Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches

Abstract

The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed by the emergence of resistance. The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics. Today, research is active in finding new treatments for multidrug-resistant pathogens. In a step to guide the efforts, the WHO has published a list of the most dangerous bacteria that are resistant to current treatments and requires the development of new antibiotics for combating the resistance. Among the list are various Gram-positive bacteria that are responsible for serious healthcare and community-associated infections. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and drug-resistant Streptococcus pneumoniae are of particular concern. The resistance of bacteria is an evolving phenomenon that arises from genetic mutations and/or acquired genomes. Thus, antimicrobial resistance demands continuous efforts to create strategies to combat this problem and optimize the use of antibiotics. This article aims to provide a review of the most critical resistant Gram-positive bacterial pathogens, their mechanisms of resistance, and the new treatments and approaches reported to circumvent this problem.

Keywords: Gram-positive; MRSA; antibiotic; antimicrobial; bacteriophage; probiotic; resistance; β-lactam.

Figure 1

Diagram illustrating the cell wall structure of Gram-positive bacteria.

Figure 2

Mechanisms of resistance of Gram-positive bacteria.

Figure 3

Chemical structures of ceftaroline (1), ceftobiprole (2), tedizolid phosphate (3),besifloxacin (4), delafloxacin (5),ozenoxacin (6), and omadacycline (7).

Figure 4

Chemical structures of vancomycin (8), dalbavancin (9), telavancin (10), and oritavancin (11).

Figure 5

Chemical structures of teixobactin (12), malacidins (13), dodecyl 4,6-dideoxy-α-D-Xylo-hexopyranoside (14), cannabichromene (15), cannabigerol (16), cannabidiol (17), cannabinol (18), ∆9-tetrahydrocannabinol (19), DCAP (20), and Odilorhabdins (21).