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.