Activity of the Novel Tetracyclines, Tigecycline, Eravacycline, and Omadacycline, Against .

BACKGROUND

Tigecycline, eravacycline, and omadacycline are recently developed tetracyclines. Susceptibility of microbes to these tetracyclines and their molecular mechanisms have not been well elucidated. We investigated the susceptibility of to tigecycline, eravacycline, and omadacycline and its resistance mechanisms against these tetracyclines.

METHODS

A total of 207 non-duplicate isolates were collected from different inpatients. The minimum inhibitory concentrations (MICs) of the tetracyclines were determined by broth microdilution. Tigecycline-, eravacycline-, or omadacycline-resistant isolates were induced under pressure. The tet genes and mutations in the 16S rRNA was detected by PCR and sequencing.

RESULTS

Eravacycline had a lower MIC (0.06 mg/L) than tigecycline (0.125 mg/L) or omadacycline (0.125 mg/L) against isolates. We found that 136 isolates (65.7%) had the gene, and 15 (7.2%) isolates were positive for however, their presence was not correlated with high tigecycline, eravacycline, or omadacycline (≥1 mg/L) MICs. Compared with the initial MIC after 160 days of induction, the MICs of tigecycline or eravacycline against three isolates increased ≥eight-fold, while those of omadacycline against two isolates increased 64-fold. Mutations in the 16S rRNA genes (C1036T and/or G460A) were observed in omadacycline-induced resistant isolates, and increased RR (the genes encoding 16SrRNA (four copies, RR1-RR4) copy number of 16S rRNA genes with mutations was associated with increased resistance to omadacycline.

CONCLUSIONS

Tigecycline, eravacycline, and omadacycline exhibited robust antimicrobial effects against . Mutations in the 16S rRNA genes contributed to omadacycline resistance in .