Defining the Role of Novel β-Lactam Agents That Target Carbapenem-Resistant Gram-Negative Organisms

Abstract

With the current carbapenem-resistant organism crisis, conventional approaches to optimizing pharmacokinetic-pharmacodynamic parameters are frequently inadequate, and traditional salvage agents (eg, colistin, tigecycline, etc) confer high toxicity and/or have low efficacy. However, several β-lactam agents with activity against carbapenem-resistant organisms were approved recently by the US Food and Drug Administration, and more are anticipated to be approved in the near future. The primary goal of this review is to assist infectious disease practitioners with preferentially selecting 1 agent over another when treating patients infected with a carbapenem-resistant organism. However, resistance to some of these antibiotics has already developed. Antibiotic stewardship programs can ensure that they are reserved for situations in which other options are lacking and are paramount for the survival of these agents.

Keywords: aztreonam-avibactam; cefiderocol; ceftazidime-avibactam; ceftolozane-tazobactam; imipenem-cilastatin–relebactam; meropenem-vaborbactam.

Figure 1.

Select antibiotics with activity against carbapenem-resistant organisms. Green, susceptibility anticipated to be >80%; yellow, susceptibility anticipated to be 30% to 80%; red, intrinsic resistance or susceptibility anticipated to be <30%. ¹, US Food and Drug Administration–approved agent; ², synthetic tetracycline derivative; ³, imipenem-cilastatin–relebactam; ⁴, synthetic aminoglycoside; ⁵, polymyxin class. Abbreviations: KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase.