–8.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We are thankful to the National Reference Laboratory for C. difficile (Huhulescu S. and Indra A.) for kindly performing in vitro susceptibility testing and PCR-ribotyping.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Medicine, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    J. M. Wenisch

  2. Department of Epidemiology, Austrian Agency for Health and Food Safety, Vienna, Austria

    D. Schmid, H.-W. Kuo & F. Allerberger

  3. Institute of Medical Microbiology, Infectious Diseases and Hygiene, Paracelsus Medical University, Salzburg, Austria

    F. Allerberger

  4. Institute of Pathology and Microbiology, Kaiser Franz Josef Hospital, Vienna, Austria

    G. Tucek

  5. Fourth Medical Department with Infectious Diseases and Tropical Medicine, Kaiser Franz Josef Hospital, Vienna, Austria

    V. Michl, P. Tesik, H. Laferl & C. Wenisch

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  1. J. M. Wenisch
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  2. D. Schmid
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  3. G. Tucek
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  4. H.-W. Kuo
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Correspondence to J. M. Wenisch.

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Wenisch, J.M., Schmid, D., Tucek, G. et al. A prospective cohort study on hospital mortality due to Clostridium difficile infection. Infection 40, 479–484 (2012). https://doi.org/10.1007/s15010-012-0258-1

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  • DOI: https://doi.org/10.1007/s15010-012-0258-1

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