Predictors of Clostridioides difficile Infection Among Asymptomatic, Colonized Patients: A Retrospective Cohort Study

Abstract

Background Asymptomatic patients colonized with Clostridioides difficile are at risk of developing C. difficile infection (CDI), but the factors associated with disease onset are poorly understood. Our aims were to identify predictors of hospital-onset CDI (HO-CDI) among colonized patients and to explore the potential benefits of primary prophylaxis to prevent CDI. Methods We conducted a retrospective cohort study in a tertiary academic institution. Colonized patients were identified by detecting the tcdB gene by polymerase chain reaction on a rectal swab. Univariate and multivariate logistic regression analyses were used to identify predictors of HO-CDI. Results There were 19 112 patients screened, from which 960 (5%) colonized patients were identified: 513 met the inclusion criteria. Overall, 39 (7.6%) developed a HO-CDI, with a 30-day attributable mortality of 15%. An increasing length of stay (adjusted odds ratio [aOR] per day, 1.03; P = .006), exposure to multiple classes of antibiotics (aOR per class, 1.45; P = .02), use of opioids (aOR, 2.78; P = .007), and cirrhosis (aOR 5.49; P = .008) were independently associated with increased risks of HO-CDI, whereas the use of laxatives was associated with a lower risk of CDI (aOR 0.36; P = .01). Among the antimicrobials, B-lactam with B-lactamase inhibitors (OR 3.65; P < .001), first-generation cephalosporins (OR 2.38; P = .03), and carbapenems (OR 2.44; P = .03) correlated with the greatest risk of HO-CDI. By contrast, patient age, the use of proton pump inhibitors, and the use of primary prophylaxis were not significant predictors of HO-CDI. Conclusions This study identifies several factors that are associated with CDI among colonized patients. Whether modifying these variables could decrease the risk of CDI should be investigated.

A multisite genomic epidemiology study of Clostridioides difficile infections in the U.S. supports differential roles of healthcare versus community spread for two common strains

“…We then systematically examined to what extent the data violated the strict clock and constant demographic model prior assumptions and thus, to what extent more complex models were warranted. To assess whether the data violated a strict clock assumption, we evaluated whether the coefficient of variation parameter in the models with an uncorrelated relaxed lognormal clock had a 95% highest posterior density interval (HPD) that overlapped 0; if not, we used this as evidence of the assumptions of a strict clock being violated and applied an uncorrelated relaxed lognormal clock with a lognormal prior distribution with a mean of 5.0x10 - 7 and standard deviation of 8x10 -7 based on previous evolutionary rate estimates (while allowing still allowing for significant deviation) [29,36]. To assess to what extent the data violated a constant demographic model, we ran models with exponential growth demographic model prior, and evaluated whether the 95% credible interval of the exponential growth rate parameter overlapped 0.…”

“…While C. difficile infection (CDI) is classically considered nosocomial [3], recent molecular epidemiologic research suggests that less than 40% of CDI cases are linkable to other symptomatic CDI cases within the same hospital [4][5][6]. This insight has disrupted the paradigm of C. difficile as an exclusively nosocomial pathogen and expanded interest into the roles of alternative routes of C. difficile transmission, including community-based acquisition with subsequent progression to CDI within healthcare settings [7].…”

Anti-virulence strategies for Clostridioides difficile infection: advances and roadblocks

“…Specifically for CD infections, much consideration has to be given to the likelihood that humans and animals can asymptomatically harbor the organism for years. 29 , 30 Any intervention may have to be administered for extended time periods to ensure complete clearance of the organism; this warrants additional considerations of safety and tolerability. Finally, many at-risk patients may be immunocompromised; 31 , 32 therefore, the most appropriate interventions are those that can be tolerated by these individuals as well.…”

Computational modeling of the gut microbiota reveals putative metabolic mechanisms of recurrent Clostridioides difficile infection

“…The advent of high-throughput technologies such as 16S rRNA-encoding gene sequencing has yielded unprecedent insights into the composition of in vivo bacterial communities [ 20 – 22 ]. Despite numerous 16S-based studies that have attempted to correlate CDI disease state to gut bacterial composition [ 13 , 23 – 26 ], we still do not understand why some exposed individuals develop CDI while other individuals are asymptomatic [ 9 , 27 , 28 ] and why some infections become recurrent while other infections are effectively treated with antibiotics [ 29 – 32 ]. Furthermore, microbial communities being transplanted with FMT are poorly understood both with regard to their composition and the health-promoting metabolic functions being introduced [ 33 – 35 ].…”