Background: Clostridioides difficile  resistant to macrolide-lincosamide-streptogramin B (MLS_B) 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 MLS_B carried the erythromycin resistance methylase gene (ermB ). The statistically significant factors associated with C. difficile  infection (CDI) induced by A⁻B⁺ isolates with MLS_B 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 MLS_B 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