Identifying the Source of C difficile in Hospitalized Patients

Clostridium difficile is a leading cause of healthcare-associated infections, with as many as 500,000 cases occurring annually in the United States.¹ Efforts to prevent transmission within hospitals typically focus on patients with symptomatic Clostridium difficile infection (CDI). Although asymptomatic, colonized patients can also transmit infection to other patients, and current recommendations do not include active surveillance testing to detect these carriers. This lack of surveillance may need adjustment in the near future, as recent studies have demonstrated that asymptomatic patients have higher rates of skin and environmental contamination and may contribute to approximately 84% of onward transmission of CDI.^4,5

In a study published in May in Clinical Infectious Diseases, Kong et al investigated the relative contributions of symptomatic patients and asymptomatic carriers in CDI transmission, using pulsed-field gel electrophoresis, multilocus sequence typing, and whole-genome sequencing (WGS).² Isolates were obtained from patients at 6 Canadian hospitals during a previous study, and 554 were sequenced in the present study, including 353 from colonized patients and 201 from infected patients.

The following results were reported:

• The most prevalent strain was NAP1/027/ST1, which was found in 62% of infected patients and 26% of colonized patients.
• A donor with a plausible ward link was identified for 40% of CDI cases, “using [WGS]  with a threshold of ≤2 single nucleotide variants to determine relatedness.”²
• 32% of CDI cases “could be linked to both infected and colonized patients.”²
• 14% and 6% of CDI cases were exclusively linked to infected and colonized donors, respectively.

Kong et al concluded that “CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of the NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics.”

To further discuss C difficile tracking in hospitals, Infectious Disease Advisor interviewed Scott Curry, MD, assistant professor of medicine in the Division of Infectious Diseases and assistant hospital epidemiologist at the Medical University of South Carolina, Charleston.

Infectious Disease Advisor: What are some of the challenges of tracking C difficile to its source and containing CDI in hospitalized patients?

Dr Curry: C difficile spores have nearly indefinite viability, and the infectious dose in animal models is very low. This makes source attribution very difficult, as the source of a C difficile patient can be

separated widely in space and time from the next patient. Thus, it is easy for a study using a design of limited sampling of carriers, such as that of Kong et al, to misattribute the source of a given patient with CDI. For example, say that genotyping C difficile from a patient with hospital-acquired CDI results in matches to 4 identical genotypes. One is found in a patient who had active CDI during the same week in the same hospital, but on a ward several floors away. The second is found in a patient with CDI who had occupied a different room in the same ward 3 months before. The third is found in an asymptomatic carrier who occupied the same room in the same ward 2 months prior. The fourth is from a community-onset case in a neighboring hospital 2 weeks before.

In each of these scenarios, a plausible direct chain of transmission could be made. Physicians, respiratory therapists, dietitians, and others are in direct contact with patients and move widely over space and time within hospitals, allowing for non-ward-based transmission events to occur. Likewise, patients move around a lot within hospitals in ways not often well accounted for in these studies, as in the case of the CT scanner bed found to be associated strongly with a C difficile outbreak.³ Patient visitors and family members may also transmit C difficile widely over time and space.

Terminal disinfection is often inadequate to remove C difficile reliably from hospital surfaces. This allows for transmission over wide periods of time from rooms and shared equipment. Because asymptomatic carriers vastly outnumber patients with CDI, the extent of transmission of C difficile within hospitals is very difficult to quantify with studies of short duration that do not include the entire population at risk.

Infectious Disease Advisor: What are the differences in measures used to prevent transmission in the intensive care unit vs in general medical wards?

Dr Curry: Ideally, there aren’t any differences in infection prevention measures for intensive care unit settings vs floor wards. In both settings, it is critical to maintain glove use for contact with patients with CDI and to avoid use of shared equipment such as blood pressure cuffs and thermometers. Rooms in both settings need to be disinfected with agents that are sporicidal for C difficile. This can cause equipment damage in the case of 5000 ppm sodium hypochlorite (bleach); thus, there is often reluctance to move toward universal use in hospitals of terminal disinfectants that are effective against C difficile.

Infectious Disease Advisor: What are the implications of the findings from the Kong et al study?

Dr Curry: The Kong study adds to the body of evidence that implicates both patients with CDI and colonized patients as sources of transmission of C difficile in hospitals.^4,5 The exclusive focus on ward links as the most plausible in the chain of CDI transmission results in what I think is an underestimate of the likelihood that carriers are a major contributor to the problem. But even if we accept their estimates that something other than known patients with CDI are the source of C difficile transmission in ~50% of cases using WGS, that means that interrupting the chain of transmission for CDI is going to require focus not only on infection control practice for patients with known C difficile infection.

Infectious Disease Advisor: What should be the focus of further research on this topic?

Dr Curry: The field urgently needs to understand what the natural history of C difficile colonization is, using longitudinally sampled hospitalized cohorts. This will answer key questions about the risk factors for, incubation period of, transmission dynamics of, and duration of asymptomatic carriage of C difficile. Ultimately, this can lead to a refinement and additional studies that look at 2 contrasting approaches to C difficile control: enhanced horizontal controls that emphasize universal disinfection practices effective against C difficile contamination, and enhanced vertical controls for C difficile that emphasize surveillance testing of hospitalized patients for C difficile colonization followed by isolation practices aimed at colonized patients, which has been studied with excellent success by Yves Longtin and colleagues in Canada.⁶

I do not accept that a certain level of C difficile infection is the inevitable consequence of hospital care, but studies such as Kong’s emphasize that the road to zero C difficile is going to be a long one until we fully turn our attention to matters beyond antibiotic restriction and infection control measures for symptomatic patients with CDI.

References

1. O’Hagan JJ, McDonald LC. The challenges of tracking Clostridium difficile to its source in hospitalized patients [published online May 28, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy461
2. Kong LY, Eyre DW, Corbeil J, et al. Clostridium difficile: investigating transmission patterns between infected and colonized patients using whole genome sequencing [published online May 28, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy457
3. Murray SG, Yim JWL, Croci R, et al. Using spatial and temporal mapping to identify nosocomial disease transmission of Clostridium difficile. JAMA Intern Med. 2017;177(12):1863-1865. 
4. Eyre DW, Griffiths D, Vaughan A, et al. Asymptomatic Clostridium difficile colonisation and onward transmission. PLoS One. 2013;8(11):e78445.
5. Curry SR, Muto CA, Schlackman JL, 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(8):1094-1102.
6. Longtin Y, Paquet-Bolduc B, Gilca R, 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(6):796-804.