High-Level Resistance of Toxigenic Clostridioides difficile Genotype to Macrolide-Lincosamide- Streptogramin B in Community Acquired Patients in Eastern China

Abstract

Longyou Zhao, 1,* Yun Luo, 2,* Qiao Bian, 3, 4 Liqian Wang, 5 Julian Ye, 6 Xiaojun Song, 4, 7 Jianmin Jiang, 6, 8 Yi-Wei Tang, 9–11 Xianjun Wang, 5 Dazhi Jin 4, 7 1Lishui Second People’s Hospital, Lishui, Zhejiang, People’s Republic of China; 2School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia; 3School of Medicine, Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 4Centre of Laboratory Medicine, Zhejiang Provincial People Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Laboratory Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, People’s Republic of China; 7School of Laboratory Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 8Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 9Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 10Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA; 11Cepheid, Danaher Diagnostic Platform, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dazhi JinCentre of Laboratory Medicine, Zhejiang Provincial People Hospital, People’s Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang 310014, People’s Republic of ChinaTel/Fax [phone]Email [email protected] Wang Tel/Fax [phone]Email [email protected]: Clostridioides difficile resistant to macrolide-lincosamide-streptogramin B (MLSB) has not been reported in China.Methods: In a cross-sectional study in two tertiary hospitals, C. difficile isolates from stool specimens from community-onset, hospital-associated diarrheal patients were analyzed for toxin genes, genotype, and antibiotic resistance, and the patients’ clinical charts were reviewed.Results: A total of 190 (15.2%) isolates (102 A+B+ and 88 A−B+) from 1250 community acquired (CA) patients were recovered and all were susceptible to vancomycin and metronidazole. High-level resistance (minimum inhibitory concentration > 128 mg/L) to erythromycin and clindamycin was recorded in 77.9% and 88.4% of the tested isolates, respectively. Furthermore, 89.3% (159/178) of the isolates resistant to MLSB carried the erythromycin resistance methylase gene (ermB). The statistically significant factors associated with C. difficile infection (CDI) induced by A−B+ isolates with MLSB resistance included a severity score of > 2 (odds ratio [95% confidence interval], 7.43 [2.31– 23.87]) and platelet count (cells × 10 9 cells/L) < 100 [5.19 (1.58– 17.04)]. The proportion of A−B+ increased with enhanced CDI severity (x 2 = 21.62, P < 0.001), which was significantly higher than that of ermB-positive A+B+ in severity score of 4 (x 2 = 8.61, P = 0.003). The average severity score of ermB-positive isolates was significantly higher than that of ermB-negative isolates in A−B+ (Z = − 2.41, P = 0.016).Conclusion: The ermB-positive A−B+ C. difficile with MLSB resistance is described for the first time as a potential epidemic clone inducing severe CDI in CA diarrheal patients in Eastern China.Keywords: Clostridioides difficile, molecular characteristic, macrolide-lincosamide-streptogramin B resistance

Keywords

• clostridioides difficile
• molecular characteristic
• macrolide-lincosamide-streptogramin b resistance