Expert opinion on antimicrobial therapies: is there enough scientific evidence to state that targeted therapies outperform non-targeted ones?

ABSTRACT

Introduction

Different active and passive strategies have been developed to fight against pathogenic bacteria. Those actions are undertaken to reduce the bacterial burden while minimizing the possibilities to develop not only antimicrobial resistance but also antimicrobial side-effects such as allergic or hypersensitivity reactions.

Areas covered

We have reviewed preclinical results that evidence that targeted antimicrobial therapies outperform non-targeted ones. Active selective targeting against pathogenic bacteria has been achieved through the functionalization of antimicrobials, either alone or encapsulated within micro- or nanocarriers, with various recognition moieties. These moieties include peptides, aptamers, antibodies, carbohydrates, extracellular vesicles, cell membranes, infective agents, and other affinity ligands with specific bacterial tropism. Those selective ligands increase retention and enhance effectiveness reducing the side-effects and the required dose to exert the antimicrobial action at the site of infection.

Expert opinion

When using targeted antimicrobial therapies not only reduced side-effects are observed, but also, compared to the administration of equivalent doses of the non-targeted drugs, a superior efficacy has been demonstrated against planktonic, sessile, and intracellular pathogenic bacterial persisters. The translation of those targeted therapies to subsequent phases of clinical development still requires the demonstration of a reduction in the probabilities for the pathogen to develop resistance when using targeted approaches.

KEYWORDS:

• Active targeting
• antibiotic-mediated targeting
• antibodies
• antimicrobial resistance
• antimicrobial therapy
• aptamers
• bacteriophages
• targeted nanoparticles

Article highlights

• Preclinical reports describing the bactericidal ability of antimicrobials functionalized with homing molecules having specific tropism as well as with different selective recognition ligands are reviewed.

• Antimicrobials conjugated with peptides, aptamers, antibodies, carbohydrates, extracellular vesicles, cell membranes, infective agents, and other affinity ligands outperform non-targeted approaches.

• A compilation of preclinical efficacy studies on antimicrobials targeted with selective targeting moieties is here reported.

• Targeted antimicrobials demonstrate therapeutic benefits and reduced off-target effects over the administration of equivalent doses of the non-targeted ones.

• Selective ligands increase antimicrobial retention and enhance their effectiveness by reducing the required dose to exert the antimicrobial action against planktonic, sessile and intracellular pathogens.

• The translation of those targeted therapies to subsequent phases of clinical development still requires a previously demonstrated reduction in the probabilities for the pathogen to develop resistance when using targeted systems.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the Spanish Ministry of Science and Innovation [PID2020-113987RB-I00 and PDC2021-121405-I00] and European Union [“NextGenerationEU”/PRTR].