Outcomes, Disease Severity in Patients With Clostridioides difficile Infection With Binary Toxin-Expressing Strains

Clostridioides difficile bacteria
Illustration of the bacteria Clostridioides difficile. These rod shaped bacteria have flagella, which are used for motility. Clostridioides difficile (formerly known as Clostridium difficile) are anaerobic bacteria prevalent in soil. In humans, the bacteria can become established in the colon and disrupt the normal gut microbiota, particularly in people taking antibiotics. Toxins released by Clostridioides difficile can produce diarrhoea and inflammation.
Investigators conducted a study that assessed disease severity and outcomes in patients with Clostridioides difficile infection with C difficile binary toxin-expressing strains.

Patients with Clostridioides difficile infection (CDI) with a C difficile binary toxin (CDT)-expressing strain had increased disease severity and worse clinical outcomes compared with those with CDI without CDT-expressing strains, according to results of a retrospective study published in Open Forum Infectious Diseases.

Between 2015 and 2017, investigators retrospectively collected stool samples from patients with CDI to test for the presence of CDT via enzyme-linked immunosorbent assay (ELISA). They noted that “CDT [comprises] CdtA, an actin-specific ADP-ribosyl transferase, and CdtB, the receptor-binding component.” The investigators also performed quantitative polymerase chain reaction (qPCR) testing to detect the presence of the CdtB gene using DNA extracted from stool samples. To determine whether patients with a stool sample positive for CDT had altered fecal microbiota, they used 16 S rRNA gene sequencing. After stratification of patients by CDT status, the investigators sought to assess whether disease severity and clinical outcomes are correlated with CDT positivity.

A total of 215 patients were included in the analysis, of whom 32 were positive for CDT and 182 were negative for CDT. Among patients in both the positive and negative CDT groups, the mean age was 64.7 and 59.2 years, 50% and 50.1% were women, and 45.2% and 19.5% had leukocyte counts greater than 15,000/mcL, respectively.

The investigators found that patients in the positive CDT group were significantly more likely to have increased leukocyte counts (P =.01) and an increased bacterial burden (P =.001) compared with those in the negative CDT group.

Further analysis between patients in the positive vs negative CDT groups showed that the mean length of hospitalization was significantly increased among those in the positive CDT group (18 days vs 11.5 days; P =.05). In addition, patients in the positive CDT group were significantly more likely to require intensive care unit (ICU) admission (P =.01) as well as longer ICU stays (P =.001). The rate of 90-day mortality was also significantly increased among patients in the positive CDT group (P =.03).

The investigators found no significant differences in gut microbiome diversity between patients in the positive and negative CDT groups (P =.026), indicating that increases in CDI severity related to CDT positivity may not be associated with decreases in microbiome diversity.

This study was limited by the small number of patients tested for CdtB via qPCR, which impeded the investigators’ ability to draw conclusions about ICU admissions and 90-day mortality.

Based on these findings, the investigators concluded that “characterizing [CDI] with CDT-expressing strains may be beneficial in clinical disease diagnosis and treatment.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Young MK, Leslie JL, Madden GR, et al. Binary toxin expression by Clostridioides difficile is associated with worse disease. Open Forum Infect Dis. Published online January 10, 2022. doi:10.1093/ofid/ofac001