Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms

Sena Nur Başaran; Lütfiye Öksüz

doi:10.1007/s00203-025-04298-z

Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms

Arch Microbiol. 2025 Apr 2;207(5):110. doi: 10.1007/s00203-025-04298-z.

Authors

Sena Nur Başaran^{1

2

3}, Lütfiye Öksüz⁴

Affiliations

¹ Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. snbasaran@agri.edu.tr.
² Istanbul University, Institute of Graduate Studies in Health Sciences, Istanbul, Turkey. snbasaran@agri.edu.tr.
³ Department of Medical Microbiology, Faculty of Medicine, Agri Ibrahim Cecen University, Agri, Turkey. snbasaran@agri.edu.tr.
⁴ Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

PMID: 40172627
DOI: 10.1007/s00203-025-04298-z

Abstract

Antimicrobial resistance stands as one of the most urgent global health concerns in the twenty-first century, with projections suggesting that deaths related to drug-resistant infections could escalate to 10 million by 2050 if proactive measures are not implemented. In intensive care settings, managing infections caused by multidrug-resistant (MDR) Gram-negative bacteria is particularly challenging, posing a significant threat to public health and contributing substantially to both morbidity and mortality. There are numerous studies on the antibiotics responsible for resistance in Gram-negative bacteria, but comprehensive research on resistance mechanisms against new antibiotics is rare. Considering the possibility that antibiotics may no longer be effective in combating diseases, it is crucial to comprehend the problem of emerging resistance to newly developed antibiotics and to implement preventive measures to curb the spread of resistance. Mutations in porins and efflux pumps play a crucial role in antibiotic resistance by altering drug permeability and active efflux. Porin modifications reduce the influx of antibiotics, whereas overexpression of efflux pumps, particularly those in the resistance-nodulation-cell division (RND) family, actively expels antibiotics from bacterial cells, significantly lowering intracellular drug concentrations and leading to treatment failure.This review examines the mechanisms of action, resistance profiles, and pharmacokinetic/pharmacodynamic characteristics of newly developed antibiotics designed to combat infections caused by MDR and carbapenem-resistant Gram-negative pathogens. The antibiotics discussed include ceftazidime-avibactam, imipenem-relebactam, ceftolozane-tazobactam, meropenem-vaborbactam, aztreonam-avibactam, delafloxacin, temocillin, plazomicin, cefiderocol, and eravacycline.

Keywords: Antimicrobial resistance; Carbapenem resistance; Multidrug-resistant (MDR) Gram-negative bacteria; Newly developed antibiotics.

Publication types

Review

MeSH terms

Anti-Bacterial Agents* / pharmacology
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
Carbapenems* / pharmacology
Drug Resistance, Multiple, Bacterial* / drug effects
Gram-Negative Bacteria* / drug effects
Gram-Negative Bacteria* / genetics
Gram-Negative Bacteria* / metabolism
Gram-Negative Bacterial Infections* / drug therapy
Gram-Negative Bacterial Infections* / microbiology
Humans

Substances

Anti-Bacterial Agents
Carbapenems
Bacterial Proteins