ESKAPE and MDRO Pathogens: Infections and Antimicrobial Treatment

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 463

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Guest Editor
Infectious Diseases Clinic, Department of Medicine, Santa Maria della Misericordia Hospital, University of Perugia, 06132 Perugia, Italy
Interests: antimicrobial resistance; difficult-to-treat infections; endocarditis; antimicrobial stewardship; infection of the central nervous system
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Special Issue Information

Dear Colleagues,

ESKAPE and MDRO pathogens are still a growing concern, with an estimated enormous mortality in next decades. New antibiotics are going to be available and others are progressing in the pipeline. The appropriate use of these antibiotics should be a cornerstone of our daily activities in order to preserve them and to reduce the clinical and economical impact of antibiotic resistance.

Several questions are still open in the field of antibiotic treatment: role of combination therapy, treatment duration, antibiotics administration, and place in therapy of BLIC and new antibiotics, among many others.

This Special Issue will contribute to answering these and other arising questions about the treatment of ESKAPE and other MDRO infections.

Dr. Carlo Pallotto
Guest Editor

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Keywords

  • ESKAPE
  • MDRO
  • Escherichia coli
  • Staphylococcus aureus
  • Klebsiella pneumoniae
  • Acinetobacter baumannii
  • Pseudomonas aeruginosa
  • Enterococcus faecalis
  • Enterococcus faecium
  • Stenotrophomonas maltophilia
  • Enterobacter cloacae
  • antimicrobial stewardship

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Published Papers (1 paper)

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Research

14 pages, 1820 KiB  
Article
Broad-Spectrum Gramicidin S Derivatives with Potent Activity Against Multidrug-Resistant Gram-Negative ESKAPE Pathogens
by John T. Kalyvas, Yifei Wang, Ornella Romeo, John R. Horsley and Andrew D. Abell
Antibiotics 2025, 14(5), 423; https://doi.org/10.3390/antibiotics14050423 - 22 Apr 2025
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Abstract
Background/Objectives: Multidrug-resistant Gram-negative ESKAPE pathogens, including E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii, pose a significant global health threat. Gramicidin S, a potent cyclic antimicrobial peptide, is largely ineffective against these bacteria, and its high haemolytic toxicity [...] Read more.
Background/Objectives: Multidrug-resistant Gram-negative ESKAPE pathogens, including E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii, pose a significant global health threat. Gramicidin S, a potent cyclic antimicrobial peptide, is largely ineffective against these bacteria, and its high haemolytic toxicity limits its clinical usage. This study reports on several novel gramicidin S analogues with improved efficacy and safety profiles against multidrug-resistant Gram-negative bacteria. Methods: A total of 19 gramicidin S derivatives were synthesised using Fmoc-based solid-phase peptide synthesis with targeted substitutions to enhance cationicity and modulate hydrophobicity. Minimum inhibitory concentrations (MICs) were determined against standard Gram-negative and Gram-positive strains. Haemolytic toxicity and in vitro nephrotoxicity were evaluated using human red blood cells and HEK-293 cells, respectively. All peptides were characterised by RP-HPLC and HRMS. Results: The selective incorporation of DArg and Trp significantly enhanced activity against Gram-negative bacteria while reducing cytotoxicity. Peptide 8 improved the therapeutic index (TI) against E. coli by 10-fold (MIC: 8 µg/mL; TI: 4.10) compared to gramicidin S (MIC: 32 µg/mL; TI: 0.38). Peptide 9 exhibited an 8-fold potency increase against K. pneumoniae and a 25-fold TI improvement. Peptide 19 enhanced activity against P. aeruginosa 8-fold over gramicidin S, while peptide 7 showed a 27-fold TI enhancement. All active peptides retained broad-spectrum activity against S. aureus, including MRSA. Conclusions: The findings highlight the critical role of balancing hydrophobicity and cationicity to overcome species-specific resistance mechanisms. Our gramicidin S analogues demonstrate potent broad-spectrum activity with significantly reduced toxicity compared to the parent peptide, providing a robust platform for the development of new antibiotics against ESKAPE bacterial pathogens. Full article
(This article belongs to the Special Issue ESKAPE and MDRO Pathogens: Infections and Antimicrobial Treatment)
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