• Microbes are becoming wise to antibiotic treatments at a pace faster than new drugs can be developed.
• This poses a problem to human and animal health as agriculture prepares to feed over nine billion mouths by the year 2050, and healthcare strives to keep populations healthy in an era of ‘super-bugs’ and crowded hospitals.

This first article acts as an introduction to the key issues as part of a series on antimicrobial resistance.

What is Antimicrobial Resistance?

Antimicrobial resistance (AMR) is the term given to microbes that adapt to be resistant to antimicrobial medicines which previously offered effective treatment.

The term relates to bacteria, fungi, viruses and some parasites which have been controlled with a developing arsenal of antimicrobial technology since the 1940’s. However, the predominant problem is with bacteria.

How Does Resistance Develop?

Resistance may arise through genetic mutation or by attaining a gene from an already resistant bacterium. Once resistant, subsequent reproduction means resistance genes will be passed onto the next generation of bacteria.

Once resistance is acquired, bacteria then have a selective advantage and can reproduce quickly in the absence of competition as non-resistant bacteria are killed.

Antimicrobial resistance is developing faster than new medicines. The last new class of antimicrobial medicines was introduced in the late 1980s. This poses a global challenge as the number of drugs available to combat infections fails to keep pace.

There are several ways in which bacteria can dodge the antibiotic effects of drugs. For example, they may modify their own metabolic pathways to avoid the effects of a drug, or they can produce enzymes that break down the antimicrobial drug.

One such family of enzymes are the Extended-Spectrum beta-Lactamases (ESBLs) which confer resistance to penicillins and cephalosporins and are most widely associated with Escherichia coli and Klebsiella germs.

In addition, bacteria may also modify the site at which the antibiotic drug binds, thereby preventing it from attacking the bacteria. Penicillin resistance may arise in this way, and this is the mechanism that underpins MRSA (methicillin resistant Staphyloccocus aureus) resistance.

Finally, bacteria may pump out the antibiotic so there is less of it, therefore diminishing the efficacy of the drug. This method is involved in resistance to tetracyclines, a broad spectrum family of drugs used in human and animal health which works by getting inside bacteria and inhibiting protein synthesis.

How Is Veterinary Medicine Contributing to Resistance?

Use of any antimicrobial drug for any treatment can lead to the development of resistance. As a population is introduced to a drug’s chemistry, solutions are reached to nullify the drug’s effect.

However, there is global consensus now among medics and veterinarians that, by not using antimicrobial technologies in the optimal way, and in some cases over relying on them, resistance is being accelerated.

Generally, this could mean stopping a course of drugs too early, or prescribing drugs at too low a dose to combat infections.

Antibiotics may be used therapeutically to treat an existing infection, but there is also the routine use of antimicrobials, where drugs are issued to prevent illness or boost health without signs of infection being present.

Routine use of antimicrobials is common in some of the world’s livestock systems, especially in more intensive operations where animals are housed close together.

Veterinarians talk of two types of routine use:

• Prophylactic – Medicine given to prevent illness rather than fight infection. This could be following or in anticipation of the animal going through a period of stress, such as an operation.
• Metaphylactic – Administering treatment to the entire herd or flock due to the potential infection risk increasing through proximity to infection or the conditions in which the animals are kept.

Trucking cattle to feedlots over 1,000 miles away is not uncommon in the United States and is carried out in all weather conditions.

Examples of routine antimicrobial use extend throughout all livestock sectors and have been practised the world over. For example, it was standard European practice to give a pig antibiotics to promote health after tail docking. It still is widely practised to give cattle antimicrobials in the US after lengthy periods spent in transit to help them through what is known as ‘shipping fever’.

An easy way to administer antimicrobials this way is through incorporation in feed or water. This method saves time when farming on a large-scale, such as commercial poultry and pig units, the two types of operations that experts most associate with antimicrobial resistance.

Dairy farms routinely use antibiotics to tackle mastitis through the dry-cow period.

Such routine uses are also known as non-therapeutic or sub-therapeutic uses, since no signs of infection exist prior to the administration of antibiotics. However, veterinary guidelines, legislative changes and some policy measures have started to reduce this, with action being taken in the European Union and the US.

For example, the European Union started to gradually withdraw antibiotic growth promoters (AGP), an example of non-therapeutic use of antibiotics, between 1995 and 1999 as a ‘precautionary principle’ and then banned AGPs in 2006.

Many countries still allow antimicrobial medicines to be fed sub-therapeutically but the US has now concluded that AGPs are not in the best interest of public health.

Further Reading

To read more about about antimicrobial resistance on the World Health Organisation web site, click here.