Novel Antimicrobials and the Antimicrobial Activity: New Advances

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (15 September 2025) | Viewed by 1785

Special Issue Editors


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Guest Editor
Laboratory of Clinical Microbiology and Virology, ASST Valle Olona, 21013 Gallarate, VA, Italy
Interests: antimicrobial resistance; resistance mechanisms; molecular microbiology; antimicrobial activity; carbapenem resistance
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Treatment of Infectious Diseases, ASST Fatebenefratelli Sacco University Hospital, Milano, Italy
Interests: therapeutic drug monitoring; pharmacokinetics; drug–drug interaction; antimicrobial therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antibiotic therapy is a key weapon in the eradication of infections throughout communities and hospital settings. The increasingly alarming worldwide phenomenon of antibiotic resistance complicates the drafting of antibiotic therapy plans. Gram-negative carbapenem-resistant (GN-CRE) bacteria, vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) cause the most deaths from infections worldwide. Phenotypic and genotypic knowledge of these multidrug-resistant microorganisms as well as their mechanisms of resistance are crucial. At the same time, the multidisciplinary development of new antibiotic molecules that can counteract antibiotic resistance is crucial in order to develop new treatment modalities for precision medicine that can overcome antibiotic resistance mechanisms. This Special Issue aims to provide up-to-date basic and clinical research, reviews and communications on new antibiotic molecules from microbiological, pharmacokinetic/pharmacodynamic and clinical points of view in order to strategically implement and stratify treatment plans for MDR infections.

Dr. Davide Carcione
Dr. Luigi Principe
Dr. Cattaneo Dario
Guest Editors

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Keywords

  • multi-drug resistance
  • infection
  • mechanism of action
  • resistance mechanisms
  • therapeutic medicine
  • diagnostic tools
  • antimicrobial stewardship
  • pharmacokinetics/pharmacodynamics

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Published Papers (1 paper)

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Review

25 pages, 1269 KB  
Review
Cefepime and New Cefepime/Beta-Lactamase Inhibitor Combination for the Treatment of Gram-Negative Bacteria: Chemical Structure and Mechanism of Action, Microbiological Target, Clinical Use and PK/PD Characteristics
by Davide Carcione, Gioconda Brigante, Antonella Carducci, Jari Intra, Simone Ambretti, Floriana Campanile, Gabriele Arcari, Nicasio Mancini, Dario Cattaneo, Floriana Gona, Mariagrazia Perilli, Alessandra Piccirilli, Nicholas Geremia, Verena Zerbato, Stefano Di Bella, Giovanna Maria Nicolò and Luigi Principe
Pharmaceuticals 2026, 19(2), 283; https://doi.org/10.3390/ph19020283 - 7 Feb 2026
Viewed by 986
Abstract
The global spread of multidrug-resistant (MDR) Gram-negative bacteria, particularly extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, presents a significant public health challenge by limiting effective antimicrobial treatment options. Cefepime, a fourth-generation cephalosporin with broad-spectrum activity, is [...] Read more.
The global spread of multidrug-resistant (MDR) Gram-negative bacteria, particularly extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, presents a significant public health challenge by limiting effective antimicrobial treatment options. Cefepime, a fourth-generation cephalosporin with broad-spectrum activity, is increasingly compromised by β-lactamase production, efflux pumps, and porin loss. In response, novel cefepime-based β-lactam/β-lactamase inhibitor (BL/BLI) combinations have been developed to overcome these resistance mechanisms. This review examines preclinical and clinical studies on cefepime-based BL/BLI combinations, specifically cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, and cefepime/nacubactam, as found in the PubMed database. Key findings include the restoration of activity against class A ESBLs with cefepime/enmetazobactam, while cefepime/taniborbactam and cefepime/zidebactam show broader inhibition of serine β-lactamases and selected metallo-β-lactamases. Additionally, zidebactam and nacubactam target penicillin-binding protein 2, enhancing bactericidal potency. Preclinical and early-phase clinical trial data indicate potent in vitro activity and favorable pharmacokinetic/pharmacodynamic (PK/PD) profiles. Specifically, the combination of cefepime with enmetazobactam has demonstrated an optimal Cmax/MIC ratio of 8–10, supporting its efficacy in treating MDR Gram-negative infections. Phase III studies are ongoing to confirm efficacy in complicated infections. Cefepime-based BL/BLI combinations are emerging as promising carbapenem-sparing agents, offering broad-spectrum activity, dual mechanisms of action, and encouraging clinical outcomes. These findings support their inclusion in antimicrobial stewardship strategies aimed at mitigating resistance. Full article
(This article belongs to the Special Issue Novel Antimicrobials and the Antimicrobial Activity: New Advances)
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