J Korean Med Sci.  2011 Jul;26(7):859-864. 10.3346/jkms.2011.26.7.859.

Risk Factors for Recurrence of Clostridium difficile Infection: Effect of Vancomycin-resistant Enterococci Colonization

• Choi HK
• Kim KH
• Lee SH
• Lee SJ

• KMID: 1094254
• DOI: http://doi.org/10.3346/jkms.2011.26.7.859

Abstract

Recurrent Clostridium difficile infection (CDI) is one of the most difficult problems in healthcare infection control. We evaluated the risk factors associated with recurrence in patients with CDI. A retrospective cohort study of 84 patients with CDI from December 2008 through October 2010 was performed at Pusan National University Yangsan Hospital. Recurrence occurred in 13.1% (11/84) of the cases and in-hospital mortality rate was 7.1% (6/84). Stool colonization with vancomycin-resistant enterococci (VRE) (P = 0.006), exposure to more than 3 antibiotics (P = 0.009), low hemoglobin levels (P = 0.025) and continued use of previous antibiotics (P = 0.05) were found to be more frequent in the recurrent group. Multivariate analysis indicated that, stool VRE colonization was independently associated with CDI recurrence (odds ratio, 14.519; 95% confidence interval, 1.157-182.229; P = 0.038). This result suggests that stool VRE colonization is a significant risk factor for CDI recurrence.

Keyword

Clostridium difficile; Recurrence; Risk factors; VRE

MeSH Terms

Adolescent
Adult
Aged
Aged, 80 and over
Anti-Bacterial Agents/*therapeutic use
*Clostridium difficile
Cohort Studies
Enterococcus/*isolation & purification
Enterocolitis, Pseudomembranous/drug therapy/*etiology/mortality
Feces/microbiology
Female
Hemoglobins/analysis
Hospital Mortality
Humans
Logistic Models
Male
Middle Aged
Odds Ratio
Recurrence
Retrospective Studies
Risk Factors
Vancomycin/*therapeutic use
*Vancomycin Resistance

Reference

1. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilcox MH. 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. 31:431–455.

2. Maroo S, Lamont JT. Recurrent clostridium difficile. Gastroenterology. 2006. 130:1311–1316.

3. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987. 40:373–383.

4. Cadena J, Thompson GR 3rd, Patterson JE, Nakashima B, Owens A, Echevarria K, Mortensen EM. Clinical predictors and risk factors for relapsing Clostridium difficile infection. Am J Med Sci. 2010. 339:350–355.

5. Fekety R, McFarland LV, Surawicz CM, Greenberg RN, Elmer GW, Mulligan ME. Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin Infect Dis. 1997. 24:324–333.

6. McFarland LV, Surawicz CM, Rubin M, Fekety R, Elmer GW, Greenberg RN. Recurrent Clostridium difficile disease: epidemiology and clinical characteristics. Infect Control Hosp Epidemiol. 1999. 20:43–50.

7. Lee JH, Lee SY, Kim YS, Park SW, Jo SY, Ryu SH, Moon JS, Whang DH, Shin BM. The incidence and clinical features of Clostridium difficile infection; single center study. Korean J Gastroenterol. 2010. 55:175–182.

8. Lee YJ, Choi MG, Lim CH, Jung WR, Cho HS, Sung HY, Nam KW, Chang JH, Cho YK, Park JM, Kim SW, Chung IS. Change of Clostridium difficile colitis during recent 10 years in Korea. Korean J Gastroenterol. 2010. 55:169–174.

9. Byun TJ, Han DS, Ahn SB, Cho HS, Kim TY, Eun CS, Jeon YC, Sohn JH, Kang JO. Clinical characteristics and changing epidemiology of Clostridium difficile-associated disease (CDAD). Korean J Gastroenterol. 2009. 54:13–19.

10. Garey KW, Sethi S, Yadav Y, DuPont HL. Meta-analysis to assess risk factors for recurrent Clostridium difficile infection. J Hosp Infect. 2008. 70:298–304.

11. Kim JW, Lee KL, Jeong JB, Kim BG, Shin S, Kim JS, Jung HC, Song IS. Proton pump inhibitors as a risk factor for recurrence of Clostridium-difficile-associated diarrhea. World J Gastroenterol. 2010. 16:3573–3577.

12. Tal S, Gurevich A, Guller V, Gurevich I, Berger D, Levi S. Risk factors for recurrence of Clostridium difficile-associated diarrhea in the elderly. Scand J Infect Dis. 2002. 34:594–597.

13. Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001. 357:189–193.

14. Leav BA, Blair B, Leney M, Knauber M, Reilly C, Lowy I, Gerding DN, Kelly CP, Katchar K, Baxter R, Ambrosino D, Molrine D. Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI). Vaccine. 2010. 28:965–969.

15. Pepin J, Alary ME, Valiquette L, Raiche E, Ruel J, Fulop K, Godin D, Bourassa C. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005. 40:1591–1597.

16. Jung KS, Park JJ, Chon YE, Jung ES, Lee HJ, Jang HW, Lee KJ, Lee SH, Moon CM, Lee JH, Shin JK, Jeon SM, Hong SP, Kim TI, Kim WH, Cheon JH. Risk factors for treatment failure and recurrence after metronidazole treatment for Clostridium difficile-associated diarrhea. Gut Liver. 2010. 4:332–337.

17. Sethi AK, Al-Nassir WN, Nerandzic MM, Donskey CJ. Skin and environmental contamination with vancomycin-resistant Enterococci in patients receiving oral metronidazole or oral vancomycin treatment for Clostridium difficile-associated disease. Infect Control Hosp Epidemiol. 2009. 30:13–17.

18. Boyce JM, Opal SM, Chow JW, Zervos MJ, Potter-Bynoe G, Sherman CB, Romulo RL, Fortna S, Medeiros AA. Outbreak of multidrug-resistant Enterococcus faecium with transferable vanB class vancomycin resistance. J Clin Microbiol. 1994. 32:1148–1153.

19. Drees M, Snydman DR, Schmid CH, Barefoot L, Hansjosten K, Vue PM, Cronin M, Nasraway SA, Golan Y. Antibiotic exposure and room contamination among patients colonized with vancomycin-resistant enterococci. Infect Control Hosp Epidemiol. 2008. 29:709–715.

20. Gerding DN. Metronidazole for Clostridium difficile-associated disease: is it okay for Mom? Clin Infect Dis. 2005. 40:1598–1600.

21. Al-Nassir WN, Sethi AK, Li Y, Pultz MJ, Riggs MM, Donskey CJ. Both oral metronidazole and oral vancomycin promote persistent overgrowth of vancomycin-resistant enterococci during treatment of Clostridium difficile-associated disease. Antimicrob Agents Chemother. 2008. 52:2403–2406.

22. Harbarth S, Cosgrove S, Carmeli Y. Effects of antibiotics on nosocomial epidemiology of vancomycin-resistant enterococci. Antimicrob Agents Chemother. 2002. 46:1619–1628.

23. Lester CH, Frimodt-Møller N, Sørensen TL, Monnet DL, Hammerum AM. In vivo transfer of the vanA resistance gene from an Enterococcus faecium isolate of animal origin to an E. faecium isolate of human origin in the intestines of human volunteers. Antimicrob Agents Chemother. 2006. 50:596–599.

24. Salgado CD, Giannetta ET, Farr BM. Failure to develop vancomycin-resistant Enterococcus with oral vancomycin treatment of Clostridium difficile. Infect Control Hosp Epidemiol. 2004. 25:413–417.

25. Miller M, Bernard L, Thompson M, Grima D, Pepin J. Lack of increased colonization with vancomycin-resistant enterococci during preferential use of vancomycin for treatment during an outbreak of healthcare-associated Clostridium difficile infection. Infect Control Hosp Epidemiol. 2010. 31:710–715.

26. Gerding DN. Is there a relationship between vancomycin-resistant enterococcal infection and Clostridium difficile infection? Clin Infect Dis. 1997. 25:Suppl 2. S206–S210.

27. Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J Clin Gastroenterol. 2010. 44:354–360.

28. Chang JY, Antonopoulos DA, Kalra A, Tonelli A, Khalife WT, Schmidt TM, Young VB. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis. 2008. 197:435–438.

29. Aslam S, Hamill RJ, Musher DM. Treatment of Clostridium difficile-associated disease: old therapies and new strategies. Lancet Infect Dis. 2005. 5:549–557.

30. Tae CH, Jung SA, Song HJ, Kim SE, Choi HJ, Lee M, Hwang Y, Kim H, Lee K. The first case of antibiotic-associated colitis by Clostridium difficile PCR ribotype 027 in Korea. J Korean Med Sci. 2009. 24:520–524.