4.1.16 Antibiotics

• When humans experience a pathogenic bacterial infection they are often prescribed antibiotics by a healthcare professional
• Antibiotics are chemical substances that inhibit or kill bacterial cells with little or no harm to human tissue
  • Many antibiotics are derived from naturally occurring substances that are harmful to prokaryotic cells (structurally or physiologically) but usually do not affect eukaryotic cells
  • The aim of antibiotic use is to aid the body’s immune system with fighting a bacterial infection

• Penicillin is a well-known example; it was the first antibiotic to be discovered in 1928 by Sir Alexander Fleming
• Antibiotics are either described as being bactericidal (they kill) or bacteriostatic (they inhibit growth processes), they target prokaryotic features but can affect both pathogenic and mutualistic bacteria living on or in the body
• Some antibiotics are derived from fungi while others are synthetic or semi-synthetic
• Broad-spectrum antibiotics act on a wide range of bacteria while narrow-spectrum antibiotics act on a very small number of bacteria
  • Doctors often prescribe broad-spectrum antibiotics (e.g. Amoxicillin) unless a culture has been taken to prove the need for a narrow-spectrum antibiotic

Common Antibiotics & their Mechanisms of Action

• In all species, there exists genetic diversity within populations, and the same applies to disease-causing bacteria
• Individual bacterial cells may possess alleles that confer resistance to the effects of the antibiotic
  • These alleles are generated through random mutation and are not caused by antibiotic use, but antibiotic use exerts selection pressures that can result in an increase in their frequency

• Bacteria have a single loop of DNA with only one copy of each gene so when a new allele arises it is immediately displayed in the phenotype
• When an antibiotic is present:
  • Individuals with the allele for antibiotic resistance have a massive selective advantage so they are more likely to survive, reproduce and pass genome (including resistance alleles)
  • Those without alleles are less likely to die and reproduce
  • Over several generations, the entire population of bacteria may be antibiotic-resistant

• Antibiotic resistance is an important example of natural selection
  • Some pathogenic bacteria have become resistant to penicillin as they have acquired genes that code for the production of the enzyme β-lactamase (also known as penicillinase), which breaks down penicillin

Bacteria evolve rapidly as they reproduce quickly and acquire random mutations – some of which confer resistance

Examples of Antibiotic Resistance Genes

Consequences of antibiotic resistance

• Commonly prescribed antibiotics are becoming less effective for many reasons, the main being:
  • Overuse of antibiotics and antibiotics being prescribed when not necessary
  • Large scale use of antibiotics in farming to prevent disease when livestock are kept in close quarters, even when animals are not sick
  • Patients failing to complete the full course of antibiotics prescribed by doctors

• These factors have led to a reduction in the effectiveness of antibiotics, and an increase in the incidence of antibiotic resistance
• Bacteria living where there is widespread use of many different antibiotics may have plasmids containing resistance genes for several different antibiotics, giving them multiple resistance and presenting a significant problem for doctors
• In addition, resistance may first appear in a non-pathogenic bacterium, but then be passed on to a pathogenic species by horizontal transmission
• There is a constant race to find new antibiotics as resistant strains are continuously evolving

Staphylococcus aureus

• The most common example of a resistant bacteria is a strain of Staphylococcus aureus that has developed resistance to a powerful antibiotic, methicillin and is now known as MRSA (Methicillin-resistant Staphylococcus aureus)
• Some MRSA strains have also become resistant to other antibiotics (eg. penicillin)
• S.aureus usually lives on human skin, without causing disease however when there is an opportunity for the pathogen to enter the body (e.g. surgical wound) they can cause serious disease

Clostridium difficile

• Clostridium difficile is a bacteria present in the human gut
• The numbers of C.diff are usually kept low due to the presence of other gut bacteria
• A course of antibiotics can kill these 'friendly' gut bacteria, allowing C.diff to increase in numbers
• A C.diff infection can cause diarrhoea and fever as they disrupt the epithelium of the intestine

Reducing antibiotic resistance & its impact

• Ways to prevent the incidence of antibiotic resistance increasing include:
  • Tighter controls in countries in which antibiotics are sold without a doctor’s prescription
  • Doctors avoiding the overuse of antibiotics, prescribing them only when needed (patients must only be given antibiotics when absolutely essential) – doctors should test the bacteria first to make sure that they prescribe the correct antibiotic
  • Antibiotics not being used in non-serious infections that the immune system will ‘clear up’ (patients must not keep unused antibiotics for self-medication of such non-serious infections in the future)
  • When prescribed a course of antibiotics, the patient finishing the entire course (even if they feel better after a few days) so that all the bacteria are killed, and none are left to mutate to become resistant strains
  • Antibiotics not being used for viral infections (antibiotics have no effect on viruses anyway, and this just provides an unnecessary chance for bacteria to develop resistance)
  • The use of ‘wide-spectrum’ antibiotics being reduced and instead those antibiotics that are highly specific to the infection (‘narrow-spectrum’ antibiotics) being used
  • The type of antibiotics prescribed being changed so that the same antibiotic is not always prescribed for the same infections and diseases (this reduces the chance of a resistant strain developing)
  • The use of antibiotics being reduced and more tightly controlled in industries such as agriculture – controls are now in place to limit their use in farming, where antibiotics are used to prevent, rather than cure, bacterial infections

• The spread of already-resistant strains can be limited by:
  • Ensuring good hygiene practices such as handwashing and the use of hand sanitisers (this has reduced the rates of resistant strains of bacteria, such as MRSA, in hospitals)
  • Isolating infected patients to prevent the spread of resistant strains, in particular in surgical wards where MRSA can infect surgical wounds