Genome Sequencing Identifies Patterns in C diff Transmission and Infection

McGill University researchers find that infection with C difficile might more likely be linked to infected than colonized donors.

A genomics study published in Clinical Infectious Diseases shows that transmission of Clostridium difficile is highly related to contact with colonized patients, whereas infections of C difficile are more likely to occur following contact with other infected patients vs colonized patients. Additionally, the NAP1/027/ST1 strain appears to be most prevalent in colonized and infected patients.

“Using whole-genome sequencing of isolates from a cohort of patients with C. difficile infection and colonization, we found that incident C. difficile infection cases were more likely to be linked to an infected than a colonized donor,” Ling Y. Kong, MD, of the Division of Infectious Diseases and Department of Medical Microbiology at McGill University Health Centre, in Montréal, Canada, told Contagion ®. “Transmission dynamics are likely strain-dependent, and in our cohort, the findings reflect the high prevalence of the hypervirulent NAP1/027/ST1 strain.”

The investigators of this study identified isolates of Canadian patients with C difficile infection and colonization who participated in a previous study between 2006 to 2007. All patients attended university-affiliated hospitals with either high or low incidences of C difficile infections. Pulsed-field gel electrophoresis, whole genome sequencing, and multilocus sequence typing were used for typing these patients. To identify potential infection donors for each case of C difficile infection, the investigators combined both ward movement and typing data. The researchers examined the proportion of potential infection donors that were colonized and/or infected with C difficile.

A total of 544 isolates, including colonized (n = 353) and infection (n = 201) cases, were identified and successfully sequenced with whole genome sequencing. The most common C difficile strain identified was the NAP1/027/ST1 (ribotype 027) strain, found in 62% of infected and 26% of colonized patients. Approximately 40% of C difficile infection cases had a donor with a possible ward link, according to whole genome sequencing. Overall, more than half (52%) of infection cases presented a genetic link to a prior sample, and up to one-third (32%) of infection cases were found to be associated with infected as well as colonized donors.

The study may hold limited generalizability to centers outside of Canada. Additionally, the study is further limited by the incomplete sampling of participating centers.

In an accompanying editorial by Justin J. O’Hagan, ScD, and L. Clifford McDonald, MD, the authors note that this study provides immense value in the research of C difficile infection by “ its size, quality, and the combination of genomic information with patient movement data to identify possible transmission sources.”

In addition, the authors of the editorial added that the study by Kong et al indicates “that it is still unclear whether symptomatic case- or asymptomatic colonized-patients are most responsible for hospital transmission of C difficile; however, current infection control practices that focus on cases are still justified, given both the increased shedding of symptomatic case-patients and their ease of identification.” A promising approach to study health care infections suggested by the authors includes “the use of genetic and patient movement data to identify a subset of patients enriched for true transmission events.”

According to Dr Kong and her research team, their study demonstrates that “colonized patients may be a source of onward transmission to incident CDI cases, but that spread from infected donors is likely more frequent.” Lower levels of shedding often observed in colonized patients without diarrhea compared with C difficile-infected patients may likely explain these findings.

“Our study provides evidence for continuing the focus of infection control efforts on symptomatic patients as main contributors to transmitting infection, especially in a setting of outbreak with a virulent strain,” added Dr Kong. “A similar large-scale study in a non-epidemic setting without a dominant hypervirulent strain would be needed to clarify the contribution of colonized patients in transmission, as they may play a bigger role in a different context.”