Cephalosporin resistance, tolerance, and approaches to improve their activities.

Autor: Araten AH; Department of Molecular Biology, Princeton University, Princeton, NJ, USA., Brooks RS; Department of English, Princeton University, Princeton, NJ, USA., Choi SDW; Department of Molecular Biology, Princeton University, Princeton, NJ, USA., Esguerra LL; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA., Savchyn D; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA., Wu EJ; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA., Leon G; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA., Sniezek KJ; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA., Brynildsen MP; Department of Molecular Biology, Princeton University, Princeton, NJ, USA. mbrynild@princeton.edu.; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA. mbrynild@princeton.edu.
Jazyk: angličtina
Zdroj: The Journal of antibiotics [J Antibiot (Tokyo)] 2024 Mar; Vol. 77 (3), pp. 135-146. Date of Electronic Publication: 2023 Dec 19.
DOI: 10.1038/s41429-023-00687-y
Abstrakt: Cephalosporins comprise a β-lactam antibiotic class whose first members were discovered in 1945 from the fungus Cephalosporium acremonium. Their clinical use for Gram-negative bacterial infections is widespread due to their ability to traverse outer membranes through porins to gain access to the periplasm and disrupt peptidoglycan synthesis. More recent members of the cephalosporin class are administered as last resort treatments for complicated urinary tract infections, MRSA, and other multi-drug resistant pathogens, such as Neisseria gonorrhoeae. Unfortunately, there has been a global increase in cephalosporin-resistant strains, heteroresistance to this drug class has been a topic of increasing concern, and tolerance and persistence are recognized as potential causes of cephalosporin treatment failure. In this review, we summarize the cephalosporin antibiotic class from discovery to their mechanisms of action, and discuss the causes of cephalosporin treatment failure, which include resistance, tolerance, and phenomena when those qualities are exhibited by only small subpopulations of bacterial cultures (heteroresistance and persistence). Further, we discuss how recent efforts with cephalosporin conjugates and combination treatments aim to reinvigorate this antibiotic class.
(© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)
Databáze: MEDLINE
Externí odkaz: