ABSTRACT

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 β-lactam/β-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 β-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.

摘要

简介： 多重耐药性肺炎克雷伯菌是目前细菌耐药性中最紧迫的新兴问题之一。由于缺乏可用的治疗选择，肺炎克雷伯菌感染的治疗通常存在问题，并在发病率、死亡率和医疗保健相关成本方面产生相关影响。在头孢他啶-阿维巴坦（已获批准的新型β-内酰胺/β-内酰胺酶抑制剂组合之一）上市后不久，就有关于头孢他啶-阿维巴坦耐药菌株在治疗期间产生耐药性的报告发表。作为医院相关病原体，肺炎克雷伯菌持续暴露于多种抗生素导致恒定的选择压力，这反过来又导致额外的正选择突变。

涵盖的领域：本文作者介绍了肺炎克雷伯菌对不同抗菌药物的耐药机制，包括头孢他啶-阿维巴坦的最新数据。

专家意见：肺炎克雷伯菌是一种医院内病原体，通常与医院爆发有关，对主要的 β-内酰胺类抗生素和多种其他抗生素类具有抗菌素耐药性的倾向。随着耐药性的发展并了解所涉及的机制，我们可以通过谨慎管理和合理使用来提高当前抗菌药物的功效，以保持其潜在效用。关于抗生素耐药机制的知识应用于指导可能不受或可以规避耐药机制的新型治疗剂的设计。