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New β-Lactam-β-Lactamase Inhibitor Combinations

Yahav D, Giske CG, Grāmatniece A, Abodakpi H, Tam VH, Leibovici L

Clinical microbiology reviews, 2020

398 citations

Abstract

The limited armamentarium against drug-resistant Gram-negative bacilli has led to the development of several novel β-lactam-β-lactamase inhibitor combinations (BLBLIs). In this review, we summarize their spectrum of in vitro activities, mechanisms of resistance, and pharmacokinetic-pharmacodynamic (PK-PD) characteristics. A summary of available clinical data is provided per drug. Four approved BLBLIs are discussed in detail. All are options for treating multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa Ceftazidime-avibactam is a potential drug for treating Enterobacterales producing extended-spectrum β-lactamase (ESBL), Klebsiella pneumoniae carbapenemase (KPC), AmpC, and some class D β-lactamases (OXA-48) in addition to carbapenem-resistant Pseudomonas aeruginosa Ceftolozane-tazobactam is a treatment option mainly for carbapenem-resistant P. aeruginosa (non-carbapenemase producing), with some activity against ESBL-producing Enterobacterales Meropenem-vaborbactam has emerged as treatment option for Enterobacterales producing ESBL, KPC, or AmpC, with similar activity as meropenem against P. aeruginosa Imipenem-relebactam has documented activity against Enterobacterales producing ESBL, KPC, and AmpC, with the combination having some additional activity against P. aeruginosa relative to imipenem. None of these drugs present in vitro activity against Enterobacterales or P. aeruginosa producing metallo-β-lactamase (MBL) or against carbapenemase-producing…

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