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New β-Lactam-β-Lactamase Inhibitor Combinations.

  • Yahav, Dafna1, 2
  • Giske, Christian G3
  • Grāmatniece, Alise3, 4
  • Abodakpi, Henrietta5
  • Tam, Vincent H5
  • Leibovici, Leonard2, 6
  • 1 Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel [email protected] , (Israel)
  • 2 Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel. , (Israel)
  • 3 Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden. , (Sweden)
  • 4 Pauls Stradins University Hospital, University of Latvia, Riga, Latvia. , (Latvia)
  • 5 Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA.
  • 6 Medicine E, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel. , (Israel)
Published Article
Clinical Microbiology Reviews
American Society for Microbiology
Publication Date
Dec 16, 2020
DOI: 10.1128/CMR.00115-20
PMID: 33177185


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 Acinetobacter baumannii Clinical data regarding the use of these drugs to treat MDR bacteria are limited and rely mostly on nonrandomized studies. An overview on eight BLBLIs in development is also provided. These drugs provide various levels of in vitro coverage of carbapenem-resistant Enterobacterales, with several drugs presenting in vitro activity against MBLs (cefepime-zidebactam, aztreonam-avibactam, meropenem-nacubactam, and cefepime-taniborbactam). Among these drugs, some also present in vitro activity against carbapenem-resistant P. aeruginosa (cefepime-zidebactam and cefepime-taniborbactam) and A. baumannii (cefepime-zidebactam and sulbactam-durlobactam). Copyright © 2020 American Society for Microbiology.

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