Molecular epidemiology of <i>Clostridioides difficile</i> colonization in patients with chronic kidney disease in eastern China

ABSTRACT Clostridioides difficile colonization (CDC) is considered an important potential reservoir for subsequent infection, yet its role in patients with chronic kidney disease (CKD) remains unclear. A over 2-year cross-sectional study was conducted at one hospital in Zhejiang, China. Fecal specimens collected from outpatients in the nephrology department were subjected to C. difficile isolation. Isolates were further characterized through toxin gene detection, multilocus sequence typing, whole-genome sequencing, and antimicrobial susceptibility testing. Demographic data were also collected for statistical analysis. Among the 323 patients with CKD enrolled in this study, approximately 5.0% (16/323) were colonized with C. difficile . The 16 C. difficile isolates comprised 9 toxin A-negative, toxin B-positive, and binary toxin-negative (A − B + CDT − ), 1 A − B + CDT + , 2 A + B + CDT − , and 4 A − B − CDT − , yielding 8 sequence types. All the isolates were susceptible to vancomycin and metronidazole, and significant associations were found between resistance to erythromycin and tetracycline and toxin genotypes ( P = 0.009 and 0.002). Multivariable regression analysis revealed that hyperphosphatemia (OR = 1.18; 95% CI, 1.048–1.065) and hemodialysis frequency (OR = 1.10; 95% CI, 1.023–1.467) were independent risk factors for CDC. This study provides the first systematic characterization of the epidemiological profile of CDC in patients with CKD in China; hyperphosphatemia and high-frequency hemodialysis were first identified as independent risk factors for CDC. IMPORTANCE Clostridioides difficile is one of the main causative agents of antibiotic-associated and hospital-associated diarrhea. This study provides the first systematic molecular epidemiological analysis of Clostridioides difficile colonization (CDC) among outpatients with chronic kidney disease (CKD) in eastern China, revealing a colonization rate of 5.0%. Hyperphosphatemia and frequent hemodialysis were established as independent risk factors for CDC. While all isolates retained susceptibility to first-line antimicrobials, they exhibited substantial resistance to fluoroquinolones and clindamycin. These findings address a significant gap in local epidemiological data related to this high-risk cohort and indicate that CKD outpatients may represent an underrecognized potential source for the transmission of antimicrobial-resistant C. difficile . Consequently, this study offers an evidence base to strengthen infection prevention and control in nephrology care settings across China. In addition, these preliminary findings also suggest that active surveillance and risk-stratified strategies may be worth considering in other immunocompromised populations.