Multidrug-resistant Klebsiella pneumoniae: mechanisms of resistance including updated data for novel β-lactam-β-lactamase inhibitor combinations

Introduction: Multi-drug-resistant Klebsiella pneumoniae is currently one of the most pressing emerging issues in bacterial resistance. Treatment of K.pneumoniae infections is often problematic due to the lack of available therapeutic options, with a relevant impact in terms of morbidity, mortality and healthcare-associated costs. Soon after the launch of Ceftazidime-Avibactam, one of the approved new beta-lactam/beta-lactamase inhibitor combinations, reports of ceftazidime-avibactam-resistant strains developing resistance during treatment were published. Being a hospital-associated pathogen, K.pneumoniae is continuously exposed to multiple antibiotics resulting in constant selective pressure, which in turn leads to additional mutations that are positively selected. Areas covered: Herein the authors present the K.pneumoniae mechanisms of resistance to different antimicrobials, including updated data for ceftazidime-avibactam. Expert opinion: K.pneumoniae is a nosocomial pathogen commonly implicated in hospital outbreaks with a propensity for antimicrobial resistance toward mainstay beta-lactam antibiotics and multiple other antibiotic classes. Following the development of drug resistance and understanding the mechanisms involved, we can improve the efficacy of current antimicrobials, by applying careful stewardship and rational use to preserve their potential utility. The knowledge on antibiotic resistance mechanisms should be used to inform the design of novel therapeutic agents that might not be subject to, or can circumvent, mechanisms of resistance.