Standard of Care Leads to Underdiagnosis of CDI

Standard-of-care testing practices likely underestimate the incidence of Clostridioides difficile infection, according to a recent study.

The study, published in Emerging Infectious Diseases, included hospitalized patients aged 50 or older with diarrhea in Louisville, Kentucky, from Oct. 14, 2019, to Oct. 13, 2020. Surveillance was paused from April 12 to Aug. 16, 2020, because of COVID-19 restrictions.

“Clostridioides difficile (C diff) is a bacterium that can lead to life-threatening diarrhea, and the CDC has identified it as an urgent public health threat,” the study’s lead author, Julio Ramirez, MD, chief scientific officer at Norton Infectious Diseases Institute, told Contagion. “Typically, physicians order a C diff test for hospitalized patients with diarrhea when they suspect a C diff infection. However, in our study, we collected stool samples from all hospitalized patients with diarrhea and tested them for C diff allowing us to identify almost 30% more cases of C diff than physicians alone.”

The study included 1541 incident diarrhea cases per 85,719 before the pause. Standard-of-care stool specimens were collected from 680 patients, or 79.3 per 10,000 patient-days. Study specimens were collected from 1047 patients or 122.1 per 10,000 patient-days. After the pause, investigators identified 319 incident diarrhea cases, and study specimens were collected in 144 participants.

Stool samples were screened with a rapid test and those that were glutamate dehydrogenase (GDH)‒positive or GDH-negative/toxin-positive were sent to a Pfizer lab for a PCR nucleic acid amplification testing. Those that were NAAT positive underwent cell cytotoxicity neutralization assay (CCNA) testing. After the pause, all samples were sent to the lab for further testing.

“Our findings have significant implications for the CDC's efforts to determine the true burden of C diff in the USA,” Ramirez said. “By testing all cases of diarrhea, we were able to provide more realistic data about the prevalence of C diff, which can help guide public health interventions and resource allocation.”

The study found 154 CDI cases per 100,000 population/year, compared with 121 identified by the standard of care among participants aged 50 and older. CDI incidence increased with age, to 226/100,000 population/year among those aged 65 and older and 334/100,000 population/year among those 75 and older. After sensitivity analysis accounting for specimens that were not NAAT/CCNA tested, CDI incidence rates were 202 cases/100,000 population/year among those aged 50 and older, 296 among those aged 65 years and older and 438 among those aged 75 and older.

The study’s CDI incidence was 44% higher than cases reported in the CDC EIP CDI surveillance system in 2019, and 24.4% more hospitalized primary CDI case-patients were identified by the study than by standard-of-care testing.

“Clinicians should be vigilant about the possibility of C diff infection in hospitalized patients with diarrhea and maintain a low threshold for suspicion,” Ramirez said. “Early diagnosis, appropriate treatment and optimal infection control measurements can improve patient outcomes and prevent the spread of the infection.”

Among hospitalized patients with CDI, about one-fifth had pseudomembranous colitis, one-third were admitted to intensive care units and one-fifth died within 90 days.

“Ultimately, the development of a successful C diff vaccine should be a priority to prevent C diff infections and reduce the significant burden of disease associated with this bacterium,” Ramirez said.