Therapeutic Strategies To Counteract Antibiotic Resistance in MRSA Biofilm-Associated Infections

ChemMedChem. 2021 Jan 8;16(1):65-80. doi: 10.1002/cmdc.202000677. Epub 2020 Nov 6.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the leading causes of persistent human infections. This pathogen is widespread and is able to colonize asymptomatically about a third of the population, causing moderate to severe infections. It is currently considered the most common cause of nosocomial infections and one of the main causes of death in hospitalized patients. Due to its high morbidity and mortality rate and its ability to resist most antibiotics on the market, it has been termed a "superbug". Its ability to form biofilms on biotic and abiotic surfaces seems to be the primarily means of MRSA antibiotic resistance and pervasiveness. Importantly, more than 80 % of bacterial infections are biofilm-mediated. Biofilm formation on indwelling catheters, prosthetic devices and implants is recognized as the cause of serious chronic infections in hospital environments. In this review we discuss the most relevant literature of the last five years concerning the development of synthetic small molecules able to inhibit biofilm formation or to eradicate or disperse pre-formed biofilms in the fight against MRSA diseases. The aim is to provide guidelines for the development of new anti-virulence strategies based on the knowledge so far acquired, and, to identify the main flaws of this research field, which have hindered the generation of new market-approved anti-MRSA drugs that are able to act against biofilm-associated infections.

Keywords: MRSA; antibiotic resistance; antivirulence; biofilms; eradicating agents.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Drug Resistance, Bacterial / drug effects
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / physiology*
  • Oxazolidinones / chemistry
  • Oxazolidinones / pharmacology
  • Oxazolidinones / therapeutic use
  • Phenazines / chemistry
  • Phenazines / pharmacology
  • Phenazines / therapeutic use
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • beta-Lactams / pharmacology
  • beta-Lactams / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Oxazolidinones
  • Phenazines
  • Protein Kinase Inhibitors
  • beta-Lactams