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
. 2023 Apr 16;12(4):761.
doi: 10.3390/antibiotics12040761.

Novel Antimicrobial Agents for Gram-Negative Pathogens

Affiliations
Review

Novel Antimicrobial Agents for Gram-Negative Pathogens

Marios Karvouniaris et al. Antibiotics (Basel). .

Abstract

Gram-negative bacterial resistance to antimicrobials has had an exponential increase at a global level during the last decades and represent an everyday challenge, especially for the hospital practice of our era. Concerted efforts from the researchers and the industry have recently provided several novel promising antimicrobials, resilient to various bacterial resistance mechanisms. There are new antimicrobials that became commercially available during the last five years, namely, cefiderocol, imipenem-cilastatin-relebactam, eravacycline, omadacycline, and plazomicin. Furthermore, other agents are in advanced development, having reached phase 3 clinical trials, namely, aztreonam-avibactam, cefepime-enmetazobactam, cefepime-taniborbactam, cefepime-zidebactam, sulopenem, tebipenem, and benapenem. In this present review, we critically discuss the characteristics of the above-mentioned antimicrobials, their pharmacokinetic/pharmacodynamic properties and the current clinical data.

Keywords: Acinetobacter baumannii; Enterobacterales; Gram-negative; Pseudomonas aeruginosa; beta-lactamase; carbapenemases; pharmacodynamics; pharmacokinetics.

PubMed Disclaimer

Conflict of interest statement

D.K. declares honoraria from MSD for moderation in satellite symposium. The other authors declare no conflict of interest related to the current manuscript.

References

    1. Magiorakos A.-P., Srinivasan A., Carey R.B., Carmeli Y., Falagas M.E., Giske C.G., Harbarth S., Hindler J.F., Kahlmeter G., Olsson-Liljequist B., et al. Multidrug-Resistant, Extensively Drug-Resistant and Pandrug-Resistant Bacteria: An International Expert Proposal for Interim Standard Definitions for Acquired Resistance. Clin. Microbiol. Infect. 2012;18:268–281. doi: 10.1111/j.1469-0691.2011.03570.x. - DOI - PubMed
    1. Murray C.J., Ikuta K.S., Sharara F., Swetschinski L., Robles Aguilar G., Gray A., Han C., Bisignano C., Rao P., Wool E., et al. Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. Lancet. 2022;399:629–655. doi: 10.1016/S0140-6736(21)02724-0. - DOI - PMC - PubMed
    1. Tooke C.L., Hinchliffe P., Bragginton E.C., Colenso C.K., Hirvonen V.H.A., Takebayashi Y., Spencer J. β-Lactamases and β-Lactamase Inhibitors in the 21st Century. J. Mol. Biol. 2019;431:3472–3500. doi: 10.1016/j.jmb.2019.04.002. - DOI - PMC - PubMed
    1. He Y., Lei J., Pan X., Huang X., Zhao Y. The Hydrolytic Water Molecule of Class A β-Lactamase Relies on the Acyl-Enzyme Intermediate ES* for Proper Coordination and Catalysis. Sci. Rep. 2020;10:10205. doi: 10.1038/s41598-020-66431-w. - DOI - PMC - PubMed
    1. Hobson C.A., Cointe A., Jacquier H., Choudhury A., Magnan M., Courroux C., Tenaillon O., Bonacorsi S., Birgy A. Cross-Resistance to Cefiderocol and Ceftazidime–Avibactam in KPC β-Lactamase Mutants and the Inoculum Effect. Clin. Microbiol. Infect. 2021;27:1172.e7–1172.e10. doi: 10.1016/j.cmi.2021.04.016. - DOI - PubMed

LinkOut - more resources