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Predictors and burden of hospital readmission with recurrent Clostridioides difficile infection: a French nation-wide inception cohort study

  • Aurélien Dinh
  • Alban Le Monnier
  • Corinne Emery
  • Sarah Alami
  • Élodie Torreton
  • Anne Duburcq
  • François BarbierEmail author
Original Article

Abstract

To investigate the predictors and burden of hospital readmission with recurrent Clostridioides difficile infection (rCDI) in a large European healthcare system with a low prevalence of hyper-virulent C. difficile clones. We conducted an inception cohort study based on an exhaustive health insurance database and including all survivors of a first hospital stay with CDI over a one-year period (2015) in France. Readmissions with rCDI were defined as a novel hospital stay with CDI within 12 weeks following discharge of the index hospitalization. Risk factors for readmission with rCDI were investigated through multivariate logistic regression analyses. Among the 14,739 survivors of the index hospital stay (females, 57.3%; median age, 74 [58–84] years), 2135 (14.5%) required at least one readmission with rCDI. Independent predictors of readmission were age ≥ 65 years (adjusted odds ratio (aOR), 1.34, 95% confidence interval (CI), 1.21–1.49, P < 0.0001), immunosuppression (aOR, 1.27, 95% CI, 1.15–1.41, P < 0.0001), chronic renal failure (aOR, 1.29, 95% CI, 1.14–1.46, P < 0.0001), and a previous history of CDI (aOR, 2.05, 95% CI, 1.55–2.71, P < 0.0001). The cumulative number of risk factors was independently associated with the hazard of readmission. Mean acute care costs attributable to rCDI were 5619 ± 3594 Euros for readmissions with rCDI as primary diagnosis (mean length of stay, 11.3 ± 10.2 days) and 4851 ± 445 Euros for those with rCDI as secondary diagnosis (mean length of stay, 16.8 ± 18.2 days), for an estimated annual nation-wide cost of 14,946,632 Euros. Hospital readmissions with rCDI are common after an index episode and drive major healthcare expenditures with substantial bed occupancy, strengthening the need for efficient secondary prevention strategies in high-risk patients.

Key-words

Clostridium difficile Hospital-acquired diarrhea Pseudomembranous colitis Healthcare costs Prevention Risk factors 

Notes

Author contribution

Concept and design: A. Dinh, S. Alimi., A. Duburcq and F. Barbier.

Acquisition of data: C. Emery, E. Torreton and A. Duburcq.

Statistical analysis: C. Emery, E. Torreton and A. Duburcq.

Interpretation of results: A. Dinh, A. Le Monnier, A. Duburcq and F. Barbier.

Writing of the manuscript: A. Dinh, A. Le Monnier and F. Barbier.

Critical revision of the manuscript for important intellectual content: all authors.

Funding

This study was supported by MSD.

Compliance with ethical standards

The database exploited for this study is registered at the Commission Nationale de l’Informatique et des Libertés (registration number, 2019044), in compliance with French law on electronic data sources. The protocol of this retrospective observational study was not submitted to an ethical committee since all data were fully anonymized at baseline.

Conflict of interest

FB: MSD (conference and lecture fees, conference invitation), Pfizer (conference invitation), BioMérieux (conference fees).

AD: MSD (conference and lecture fees, conference invitation), Pfizer (conference invitation), InfectoPharm (conference and lecture fees), Sanofi-Pasteur (conference and lecture fees), Correvio (conference and lecture fees).

ALM: MSD (conference invitation), Astellas (conference and lecture fees, conference invitation), Pfizer (conference invitation), Cepheid (conference and lecture fees), bioMérieux (conference and lecture fees), Sanofi-Pasteur (conference and lecture fees).

Other authors: no conflict of interest to declare.

Supplementary material

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ESM 1 (DOCX 30 kb)

References

  1. 1.
    Evans CT, Safdar N (2015) Current trends in the epidemiology and outcomes of Clostridium difficile infection. Clin Infect Dis 60(Suppl 2):S66–S71CrossRefGoogle Scholar
  2. 2.
    Lessa FC, Winston LG, McDonald LC (2015) Burden of Clostridium difficile infection in the United States. N Engl J Med 372:2369–2370CrossRefGoogle Scholar
  3. 3.
    Chitnis AS, Holzbauer SM, Belflower RM, Winston LG, Bamberg WM, Lyons C et al (2013) Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med 173:1359–1367CrossRefGoogle Scholar
  4. 4.
    Gao T, He B, Pan Y, Deng Q, Sun H, Liu X et al (2015) Association of Clostridium difficile infection in hospital mortality: a systematic review and meta-analysis. Am J Infect Control 43:1316–1320CrossRefGoogle Scholar
  5. 5.
    Barbut F, Bouee S, Longepierre L, Goldberg M, Bensoussan C, Levy-Bachelot L (2018) Excess mortality between 2007 and 2014 among patients with Clostridium difficile infection: a French health insurance database analysis. J Hosp Infect 98:21–28CrossRefGoogle Scholar
  6. 6.
    Le Monnier A, Duburcq A, Zahar JR, Corvec S, Guillard T, Cattoir V et al (2015) Hospital cost of Clostridium difficile infection including the contribution of recurrences in French acute-care hospitals. J Hosp Infect 91:117–122CrossRefGoogle Scholar
  7. 7.
    Dubberke ER, Olsen MA (2012) Burden of Clostridium difficile on the healthcare system. Clin Infect Dis 55(Suppl 2):S88–S92CrossRefGoogle Scholar
  8. 8.
    Ma GK, Brensinger CM, Wu Q, Lewis JD (2017) Increasing incidence of multiply recurrent Clostridium difficile infection in the United States: a cohort study. Ann Intern Med 167:152–158CrossRefGoogle Scholar
  9. 9.
    Debast SB, Bauer MP, Kuijper EJ (2014) European society of clinical microbiology and infectious diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect 20(Suppl 2):1–26CrossRefGoogle Scholar
  10. 10.
    Rodrigues R, Barber GE, Ananthakrishnan AN (2017) A comprehensive study of costs associated with recurrent Clostridium difficile infection. Infect Control Hosp Epidemiol 38:196–202CrossRefGoogle Scholar
  11. 11.
    Dubberke ER, Schaefer E, Reske KA, Zilberberg M, Hollenbeak CS, Olsen MA (2014) Attributable inpatient costs of recurrent Clostridium difficile infections. Infect Control Hosp Epidemiol 35:1400–1407CrossRefGoogle Scholar
  12. 12.
    Zhang D, Prabhu VS, Marcella SW (2018) Attributable healthcare resource utilization and costs for patients with primary and recurrent Clostridium difficile infection in the United States. Clin Infect Dis 66:1326–1332CrossRefGoogle Scholar
  13. 13.
    Martin J, Wilcox M (2016) New and emerging therapies for Clostridium difficile infection. Curr Opin Infect Dis 29:546–554CrossRefGoogle Scholar
  14. 14.
    van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM et al (2013) Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 368:407–415CrossRefGoogle Scholar
  15. 15.
    Wilcox MH, Gerding DN, Poxton IR, Kelly C, Nathan R, Birch T et al (2017) Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med 376:305–317CrossRefGoogle Scholar
  16. 16.
    Guery B, Menichetti F, Anttila VJ, Adomakoh N, Aguado JM, Bisnauthsing K et al (2018) Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect Dis 18:296–307CrossRefGoogle Scholar
  17. 17.
    Olsen MA, Yan Y, Reske KA, Zilberberg M, Dubberke ER (2015) Impact of Clostridium difficile recurrence on hospital readmissions. Am J Infect Control 43:318–322CrossRefGoogle Scholar
  18. 18.
    Collins CE, Ayturk MD, Anderson FA Jr, Santry HP (2015) Predictors and outcomes of readmission for Clostridium difficile in a national sample of medicare beneficiaries. J Gastrointest Surg 19:88–99 discussion 99CrossRefGoogle Scholar
  19. 19.
    Kurti Z, Lovasz BD, Mandel MD, Csima Z, Golovics PA, Csako BD et al (2015) Burden of Clostridium difficile infection between 2010 and 2013: trends and outcomes from an academic center in Eastern Europe. World J Gastroenterol 21:6728–6735CrossRefGoogle Scholar
  20. 20.
    Zilberberg MD, Nathanson BH, Marcella S, Hawkshead JJ 3rd, Shorr AF (2018) Hospital readmission with Clostridium difficile infection as a secondary diagnosis is associated with worsened outcomes and greater revenue loss relative to principal diagnosis: a retrospective cohort study. Medicine (Baltimore) 97:e12212CrossRefGoogle Scholar
  21. 21.
    Couturier J, Davies K, Gateau C, Barbut F (2018) Ribotypes and new virulent strains across Europe. Adv Exp Med Biol 1050:45–58CrossRefGoogle Scholar
  22. 22.
    Davies KA, Ashwin H, Longshaw CM, Burns DA, Davis GL, Wilcox MH (2016) Diversity of Clostridium difficile PCR ribotypes in Europe: results from the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), 2012 and 2013. Euro Surveill 21Google Scholar
  23. 23.
    Cornely OA, Crook DW, Esposito R, Poirier A, Somero MS, Weiss K et al (2012) Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis 12:281–289CrossRefGoogle Scholar
  24. 24.
    Eyre DW, Walker AS, Wyllie D, Dingle KE, Griffiths D, Finney J et al (2012) Predictors of first recurrence of Clostridium difficile infection: implications for initial management. Clin Infect Dis 55(Suppl 2):S77–S87CrossRefGoogle Scholar
  25. 25.
    Garey KW, Sethi S, Yadav Y, DuPont HL (2008) Meta-analysis to assess risk factors for recurrent Clostridium difficile infection. J Hosp Infect 70:298–304CrossRefGoogle Scholar
  26. 26.
    D'Agostino RB Sr, Collins SH, Pencina KM, Kean Y, Gorbach S (2014) Risk estimation for recurrent Clostridium difficile infection based on clinical factors. Clin Infect Dis 58:1386–1393CrossRefGoogle Scholar
  27. 27.
    McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE et al (2018) 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 66:987–994CrossRefGoogle Scholar
  28. 28.
    Le P, Nghiem VT, Mullen PD, Deshpande A (2018) Cost-effectiveness of competing treatment strategies for Clostridium difficile infection: a systematic review. Infect Control Hosp Epidemiol 39:412–424CrossRefGoogle Scholar
  29. 29.
    Cornely OA, Watt M, McCrea C, Goldenberg SD, De Nigris E (2018) Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients aged >/=60 years (EXTEND): analysis of cost-effectiveness. J Antimicrob Chemother 73:2529–2539CrossRefGoogle Scholar
  30. 30.
    Prabhu VS, Dubberke ER, Dorr MB, Elbasha E, Cossrow N, Jiang Y et al (2018) Cost-effectiveness of bezlotoxumab compared with placebo for the prevention of recurrent Clostridium difficile infection. Clin Infect Dis 66:355–362CrossRefGoogle Scholar
  31. 31.
    Gerding DN, Kelly CP, Rahav G, Lee C, Dubberke ER, Kumar PN et al (2018) Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis 67:649–656CrossRefGoogle Scholar
  32. 32.
    Juul FE, Garborg K, Bretthauer M, Skudal H, Oines MN, Wiig H et al (2018) Fecal microbiota transplantation for primary Clostridium difficile infection. N Engl J Med 378:2535–2536CrossRefGoogle Scholar
  33. 33.
    Wilcox MH, Ahir H, Coia JE, Dodgson A, Hopkins S, Llewelyn MJ et al (2017) Impact of recurrent Clostridium difficile infection: hospitalization and patient quality of life. J Antimicrob Chemother 72:2647–2656CrossRefGoogle Scholar
  34. 34.
    Beinortas T, Burr NE, Wilcox MH, Subramanian V (2018) Comparative efficacy of treatments for Clostridium difficile infection: a systematic review and network meta-analysis. Lancet Infect Dis 18:1035–1044CrossRefGoogle Scholar
  35. 35.
    Gupta SB, Mehta V, Dubberke ER, Zhao X, Dorr MB, Guris D et al (2016) Antibodies to toxin B are protective against Clostridium difficile infection recurrence. Clin Infect Dis 63:730–734CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Aurélien Dinh
    • 1
    • 2
  • Alban Le Monnier
    • 3
    • 4
  • Corinne Emery
    • 5
  • Sarah Alami
    • 6
  • Élodie Torreton
    • 5
  • Anne Duburcq
    • 5
  • François Barbier
    • 7
    Email author
  1. 1.Infectious Diseases Unit, APHPRaymond-Poincaré University HospitalGarchesFrance
  2. 2.Versailles-Saint Quentin UniversityVersaillesFrance
  3. 3.Department of Clinical MicrobiologyGH Paris Saint-Joseph HospitalParisFrance
  4. 4.EA4043-UBaPSSaclay - Paris Sud UniversityChâtenay-MalabryFrance
  5. 5.CEMKA-EVALBourg-la-ReineFrance
  6. 6.MSDCourbevoieFrance
  7. 7.Medical Intensive Care UnitLa Source Hospital, CHR OrléansOrléansFrance

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