Diverse evolutionary trajectories of Klebsiella pneumoniae carbapenemase: unraveling the impact of amino acid substitutions on β-lactam susceptibility and the role of avibactam in driving resistance

Abstract

The rapid evolution of KPC carbapenemases, including resistance to ceftazidime-avibactam, threatens the effectiveness of last-resort antibiotics against Klebsiella pneumoniae infections, necessitating understanding of of the underlying selection pressures. This study investigates the evolutionary mechanisms driving KPC diversification and resistance to ceftazidime-avibactam, providing crucial information for developing effective strategies to combat carbapenem-resistant Klebsiella pneumoniae (CRKP) infections and preserve antibiotic efficacy.