Hospital-Onset C Diff Not Linked to Cross-Transmission


Findings showed colonization with toxigenic C. difficile was associated with a greater risk of CDI during hospitalization than cross-transmission.

Evan Snitkin, PhD | Credit: Michigan Medicine

Evan Snitkin, PhD

Credit: Michigan Medicine

The risk of Clostridioides difficile (C. difficile) infection (CDI) could begin outside of the hospital according to the results of a prospective observational study of patients admitted to a US-based intensive care unit.

Of the patients who cultured negative on admission to the unit, only 1% acquired C. difficile through cross-transmission. However, patients who carried toxigenic C. difficile on admission had a 24-times greater risk for developing healthcare-onset CDI than noncarriers.1

“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,” said Evan Snitkin, PhD, of the departments of microbiology/immunology and internal medicine/infectious diseases at University of Michigan Medical School.2

The US Centers for Disease Control and Prevention estimates C. difficile causes almost 500,000 infections in the United States each year. Risk factors include being over the age of 65 years, staying in a hospital or nursing home, having a weakened immune system, and being previously infected with C. difficile. About 1 in 6 patients who get CDI will get it again in the subsequent 2-8 weeks.3

To assess the impact of asymptomatic C. difficile carriers on transmission in a hospital unit, Snitkin and a team of investigators conducted a longitudinal, observational, single-center study of patients admitted to the intensive care unit at Rush University Medical Center between April 3, 2017 and January 15, 2018. Investigators collected a rectal or stool swab from all patients aged 18 years or older on admission and every day during their stay until discharge. Patients were excluded from the study if they declined a rectal or stool swab, had an ostomy or fibromuscular dysplasia, were neutropenic or hemodynamically stable, or were discharged.1

In total, investigators collected 3952 rectal swab and stool samples from 1289 admissions among 1111 patients. A median of 2 samples were collected per admission (interquartile range [IQR], 1-3) and the median length of stay per admission was 3 days (IQR, 2–6). The cohort had a mean age of 62.7 years (IQR, 50.0-72.7), 48% were male, and 56.2% (n=724) were admitted through an emergency department.1

In total, investigators recovered 448 C. difficile isolates via enrichment culture for toxigenic and non-toxigenic strains. Using admission and prospective daily culture-based screening for C. difficile, investigators applied whole-genome sequencing to 425 identified isolates and assessed epidemiological evidence of C. difficile importation and acquisition, examining genomic evidence of C. difficile transmission from C. difficile carriers to describe the association between C. difficile importation and CDI during hospitalization.1

Among 179 unique patient sequence type combinations, investigators identified 40 unique sequence types. The most common was ST42 (14.0%) followed by ST3 (10.6%) and ST26 (9.5%). Investigators noted these sequence types are commonly associated with ribotypes 106 (ST42), 001 (ST3) and 015 (ST26.) In total, 64.8% of strains had the tcdA or tcdB toxin loci detected in the whole-genome sequencing data and were defined as toxigenic.1

The overall screening prevalence of toxigenic C. difficile was 9.3%. Among 1141 admissions that qualified for importation analyses, 67 patients imported toxigenic C. difficile. Of the 584 admissions qualifying for acquisition analysis, there were 4 toxigenic C. difficile acquisitions among 27 non-toxigenic C. difficile importers compared to 28 toxigenic C. difficile acquisitions among 557 individuals with no C. difficile detected on admission, with significantly more acquisitions among the non-toxigenic C. difficile carriers (P < .001).1

Investigators applied a threshold of 2 single nucleotide variants to genomic linkages involving the 32 culture-based acquisitions of toxigenic C. difficile with available sequences and determined 6 (18.8%) of 32 culture-based acquisitions could be genomically linked with high confidence to another isolate within the unit. Among these 6 acquisitions, 1 acquirer was linked to a patient who was known to import C. difficile into the ICU, 2 acquirers were genomically linked to each other, and the other 3 were genomically linked to patients who did not qualify for importation analysis.1

In an unadjusted survival analysis, patients who carried toxigenic C. difficile on admission were significantly more likely to develop healthcare facility-onset CDI than patients who did not carry any C. difficile on admission (hazard ratio, 24.4; 95% confidence interval, 6.89–86.5; P < .001).1

“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 Vincent Young, MD, PhD, of the departments of microbiology/immunology and internal medicine/infectious diseases at University of Michigan Medical School.2


  1. 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).
  2. Michigan Medicine. The surprising origin of a deadly hospital infection. EurekAlert! Published September 18, 2023. Accessed September 18, 2023.
  3. Centers for Disease Control and Prevention. What is C. Diff? C. Diff (Clostridioides difficile). Accessed September 18, 2023.
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