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Novel Antimicrobials, Drug Delivery Systems and Antivirulence Targets in the Pipeline—From Bench to Bedside

Authors :
Oana Săndulescu
Ioana Viziteu
Anca Streinu-Cercel
Victor Daniel Miron
Liliana Lucia Preoțescu
Narcis Chirca
Simona Elena Albu
Mihai Craiu
Adrian Streinu-Cercel
Source :
Applied Sciences. 12:11615
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

In a fast-paced medical reality, biosciences and bioengineering have become essential components in medical research and development. The aim of this paper is to characterize the recent progresses made in fighting antimicrobial resistance, particularly in relation to WHO’s priority pathogens, by providing an in-depth review of novel antimicrobials, drug delivery systems for targeted antimicrobial action and novel antivirulence targets. We systematically searched the ClinicalTrials.gov database to identify clinical trials targeting WHO’s priority 1 (critical) pathogens: carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant ESBL-producing Enterobacteriaceae. We identified a limited number of clinical trials, specifically for: one novel betalactamase inhibitor for Acinetobacter spp., one anti-virulence human monoclonal antibody for Pseudomonas spp. and no novel antimicrobials for carbapenem-resistant Enterobacteriaceae. We also performed a review of field literature to exemplify the main applications of drug delivery systems in infectious diseases, particularly in achieving targeted antibiotic distribution, in enhancing local activity with reduced off-target effects, triggered antibiotic release and triggered antibacterial photodynamic therapy. We conclude by presenting novel targets for antivirulence therapeutics that act by disrupting quorum sensing, inhibiting bacterial adherence and biofilm formation, silencing virulence traits and neutralizing bacterial toxins. Furthermore, the main principles of rational antimicrobial use are highlighted, in an effort to describe potential areas for targeted intervention, from diagnostic stewardship to antimicrobial stewardship.

Details

ISSN :
20763417
Volume :
12
Database :
OpenAIRE
Journal :
Applied Sciences
Accession number :
edsair.doi...........7b65dbd7a8471d79f19d38813a789014
Full Text :
https://doi.org/10.3390/app122211615