Antibiotic Resistance Overview

Antibiotic Resistance

• Antibiotic resistance is a significant global health concern, projected to kill more people than cancer and diabetes by 2050
• 80% of antibiotics are given to livestock to promote growth and prevent diseases
• 50% of antibiotics given to humans are inappropriately or unnecessarily prescribed
• Antibiotic resistance mechanisms can develop through misuse or incorrect use of antimicrobials, including: administering drugs for too short a time or at insufficient dosage levels for viral infections, and improper diagnosis leading to the use of broad-spectrum antibiotics when more targeted treatment should be used.

Learning Objectives

• The history of antibiotics and resistance, including the discovery of penicillin
• How antimicrobial resistance emerges
• 5 key mechanisms of antibiotic resistance
• The acquisition and origins of antibiotic resistance
• The dangers and consequences of antibiotic resistance
• Multidrug-resistant organisms (MDR) and examples of organisms of concern
• How to overcome antibiotic resistance

Introduction

• Louis Pasteur's observations in 1877 of saprophytic bacteria inhibiting anthrax bacteria were early steps in understanding antibiotic properties
• Alexander Fleming's accidental discovery of penicillin in 1928 revolutionized medicine, leading to the development of other antibiotics.
• Chain and Florey purified penicillin.
• This resulted in the first antibiotic use during WWII on wounded soldiers

History of Antibiotics

• Penicillin was isolated from other microorganisms, leading to the term "antibiotics"
• Other antibiotics like streptomycin, chloramphenicol, erythromycin, and vancomycin emerged in the 1940s and 1950s
• Advancements with penicillin were threatened by the development of beta-lactams to combat this threat
• Methicillin-resistant Staphylococcus aureus (MRSA) was first documented in the UK (1962) and later in the USA (1968)
• Vancomycin was introduced as a treatment for MRSA in 1972, though the emergence of vancomycin-resistant strains soon followed in the 1980s

How Antibiotic Resistance Occurs

• Some bacteria are naturally resistant to certain antibiotics.
• Antibiotics kill susceptible bacteria, leaving resistant bacteria to multiply and spread in the body.
• Resistant bacteria can transfer their resistance to other bacteria.

Mechanism of Antibiotic Resistance

• Intrinsic (Natural):

  • Some bacteria naturally lack the target that the antibiotic attacks.
  • For example some bacteria have an absence of a cell wall, making them naturally resistant to penicillins

• Acquired (Genetic):

  • Chromosomal Methods: Mutations in the bacteria's DNA causing them to be less susceptible to antibiotics
  • Extra-Chromosomal Methods: Transferring resistance genes between bacteria via plasmids, making a larger population of bacteria resistant.

Mechanism of Antimicrobial Resistance-Impermeability Changes

• Bacteria can modify their cell walls or membranes to prevent antibiotics from entering.
• For instance, Staphylococcus aureus makes thickened cell walls, making it difficult for vancomycin to penetrate.

Intrinsic Resistance: Enzymatic Inactivation

• Bacteria produce enzymes that deactivate antibiotics.
• For example, Cephalosporinase in Klebsiella disables certain antibiotics
• Staphylococcus aureus also generates enzymes to break down drugs like methicillin.

Mechanism of Antimicrobial Resistance-Active Efflux

• Bacteria can actively pump antibiotics out of their cells, reducing the antibiotic's effectiveness
• Mechanisms include proteins like porins or glycoproteins in bacteria cells that actively push the antibiotics out.
• This reduces effective antibiotic concentration

Mechanism of Antimicrobial Resistance-Permeability

• Bacteria use the cell wall (e.g., LPS layer) to limit the entry of antibiotics
• This creates barriers to certain antibiotics entering some type of bacteria
• This can involve altering the porins in the bacterial cell membrane

Mechanism of Antimicrobial Resistance - Target Site Modification

• Bacteria can change the target site that antibiotics usually act on, reducing their effect
• In Staphylococcus aureus and penicillin, penicillin binds to penicillin-binding proteins (PBPs), but resistant strains modify these in a way to hinder the drug from binding

Acquisition origin of antibiotic resistance - Misuse of Antibiotics

• Treating viral infections with antibiotics is common misuse.
• Administering antibiotics incorrectly (e.g., too short duration or too low doses) allows some bacteria to survive.

Threat and Consequences of Antibiotic Resistance

• Resistance in bacteria like Neisseria gonorrhoeae is very high
• 440,000 new cases of drug-resistant bacteria are reported annually
• Some experts fear a "post-antibiotic era" where simple infections could become life-threatening once again.
• The cost of treating patients could double

Consequences of Antibiotic Resistance

• Delay or lack of adequate treatment for infected patients
• Increased hospital stays
• Greater complications from infections
• Often results in death

Multidrug-Resistant Organisms of Concern

• Mycobacterium tuberculosis (extensive and total drug resistance)
• Vancomycin-resistant Enterococci (VRE), a problem for certain patients
• Pseudomonas aeruginosa, common in burn wounds and cystic fibrosis patients
• Acinetobacter baumannii, mainly a hospital-acquired infection
• Staphylococcus aureus (MRSA), a common cause of infections
• Clostridium difficile, linked to antibiotic use

Can Antimicrobial Resistance be Overcome?

• Four main strategies:
  1. Preventing infections (hygiene, vaccination)
  2. Preventing the spread of infections (isolating patients)
  3. Tracking resistant strains and identifying carriers
  4. Improving antibiotic use (rational prescribing, developing new drugs, testing for resistance)

This quiz explores the critical issue of antibiotic resistance, discussing its history, mechanisms of emergence, and the consequences of misuse. Learn about the origin and the rise of multidrug-resistant organisms in a health context that impacts us all.