Innovative and Nonconventional Antimicrobial Strategies Against Multi-Resistant Bacteria

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Novel Antimicrobial Agents".

Deadline for manuscript submissions: 15 September 2024 | Viewed by 1613

Special Issue Editor

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Guest Editor
Associate Professor, Department Veterinary Medicine, Università degli Studi di Perugia, 06126 Perugia, Italy
Interests: antimicrobial resistance in zoonosic bacteria; phenotipic and genotipic characterization of antimicrobial-resistance mechanisms, including bacterial biofilm-forming ability; phenotypic and genetic mechanisms underlying the efflux-mediated resistance in zoonosic bacteria

Special Issue Information

Dear Colleagues,

The phenomenon of antibiotic resistance is one of the most significant public health problems to date. The ever-increasing emergence of multi-resistant microbial species in both animals and humans, as well as the limited efficacy of conventional antimicrobial therapies, means it is necessary to study new therapeutic strategies against multi-resistant bacteria. Thereby, this Special Issue is dedicated to the discovery of novel promising candidates for the future development of innovative, nonconventional antimicrobial agents against pathogenic bacteria of zoonotic and veterinary clinical interest. Moreover, this Special Issue promotes the study of natural compounds with a green and sustainable impact as antimicrobial agents and the investigation of their mechanisms of action.

Acknowledgment: Ms. Valeria Toppi will be participating in this Special Issue as a specialist advisor. We would like to thank her for her contributions to this Special Issue.

Dr. Patrizia Casagrande-Proietti
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


  • antibiotic resistance
  • multi-resistant bacteria
  • innovative agents
  • natural compound
  • green impact
  • veterinary medicine

Published Papers (1 paper)

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18 pages, 8895 KiB  
Combination Therapy with Ciprofloxacin and Pentamidine against Multidrug-Resistant Pseudomonas aeruginosa: Assessment of In Vitro and In Vivo Efficacy and the Role of Resistance–Nodulation–Division (RND) Efflux Pumps
by Megan Fletcher, Alex McCormack, Benjamin J. Parcell and Peter J. Coote
Antibiotics 2023, 12(8), 1236; - 26 Jul 2023
Cited by 2 | Viewed by 1368
The aim of this work was to (i) evaluate the efficacy of a combination treatment of pentamidine with ciprofloxacin against Galleria mellonella larvae infected with an MDR strain of P. aeruginosa and (ii) determine if pentamidine acts as an efflux-pump inhibitor. Resistant clinical [...] Read more.
The aim of this work was to (i) evaluate the efficacy of a combination treatment of pentamidine with ciprofloxacin against Galleria mellonella larvae infected with an MDR strain of P. aeruginosa and (ii) determine if pentamidine acts as an efflux-pump inhibitor. Resistant clinical isolates, mutant strains overexpressing one of three RND efflux pumps (MexAB-OprM, MexCD-OprJ, and MexEF-OprN), and a strain with the same three pumps deleted were used. MIC assays confirmed that the clinical isolates and the mutants overexpressing efflux pumps were resistant to ciprofloxacin and pentamidine. The deletion of the three efflux pumps induced sensitivity to both compounds. Exposure to pentamidine and ciprofloxacin in combination resulted in the synergistic inhibition of all resistant strains in vitro, but no synergy was observed versus the efflux-pump deletion strain. The treatment of infected G. mellonella larvae with the combination of pentamidine and ciprofloxacin resulted in enhanced efficacy compared with the monotherapies and significantly reduced the number of proliferating bacteria. Our measurement of efflux activity from cells revealed that pentamidine had a specific inhibitory effect on the MexCD-OprJ and MexEF-OprN efflux pumps. However, the efflux activity and membrane permeability assays revealed that pentamidine also disrupted the membrane of all cells. In conclusion, pentamidine does possess some efflux-pump inhibitory activity, in addition to a more general disruptive effect on membrane integrity that accounts for its ability to potentiate ciprofloxacin activity. Notably, the enhanced efficacy of combination therapy with pentamidine and ciprofloxacin versus MDR P. aeruginosa strains in vivo merits further investigation into its potential to treat infections via this pathogen in patients. Full article
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