Screening for Asymptomatic C difficile in ICU Admissions Reveals Risk for Infections

A longitudinal genomic screening for Clostridioides difficile among all patients admitted to an intensive care unit revealed that asymptomatic carriers are at greater risk of developing infection than in transmitting to other patients.

Although conducting such surveillance may counter the preference of hospitals to minimize their ranking on this metric, the investigators suggest that their findings can inform strategies to reduce Clostridioides difficile infection (CDI), the leading healthcare-associated infection in the United States.

“Current prevention strategies are limited by their failure to account for patients who carry C difficile asymptomatically, who may act as hidden reservoirs transmitting infections to other patients,” commented Arianna Miles-Jay, PhD, Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, and colleagues.

“To make further gains in reducing rates of CDI, it is necessary to better understand the sources of C difficile beyond cases with CDI within the hospital,” they argued.

To improve understanding of the role of asymptomatic carriers, the investigators conducted admission and daily longitudinal culture-based screening for C difficile in an ICU over nine months, performing whole-genome sequencing on all recovered isolates, and applying epidemiological tracking of C difficile importation and acquisition during hospitalizations.

Approximately 4000 rectal swab and stool samples from 1289 ICU admissions of 1111 patients yielded 448 C difficile isolates, with 425 successfully whole-genomic sequenced.The investigators noted a high exposure to antibiotics (71.8%) during ICU admission, with most admitted through the emergency medicine department.

Multiple strains of C difficile were often present in a single patient. Among 80 admissions with at least two C difficile isolates and sequence-typed genomes, 13 (15%) included multiple strain types: 7 with at least 2 different toxigenic strains; 5 with a mix of toxigenic and non-toxigenic strains; and 1 with at least 2 different non-toxigenic strains.

Seeking to ascertain whether harboring a non-toxigenic strain protected against acquiring a toxigenic strain, the investigators determined that among 584 admissions qualifying for that analysis, 4 of 27 (14.8%) with non-toxigenic strains subsequently acquired a toxigenic strain, compared to 28 acquisitions among 557 individuals (5.0%) with no C difficile detected on admission.

“Our data do not support non-toxigenic C difficile as protecting against colonization with toxigenic strains,” Miles-Jay and colleagues observed.“Instead, they indicate that presence of non-toxigenic strains may be a marker of a gut environment conducive to toxigenic C difficile acquisition.”

The investigators reported that despite a high burden of carriage, with 9.3% of admissions having toxigenic C difficile detected in at least 1 sample, only 1% of patients with negative culture on admission subsequently acquired C difficile via cross-transmission.

“While patients who carried toxigenic C difficile on admission posed minimal risk to others, they themselves had a 24 times greater risk for developing a healthcare-onset C difficile infection than noncarriers,” Miles-Jay and colleagues reported.

They suggest that current infection prevention practices can be effective in preventing nosocomial cross-transmission of C difficile, but that additional progress will require better targeting of the transition from asymptomatic carriage to infection.