Skip to main content
×
Home

Comorbidities, Exposure to Medications, and the Risk of Community-Acquired Clostridium difficile Infection: A Systematic Review and Meta-analysis

  • Luis Furuya-Kanamori (a1), Jennifer C. Stone (a2), Justin Clark (a3), Samantha J. McKenzie (a2), Laith Yakob (a4), David L. Paterson (a5), Thomas V. Riley (a6), Suhail A. R. Doi (a2) and Archie C. Clements (a1)...
Abstract
Background

Clostridium difficile infection (CDI) has been extensively described in healthcare settings; however, risk factors associated with community-acquired (CA) CDI remain uncertain. This study aimed to synthesize the current evidence for an association between commonly prescribed medications and comorbidities with CA-CDI.

Methods

A systematic search was conducted in 5 electronic databases for epidemiologic studies that examined the association between the presence of comorbidities and exposure to medications with the risk of CA-CDI. Pooled odds ratios were estimated using 3 meta-analytic methods. Subgroup analyses by location of studies and by life stages were conducted.

Results

Twelve publications (n=56,776 patients) met inclusion criteria. Antimicrobial (odds ratio, 6.18; 95% CI, 3.80–10.04) and corticosteroid (1.81; 1.15–2.84) exposure were associated with increased risk of CA-CDI. Among the comorbidities, inflammatory bowel disease (odds ratio, 3.72; 95% CI, 1.52–9.12), renal failure (2.64; 1.23–5.68), hematologic cancer (1.75; 1.02–5.68), and diabetes mellitus (1.15; 1.05–1.27) were associated with CA-CDI. By location, antimicrobial exposure was associated with a higher risk of CA-CDI in the United States, whereas proton-pump inhibitor exposure was associated with a higher risk in Europe. By life stages, the risk of CA-CDI associated with antimicrobial exposure greatly increased in adults older than 65 years.

Conclusions

Antimicrobial exposure was the strongest risk factor associated with CA-CDI. Further studies are required to investigate the risk of CA-CDI associated with medications commonly prescribed in the community. Patients with diarrhea who have inflammatory bowel disease, renal failure, hematologic cancer, or diabetes are appropriate populations for interventional studies of screening.

Infect Control Hosp Epidemiol 2014;00(0):1–10

Copyright
Corresponding author
Address correspondence to Luis Furuya-Kanamori, MEpi, Research School of Population Health, Australian National University, Canberra, ACT 2601, Australia (Luis.Furuya-Kanamori@anu.edu.au).
References
Hide All
1. Freeman J, Bauer MP, Baines SD, et al. The changing epidemiology of Clostridium difficile infections. Clin Microbiol Rev 2010;23:529549.
2. Kuntz JL, Chrischilles EA, Pendergast JF, Herwaldt LA, Polgreen PM. Incidence of and risk factors for community-associated Clostridium difficile infection: a nested case-control study. BMC Infect Dis 2011;11:194.
3. Deshpande A, Pasupuleti P, Thota P, et al. Community-associated Clostridium difficile infection antibiotics: a meta-analysis. J Antimicrob Chemother 2013;68:19511961.
4. Brown KA, Khanafer N, Daneman N, Fisman DN. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother 2013;57:23262332.
5. Noma H. Confidence intervals for a random-effects meta-analysis based on Bartlett-type corrections. Stat Med 2011;30:33043312.
6. Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol 2012;107:10111019.
7. Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN. Clostridium difficile–associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol 2012;107:10011010.
8. Tleyjeh IM, Abdulhak AB, Riaz M, et al. The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis. PLOS One 2013;8:e56498.
9. Tleyjeh IM, Bin Abdulhak AA, Riaz M, et al. Association between proton pump inhibitor therapy and Clostridium difficile infection: a contemporary systematic review and meta-analysis. PLOS One 2012;7:e50836.
10. Heidelbaugh JJ, Goldberg KL, Inadomi JM. Adverse risks associated with proton pump inhibitors: a systematic review. Gastroenterol Hepatol 2009;5:725734.
11. Shukla S, Shukla A, Guha S, Mehboob S. Use of proton pump inhibitors and risk of Clostridium difficile–associated diarrhea: a meta-analysis. Gastroenterology 2010;138:S209.
12. Goodhand JR, Alazawi W, Rampton D. Systematic review: Clostridium difficile and inflammatory bowel disease. Aliment Pharmacol Ther 2011;33:428441.
13. Ahmed N, Kuo YH, Kuo YL, Davis JM. Risk factors for mortality in patients admitted with the primary diagnosis of Clostridium difficile colitis: a retrospective cohort study using Nationwide Inpatient Sample (NIS) database. Surg Infect 2011;12:S73S74.
14. Bajaj JS, O'Leary JG, Reddy KR, et al. Second infections independently increase mortality in hospitalized patients with cirrhosis: the North American Consortium for the Study of End-Stage Liver Disease (NACSELD) experience. Hepatology 2012;56:23282335.
15. Waffenschmidt S, Janzen T, Hausner E, Kaiser T. Simple search techniques in PubMed are potentially suitable for evaluating the completeness of systematic reviews. J Clin Epidemiol 2013;66:660665.
16. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177188.
17. Senn S. Trying to be precise about vagueness. Stat Med 2007;26:14171430.
18. Al Khalaf MM, Thalib L, Doi SA. Combining heterogenous studies using the random-effects model is a mistake and leads to inconclusive meta-analyses. J Clin Epidemiol 2011;64:119123.
19. Poole C, Greenland S. Random-effects meta-analyses are not always conservative. Am J Epidemiol 1999;150:469475.
20. Doi SA, Thalib L. A quality-effects model for meta-analysis. Epidemiology 2008;19:94100.
21. Doi SA, Barendregt JJ, Mozurkewich EL. Meta-analysis of heterogeneous clinical trials: an empirical example. Contemp Clin Trials 2011;32:288298.
22. Barendregt JJ, Doi SA. An easy fix for the RE model: the IVhet model. In MetaXL User Guide version 20. Brisbane, Australia, 2014:2529. Available at: http://www.epigear.com/index_files/MetaXL%20User%20Guide.pdf. Accessed August 1, 2014.
23. Onitilo AA, Doi SAR, Barendregt JJ. Meta-analysis II: interpretation and use of outputs. In Doi SAR, Williams GM, eds. Methods of Clinical Epidemiology. Berlin: Springer Berlin Heidelberg, 2013:253266.
24. Sterne JAC, Sutton AJ, Ioannidis JPA, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 2011;343:d4002.
25. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile–associated disease. JAMA 2005;294:29892995.
26. Delaney JA, Dial S, Barkun A, Suissa S. Antimicrobial drugs and community-acquired Clostridium difficile–associated disease, UK. Emerg Infect Dis 2007;13:761763.
27. Dial S, Delaney JA, Schneider V, Suissa S. Proton pump inhibitor use and risk of community-acquired Clostridium difficile–associated disease defined by prescription for oral vancomycin therapy. Can Med Assoc J 2006;175:745748.
28. Soes LM, Holt HM, Bottiger B, et al. Risk factors for Clostridium difficile infection in the community: a case-control study in patients in general practice, Denmark, 2009-2011. Epidemiol Infect 2014;142:14371448.
29. Soes LM, Holt HM, Bottiger B, et al. The incidence and clinical symptomatology of Clostridium difficile infections in a community setting in a cohort of Danish patients attending general practice. Euro J Clin Microbiol 2014;33:957967.
30. Kutty PK, Woods CW, Sena AC, et al. Risk factors for and estimated incidence of community-associated Clostridium difficile infection, North Carolina, USA. Emerg Infect Dis 2010;16:197204.
31. Marwick CA, Yu N, Lockhart MC, et al. Community-associated Clostridium difficile infection among older people in Tayside, Scotland, is associated with antibiotic exposure and care home residence: cohort study with nested case-control. J Antimicrob Chemother 2013;68:29272933.
32. Lowe DO, Mamdani MM, Kopp A, Low DE, Juurlink DN. Proton pump inhibitors and hospitalization for Clostridium difficile–associated disease: a population-based study. Clin Infect Dis 2006;43:12721276.
33. Durand C, Willett KC, Desilets AR. Proton pump inhibitor use in hospitalized patients: is overutilization becoming a problem? Clin Med Insights Gastroenterol 2012;5:6576.
34. Johnson S, Gerding DN. Clostridium difficile-associated diarrhea. Clin Infect Dis 1998;26:10271034.
35. Jump RL, Pultz MJ, Donskey CJ. Vegetative Clostridium difficile survives in room air on moist surfaces and in gastric contents with reduced acidity: a potential mechanism to explain the association between proton pump inhibitors and C. difficile–associated diarrhea? Antimicrob Agents Chemother 2007;51:28832887.
36. Hernández-Díaz S, Rodríguez LAG. Steroids and risk of upper gastrointestinal complications. Am J Epidemiol 2001;153:10891093.
37. Patrick DM, Marra F, Hutchinson J, Monnet DL, Ng H, Bowie WR. Per capita antibiotic consumption: how does a North American jurisdiction compare with Europe? Clin Infect Dis 2004;39:1117.
38. 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;15:230233.
39. Sandora TJ, Flaherty K, Helsing L, et al. Epidemiology and risk factors for Clostridium difficile infection in children. Am J Infect Control 2009;37:E61.
40. Lessa FC, Gould CV, McDonald LC. Current status of Clostridium difficile infection epidemiology. Clin Infect Dis 2012;55:S65S70.
41. Khanna S, Baddour LM, Huskins WC, et al. The epidemiology of Clostridium difficile infection in children: a population-based study. Clin Infect Dis 2013;56:14011406.
42. Simor AE, Bradley SF, Strausbaugh LJ, Crossley K, Nicolle LE. Clostridium difficile in long-term-care facilities for the elderly. Infect Control Hosp Epidemiol 2002;23:696703.
43. Brockwell SE, Gordon IR. A comparison of statistical methods for meta-analysis. Stat Med 2001;20:825840.
44. Vesteinsdottir I, Gudlaugsdottir S, Einarsdottir R, Kalaitzakis E, Sigurdardottir O, Bjornsson ES. Risk factors for Clostridium difficile toxin-positive diarrhea: a population-based prospective case-control study. Eur J Clin Microbiol 2012;31:26012610.
45. Furuya-Kanamori L, Robson J, Soares Magalhãesa RJ, et al. A population-based spatio-temporal analysis of Clostridium difficile infection in Queensland, Australia over a 10-year period. J Infect (in press).
46. Dial S, Kezouh A, Dascal A, Barkun A, Suissa S. Patterns of antibiotic use and risk of hospital admission because of Clostridium difficile infection. Can Med Assoc J 2008;179:767772.
47. Naggie S, Miller BA, Zuzak KB, et al. A case-control study of community-associated Clostridium difficile infection: no role for proton pump inhibitors. Am J Med 2011;124(276):e271e277.
48. Suissa D, Delaney JAC, Dial S, Brassard P. Non-steroidal anti-inflammatory drugs and the risk of Clostridium difficile–associated disease. Br J Clin Pharmacol 2012;74:370375.
49. Wilcox MH, Mooney L, Bendall R, Settle CD, Fawley WN. A case-control study of community-associated Clostridium difficile infection. J Antimicrob Chemother 2008;62:388396.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Infection Control & Hospital Epidemiology
  • ISSN: 0899-823X
  • EISSN: 1559-6834
  • URL: /core/journals/infection-control-and-hospital-epidemiology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×
Type Description Title
WORD
Supplementary Materials

Furuya-Kanamori Supplementary Material
Appendices

 Word (722 KB)
722 KB

Metrics

Full text views

Total number of HTML views: 34
Total number of PDF views: 216 *
Loading metrics...

Abstract views

Total abstract views: 830 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 24th November 2017. This data will be updated every 24 hours.