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Asymptomatic C. Difficile Carriers Prone to Progress to Infection in the Hospital

NEW YORK – A new genomic analysis suggests that patients in the intensive care unit who arrive as asymptomatic carriers of Clostridium difficile may be especially susceptible to developing healthcare-associated C. difficile infections, whereas few non-carriers acquire the infection from C. difficile carriers during their hospital stay.

"Despite enhanced infection prevention efforts, [C. difficile] remains the leading cause of healthcare-associated infections in the United States," co-first and corresponding author Evan Snitkin, a researcher at the University of Michigan, wrote in Nature Medicine on Monday.

A possible reason, they argued, is that "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."

To explore that possibility further, the researchers began by searching for C. difficile in 3,952 rectal swab or stool samples collected over time from nearly 1,300 individuals admitted to the intensive care unit, including 1,111 patients sampled daily after admission to the health center. Using an enrichment culture method, they identified 448 samples that screened positive for toxigenic or non-toxigenic C. difficile strains, which were subsequently profiled by short-read whole-genome sequencing.

"Past work has consistently shown that the majority of C. difficile infections in hospitals could not be explained by transmission from other patients with infections," Snitkin said in an email. "Our work set out to examine the role of patients asymptomatically carrying C. difficile as potential sources of cross-transmission of C. difficile in a hospital ICU."

The team’s epidemiological, strain prevalence, and phylogenetic analyses — which included genome sequences from 425 C. difficile isolates — suggested that infections more often stemmed from a transition of asymptomatic carriers than from transmission between carriers or to individuals who were C. difficile-free at admission.

Although some 9 percent of patients were asymptomatic carriers of C. difficile when they were admitted to the hospital, for example, just 1 percent of patients who started off negative for C. difficile went on to contract a C. difficile infection during their hospital stay.

In contrast, the team found that patients who were asymptomatically colonized with toxigenic forms of the bug at admission were far more likely to develop a C. difficile infection during their time in the hospital than individuals who were not colonized at admission.

"[W]hile carriers presented minimal risk for transmitting to others, patients carrying C. difficile on admission to the unit were themselves at 20-times the risk of developing a C. difficile infection in the hospital as compared to non-carriers," Snitkin said.

Given these results, the team highlighted the importance of tracking — and potentially interfering with — the transition from harmless to infectious forms of C. difficile in patients who are already colonized with toxigenic strains, even if they start off symptom-free.

"Our findings suggest that measures in place in the ICU at the time of the study — high rates of compliance with hand hygiene among healthcare personnel, routine environmental disinfection with an agent active against C. diff., and single patient rooms — were effective in preventing C. difficile transmission," Snitkin suggested.

"This indicates that to make further progress in protecting patients from developing C. difficile infections will require improving our understanding of the triggers that lead patients asymptomatically carrying C. difficile to transition to having infections," he wrote.