New approaches for combating polyresistant ESKAPE pathogens

Antibiotic resistance of microorganisms is the most pressing global health problem due to the ever-increasing number of deaths caused by ineffective antibiotic therapy. The COVID-19 pandemic has only exacerbated pre-existing issue of increasing resistance of bacterial strains worldwide. Lack of public awareness about proper use of antibiotics directly impacts on uncontrolled antibiotic administration associated with weak antibiotic dispensing controls as well as limited access to health facilities in low- and middle-income countries. It is reported that 68.9% of COVID-19 patients used antibiotics for prophylaxis against bacterial complications or to treat coronavirus infection (mainly azithromycin and ceftriaxone) before hospitalization, with a self-medication rate of 33.0%. The most antibiotic-resistant and dangerous to global public health group of microorganisms is known as ESKAPE: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species. The proportion of resistant strains among these microorganisms can reach 95%. In light of the rapid increase in the number of infections caused by antibiotic-resistant strains, a need to create new antibacterial drugs is the most urgent task. The development of new antibiotics is a high-cost goal and it’s often ineffective. Therefore, more and more often their developers resort to the use of antibiotics combinations or using them together with adjuvants of different mechanisms of action. In recent years, special devices and coatings with nanoparticles of various metals deposited on their surface have become increasingly widespread. Some successes achieved in the use of antimicrobial peptides have been leveled by the loss of activity in the human body and their high production cost. In this regard, the use of bacteriophages, especially in combination with antibiotics, has been becoming a promising approach. The observed synergism both in vitro and in vivo experiments allow to hope for certain successes in the fight against ESKAPE group multidrug-resistant pathogens.