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Rethinking the Source of C. Diff Hospital Infections

It turns out that the origin of the common hospital infection, Clostridioides difficile, stems from within the patients themselves rather than from person-to-person transmission.

Hospitals are struggling to control Clostridioides difficile (C. Diff) infections, especially in intensive care units (ICU).1,2 While C. diff is a major cause of illness and symptoms like diarrhea in hospitals, a recent report suggests it might not be spreading as much between patients as previously thought.3 

Drs. Evan Snitkin and Vincent Young from the Departments of Microbiology and Immunology and Internal Medicine/Infectious Diseases at University of Michigan Medical School, and Dr. Mary Hayden of Rush University Medical Center, suspected a hidden reservoir: people who carry C. diff without symptoms. These asymptomatic carriers might be shedding the bacteria and putting others at risk because they aren’t isolated or subject to the same cleaning protocols.

In their study, published in Nature Medicine, the scientists screened ICU patients for C. diff throughout their stay and analysed the genetic makeup of the bacteria.4 This helped them shine a light on how often C. diff enters the ICU from outside sources, how likely it is to spread between carriers and patients, and the link between carrying C. diff and developing a full-blown infection.

While current ICU hygiene practices work to prevent C. diff from spreading between patients, those already carrying the bacteria are more likely to develop the infection themselves. Future efforts might be more successful focusing on curbing C. diff infections in carriers rather than solely stopping transmission.

Uncovering the ICU’s bacterial zoo

The researchers took a deep dive into how C. diff behaves in intensive care units by following patients throughout their stay. They collected stool samples from over a thousand patients on multiple occasions during their ICU admissions to track its presence over time. This was purely observational, meaning they monitored patients without interfering with their treatment. This study was conducted in a single ICU at Rush University Medical Center, so the findings may not apply to all hospitals.

They grew C. diff bacteria from patient samples and analyzed their genetic makeup to understand the types of C. diff present and how they might be related. They also gathered information about the patients, including age, ethnicity, health conditions, and how they entered the ICU, to see which, if any, factors were linked to C. diff carriage.

A mixed bag of strains

The team delved into the genetics of C. diff bacteria in the ICU, finding a mix of 40 different strains. Some strains were more common than others, and these are often associated with antibiotic resistance. The researchers also looked for toxin production – the key to C. diff causing illness. They determined that over 64% of the C. diff bacterial strains produced toxins. Surprisingly, one strain (ST3) seemed to have both toxin-producing and non-toxin-producing variations.

After tracking the prevalence of C. diff strains over time, they found that they were relatively stable, implying a continuous presence of the bacteria in the ICU rather than sudden outbreaks. Remarkably, in 15% of patients, the researchers identified multiple C. diff strains during a single stay. Could this be due to new infections on top of existing ones, or patients harboring multiple strains at the same time?

To understand how C. diff spreads, the researchers looked at how often patients brought the bacteria into the ICU versus catching it during their stay. They found that nearly 6% of patients came in with C. diff, while a little over 1.6 patients per 100 ICU days acquired it there. Notably, one of the cases they examined involved a concerning epidemic strain.
Finally, the study identified some patients who carried C. diff for extended periods without getting sick. These patients seemed to harbor very similar strains throughout their carriage. The researchers wondered if non-toxin-producing C. diff might protect patients from getting sick with toxin-producing strains. However, they found the opposite – patients carrying nontoxic strains were more likely to acquire toxic strains later, suggesting their gut environment might be more susceptible to C. diff colonization in general.

Packing your own bugs

How often does C. diff spread from already infected patients to others in the ICU? They compared the genetic fingerprints of C. diff bacteria from patients who supposedly acquired the infection during their stay. If the fingerprints were very similar, it suggested recent transmission from another patient.

Surprisingly, the researchers found this type of transmission in only a small number of cases (6 out of 32). They explored why they might have missed more transmissions and found two possibilities: first, some patients might have been carrying C. diff on admission that they didn’t detect with the initial test. Second, patients might shed C. diff bacteria intermittently, meaning a negative test doesn’t necessarily rule out infection. The study suggests that undetected C. diff carriage at admission might be a bigger factor in ICU patients developing C. diff than previously thought.

On the other hand, 60% of patients who exhibited C. diff infections actually brought the bacteria into the ICU with them. While some patients developed a symptomatic C. diff infection during their stay, only one case was likely due to transmission from another patient in the ICU. This suggests that bringing C. Diff into the ICU might be a bigger risk factor for developing the infection than catching it from other patients within the ICU.

C. diff infection might be caused more by the patients’ own health than by contracting it in the hospital. “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 Dr. Young in a recent press release.5


  1. Canada, P.H.A. of (2014) Government of Canada, Available at: (Accessed: 27 June 2024).
  2. Prechter, F. et al. (2017) ‘Sleeping with the enemy: Clostridium difficile infection in the intensive care unit’, Critical Care, 21(1). doi:10.1186/s13054-017-1819-6.
  3. Riddle DJ, Dubberke ER. Clostridium difficile infection in the intensive care unit. Infect Dis Clin North Am. 2009;23(3):727–743. doi:10.1016/j.idc.2009.04.011
  4. Miles-Jay A, Snitkin ES, Lin MY, et al. Longitudinal genomic surveillance of carriage and transmission of Clostridioides difficile in an intensive care unit. Nat Med. 2023;29(10):2526–2534. doi:10.1038/s41591-023-02549-4
  5. The surprising origin of a deadly hospital infection (2023) EurekAlert! Available at: (Accessed: 27 June 2024).
Melody Sayrany MSc
Melody Sayrany MSc
Melody Sayrany is a seasoned science writer with a host of experiences in cancer, neuroscience, aging, and metabolism research. She completed her BSc at The University of California, San Diego, and her MSc in biology, focusing on metabolic diseases during aging, at the University of British Columbia. Melody is passionate about science communication, and she aims to bridge the gap between complex scientific concepts and the broader community through compelling storytelling.


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