Comparison of antimicrobial activities and resistance mechanisms of eravacycline and tigecycline against clinical isolates in China.

Tigecycline (TGC) is currently used to treat carbapenem-resistant (CRAB) infections, while eravacycline (ERV), a new-generation tetracycline, holds promise as a novel therapeutic option for these infections. However, differences in resistance mechanism between ERV and TGC against remain unclear. This study sought to compare the characteristics and mechanisms of ERV and TGC resistance among clinical isolates. A total of 492 isolates, including 253 CRAB and 239 carbapenem-sensitive (CSAB) isolates, were collected from hospitalized patients in China. The MICs of ERV and TGC against were determined by broth microdilution. Genetic mutations and expressions of , and in resistant strains were examined by PCR and qPCR, respectively. The recombination experiments were used to verify the resistance mechanism of ERV and TGC in . The MIC of ERV in CRAB and CSAB isolates were lower than those of TGC. A total of 24 strains resistant to ERV and/or TGC were categorized into three groups: only ERV-resistant ( = 2), both ERV- and TGC-resistant ( = 7), and only TGC-resistant ( = 15). ST208 (75%,  = 18) was a major clone that has disseminated in all three groups. The IS insertion in was identified in 66.7% (6/9) of strains in the only ERV-resistant and both ERV- and TGC-resistant groups, while the IS insertion in was found in 53.3% (8/15) of strains in the only TGC-resistant group. The and expressions were significantly increased in the only ERV-resistant and both ERV- and TGC-resistant groups, while the and expressions were significantly increased and was significantly decreased in the only TGC-resistant group. Expression of with the IS insertion in ERV- and TGC-sensitive strains significantly increased the ERV and TGC MICs and upregulated and expressions. Complementation of the wildtype in TGC-resistant strains with the IS insertion in restored TGC sensitivity and significantly downregulated expression. In conclusion, our data illustrates that ERV is more effective against clinical isolates than TGC. ERV resistance is correlated with the IS insertion in , while TGC resistance is associated with the IS insertion in or in