Clostridium difficile Infections: New Data Offer Insights Into Illness

According to researchers, 29% of cases of C difficile infections are associated with asymptomatic carriers.

Clostridium difficile, the most common cause of nosocomial infectious diarrhea, is listed by the Centers for Disease Control and Prevention as an urgent public health threat. Not surprisingly, C difficile infection (CDI) was one major focus at the inaugural ASM Microbe 2016 conference. Changing paradigms surrounding CDI were highlighted in several presentations.

New Data Expands Scope of CDI Transmission

According to a 2013 study published by Curry and colleagues in Clinical Infectious Diseases, 29% of cases of CDI are associated with asymptomatic carriers.1 Javeria Haque, MD, of the Medical College of Wisconsin, further highlighted the increasing importance of asymptomatic carriers by presenting 2 studies at the meeting that were conducted in inpatient hematology-oncology units at Froedert Hospital in Milwaukee.2-3 In these studies, the majority of patients testing positive for C difficile were colonized at the time of hospital admission. One study showed a strong association between being an asymptomatic carrier and developing colitis, with a relative risk of 4.32 (95% confidence interval [CI] 2.596, 7.2, P <0.0001) for patients testing positive for C difficile during surveillance. The timing of colonization appeared to matter; the relative risk for colitis was 3.8 (95% CI 2.01, 7.1, P <0.0001) for patients colonized at the time of hospital admission but 5.13 (95% CI 2.74, 9.62, P <.0001) for patients whose colonization was acquired during their hospital stay.

Historically, CDI has been considered a hospital-onset infection that is transmitted from and genetically related to other hospital cases. However, Mark Wilcox, PhD, of the University of Leeds, presented whole genome sequencing studies demonstrating that only a minority—about a third—of cases collected in various regions of the United Kingdom were related genomically.4

Ying Tabak, PhD, of Becton, Dickinson and Company, Franklin Lakes, NJ, and Andrew DeRyke, PharmD, of Merck and Company, Kenilworth, NJ, presented an analysis of automated clinical data from 154 US hospitals between January 2008 and December 2015, which noted that the increase in the total number of CDI cases was driven primarily by an increase in community-onset infections. Community-onset, community-associated infections rose by 112%, and community-onset, hospital-associated infections rose by 42%. In 2015, community-onset infections, with or without a hospital stay, accounted for 81% of all CDI cases.5

Dr Wilcox also presented data showing close overlap between C difficile strains seen in asymptomatic infants and those seen in adult CDI cases, suggesting asymptomatic, colonized children as a potential reservoir for C difficile transmission. Approximately one-third of young children are colonized by C difficile.

Tom Riley, PhD, of the University of Western Australia, discussed food as an important reservoir for community-acquired CDI.6 Although antibiotic use remains high in meat production settings, studies suggest contaminated meat is less of a problem than root vegetables such as onions and potatoes. Dr Riley cited gardening centers, which can use compost or mulch containing contaminated vegetables, and sod farms, which in Australia receive the bulk of pig manure from production facilities, as additional reservoirs for CDI. Dr Riley emphasized, however, the links with production farms, concluding that, “Anywhere there is production animal manure, there is a problem.”

The CDI BI/NAP1/027 strain, which emerged in 2004 in Pittsburgh and Quebec, is of particular concern because of its association with increased CDI mortality and complication rates.

As discussed by Ed Kuijper, MD, PhD, of Leiden University Medical Center, the Netherlands, this strain has emerged in Latin America and China,7 and as noted by John Segreti, MD, of Rush Medical College, Chicago, the BI/NAP1/027 strain has become endemic in Chicago.8

Amos Adler, MD, of the Tel Aviv Sourasky Medical Center, presented a prospective case-control study showing that the BI/NAP1/027 strain is the most common among community-onset, hospital-acquired cases of CDI in that medical center.9 Dr Segreti also noted, however, that the prevalence of the BI/NAP1/027 strain has declined recently in the United States and the United Kingdom, although potential causes for this decline were not given. This is consistent with data presented by George Broukhanski, PhD, of Public Health Ontario, demonstrating a decline in prevalence of the initial ribotype 027 strain in Ontario hospitals since 2011.10 Dr Broukhanski did note, however, that Public Health Ontario has identified 16 variants of the BI/NAP1/027 strain and that 1 variant, 27.5, has increased geographically and proportionally over 4 years. This variant, which was associated with a major CDI outbreak in Ontario, can persist in the hospital setting because of its resistance to disinfectants, higher numbers of spores, and increased spore adhesion to fomites.

Today, we have more tools than ever to combat this urgent public health threat. Understanding how C difficile is evolving within health care systems and the environment remains key to developing effective treatments and implementing sound prevention strategies.

Ciaran Kelly, MD, is a professor of medicine at Harvard Medical School and director of Gastroenterology Fellowship Training at Beth Israel Deaconess Medical Center in Boston.

He reports consulting and/or advisory roles with CourMerck, Seres Therapeutics, Summit and Takeda.

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  1. Sheitoyan-Pesant C, Abou Chakra CN, Pépin J, Marcil-Héguy A, Nault V, Valiquette L. Clinical and healthcare burden of multiple recurrences of Clostridium difficile Infection. Clin Infect Dis. 2016;62(5):574-580. doi: 10.1093/cid.civ958
  2. Haque J, Ledeboer NA, Michaelis L, et al. Slide Session 206.  Impact of Clostridium difficile colonization on the subsequent development of C difficile colitis in a hematology oncology inpatient population – a prospective cohort. Presented at: ASM Microbe 2016. June 16-20, 2016; Boston.
  3. Haque J, Ledeboer NA, Michaelis L, et al. Slide Session 206. Clostridium difficile colitis: does it matter when colonization occurs? Presented at: ASM Microbe 2016. June 16-20, 2016; Boston.
  4. Wilcox M. Symposium 255. Novel molecular typing tools to better elucidate transmission pathways. Presented at: ASM Microbe 2016. June 16-20, 2016; Boston.
  5. Tabak YP, DeRyke CA, Gupta V, et al. Poster Session 52, Abstract 290. Trend of Clostridium difficile infections by onset settings: a multicenter study. Presented at: ASM Microbe 2016. June 16-20, 2016; Boston.
  6. Riley T. Symposium 255. Food as an important reservoir for community-acquired Clostridium difficile Infection. Presented at: ASM Microbe 2016. June 16-20, 2016; Boston.
  7. Kuijper EJ. Sympoisium 255. Current epidemiology of C difficile infection worldwide. Presented at: ASM Microbe 2016. June 16-20, 2016; Boston.
  8. Segreti J, Muto CA, Gerding DN. More than a gut reaction: effective strategies to treat and prevent recurrent C difficile infection. Presented at: ASM Microbe 2016. June 16-20, 2016; Boston.
  9. Miller-Roll T, Na’amnih W, Cohen D, Carmeli Y, Adler A. The role of molecular types and antimicrobial susceptibility patterns of Clostridium difficile isolates in different epidemiological settings. Presented at: ASM Microbe 2016. June 16-20, 2016; Boston.
  10. Broukhanski G, Wang A. Slide Session 206. New variants of hypervirulent NAP1 strain of Clostridium difficile emerging and spreading in the province of Ontario, Canada. Presented at: ASM Microbe 2016. June 16-20, 2016; Boston.