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Scanning electron micrograph of methicillin-resistant Staphylococcus aureus bacteria (yellow, round items) killing and escaping from a human white cell. Photo: NIAID via Flickr (CC BY).
Scanning electron micrograph of methicillin-resistant Staphylococcus aureus bacteria (yellow, round items) killing and escaping from a human white cell. Photo: NIAID via Flickr (CC BY).
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Restrict antibiotics to medical use, or they will soon become ineffective

Laura J V Piddock, Richard Meek, Victoria Wells, Hrushi Vyas

23rd October 2015

Antibiotics have saved countless millions of lives since the 1930s, but their power is failing due to their massive use in factory farming, horticulture, aquaculture and industry, says a new report from the All Party Parliamentary Group on Antibiotics. We must stop all inessential uses of antibiotics, or face a future where we risk death from minor injuries and routine surgery.

We now need to value antibiotics more highly, and recognise that they are a finite and diminishing resource whose use must be carefully managed. Their use outside human medicine needs to be reduced to the absolute minimum.

The discovery of antibiotics transformed human medicine and vanquished many infectious diseases in the developed world.

Yet resistance was detected in the 1940s, and since then our arsenal of effective antibiotics has dwindled quickly.

Antibiotic resistance not only compromises the efficacy of infection treatments but of other areas of medicine such as surgery.

And now the global crisis of antibiotic resistance has reached a point where a simple injury may once again prove fatal.

Antibiotics are commonly used in a wide variety of non-medical settings, which provide many opportunities for the development and spread of antimicrobial resistance.

And as we make clear in our new report, 'Non-medical uses of antibacterial compounds (antibiotics): time to restrict their use?', it is vital that these non-essential uses are stopped.

The origins of antibiotic resistance

Antibiotic resistance is the product of evolution. When bacteria are exposed to an antibiotic, those that are resistant survive, multiply and spread.

Resistance can arise from mutations in bacterial DNA or spread by the sharing of genes that code for resistance, which can be transferred even between distantly related species if they are present in the same environment.

Hence, resistance to a drug in a bacterium that does not infect people can be transferred to one that does, leading to infections that are difficult to treat. Low, sub-therapeutic levels of antibiotics make it easy for resistant bacteria to survive and can select mutations and gene exchange, promoting both development and spread of resistance.

Much attention has focused on the misuse of antibiotics in human medicine. Although important, this ignores the common, widespread use of antibiotics outside people which often occurs at low levels that promote resistance and its spread.

There is therefore an urgent need to assess the extent and implications of antibiotic use outside medicine.

Use as animal growth promoters

For reasons that remain unclear, antibiotics can enhance the growth of animals. Outside the EU, this has led to the widespread use of antibiotics in feed and water of food animals. Unfortunately, this type of dosing is not controlled and often large groups of animals are treated simultaneously.

In these cases, animals can receive sub-optimal doses, allowing resistant bacteria on their skin or in their gut to multiply and contaminate the environment.

If the antibiotic used on the animals is similar to one used in human medicine, these bacteria may be resistant to the human drug as well. This is called cross-resistance.

Therefore, alternatives to antibiotics for growth promotion in use in the EU, which include better hygiene, vaccination and improved feedstuffs, should be extended globally.

Veterinary use

Antibiotics are also widely used in veterinary medicine to treat and prevent disease. Ideally, individual animals should be treated according to their specific infection; however the lack of rapid tests make diagnosis difficult, and so herd and flocks of animals are often treated collectively.

Much like growth promoters, the antibiotics are provided in food or water, and the result can be low, sub-optimal antibiotic exposure in individual animals that promotes the emergence and spread of resistant bacteria.

Some of these antibiotics are used in human medicine as well, so transfer of bacteria of animal origin to people or antibiotic resistance genes to human infecting bacteria has implications for human health.

Other approaches to using antibiotics in animals could include innovative methods such as phage (bacterial virus) therapy or probiotics.

Use in aquaculture

Aquaculture (farming of fish and other marine life) is a huge global industry. Large scale farming is stressful to fish and impairs their immune systems. This leaves them vulnerable to infections and results in widespread preventative use of antibiotics administered as feed.

This type of dosing can result in low antibiotic levels in individual fish, which can give rise to resistant bacteria which are easily spread due to high fish densities. Unmetabolised antibiotics and resistant bacteria can be carried large distances through the water to other farms and to wild animals.

Fishing practices, industry, and environmental proximity allow many opportunities for the spread of resistance to terrestrial bacteria. Indeed antibiotic resistance genes arising in aquaculture have been transferred to human-infecting bacteria. An outbreak of antibiotic-resistant cholera in Latin America in the 1990s was linked to the use of antibiotics in the Ecuadorean shrimp industry.

Various other approaches to replace antibiotics already in place in some countries should be extended throughout the world; these include better hygiene and fish vaccination.

Use in horticulture

Although not used as widely as in animal farming, antibiotics are used to control some plant pathogens. For example, streptomycin was widely used to treat fire blight, a bacterial infection of apple and pear trees with Erwinia amylovora.

Streptomycin-resistant Erwinia have since been identified across North America, Europe, Israel, and New Zealand. The resistance gene has also spread to pig-infecting E. coli and human-infecting Campylobacter jejuni.

The use of manure containing antibiotic residues or resistant bacteria can also spread antibiotic resistance to plants. The consumption of food produce could expose microbes in the human gut to resistant bacteria.

The use of antibiotics on plants should be stopped.

Use in bee-keeping

One underappreciated use of antibiotics is in bee-keeping to control disease outbreaks, rather than burning infected hives. Resistance genes seen in bee-infecting bacteria have also been found in bacteria in cheese, meats, and other foodstuffs, as well as some human-infecting bacteria.

Another problem is that honeybees do not metabolize antibiotics, which could be passed on into honey and inadvertently consumed by humans, selecting resistant bacteria in the human gut.

Industrial use

There are many industrial uses of antibiotics. One example is the use of naturally occurring compounds in food preservation. Lactic acid-producing bacteria (LAB) are common, safe, and have a preservative role in some foods. They also produce bacteriocins - antibacterial proteins.

Since LAB are already common in food, bacteriocins are likely to be safe for human consumption, although only one is widely used at present. There has been some interest in the use of bacteriocins in human medicine, and their activity against a range of bacteria has been demonstrated.

However, resistance has also already been demonstrated, and clinical use would likely make this worse.

Antibiotics have also been used by the brewing industry to prevent bacterial contamination. The grains produced during brewing are also sometimes fed to farm animals, providing another route by which animals may be exposed to antibiotic residues.

Yet another industrial use of antibiotics is to prevent biofouling - the build-up of bacterial biofilms (slimy layers of bacteria growing as a collective,) that support larger organisms such as barnacles on boat hulls.

Having been banned on boats shorter than 25m, some boat owners have resorted to mixing antibiotics obtained from veterinarians with antifouling paint. This has the potential to select for antibiotic-resistant biofilm-causing bacteria.

The industrial use of antibiotics that can select bacteria resistant to drugs used in human medicine should be stopped.

Domestic use

Numerous antibacterial products are available for use in the home. Many of these, including some solid products like toys, contain triclosan, a synthetic compound with antibacterial properties.

Triclosan is active against many types of bacteria by targeting a specific protein. Resistance to triclosan can also give resistance to antibiotics that target similar proteins in human-infecting bacteria, such as the drug isoniazid used to treat TB.

Triclosan can also select bacteria resistant to several antibiotics used in human medicine, via increased antibiotic export from the bacterial cell.

The use of triclosan in all settings should be stopped.

Pollution of the water supply

Human activities can lead to environmental contamination with both antibiotics and antibiotic-resistant bacteria. Antibiotics may not be fully metabolised by the human body and a large percentage of an initial dose, along with resistant bacteria, may be excreted in faeces or urine. The accumulation of antibiotics in the environment can reach levels that select resistant bacteria.

Although water treatment vastly reduces the number of bacteria in drinking water, it may favour the growth of some resistant strains, as sometimes these can survive treatments such as chlorination. Biofilms in these systems are also treated and these are not always eradicated.

Contamination of water supplies is a route by which antibiotics and antibiotic-resistant bacteria can be widely disseminated. Effluent discharge from wastewater treatment plants and pharmaceutical production facilities are a further source of environmental contamination with antibiotics and may also play an important role in the spread of resistance.

The numbers of several antibiotic-resistant bacteria have been found to be higher downstream of such plants.

Many factors therefore contribute to the contamination of water supplies with antibiotics and antibiotic-resistant bacteria. More attention needs to be given to water management to minimise contamination that promotes the emergence and spread of resistant bacteria.

Antibiotics use outside medicine must be reduced to a minimum

Antibiotics have transformed human medicine, but their powers have been exploited in many other areas. Unfortunately, mankind has taken them for granted, and their over-use has undermined the very features that contributed so much to human health.

We now need to value antibiotics more highly, and recognise that they are a finite and diminishing resource whose use must be carefully managed.

While appropriate human use is very important, the use of antibiotics outside human medicine needs to be examined and reduced to the absolute minimum.

 


 

The report: 'Non-medical uses of antibacterial compounds (antibiotics): time to restrict their use?' is by the All Party Parliamentary Group on Antibiotics.

Laura J V Piddock is Professor of Microbiology and Deputy Director of the Institute of Microbiology & Infection at the University of Birmingham. She is also the British Society for Antimicrobial Chemotherapy Chair (BSAC) in public engagement and in that capacity is the Director of the public awareness initiative, Antibiotic Action.

Hrushi Vyas and Richard W Meek were Antibiotic Action interns. HV was funded by BSAC; RWM was supported by a studentship from the Midlands Integrative Biosciences Doctoral Training Partnership (MIBTP) funded by BBSRC grant BB/J014532/1.

Victoria Wells is BSAC's Science Communicator Officer.

The authors of this article are also the authors of the report.

 

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