Clostridioides difficile Infection Cases and the Causative Strains in a Large Chinese Tertiary Hospital in 2023-2024

Xin Lu^1,2Yiqi Liang^1,2Yu Feng^1,2,3Tingting Wang⁴Zhiyong Zong^1,2,5Xiaohui Wang^1,2,3,6*

• ¹Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
• ²Division of Infectious Diseases, State Key Laboratory of Biotherapy, Chengdu, China
• ³Center for Pathogen Research, West China Hospital of Sichuan University, Chengdu, China
• ⁴Clinical Laboratory Medicine Research Center, Sichuan University West China Hospital Department of Laboratory Medicine, Chengdu, China
• ⁵Center for Pathogen Research, West China Hospital, Sichuan University, Chengdu, China
• ⁶Sichuan Public Health General Clinical Center (Jincheng Hospital of West China Hospital, Sichuan University), Chengdu, China

Background Clostridioides difficile is a global urgent-threat pathogen, with prevalence and clinical impact varying over time and across regions. This study aims to elucidate the landscape of C. difficile infection (CDI) and its causative strains in Southwest China after the COVID-19 pandemic. Methods This retrospective study enrolled CDI patients hospitalized between June 2023 and May 2024 at a large tertiary hospital in Southwest China, who were diagnosed via glutamate dehydrogenase (GDH) combined with toxin A/B testing. Toxigenic isolates from positive stool samples were submitted for antimicrobial susceptibility testing and whole-genome sequencing (WGS). Multilocus sequence typing (ST), identification of resistance determinants, and core-genome SNP (cgSNP) analysis were integrated with clinical data. Results 157 CDI patients were identified among 2,917 suspected patients with diarrhea. 67.5% of patients were male, 51.0% were ≥ 65 years, 20.4% had severe CDI, and two patients were fulminant. All 109 isolates remained susceptible to vancomycin and fidaxomicin. The moxifloxacin resistance rate reached as high as 56.0%, primarily driven by gyrA Thr82Ile and gyrB Asp426Val/Ser366Ala mutations. ST3 (23.9%) remains the most prevalent clone. ST81 (18.3%), all resistant to moxifloxacin and 20% resistant to metronidazole, has replaced ST37 (7.3%) as the second-most prevalent clone. ST5 (4.6%) was the main prevalent clone producing the binary toxin, and no ST1/RT027 was identified. The cfr(B) resistance gene was first detected in a ST54 isolate from China. CgSNP analysis identified 4 genetically highly related ST3 clone groups (≤ 2 SNPs within 124 days). Conclusions In the post-pandemic era, the clinical burden of CDI in Southwest China cannot be overlooked. ST81 with high-level fluoroquinolone resistance has increased significantly and deserves more attention. Integration of data on clinical cases and their pathogenic strains through sustained clinical case monitoring, genomic surveillance of isolates, and antimicrobial resistance pattern surveys provides early warning for future clonal dissemination and supports clinical management and public health decisions.