ABSTRACT

Introduction

The emergence of carbapenemase resistant Gram-negative is designated as an ‘urgent’ priority of public health. Carbapenemase producing Klebsiella pneumoniae (CPKP) is linked with significant mortality. Conventionally used antibiotics (polymyxins, tigecycline, aminoglycosides, etc.) are associated with poor efficacy and toxicity profiles are quite worrisome.

Areas covered

This article reviews mechanism of resistance and evidence regarding novel treatments of infections caused by CPKP, focusing mainly on currently approved new therapies and implications on future therapeutic strategies. A review of novel β-lactam/β-lactamase inhibitors (BLI) recently approved and in clinical development as well as cefiderocol, eravacycline and apramycin are discussed.

Expert opinion

Newly approved and forthcoming antimicrobial agents are promising to combat infections caused by CPKP. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam are novel agents with favorable outcome and associated with improved mortality in KPC-producing K. pneumoniae infections. However, are inactive against metallo-β-lactamases (MBL). Novel BLI in later stage of development, i.e. aztreonam-avibactam, cefepime-zidebactam, cefepime-taniborbactam, and meropenem-nacubactam as well as cefiderocol are active in vitro against both KPC and MBL. Potential expectations of future therapeutic strategies are improved potency against CPKP, more tolerable safety profile, and capability of overcoming current resistance mechanism of multidrug-resistant K. pneumoniae.

中文翻译：

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产生碳青霉烯酶的肺炎克雷伯菌：对未来治疗策略的影响

摘要

介绍

耐碳青霉烯酶革兰氏阴性菌的出现被指定为公共卫生的“紧急”优先事项。产生碳青霉烯酶的肺炎克雷伯菌(CPKP) 与显着的死亡率有关。常规使用的抗生素（多粘菌素、替加环素、氨基糖苷类等）与疗效差有关，毒性特征相当令人担忧。

涵盖的领域

本文回顾了 CPKP 引起的感染的新疗法的耐药机制和证据，主要关注目前批准的新疗法和对未来治疗策略的影响。讨论了最近批准并处于临床开发中的新型 β-内酰胺/β-内酰胺酶抑制剂 (BLI) 以及头孢地洛、依拉环素和安普霉素的综述。

专家意见

新批准和即将上市的抗菌药物有望对抗由 CPKP 引起的感染。头孢他啶-阿维巴坦、美罗培南-vaborbactam 和亚胺培南-西司他丁-瑞巴坦是具有良好结果的新型药物，并与产生 KPC 的肺炎克雷伯菌感染的死亡率降低 相关。然而，对金属-β-内酰胺酶 (MBL) 无活性。处于开发后期的新型BLI，即氨曲南-阿维巴坦、头孢吡肟-齐地巴坦、头孢吡肟-坦尼硼巴坦、美罗培南-萘巴坦以及头孢地洛在 体外具有活性反对KPC和MBL。未来治疗策略的潜在期望是提高对 CPKP 的效力、更可耐受的安全性以及克服当前多重耐药肺炎克雷伯菌耐药机制的 能力。