Primary Prevention of Clostridium difficile-Associated Diarrhea: Current Controversies and Future Tools
- 313 Downloads
Purpose of Review
Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in hospitalized patients and rates in most places have not decreased significantly despite broad efforts by both hospitals and public health entities. This review aims to provide readers with a better understanding of the limitations of current prevention strategies. We also review potential future tools that may be available for the primary prevention of CDI in the next decade.
Research over the last decade has expanded our appreciation of the role of asymptomatic shedding in the healthcare setting and in the community. This review demonstrates that poor quality data underlies even well-established guidance from national authorities on basic topics such as contact precautions, avoidance of alcohol-based hand hygiene products, CDI testing, supplemental cleaning modalities, and the use of bleach solutions. Additionally, we review research on novel preventative interventions such as identification of asymptomatic carriers, supplemental environmental cleaning technologies, vaccines, and the manipulation of the intestinal microbiome. While there is preliminary data that supports further research in all of these areas, the research is not yet robust enough on which to base local or national policy recommendations, though late-phase human clinical trials of CDI vaccine trials are ongoing.
Over the last decade, researchers have begun to reassess the traditional infection prevention model for CDI. Data suggesting a greater role for asymptomatic shedders has increased our understanding of current vertical prevention techniques and is forcing researchers to look more at new processes and technologies to decrease disease incidence.
KeywordsClostridium difficile Review Prevention
Compliance with Ethical Standards
Conflict of Interest
Zachary Rubin and Elise Martin are receiving research funding from Pfizer for an ongoing clinical trial on a CDI vaccine. Paul Allyn owns stock in Pfizer.
Human and Animal Rights and Informed Consent
This article cites one study with human subjects performed by Zachary Rubin, which previously was reviewed and approved by the local IRB. All other studies cited with human or animal subjects were not performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 3.Reveles KR, Lee GC, Boyd NK, Frei CR. The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010. Am J Infect Dis. 2014;42:1028–32.Google Scholar
- 7.CDC. Antimicrobial resistance threats. https://www.cdc.gov/drugresistance/biggest_threats.html.
- 8.•• McDonald LC, Gerding DN, Johnson S, et al. 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. 2018. This article provides the most up to date guidance from public health. Google Scholar
- 10.Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines: guidelines for Clostridium difficile infection in adults: 2010 update by the Society of Healthcare Epidemiology of America (SHEA) and in the Infectious Diseases Society of America. Infect Control Hosp Epidemiol. 2010;31:431–55.Google Scholar
- 12.Curry SR, Muto CA, Schlackman JL, Pasculle AW, Shutt KA, Marsh JW, et al. Use of multilocus variable number of tandem repeats analysis genotyping to determine the role of asymptomatic carriers in Clostridium difficile transmission. Clin Infect Dis. 2013;57:1094–102.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.• Fuyura-Kanamori L, Riley TV, Paterson DL, et al. Comparison of Clostridium difficile ribotypes circulating in Australian hospitals and communities. J Clin Microbiol. 2017;55:216–25. Provocative study looking at the interaction between the community and the hospital CDI suggesting that the community maybe the source of significant hospital-onset CDI. CrossRefGoogle Scholar
- 18.• Eyre DW, Cule ML, Wilson DJ, Griffiths D, Vaughan A, O'Connor L, et al. Diverse sources of C. difficile infection identified on whole genome sequencing. New England J Med. 2013;369:1195–205. Despite some methodologic concerns, this is the largest study demonstrating the likely large contribution of asymptomatic CD carriers to endemic CDI incidence. CrossRefGoogle Scholar
- 26.• Longtin Y, Paquet-Bolduc B, Gilca R, Garenc C, Fortin E, Longtin J, et al. Effect of detecting and isolating Clostridium difficile carriers at hospital admission on the incidence of C. difficile infections: a quasi-experimental controlled study. JAMA Intern Med. 2016;176:796–804. Study demonstrating that CDI incidence decreases with aggressive screening and isolation of CD carriers in addition to symptomatic cases. CrossRefPubMedGoogle Scholar
- 27.WHO guidelines on hand hygiene in health care: first global patient safety challenge clean care is safer care. Geneva: World Health Organization; 2009.Google Scholar
- 41.• Marra AR, Schweizer ML, Edmond MB. No-touch disinfection methods to decrease multidrug-resistant organism infections: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2018;39(1):20–31. A thoughtful review of newer no-touch disinfection prevention modalities. CrossRefPubMedGoogle Scholar
- 42.• Anderson DJ, Chen LF, Weber DJ, Moehring RW, Lewis SS, Triplett PF, et al. Enhanced terminal room disinfection and acquisition and infection caused by multidrug resistant organisms and Clostridium difficile (the Benefits of Enhanced Terminal Room Disinfection study): a cluster-randomised, multicentre, crossover study. Lancet. 2017;389:805–14. Interesting, though largely negative, trial of bleach and UV light compared to standard of care. Results may have been hampered by failure to eradicate CD spores shed by asymptomatic patients in addition to reasons cited in paper and accompanying editorial. CrossRefPubMedPubMedCentralGoogle Scholar
- 52.Horn K, Otter JA. Hydrogen peroxide vapor room disinfection and hand hygiene improvements reduce Clostridium difficile infection, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and extended-spectrum β-lactamase. Am J Infect Control. 2015;43:1354–6.CrossRefPubMedGoogle Scholar
- 55.Gateau C, Couturier J, Coia J, Barbut F. How to: diagnose infection caused by Clostridium difficile. Clin Microbiol Infect. 2018; in press.Google Scholar
- 57.Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald L, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and in the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431–55.CrossRefPubMedGoogle Scholar
- 59.Planche TD, Davies KA, Coen PG, Finney JM, Monahan IM, Morris KA, et al. Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C. difficile infection. Lancet Infect Dis. 2013;13(11):936–45.CrossRefPubMedPubMedCentralGoogle Scholar
- 64.• Polage CR, Gyorke CE, Kennedy MA, Leslie JL, Chin DL, Wang S, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med. 2015;175(11):1792. Important study used as justification to move away from nucleic acid testing for CDI. CrossRefPubMedPubMedCentralGoogle Scholar
- 65.Rees WD, Steiner TS. Adaptive immune response to Clostridium difficile infection: a perspective for prevention and therapy. Eur J Immunol. 2018;00:1–9.Google Scholar
- 68.Pfizer. Pfizer announces positive top-line results from phase 2 study of investigational clostridium difficile vaccine for the prevention of C. difficile infection. 2017. https://www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_positive_top_line_results_from_phase_2_study_of_investigational_clostridium_difficile_vaccine_for_the_prevention_of_c_difficile_infection. Accessed 16 Feb 2017.
- 74.Goldenberg JZ, Yap C, Lytvyn L, Lo CKF, Beardsley J, Mertz D, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Systemat Rev. 2017;12:CD006095.Google Scholar