High Level Ceftazidime Avibactam Resistance in Carbapenem Resistant Pseudomonas
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a critical nosocomial pathogen with limited therapeutic options. Ceftazidime-avibactam (CZA) has been widely used as a last-line agent against CRPA; however, the rapid emergence of high-level CZA resistance severely compromises its clinical efficacy. This project is specifically designed to explore the genetic mechanisms underlying high-level CZA resistance in clinical CRPA isolates. By employing whole-genome sequencing (WGS) analyses, we aim to systematically identify resistance-associated mutations, including alterations in beta-lactamase genes (e.g., blaPDC, blaKPC), porin deficiency, and efflux pumps. Elucidating these mechanisms will not only deepen our understanding of bacterial adaptation to novel beta-lactam/beta-lactamase inhibitor combinations but also provide crucial evidence for optimizing antimicrobial stewardship and guiding personalized therapy against highly drug-resistant infections.