In vitro activity of eravacycline against common ribotypes of Clostridioides difficile

埃拉瓦环素对艰难梭菌常见核糖体型的体外活性

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作者:Eugénie Bassères, Khurshida Begum, Chris Lancaster, Anne J Gonzales-Luna, Travis J Carlson, Julie Miranda, Tasnuva Rashid, M Jahangir Alam, David W Eyre, Mark H Wilcox, Kevin W Garey

Background

Eravacycline is a novel synthetic fluorocycline antibacterial approved for complicated intra-abdominal infections. Objectives: The

Conclusions

This study demonstrated potent in vitro activity of eravacycline against a large collection of clinical C. difficile strains that was not affected by ribotype, susceptibility to vancomycin or the presence of certain tet resistance genes. Further development of eravacycline as an antibiotic to be used in patients with Clostridioides difficile infection is warranted.

Methods

Clinical C. difficile strains from six common or emerging ribotypes were used to test the in vitro activities of eravacycline and comparator antibiotics (fidaxomicin, vancomycin and metronidazole) by broth microdilution. In addition, MBC experiments, time-kill kinetic studies and WGS experiments were performed.

Results

A total of 234 isolates were tested, including ribotypes RT001 (n = 37), RT002 (n = 41), RT014-020 (n = 39), RT027 (n = 42), RT106 (n = 38) and RT255 (n = 37). MIC50/90 values were lowest for eravacycline (≤0.0078/0.016 mg/L), followed by fidaxomicin (0.016/0.063 mg/L), metronidazole (0.25/1.0 mg/L) and vancomycin (2.0/4.0 mg/L). MBCs were lower for eravacycline compared with vancomycin for all ribotypes tested. Both vancomycin and eravacycline demonstrated bactericidal killing, including for epidemic RT027. The presence of the tetM or tetW resistance genes did not affect the MIC of eravacycline. Conclusions: This study demonstrated potent in vitro activity of eravacycline against a large collection of clinical C. difficile strains that was not affected by ribotype, susceptibility to vancomycin or the presence of certain tet resistance genes. Further development of eravacycline as an antibiotic to be used in patients with Clostridioides difficile infection is warranted.

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