antibiotic resistance

• what is an antibiotic?

  a medicine that inhibits the growth of and destroys bacteria
• when does antibiotic resistance occur?

  when microorganism like bacteria and fungi develop the ability to develop the ability to defeat the drugs designed to kill them - this means the microorganisms are not killed and continue to grow and so are resistant
• why does antibiotic resistance develop?

  1. Selection pressure of antibiotic (sensitive cells killed) - evolving due to mutations in the population etc (natural selection)
  2. Transfer of resistance genes; species to species; genus to genus (Horizontal gene transfer)
  3. Rapid cell division
• what are the two types of resistance to antibiotics?

  1. Natural resistance (intrinsic or innate)
  2. Sensitive bacteria develop resistance (acquired)
• what is intrinsic resistance?

  The natural resistance of a microorganism like bacteria to the antibiotic:

  • lack of target structure (organism not having a target)
  • impermeable to the antibiotic
• what is acquired resistance?

  When they have the ability to survive and grow in the presence of antibiotics that were initially effective against them. Some key mechanisms to this resistance include:

  • enzymatic inactivation of antibiotic (enzymes made that inactivate the antibiotic)
  • modification of the target
  • organisms pumps out the antibiotic (efflux mechanism)
• The bacteria within your body is what becomes resistant to antibiotics. They can pass resistance on to each other.

  It is still possible for someone who has never taken antibiotics to get an antibiotic-resistant infection

  Antibiotics are only suitable for treating bacterial infections.
• what is antibiotic stewardship?

  Optimising the use of antibiotics to improve patient outcomes and reduce the development of antibiotic resistance.
• what is being done to promote antibiotic stewardship?

  • ensuring that antibiotics are used rationally and not misused
  • health promotion to avoid antibiotic use when it’s not needed e.g. coughs and colds
  • prescriber education
  • development/promotion of empiric guideline choice
  • Restriction of reserve antibiotics
  • Selective reporting of sensitivities to guide prescribing to 1st line/narrow spectrum choices
  • Review / advise on management of infection for individual patients
  • Ensuring justified indication
  • Choice
  • Dose optimisation
  • Ensuring the correct duration
• what is antimicrobial resistance?

  the ability of microorganisms (including bacteria, viruses, fungi and parasites) to resist the actions of drugs or other antimicrobial agents
• Bacteria are microbes and so are fungi, protozoa and viruses and therefore, microbial resistance covers resistance in any of these microorganisms
• what are antimicrobials?

  things that kill microbes or prevent microbes from growing which includes antibiotics
• what is microbial resistance?

  The ability of microorganisms to withstand the effects of antimicrobial drugs. A characteristic shown by microbes including bacteria.
• what are some of the mechanisms of action of antibiotics?

  1. cell wall inhibition - beta-lactam antibiotics
  2. protein synthesis inhibition - tetracycline
  3. nucleic acid synthesis inhibition - quinolones
  4. cell membrane disruption - disrupts cell membrane = leakage of cellular contents
• how do antibiotics kill bacteria via selective toxicity?

  It does greater harm to bacteria than host, done by interfering with essential biological processes common in bacteria but not human cells.
• what is LD50 and MIC?

  LD50 - 'lethal dose for 50% of the population' - measure of the lethal dose that causes death in 50% of the individuals exposed to it

  MIC - 'minimum inhibitory concentration' - lowest concentration of an antimicrobial agent that inhibits visible growth of a microorganism
• LD50 is a measure of the toxicity of a substance, indicating the dose that causes death in 50% of the population.

  MIC is a measure of an antibiotic's effectiveness, representing the lowest concentration that inhibits bacterial growth
• what are bactericidal agents?

  substances that kill bacteria
• what are bacteriostatic agents?

  substances that inhibit the growth and reproduction of bacteria
• when are bacterial agents preferred to be used?

  • preferred where the host's immune system may be compromised/less effective - when host defences cannot be relied on to remove or destroy pathogen
  • severe infections or where rapid elimination of the pathogen is crucial
  • may reduce likelihood of development of resistance
• when are bacteriostatic agents more likely to be used?

  • when host's immune system is capable of eliminating the inhibited bacteria - bacteriostatic relies on this
  • suitable for less severe infections
  • potential for resistance due to bacteria not being immediately killed
• what does a broad spectrum mean?

  means that the antibiotic is effective against a wide variety of bacteria. In other words, it can target and treat a broad range of bacterial types rather than being specific to just a few types.
• what does a narrow spectrum mean?

  means that the antibiotic is effective against a limited range of bacteria. In other words, it targets and kills or inhibits the growth of specific types of bacteria rather than a broad variety.
• what are some mechanisms of antibiotic resistance?

  1. enzymatic inactivation
  2. efflux pumps
  3. decreased permeability
  4. horizontal gene transfer
• how does enzymatic inactivation cause antibiotic resistance?

  Bacteria may produce enzymes that can chemically modify or destroy the antibiotic, rendering it ineffective.

  e.g. β-lactamases, enzymes that break down the β-lactam ring structure found in penicillins and cephalosporins.
• how does efflux pumps cause antibiotic resistance?

  can develop pumps that actively pump out antibiotics, reducing their concentration within the bacterial wall
• how can decreased permeability cause antibiotic resistance?

  lot of antibiotics goes through pores so if the number of pores decease less antibiotic can enter and reach their target
• how can horizontal gene transfer cause antibiotic resistance?

  Bacteria can acquire resistance genes from other bacteria through processes like conjugation, transformation, or transduction.

  e.g. Transfer of plasmids containing antibiotic resistance genes between bacteria.
• describe antibiotic selective pressure?

  1. Bunch of bacteria including a resistant variety get bathed in antibiotics.
  2. Most of the normal bacteria die.
  3. The resistant bacteria multiply and become more common
  4. Eventually the entire infection evolves into a resistant strain
• what is the mechanism of the spread of antibiotic resistance?

  The sequence of theses can vary - they're independent processes

  • transformation - take up free DNA
  • conjugation - gene transfer
  • transduction - bacteriophages
• what occurs in transformation in terms of horizontal gene transfer?

  Bacteria take up free DNA from the environment and incorporate it into their chromosome
• what occurs in transduction in terms of horizontal gene transfer?

  Bacteriophages (viruses that infect bacteria) transfer bacterial DNA from one bacterium to another. The DNA is packaged into a virus particle and transferred into recipient bacteria during infection
• what occurs in conjugation?

  The mechanism of gene transfer responsible for the most concerning aspects of antimicrobial resistance.

  • A sex pilus (small tube) forms between two bacterial cells through which a plasmid is transferred from one to another
• what is the misuse of antibiotics?

  • when antibiotics are prescribed unnecessarily
  • when antibiotic administration is delayed in critically ill patients
  • when broad-spectrum antibiotics are used too generously, or when narrow-spectrum antibiotics are used incorrectly
  • when dose of antibiotics is lower or higher than appropriate for the specific patient
  • when the duration of antibiotics treatment its too short or too long
  • when antibiotic treatment is not streamlined according to microbiological culture data result
• examples of how antibiotic resistance spreads:

  1. Animal agriculture - use in livestock for growth promotion/disease prevention
  2. healthcare settings - due to improper infection control practices
  3. environmental reservoirs - from water bodies/soil can be transferred to human pathogens via direct contact or ingestion