Karen Dunne examines the role of antibiotics and antibiotic

resistance

PENICILLIN, one of the first antibiotic drugs to be developed, was famously discovered by Alexander Fleming on Friday, September 28th 1928. This breakthrough won Fleming a Nobel prize as doctors were now able to treat previously lethal bacterial infections. The discovery of other antibiotics followed rapidly. These drugs saved lives and facilitated other breakthroughs, such as organ transplants.

However, the picture is no longer quite so rosy. The use of antibiotics has led to the rise of new bacterial strains that are resistant to them. These bacteria have major health implications for both human and animal health, as conditions that were readily treatable in recent decades pose renewed risks e.g. tuberculosis (TB) and MRSA.

In order to understand how this has happened (and what we can do about it), we need to look at how bacteria cause infections. Bacteria are tiny single-celled organisms, invisible to the naked eye. We can however see them once we place them in an incubator on an agar plate and provide them with moisture, warmth and food. Under these ideal conditions bacterial cells multiply at a phenomenal rate. Some types, such as E. coli, can double in number every 20 minutes. After just seven hours, a single cell can have given rise to 2,097,152 bacteria! Clumps or clusters of the bacteria will now be visible on the agar plate.

As well as being very prolific, bacteria are extremely numerous. There are far more bacteria living on your skin than there are cells in your body. Luckily, the vast majority of these bacteria are completely harmless. These bacteria are called microflora and they compete with each other for moisture, warmth and nutrients. This competition keeps the total population in check and makes it much harder for disease-causing bacteria to invade the body, as they have to compete for resources.

Healthy animals and humans have further barriers to harmful bacteria. Intact skin is very resistant to bacterial invasion. The parts of the body that come in contact with bacteria in the environment e.g. the mouth, digestive tract and airways are lined with immune system cells to “mop up” any invaders and prevent them gaining access to the vital organs and bloodstream.

For infection to occur, something must happen to disrupt these protective mechanisms. Wounds are a common example. Once the skin is broken, bacteria can invade the exposed tissues and start to multiply. This gives rise to heat, pain, swelling, redness and thick discharge or “pus”: the classic signs of a bacterial infection.

Once the signs of bacterial infection are diagnosed by a veterinary surgeon, antibiotics are administered to kill the harmful bacteria and allow the animal’s immune system to remove them from the body. Broad-spectrum antibiotics are normally effective against many types of bacteria, while narrow-spectrum ones specifically target only a few bacterial species. N.B. all antibiotics are completely ineffective against viruses.

However antibiotics, especially broad-spectrum ones, are not selective and they will kill off many of the normal microflora, not just the ones causing the infection. Billions of bacteria in the treated animal will be lost, leaving increased resources for those few that survive. These bacteria, that happened to be unaffected by the particular drug that was used, will multiply until normal numbers are restored. These bacteria are mostly harmless but in a minority of cases, they may be able to cause disease. Even if they don’t cause disease they have survived the course of antibiotics, indicating that they have resistance to that drug. Over time, especially if the antibiotic is widely or repeatedly used, these resistant bacteria will increase and make up a greater proportion of the bacterial population. This increases the risk of future treatment failure.

RESISTANCE

Bacteria have one additional trick that helps them to evade antibiotics. Once a bacterial strain develops resistance to a particular drug, it can pass the genes for that resistance on to its offspring (vertical transmission). There is no surprise here: all horse breeders are familiar with the concept of families handing down their traits. However, bacteria are also able to exchange genes between unrelated cells (horizontal transmission). You could picture it as a group of yearlings in a field that are able to exchange bits of their pedigrees by just grazing together!

This is really problematic when we look at what typically happens in the gut of an animal that is treated with antibiotics. The gut normally contains huge numbers of bacteria, where they help with digestion. Regardless of where in the body the animal has the infection, once it is treated with antibiotics a lot of changes will occur in the gut bacteria. Some strains will be killed off and others will proliferate. The more often that individual animal receives antibiotics, especially broad-spectrum ones, the higher the risk that some resistant bacteria will survive and multiply.

Once those resistant bacteria are present, they can start sharing their genes with the other bacteria around them. If a disease-causing bacteria happens to pick up those genes, it can evolve into a so-called “superbug”: a strain capable of causing disease and with the ability to be resistant to antibiotics. The problem doesn’t end there either. Some of the bacteria in an animal’s gut are shed in its droppings into the environment. They can they be picked up by other animals. So, even without any further disease outbreaks or antibiotic treatment, the resistant bacteria will spread throughout the population. A recent study by the UCD veterinary school found that antibiotic treatment of horses resulted in the detection of resistant bacteria in the droppings after four days of treatment. Horses that are admitted to veterinary hospitals but do not receive antibiotics, and those that live with antibiotic-treated horses also have more resistant strains of gut bacteria. This highlights the ease with which bacteria spread through groups of animals.

The World Health Organisation and the European Union are taking the threat of antibiotic resistance very seriously. This problem is one that has the potential to affect us all. Resistant bacteria can cross from humans to animals and vice versa. We all need to ensure these vital drugs are used in a responsible manner that preserves their efficacy. We are less than 90 years on from Mr Fleming’s breakthrough, we need his legacy of effective bacterial therapeutics to make it far beyond its 100 year anniversary.

Karen Dunne MVB MA, CertEM (Stud Med) is a veterinary surgeon and veterinary nursing programme director at Dundalk Institute of Technology. She is a member of the Equine Group of Veterinary Ireland.

Email: hq@vetireland.ie

Telephone: 01-4577976