The Collapse of Ceftazidime-Avibactam Against KPC-Producing Klebsiella pneumoniae: Emerging Resistance Mechanisms and Clinical Failure

Due to its resistance to last-line carbapenem antibiotics and its detrimental impact on treatment effectiveness, carbapenem-resistant Klebsiella pneumoniae (CRKP) presents an increasing worldwide concern. Overexpression of blaKPC and mutations in blaKPC-۲ or blaKPC-۳ are the primary causes of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) resistance to CAZ/AVI. We have a fantastic option for treating CRKP infections in the form of ceftazidime/avibactam (CAZ/AVI). Avibactam is a non-β-lactam β-lactamase inhibitor that protects ceftazidime from hydrolysis by AmpC, OXA-۴۸, Extended-spectrum β-lactamases (ESBLs), and Klebsiella pneumoniae carbapenemases (KPCs), but not metallo-β-lactamases (MBLs). Recent research has revealed that the primary resistance systems of CRKP against CZA include changes in the KPC enzyme, OmpK۳۵/۳۶, porin LamB, and penicillin-binding proteins PBP۲/۳ of the outer membrane, or the alteration of blaKPC expression. Although there is little large-scale epidemiological data available, KPC-producing K. pneumoniae has recently developed ceftazidime-avibactam resistance. Present data shows that bloodstream infections have a resistance rate of around ۱۰.۵% and a ۲۲% in-hospital fatality rate. A number of risk factors for CAZ-AVI resistance acquisition have been hypothesized, including identified pneumonia and the use of renal replacement therapies as primary drivers of CAZ-AVI resistance development and emphasizing the significance of sub-optimal drug exposure as a catalyst for resistance emergence. This study underscores the significance of proactive surveillance to track the rise of CZA resistance, emphasizing the necessity for continuous research to devise efficacious methods to combat antimicrobial resistance.

کلیدواژه ها:

Ceftazidime-avibactam resistance ، KPC producing Klebsiella pneumoniae ، Carbapenem-resistant Klebsiella pneumoniae (CRKP) ، blaKPC mutation ، Antimicrobial resistance mechanisms