Lecture 9 Flashcards
(18 cards)
Antimicrobial Resistance definition
Antimicrobial resistance refers to the ability of an organism (like bacteria, fungi, viruses, or parasites) to resist the effects of an antimicrobial drug. This means that the drugs that were once effective at killing or inhibiting the growth of these organisms no longer work as expected.
Reasons for Increasing Antimicrobial Resistance
Inappropriate Use of Antibiotics
Weak or Absent Surveillance Systems
Poor Infection Prevention and Control Practices - lead to spread of resistant bacteria
Insufficient Diagnostic, Prevention, and Therapeutic Tools
Overuse of Antibacterial Products
Disruption of Commensal Microflora
Antibiotics in Water Supplies due to agricultural runoff, hospital waste, or improper disposal
Problems Behind Antimicrobial Resistance
Treatment Failure
Increased Mortality
Increased Healthcare Costs:
Spread of Resistance in the Community
Global Spread of Resistance:
How Does Antimicrobial Resistance Occur?
Intrinsic Resistance (Naturally Occurring):
This is resistance that is naturally present due to the organism’s inherent characteristics. For example, bacteria that lack a cell wall are resistant to penicillin, which targets the cell wall.
Acquired Resistance:
Resistance that develops due to genetic changes in the organism after exposure to antibiotics.
Induced Genetic Mutation: Bacteria can mutate their DNA when exposed to antibiotics, leading to resistance.
Gene Transfer: Bacteria can acquire resistance through the transfer of genetic material from other bacteria (horizontal gene transfer).
Ways Microorganisms Can Be Resistant to Antibiotics: Production of an Enzyme that Inactivates Antibiotics (Beta-Lactams)
Bacteria can produce enzymes that break down or inactivate antibiotics
beta-lactamases destroy the beta-lactam ring in antibiotics like penicillin
This is a common resistance mechanism in Staphylococcus aureus, E. coli, and Klebsiella pneumoniae.
Ways Microorganisms Can Be Resistant to Antibiotics: Lack of Target Binding Site or Altered Binding Site:
Some bacteria may not have the target structure that the antibiotic normally binds to. For example, bacteria without a cell wall are resistant to penicillin (which targets the cell wall).
Ways Microorganisms Can Be Resistant to Antibiotics: Efflux Pump
Some bacteria have pumps that actively export the antibiotic out of the cell, reducing its effectiveness. For example, Pseudomonas species use efflux pumps.
Ways Microorganisms Can Be Resistant to Antibiotics: Alternative Metabolic Pathways
Bacteria can bypass the pathway that the antibiotic targets by using an alternative metabolic route. For example, some bacteria can bypass folate synthesis inhibition by using a different pathway.
Ways Microorganisms Can Be Resistant to Antibiotics: Decreased Permeability or Loss of Porin Channels:
Some bacteria can alter their cell membrane, reducing the number or size of porin channels, making it difficult for antibiotics to enter.
Ways Microorganisms Can Be Resistant to Antibiotics: Formation of Biofilm
Bacteria can form biofilms, which are clusters of bacteria embedded in a protective slime. This reduces antibiotic penetration and makes the bacteria more resistant. Biofilm bacteria also don’t replicate as quickly, making them less susceptible to antibiotics that target dividing cells.
Resistance Mechanisms for Common Antibiotics: Aminoglycosides e.g streptomycin
Modifying enzymes can alter aminoglycosides, making it harder for them to bind to the bacterial ribosome. Additionally, decreased porin channels can reduce the uptake of aminoglycosides.
Resistance Mechanisms for Common Antibiotics: Tetracyclines
Bacteria can reduce uptake of tetracyclines or use efflux pumps to expel the drug, preventing its effectiveness.
Resistance Mechanisms for Common Antibiotics: Quilones
Resistance can occur through altered DNA gyrase binding sites, reducing the effectiveness of quinolones like ciprofloxacin.
How Can Antibiotic Resistance Be Transferred: Horizontal Gene Transfer (HGT):
Conjugation: Direct transfer of plasmids between bacteria through a physical connection (a pilus).
Transformation: Bacteria can take up free-floating DNA from their environment.
Transduction: Bacteria can receive new genetic material from viruses (bacteriophages) that infect them.
Beta-Lactams Mechanism of Action
Beta-lactams (penicillins, cephalosporins, carbapenems, and monobactams) target the bacterial cell wall.
They bind to and inhibit penicillin-binding proteins (PBPs), which are enzymes responsible for peptidoglycan cross-linking in the bacterial cell wall.
Without functioning PBPs, the bacteria cannot maintain their cell wall structure, leading to cell lysis and death.
Extended Spectrum Beta-Lactamases (ESBL)
ESBLs are enzymes produced by some Gram-negative bacteria (like E. coli) that confer resistance to a wide range of beta-lactam antibiotics.
ESBL genes are often carried on plasmids and can be transferred to other bacteria.
Vulnerable Populations: ESBL infections are more common in immune-compromised individuals, hospitals, and nursing homes.
Transmission:
ESBL-producing bacteria can spread hand-to-hand, via breathing, or through diarrhea, skin infections, pneumonia, UTIs, and sepsis.
E-Test
The E-test is a method used to determine the Minimum Inhibitory Concentration (MIC) of an antibiotic. It uses strips impregnated with antibiotics, and the point where bacterial growth is inhibited gives the MIC value.
Solutions to the Problem of Resistance
Synergistic Action of Multiple Antimicrobials:
Combining multiple antibiotics may enhance their effectiveness and prevent the development of resistance.
Antimicrobial Stewardship:
Properly managing the use of antibiotics to ensure they are used appropriately and only when needed.
Better Diagnostics:
Improve diagnostic tools to quickly identify infections and determine the most effective antibiotic treatment.
Find New Antibiotics:
Developing new classes of antibiotics, as well as vaccines and immunotherapy, to prevent infections from occurring in the first place.
