High genetic barrier of imipenem/relebactam for in vitro resistance development in Pseudomonas aeruginosa XDR high-risk clones.

The objective of the present work was to comparatively analyze the dynamics and mechanisms of in vitro development of resistance to ceftolozane/tazobactam and imipenem/relebactam, under step-wise exposure to growing drug concentrations using XDR clinical strains belonging to major high-risk clones ST175, ST111 and ST235. Moreover the dynamics and mechanisms of imipenem/relebactam resistance development was also investigated in isogenic strains that had developed ceftolozane/tazobactam resistance during therapy.