In vitro Activity of the Novel Tetracyclines Derivative, Zifanocycline Against Mycobacterium abscessus

Qinlong Yu, Xiaoqin Niu, Bailong Hou, Minjie Mao, Li Zhu, Weifeng Shen, Wei Wang Department of Clinical Laboratory Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, 314000, People’s Republic of ChinaCorrespondence: Weifeng Shen, Department of Clinical Laboratory Medicine, The Affiliated Hospital of Jiaxing University, No. 1882, Zhong-Huan South Road, Nanhu District, Jiaxing, Zhejiang, 314000, People’s Republic of China, Tel +86-15968388122, Email [email protected] Wei Wang, Department of Clinical Laboratory Medicine, The Affiliated Hospital of Jiaxing University, No. 1882, Zhong-Huan South Road, Nanhu District, Jiaxing, Zhejiang, 314000, People’s Republic of China, Tel +86-13736893655, Email [email protected]: This study aimed to evaluate the in vitro antibacterial activity of zifanocycline against Mycobacterium abscessus.Methods: From 2019 to 2024, Mycobacterium abscessus isolates from the respiratory tract of patients were collected at a tertiary hospital in Jiaxing City. All isolates were identified for species, subtypes, and the erm 41 gene polymorphism using whole-genome sequencing (WGS). Susceptibility to zifanocycline and 13 comparators was tested using the broth microdilution method, and the combined effects of zifanocycline and seven antibacterial drugs were evaluated.Results: A total of 67 strains of Mycobacterium abscessus were collected and subjected to whole-genome sequencing. Genomic analysis identified 60 strains of Mycobacterium abscessus subsp. abscessus and 7 strains of Mycobacterium abscessus subsp. massiliense. Among the Mycobacterium abscessus subsp. abscessus strains, 57 exhibited the erm41 T28 genotype, whereas the remaining three showed the erm41 C28 genotype. In our study, zifanocycline (MIC50/MIC90, 0.06/0.25 mg/L) demonstrated a 2-fold lower MIC50 and MIC90 compared to tigecycline (MIC50/MIC90, 0.12/0.5 mg/L), and a 4-fold and 2-fold lower MIC50 and MIC90, respectively, compared to omadacycline (MIC50/MIC90, 0.25/0.5 mg/L). In addition to amikacin and linezolid, zifanocycline demonstrated significantly superior antibacterial activity compared with ciprofloxacin, moxifloxacin, trimethoprim–sulfamethoxazole, cefoxitin, doxycycline, imipenem, and clarithromycin. The combination of zifanocycline and the seven antibacterial drugs used for the treatment of Mycobacterium abscessus showed no significant interactions.Conclusion: Zifanocycline exhibits positive antibacterial activity against Mycobacterium abscessus in vitro and has potential as an alternative agent in multidrug combination therapy regimens for the treatment of this pathogen.Keywords: Mycobacterium abscessus, in vitro, tetracycline, zifanocycline