Advertisement

Risk factors for recurrent Clostridium difficile infection in a tertiary hospital in Israel

  • Wasef Na’amnih
  • Amos Adler
  • Tamar Miller-Roll
  • Dani Cohen
  • Yehuda Carmeli
Original Article
  • 180 Downloads

Abstract

To estimate the rate and identified risk factors for recurrent Clostridium difficile infection (rCDI) in Israel. We conducted a retro-prospective case-control study of all adult (age ≥ 18 years) patients with an initial episode of CDI (iCDI) at Tel Aviv Sourasky Medical Center from January 1, 2012 to December 31, 2014. We collected demographic, clinical, and epidemiological information for patients who were classified as recurrent (cases) and non-recurrent (control) groups. In total, 648 patients with iCDI were identified in the study. During the 36-month study period, 82 (12.7%) patients had at least one rCDI identified. We identified several factors as independent variables significantly associated with recurrent CDI: functional disability, severity of the initial infection, continuous non-Clostridium difficile antibiotic treatment with third-generation cephalosporins or clindamycin, and iCDI treatment with metronidazole and vancomycin; however, neutropenia had high measure of effect as a predictor for rCDI (adjusted odds ratio, 7.9; 95% confidence interval, 1.27–49.58; p = 0.026). The identification of the main modifiable risk factors for recurrent CDI, continuous non-Clostridium difficile antibiotics after diagnosis of the initial infection, and antibiotic treatment with third-generation cephalosporins or clindamycin are critical in reducing the spread of recurrent infection with Clostridium difficile in hospital.

Keywords

Risk factors Recurrent Clostridium difficile infection Israel 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilcox MH (2010) 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 31:431–455CrossRefPubMedGoogle Scholar
  2. 2.
    Maroo S, Lamont JT (2006) Recurrent clostridium difficile. Gastroenterology 130:1311–1316CrossRefPubMedGoogle Scholar
  3. 3.
    Freeman J, Bauer MP, Baines SD, Corver J, Fawley WN, Goorhuis B, Kuijper EJ, Wilcox MH (2010) The changing epidemiology of Clostridium difficile infections. Clin Microbiol Rev 23:529e549CrossRefGoogle Scholar
  4. 4.
    Pepin J, Routhier S, Gagnon S, Brazeau I (2006) Management and outcomes of a first recurrence of Clostridium difficile-associated disease in Quebec, Canada. Clin Infect Dis 42:758–764CrossRefPubMedGoogle Scholar
  5. 5.
    Garey KW, Sethi S, Yadav Y, DuPont HL (2008) Meta-analysis to assess risk factors for recurrent Clostridium difficile infection. J Hosp Infect 70:298–304CrossRefPubMedGoogle Scholar
  6. 6.
    Cornely OA, Crook DW, Esposito R, Poirier A, Somero MS, Weiss K, Sears P, Gorbach S, OPT-80-004 Clinical Study Group (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 12:281–289CrossRefPubMedGoogle Scholar
  7. 7.
    Dubberke ER, Olsen MA (2012) Burden of Clostridium difficile on the healthcare system. Clin Infect Dis 55(Suppl 2):S88–S92CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ghantoji SS, Sail K, Lairson DR, DuPont HL, Garey KW (2010) Economic healthcare costs of Clostridium difficile infection: a systematic review. J Hosp Infect 74:309–318CrossRefPubMedGoogle Scholar
  9. 9.
    Hookman P, Barkin JS (2009) Clostridium difficile associated infection, diarrhea and colitis. World J Gastroenterol 15:1554–1580CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Karas JA, Enoch DA, Aliyu SH (2010) A review of mortality due to Clostridium difficile infection. J Inf Secur 61:1–8Google Scholar
  11. 11.
    Rupnik M, Wilcox MH, Gerding DN (2009) Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 7:526–536CrossRefPubMedGoogle Scholar
  12. 12.
    Fekety R, McFarland LV, Surawicz CM, Greenberg RN, Elmer GW, Mulligan ME (1997) Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin Infect Dis 24:324–333CrossRefPubMedGoogle Scholar
  13. 13.
    McFarland LV, Surawicz CM, Rubin M, Fekety R, Elmer GW, Greenberg RN (1999) Recurrent Clostridium difficile: epidemiology and clinical characteristics. Infect Control Hosp Epidemiol 20:43–50CrossRefPubMedGoogle Scholar
  14. 14.
    Cadle RM, Mansouri MD, Logan N, Kudva DR, Musher DM (2007) Association of proton-pump inhibitors with outcomes in Clostridium difficile colitis. Am J Health Syst Pharm 64:2359–2363CrossRefPubMedGoogle Scholar
  15. 15.
    Kim JW, Lee KL, Jeong JB, Kim BG, Shin S, Kim JS, Jung HC, Song IS (2010) Proton pump inhibitors as a risk factor for recurrence of Clostridium-difficile associated diarrhea. World J Gastroenterol 16:3573–3577CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Choi HK, Kim KH, Lee SH, Lee SJ (2011) Risk factors for recurrence of Clostridium difficile infection: effect of vancomycin-resistant enterococci colonization. J Korean Med Sci 26:859–864CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hikone M, Ainoda Y, Tago S, Fujita T, Hirai Y, Takeuchi K, Totsuka K (2015) Risk factors for recurrent hospital-acquired Clostridium difficile infection in a Japanese university hospital. Clin Exp Gastroenterol 8:191–196PubMedPubMedCentralGoogle Scholar
  18. 18.
    Zilberberg MD, Reske K, Olsen M, Yan Y, Dubberke ER (2014) Risk factors for recurrent Clostridium difficile infection (CDI) hospitalization among hospitalized patients with an initial CDI episode: a retrospective cohort study. BMC Infect Dis 14:306CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Barbut F, Richard A, Hamadi K, Chomette V, Burghoffer B, Petit JC (2000) Epidemiology of recurrences or reinfections of Clostridium difficile-associated diarrhea. J Clin Microbiol 38:2386–2388PubMedPubMedCentralGoogle Scholar
  20. 20.
    Miller-Roll T, Na'amnih W, Cohen D, Carmeli Y, Adler A (2016) Molecular types and antimicrobial susceptibility patterns of Clostridium difficile isolates in different epidemiological settings in a tertiary care center in Israel. Diagn Microbiol Infect Dis 86:450–454CrossRefPubMedGoogle Scholar
  21. 21.
    Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ (2010) Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J Clin Gastroenterol 44:354–360PubMedGoogle Scholar
  22. 22.
    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 368:407–415CrossRefPubMedGoogle Scholar
  23. 23.
    Jung KS, Park JJ, Chon YE, Jung ES, Lee HJ, Jang HW et al (2010) Risk factors for treatment failure and recurrence after metronidazole treatment for Clostridium difficile-associated diarrhea. Gut Liver 4:332–337CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Cadena J, Thompson GR 3rd, Patterson JE, Nakashima B, Owens A, Echevarria K, Mortensen EM (2010) Clinical predictors and risk factors for relapsing Clostridium difficile infection. Am J Med Sci 339:350–355CrossRefPubMedGoogle Scholar
  25. 25.
    Hu MY, Katchar K, Kyne L, Maroo S, Tummala S, Dreisbach V, Xu H, Leffler DA, Kelly CP (2009) Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology 136:1206–1214CrossRefPubMedGoogle Scholar
  26. 26.
    Mullane KM, Miller MA, Weiss K, Lentnek A, Golan Y, Sears PS, Shue YK, Louie TJ, Gorbach SL (2011) Efficacy of fidaxomicin versus vancomycin as therapy for Clostridium difficile infection in individuals taking concomitant antibiotics for other concurrent infections. Clin Infect Dis 53:440–447CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lucado J, Gould C, Elixhauser A (2009) Clostridium difficile infections (CDI) in hospital stays. Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. Statistical brief #124. http://www.hcupus.ahrq.gov/reports/statbriefs/sb124.pdf (accessed 8 January 2013)
  28. 28.
    Rao K, Micic D, Chenoweth E, Deng L, Galecki AT, Ring C, Young VB, Aronoff DM, Malani PN (2013) Poor functional status as a risk factor for severe Clostridium difficile infection in hospitalized older adults. J Am Geriatr Soc 61:1738–1742CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    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–S87CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    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 20:1–26CrossRefPubMedGoogle Scholar
  31. 31.
    Taori SK, Wroe A, Poxton IR (2013) Clostridium difficile infections in South East Scotland: mortality and recurrence in a region without PCR ribotype 027. J Med Microbiol 62:1468–1477CrossRefPubMedGoogle Scholar
  32. 32.
    Garey KW, Jiang ZD, Ghantoji S, Tam VH, Arora V, Dupont HL (2010) A common polymorphism in the interleukin-8 gene promoter is associated with an increased risk for recurrent Clostridium difficile infection. Clin Infect Dis 51:1406–1410CrossRefPubMedGoogle Scholar
  33. 33.
    Kyne L, Warny M, Qamar A, Kelly CP (2000) Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med 342:390–397CrossRefPubMedGoogle Scholar
  34. 34.
    Kyne L, Warny M, Qamar A, Kelly CP (2001) Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet 357:189–193CrossRefPubMedGoogle Scholar
  35. 35.
    Huang AM, Marini BL, Frame D, Aronoff DM, Nagel JL (2014) Risk factors for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients. Transpl Infect Dis 16:744–750CrossRefPubMedGoogle Scholar
  36. 36.
    Cornely OA, Miller MA, Fantin B, Mullane K, Kean Y, Gorbach S (2013) Resolution of Clostridium difficile-associated diarrhea in patients with cancer treated with fidaxomicin or vancomycin. J Clin Oncol 31:2493–2499CrossRefPubMedGoogle Scholar
  37. 37.
    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 18:296–307CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  2. 2.Department of Epidemiology and Preventive Medicine, Clinical Microbiology LaboratoryTel-Aviv Sourasky Medical CenterTel AvivIsrael
  3. 3.Department of Geriatric RehabilitationTel-Aviv Sourasky Medical CenterTel AvivIsrael

Personalised recommendations