Therapeutic effect of eravacycline against carbapenem-resistant hypervirulentin mouse models.

Abstract

Carbapenem-resistant hypervirulent(CR-hvKP) presents a major challenge for clinical treatment due to its characteristics of drug resistance and hypervirulence. This study aims to investigate the therapeutic effect of a novel tetracycline antibiotic, eravacycline, on CR-hvKP pneumonia. We isolated three CR-hvKP strains from clinical samples and examined their associated phenotypes. Subsequently, we infected mice with strains. The results indicated that the clinical isolates KP78, KP98, and KP100 carried multiple drug resistance genes and virulence genes, exhibiting high virulence levels and significantly resistant to neutrophil-mediated intracellular killing (< 0.01). The body weight of infected mice decreased significantly (< 0.0001). At the same time, the bacteria entered the blood from the lungs and spread to other organs. After the administration of eravacycline, the body weight of the mice began to increase 36 h later. The number of bacterial colonizing in the lungs was reduced (< 0.01), the infiltration of inflammatory cells was reduced, and the interstitial vascular dilatation and congestion were alleviated. Meanwhile, eravacycline significantly suppressed the serum levels of cytokines IL-6, IL-1&#x3b2;, and MCP-1 (< 0.05). Notably, eravacycline suppressed the mRNA expression of STAT1 and p-STAT1 activation in the lung tissue of mice in the treatment group. In conclusion, clinical isolates KP78, KP98, and KP100 caused severe lung injury after invading mouse lung tissues, and eravacycline attenuated the lung injury and inflammatory response induced by CR-hvKP invasion.