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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
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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.
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