What are the types of Antimicrobial Resistance (AMR)?

From the Guidelines

Antimicrobial resistance (AMR) is primarily driven by the emergence of multidrug-resistant organisms (MDROs), including Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative bacilli like carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Enterobacterales (CRE) 1. The main types of AMR resistance include:

• Enzymatic inactivation, where bacteria produce enzymes that destroy antibiotics
• Target modification, which occurs when bacteria alter the structure of the antibiotic's target site
• Efflux pumps, which actively expel antibiotics from bacterial cells
• Permeability changes, where bacteria reduce their membrane permeability to prevent antibiotic entry
• Alternative metabolic pathways, allowing bacteria to bypass inhibited processes
• Biofilm formation, creating protective barriers against antibiotics
• Horizontal gene transfer, enabling bacteria to share resistance genes through plasmids, transposons, and bacteriophages These mechanisms often work in combination, creating multi-drug resistant "superbugs" that pose significant clinical challenges, as highlighted in the recent European Antimicrobial Resistance Surveillance Network (EARS-Net) report 1. Key statistics from the EARS-Net report include:
• More than one-half of Escherichia coli and more than one-third of Klebsiella pneumoniae isolates were resistant to at least one antimicrobial group
• An alarming increase in carbapenem resistance has been reported in several species, including K. pneumoniae (7.9% of isolates), P. aeruginosa (16.5% of isolates), and A. baumannii (>30% of isolates)
• CRE represent a significant threat to healthcare systems in all EU/EEA countries, with the situation being endemic in some regions 1.

From the FDA Drug Label

In vitro studies have shown that point mutations in the 23S rRNA are associated with linezolid resistance. Reports of vancomycin-resistant E. faecium becoming resistant to linezolid during its clinical use have been published. There has been a report of Staphylococcus aureus (methicillin-resistant) developing resistance to linezolid during its clinical use.

• Types of AMR resistance mentioned include:
  • Point mutations in the 23S rRNA
  • Vancomycin-resistant E. faecium becoming resistant to linezolid
  • Methicillin-resistant Staphylococcus aureus developing resistance to linezolid The linezolid resistance in these organisms was associated with a point mutation in the 23S rRNA (substitution of thymine for guanine at position 2576) of the organism 2

From the Research

Types of AMR Resistance

• Methicillin-resistant Staphylococcus aureus (MRSA) is a common type of AMR resistance, which is usually conferred by the acquisition of a nonnative gene encoding a penicillin-binding protein (PBP2a) 3.
• Vancomycin-resistant enterococci (VRE) is another type of AMR resistance, which has been associated with reduced susceptibility to vancomycin among MRSA isolates 4.
• Resistance to newer antimicrobial agents, such as daptomycin and linezolid, has been described among isolates of MRSA and VRE, further complicating treatment of infections caused by these organisms 4.
• Beta-lactamase production is another mechanism of resistance in S. aureus, which renders it impervious to the action of β-lactam antibiotics including methicillin 5.

Mechanisms of Resistance

• The expression of penicillin-binding protein 2a (PBP2a) is a key mechanism of methicillin resistance in S. aureus, which allows cell-wall biosynthesis to continue even in the presence of typically inhibitory concentrations of antibiotic 3, 5.
• Horizontal gene transfer and chromosomal mutation are also mechanisms by which S. aureus can evolve antibiotic resistance 6.
• Biofilm production is a special feature of S. aureus pathogenesis, which allows it to survive on both biotic and abiotic surfaces and contributes to its ability to resist antibiotics 6.

Prevalence and Impact

• MRSA is a major public health problem globally, with as many as 90% of S. aureus infections reported to be MRSA in some regions 5.
• The emergence and spread of antibiotic-resistant MRSA strains have contributed to its increased prevalence in both healthcare and community settings 5.
• MRSA is responsible for 10-fold more infections than all multi-drug resistant (MDR) Gram-negative pathogens combined, and has been classified by the World Health Organization (WHO) as one of twelve priority pathogens that threaten human health 6.