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Antibiotic Resistance – The hidden killer of the pandemic

Daisy Scott, Online Science Editor, discusses Antibiotic Resistance, how it works, why it is so dangerous and what we can do in the future to prevent it getting worse

Bacterial infections that were once easily cured have become increasingly difficult to treat due to the emergence of antibiotic resistance which now poses a substantial threat to public health. However, the data in this area are largely reported by high-income countries and the actual death rate/ occurrence is likely to be much higher

Bacterial antibiotic resistance – which occurs when changes in bacteria cause the drugs used to treat infections to become less effective – has emerged as one of the leading public health threats of the 21^st century. When the microorganisms become resistant to most antimicrobials they are often referred to as “superbugs. Superbugs are of major concern because a resistant infection may kill, can spread to others and impose a huge cost to individuals and societies

Worryingly, a report by the UK Health Security Agency’s English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) estimated that the overall proportion of bloodstream infection that were resistant to one or more antibiotics increased between 2016 and 2020 from 18.2% to 20.1%

The overall proportion of bloodstream infection that were resistant to one or more antibiotics increased between 2016 and 2020 from 18.2% to 20.1%

If left unchecked, the spread of Antibiotic Resistance could make many bacteria pathogens much more lethal in the future than they are today. The most serious concern with Antibiotic resistance is that some bacteria have become resistant to almost all of the easily available antibiotics. Important examples are –

• Methicillin-resistant Staphylococcus aureus (MRSA)
• Vancomycin-resistant Enterococcus (VRE)
• Multi-drug-resistant Mycobacterium tuberculosis (MDR-TB)

A study published in the lancet estimated that in 2019 1.27 million deaths were attributable to resistance in the 88 pathogen-drug combinations evaluated in the study

How do Antibiotics work? –

Antibiotics work at a cellular level to continually disrupt and prevent the growth of microorganisms. Whilst most antibiotics are natural compounds derived from plants and other organisms, other are chemically produced based on the structure of natural compounds

Different types of Antibiotics treat bacterial infections through different mechanisms. Whilst some antibiotics act by completely destroying the microorganisms (bactericidal antibiotics), others slow or stop their growth/ reproduction as to prevent the spread of infection (bacteriostatic antibiotics)

Bactericidal Antibiotics –

Cell wall synthesis inhibitors –

• Antibiotics that interrupt the synthesis of the cell wall of the bacteria act by disrupting synthesis of the peptidoglycan. This causes the cell to be susceptible to mechanisms that contribute to cell destruction. Whilst some bacteria have several peptidoglycan layers, other have only a single peptidoglycan layer.
  • The synthesis of peptidoglycan is mediated by a number of actors including the transpeptide enzyme. These enzymes are also capable of binding penicillin. The Beta-lactam ring of penicillin binds to the active site of the enzyme and reacts with the serine residue to the protein which in turn inhibits its action
• Pencillins, which are some of the most common antibiotics, are example of this type

Membrane Disruptors –

• Some antibiotics function by disrupting the integrity of the cell membrane, this is effective as the primary function of the cell membrane is the movement of material into and out of the cell.

Bacteriostatic antibiotics –

Protein-synthesis inhibitors –

• Whilst these do not immediately kill bacteria, these prevent the bacteria from growing which causes them to die without reproducing. While there are several ways through which these antibiotics can interfere with protein synthesis, this is generally at the ribosomal level (where proteins are synthesised)
• They may inhibit the synthesis of protein in a number of ways including –
  • Interfering with the elongation of the peptide chain
  • Inhibiting oligosaccharide side chains from attaching to glycoproteins
  • Causing the misreading of genetic information or blocking a site of the ribosome

Nucleic-acid synthesis inhibitors –

• As the name suggests, these function by interrupting the synthesis of DNA especially during DNA replication. This can be done by different mechanisms including
  • Breakage of the DNA strand – This in turn affects other cell processes
  • Inhibiting DNA replication – To prevent the unwinding of the DNA helix, which is necessary for replication, these antibiotics target enzymes that enable this process. By inhibiting DNA replication, this directly affects cell division as well as cell growth

How does antimicrobial resistance happen?

AMR is a naturally occurring process. However, increases in antibiotic resistance are driven by a combination of germs exposed to antibiotics, and the spread of those germs and their resistance mechanisms. However, the misuse and overuse of antibiotics is dramatically escalating the process. When antibiotics are used incorrectly in human or animal medicine – for too short a time, too small a dose, at inadequate strengths or for the wrong disease- the bacteria are not killed and can pass on survival traits to even more bacteria

Antibiotic resistance development –

1. Some bacterial cells in the human body are naturally drug resistant
2. Antibiotics kill bacteria but the resistant strains remain
3. Antibiotic resistant strains multiply
4. Antibiotic resistance spread

What is fuelling antibiotic resistance?

• A third of the public believe that antibiotics will treat coughs and colds
• 1 in 5 people expect antibiotics when they visit their doctors and GPs commonly express concerns that they feel pressurised by patients asking for antibiotics

AMR disproportionately affects poor individuals who have little access to second-line, more expensive antibiotics that could work when first line drugs fail

Ironically, the burden of resistance partly reflects the insufficient access to antibiotics.

• Over two-thirds of attributable deaths were due to resistance to first-line antibiotics including fluoroquinolones and beta-lactams

The true burden of resistance could be greater than that estimated in this study

• Most of the raw data in the study come from high-income countries

What can be done about AMR –

• There are several steps that can be taken to tackle AMR –
  • Boosting public awareness
  • Better surveillance
  • Improved diagnostics
  • More rational use of antibiotics
  • Access to clean water and sanitation
  • Embracing One Health

A failure to address the problem of antibiotic resistance could result in –

• An estimated 10 million deaths every year globally by 2050
• A cost of £66 trillion in lost productivity to the global economy

An estimated 10 million deaths every year globally by 2050

The development of new antibiotics has slowed down as it becomes difficult to find new versions to tackle different bacterial infections, so we all need to play our part to ensure that bacteria that are now very treatable become less so in the future