Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 May 21;14(5):528.
doi: 10.3390/antibiotics14050528.

Breaking Through Resistance: A Comparative Review of New Beta-Lactamase Inhibitors (Avibactam, Vaborbactam, Relebactam) Against Multidrug-Resistant Superbugs

Ilias Karaiskos  1 , Irene Galani  2 , George L Daikos  3 , Helen Giamarellou  1
Affiliations
Review

Breaking Through Resistance: A Comparative Review of New Beta-Lactamase Inhibitors (Avibactam, Vaborbactam, Relebactam) Against Multidrug-Resistant Superbugs

Ilias Karaiskos et al. Antibiotics (Basel). .

Abstract

The introduction of new β-lactam-β-lactamase inhibitors (BLBLIs), such as ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/cilastatin/relebactam, expands our therapeutic options against carbapenem-resistant Gram-negative bacteria, including those pathogens for which therapeutic options are limited. These new combinations are active against ESBL-, AmpC-, and KPC-producing Enterobacterales, with the exception of ceftazidime/avibactam, which is active in vitro against OXA-48. However, one drawback that must be taken seriously by the clinician is that they are ineffective against metallo-β-lactamases as well as Acinetobacter baumannii. The recent introduction of aztreonam/avibactam marks a significant advancement in our therapeutic armamentarium against metallo-β-lactamase-producing pathogens. The question to be answered is whether there is a preferred, newer BLBLI combination for the treatment of KPC-producing Enterobacterales infections. This review provides a thorough analysis of the similarities and differences between these new combinations to identify the most effective treatment options. The present review aims to provide clinicians with a detailed understanding of each BLBLI treatment option to guide the optimal use of these new agents for the effective treatment of difficult infections caused by carbapenemase-producing Enterobacterales infections. This review is based on literature retrieved from PubMed, Scopus, Web of Science, and the Cochrane Library.

Keywords: aztreonam/avibactam; ceftazidime/avibactam; ceftazidime/avibactam plus aztreonam; comparative efficacy; imipenem/cilastatin/relebactam; meropenem/vaborbactam; rapid detection; resistance mechanism; treatment failure; β-lactam–β-lactamase inhibitors.

PubMed Disclaimer

Conflict of interest statement

I.K. has received speaker honoraria from Pfizer, Menarini, and bioMérieux. G.L.D. is an advisor and consultant for, and has received honoraria from, Pfizer, and has received honoraria from MSD and Viatris. H.G. has received speaker honoraria from Pfizer and MSD. All other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The most common mechanisms of resistance to novel BLBLIs from Gram-negative bacteria [63,64,70,72,73,74,75,76,82,83].
See this image and copyright information in PMC

References

    1. Jean S.S., Harnod D., Hsueh P.R. Global Threat of Carbapenem-Resistant Gram-Negative Bacteria. Front. Cell. Infect. Microbiol. 2022;12:823684. doi: 10.3389/fcimb.2022.823684. - DOI - PMC - PubMed
    1. ECDC Antimicrobial Resistance in the EU/EEA (EARS-Net) Annual Epidemiological Report for 2023. [(accessed on 30 April 2025)]. Available online: https://www.ecdc.europa.eu/sites/default/files/documents/antimicrobial-r....
    1. Karaiskos I., Lagou S., Pontikis K., Rapti V., Poulakou G. The “Old” and the “New” Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How. Front. Public Health. 2019;7:151. doi: 10.3389/fpubh.2019.00151. - DOI - PMC - PubMed
    1. Karaiskos I., Galani I., Souli M., Giamarellou H. Novel β-lactam-β-lactamase inhibitor combinations: Expectations for the treatment of carbapenem-resistant Gram-negative pathogens. Expert. Opin. Drug Metab. Toxicol. 2019;15:133–149. doi: 10.1080/17425255.2019.1563071. - DOI - PubMed
    1. Tumbarello M., Raffaelli F., Giannella M., Mantengoli E., Mularoni A., Venditti M., De Rosa F.G., Sarmati L., Bassetti M., Brindicci G., et al. Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study. Clin. Infect. Dis. 2021;73:1664–1676. doi: 10.1093/cid/ciab176. - DOI - PubMed

LinkOut - more resources