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Review

New β-Lactam–β-Lactamase Inhibitor Combinations

Dafna Yahav, Christian G. Giske, Alise Grāmatniece, Henrietta Abodakpi, Vincent H. Tam, Leonard Leibovici
Dafna Yahav
aInfectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
bSackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel
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Christian G. Giske
cClinical Microbiology, Department of Laboratory Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
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Alise Grāmatniece
cClinical Microbiology, Department of Laboratory Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
dPauls Stradins University Hospital, University of Latvia, Riga, Latvia
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Henrietta Abodakpi
eDepartment of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
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Vincent H. Tam
eDepartment of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
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Leonard Leibovici
bSackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel
fMedicine E, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
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DOI: 10.1128/CMR.00115-20
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SUMMARY

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).

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New β-Lactam–β-Lactamase Inhibitor Combinations
Dafna Yahav, Christian G. Giske, Alise Grāmatniece, Henrietta Abodakpi, Vincent H. Tam, Leonard Leibovici
Clinical Microbiology Reviews Nov 2020, 34 (1) e00115-20; DOI: 10.1128/CMR.00115-20

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New β-Lactam–β-Lactamase Inhibitor Combinations
Dafna Yahav, Christian G. Giske, Alise Grāmatniece, Henrietta Abodakpi, Vincent H. Tam, Leonard Leibovici
Clinical Microbiology Reviews Nov 2020, 34 (1) e00115-20; DOI: 10.1128/CMR.00115-20
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  • Top
  • Article
    • SUMMARY
    • INTRODUCTION
    • CEFTAZIDIME-AVIBACTAM
    • CEFTOLOZANE-TAZOBACTAM
    • MEROPENEM-VABORBACTAM
    • IMIPENEM-RELEBACTAM
    • BLBLIs IN DEVELOPMENT PROCESS
    • INSIGHTS FROM THE EXPERTS
    • ACKNOWLEDGMENTS
    • REFERENCES
    • Author Bios
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

β-lactam–β-lactamase inhibitor combinations
ceftazidime-avibactam
ceftolozane-tazobactam
meropenem-vaborbactam
imipenem-relebactam

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