Strategies to Combat Multidrug-Resistant and Persistent Infectious Diseases

Abstract

Antibiotic failure is one of the most worrying health problems worldwide. We are currently facing an international crisis with several problematic facets: new antibiotics are no longer being discovered, resistance mechanisms are occurring in almost all clinical isolates of bacteria, and recurrent infections caused by persistent bacteria are hampering the successful treatment of infections. In this context, new anti-infectious strategies against multidrug-resistant (MDR) and persistent bacteria, as well as the rescue of Food and Drug Administration (FDA)-approved compounds (drug repurposing), are being explored. Among the highlighted new anti-infectious strategies, in this review, we focus on antimicrobial peptides, anti-virulence compounds, phage therapy, and new molecules. As drugs that are being repurposed, we highlight anti-inflammatory compounds, anti-psychotics, anti-helminthics, anti-cancerous drugs, and statins.

Keywords: anti-MDR strategies; anti-persistent treatments; drug repurposing.

Figure 1

Anti-infectious strategies investigated with the aim of combating resistant and persistent bacteria. (a) Clockwise from the top: AMPs: antimicrobial peptides, including biofilm inhibitors; QS: quorum sensing. The green triangles illustrate the acyl-homoserin lactones that bacteria secrete as QS modulators. Phage therapy includes all the clinical trials in which a combination of lytic phages or parts of these (endolysins) are used against bacterial infections with therapeutic aims. Finally, new molecules encompass all synthetic compounds displaying antibacterial activity, such as retinoids (indicated by yellow circles inserted in the membrane). (b) Repurposing encompasses all the FDA (Food and Drug Administration)-approved drugs with potentially antibacterial effects.

Figure 2

Number of annual publications available on PubMed search engine for the keywords “MDR OR multidrug resistance”, “phage therapy”, “antimicrobial peptides AND antibacterial”, “drug repurposing”, “anti-persister OR anti-persistence OR resuscitating drugs”, “anti-virulence AND antibacterial”. The number of publications is expressed on a logarithmic scale.