The Surprising Origin of a Deadly Hospital Infection

C. diff might not originate from external transmission but rather from within the infected patient themselves.

Hospital staff dedicate significant effort to safeguard patients from infections during their hospital stay. Through practices ranging from hand cleanliness to the use of isolation rooms and stringent cleaning procedures, they strive to prevent infections. Yet, even with these measures, hospital-onset infections still occur—the most common of which is caused by the bacterium Clostridioides difficile, or C. diff, the culprit of almost half a million infections in the U.S. each year.

Surprising findings from a new study in Nature Medicine suggest that the burden of C. diff infection may be less a matter of hospital transmission and more a result of characteristics associated with the patients themselves.

The study team, led by Evan Snitkin, Ph.D. and Vincent Young, M.D., Ph.D., both members of the Departments of Microbiology & Immunology and Internal Medicine/Infectious Diseases at the University of Michigan Medical School and Mary Hayden, M.D. of Rush University Medical Center, leveraged ongoing epidemiological studies focused on hospital-acquired infections that enabled them to analyze daily fecal samples from every patient within the intensive care unit at Rush University Medical Center over a nine-month period.

Arianna Miles-Jay, a postdoctoral fellow in Dr. Snitkin’s lab, analyzed the over 1,100 patients in the study and found that a little over 9% were colonized with C. diff. Using whole genome sequencing at U-M of 425 C. difficile strains isolated from nearly 4,000 fecal specimens, she compared the strains to each other to analyze spread.

“By systematically culturing every patient, we thought we could understand how transmission was happening. The surprise was that, based on the genomics, there was very little transmission.”

Essentially, there was very little evidence that the strains of C. diff from one patient to the next were the same, which would imply in-hospital acquisition. In fact, there were only six genomically supported transmissions over the study period. Instead, people who were already colonized were at greater risk of transitioning to infection.

“Something happened to these patients that we still don’t understand to trigger the transition from C. diff hanging out in the gut to the organism causing diarrhea and the other complications resulting from infection,” said Snitkin.

Hayden notes this doesn’t mean hospital infection prevention measures are not needed. In fact, the measures in place in the Rush ICU at the time of the study – high rates of compliance with hand hygiene among healthcare personnel, routine environmental disinfection with an agent active against C diff, and single patient rooms – were likely responsible for the low transmission rate.  The current study highlights, though that more steps are needed to identify patients who are colonized and try to prevent infection in them.

Where did the C. diff come from? “They are sort of all around us,” said Young. “C. diff creates spores, which are quite resistant to environmental stresses including exposure to oxygen and dehydration…for example, they are impervious to alcohol-based hand sanitizer.”

However, only about 5% of the population outside of a healthcare setting has C. diff in their gut—where it typically causes no issues.

“We need to figure out ways to prevent patients from developing an infection when we give them tube feedings, antibiotics, proton pump inhibitors—all things which predispose people to getting an actual infection with C. diff that causes damage to the intestines or worse,” said Young.

The team next hopes to build on work investigating the use of A.I. models to predict patients at risk of C. diff infection to identify patients who are likely to be colonized and who could benefit from more focused intervention.

Said Snitkin, “A lot of resources are put into gaining further improvements in preventing the spread of infections, when there is increasing support to redirect some of these resources to optimize the use of antibiotics and identify other triggers that lead patients harboring C diff and other healthcare pathogens to develop serious infections.”

Reference: “Longitudinal genomic surveillance of carriage and transmission of Clostridioides difficile in an intensive care unit” by Arianna Miles-Jay, Evan S. Snitkin, Michael Y. Lin, Teppei Shimasaki, Michael Schoeny, Christine Fukuda, Thelma Dangana, Nicholas Moore, Sarah E. Sansom, Rachel D. Yelin, Pamela Bell, Krishna Rao, Micah Keidan, Alexandra Standke, Christine Bassis, Mary K. Hayden and Vincent B. Young, 18 September 2023, Nature Medicine.
DOI: 10.1038/s41591-023-02549-4

The study was funded by the National Institutes of HealthThe National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>National Institutes of Health and the Centers for Disease Control and Prevention.

Additional authors include Arianna Miles-Jay, Michael Y. Lin, Teppei Shimasaki, Michael Schoeny, Christine Fukuda, Thelma Dangana, Nicholas Moore, Sarah E. Sansom, Rachel D. Yelin, Pamela Bell, Krishna Rao, Micah Keidan, Alexandra Standke, and Christine Bassis.