Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics

Abstract

Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta-lactamase inhibitor, 3rd/4th generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.9% (95% CI 1.1-3.0). Carbapenem treatment (Hazard Ratio (95% CI): 5.3 (1.7-16.6)), toxigenic C. difficile rectal carriage (10.3 (3.2-33.1)), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (5.4 (2.1-18.7)), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (9.7 (3.2-29.7)), but not normalized urinary 3-indoxyl sulfate levels, predicts an increased CDI risk.

Akkermansia muciniphila Ameliorates Clostridioides difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites

“…In some cases, antibiotics even promote CDIs, which can take over after the symbiotic microflora is damaged by antibiotics ( Theriot et al, 2014 ). These broad-spectrum antibiotics affect the healthy gut microbiota and hinder colonization resistance by reducing the abundance of intestinal microbes that resist C. difficile ( van Werkhoven et al, 2021 ). In turn, the reduced microbiota diversity induces an elevated level of primary bile acids (BAs), which facilitate the germination of C. difficile spores and reduce the concentration of secondary BAs that inhibit the growth of C. difficile ( de Aguiar Vallim et al, 2013 ).…”

Level of Knowledge of Medical Staff on the Basis of the Survey in Terms of Risk Management, Associated with Clostridioides difficile Infections

“…In recent years, many publications on C. difficile [23][24][25][26][27][28][29][30][31][32][33][34][35] have been published, but the vast majority of them presented general information about the microorganisms, the number of diagnosed cases, methods of diagnosis, patient treatment and transmission routes. Definitely much fewer papers discuss the issues related to the knowledge of healthcare professionals about C. difficile, seniority, the etiology of CDI in medical facilities, costs of treating patients with nosocomial infections and the responsibility of hospital management for training and supervising subordinate medical staff.…”

Gut Microbiota Composition Associated with Clostridioides difficile Colonization and Infection

“…Werkhoven and collaborators (2021) showed that the carriage of toxigenic C. difficile increased the incidence of developing CDI 10-fold after antibiotic treatment. Specifically, the use of carbapenem increased the incidence of CDI 5-fold and increased the abundance of Enterococcus 5-fold [ 13 ].…”

“…Antibiotic exposure increases the possibility of C. difficile colonization by 3.7-fold [ 12 ] and of developing CDI by 3.55-fold [ 9 ]. A previous study showed that among antibiotic-associated diarrhea (AAD) cases, the incidence of CDI was 1.14–1.89% [ 13 ], and the frequency of toxigenic C. difficile carriage was 18.1–19.0% [ 13 ].…”