Longitudinal genomic surveillance of carriage and transmission of Clostridioides difficile in an intensive care unit

Abstract

Despite enhanced infection prevention efforts, Clostridioides difficile remains the leading cause of healthcare-associated infections 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. To improve the understanding of asymptomatic carriers’ contribution to C. difficile spread, we conducted admission and daily longitudinal culture-based screening for C. difficile in a US-based intensive care unit over nine months and performed whole-genome sequencing on all recovered isolates. Despite a high burden of carriage, with 9.3% of admissions having toxigenic C. difficile detected in at least one sample, only 1% of patients culturing negative on admission to the unit 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. Together, these findings suggest that current infection prevention practices can be effective in preventing nosocomial cross-transmission of C. difficile, and that decreasing C. difficile infections in hospitals further will require interventions targeting the transition from asymptomatic carriage to infection.

Genomic surveillance ofClostridioides difficiletransmission and virulence in a healthcare setting

“…Our study has a number of important limitations. As this study focused on C. difficile colonization, disease, and transmission in two wards in the same hospital, studies with increased sample size or meta-analysis studies are necessary to understand generalizable epidemiological measurements of C. difficile -patient dynamics 73 . Additionally, our study protocol allowed for culturing all environmental/patient specimens from a carrier or patient with CDI.…”

“…Our study has a number of important limitations. As this study focused on C. difficile colonization, disease, and transmission in two wards in the same hospital system, studies with increased sample size or meta-analysis studies are necessary to understand generalizable epidemiological measurements of C. difficile -patient dynamics 15 . For example, we were unable to fully quantify in-unit transmission, as not all patients were able to provide stool specimens and/or consented to rectal swabs within 3 days of admission.…”

“…Only SNPs within the core genome of each MLST group were considered, thus core MLST SNPs were used for strain network determination. A cutoff of <=2 core MLST SNPs was used to define strain networks, as has been used previously to account for strain variation 15,47 .…”

“…Indeed, while asymptomatic carriers of C. difficile have not been a significant focus of infection prevention efforts, studies have shown these carriers do shed toxigenic C. difficile spores to their surroundings that could cause disease 14 . Though carriers have not been consistently identified as major transmitters of C. difficile that causes CDI, recent work has suggested that patients carrying C. difficile asymptomatically may be at elevated risk for development of CDI 15 . Correspondingly, it is critical to both confirm this finding in another setting, and understand the genomic factors that may influence the transition from carrier to CDI manifestation in hospitalized patient populations.…”

Approaching pathogenicClostridiafrom a One Health perspective

“…A number of global programs leverage the PD resources and repository 32 , including the US FDA’s GenomeTrakr program 23,35,54,55 , CDC’s PulseNet 37,56 , country-wide and state/province Public Health programs 23,57-59 , and surveillance programs within hospital networks 25,48,56,60,61 . Additional international consortia that incorporate surveillance for toxigenic Clostridia include the International Pathogen Surveillance Network (IPSN) 62 , formed in 2023 by the World Health Organization Hub for Pandemic and Epidemic Intelligence to advance use of pathogen genomics in informing decisions made in public health, while improve upstream events in sample collection and for downstream data analysis, and the Wellcome Trust-founded Surveillance and Epidemiology of Drug-resistant Infections Consortium (SEDRIC) 63 .…”