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

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Başaran S. N., Öksüz L.

Archives of microbiology, cilt.207, sa.5, ss.110, 2025 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 207 Sayı: 5
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1007/s00203-025-04298-z
  • Dergi Adı: Archives of microbiology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, Veterinary Science Database
  • Sayfa Sayıları: ss.110
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • İstanbul Üniversitesi Adresli: Evet

Özet

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, meropenemvaborbactam,

aztreonam-avibactam, delafloxacin, temocillin, plazomicin, cefiderocol, and eravacycline.