Resistance is not a phenomenon created by the modern antibiotic era

Many antibiotics are produced by micro-organisms which have resistance genes to protect themselves. The change and interchange of genes between micro-organisms went on long before the antibiotic era. But widespread misuse of antibiotics has promoted resistant bacteria by selection.

Bacteria selection has been happening for decades, in many medial institutions (e.g. dentistry, veterinary medicine, industry etc), from 1940 to 2019. In most European countries, the proportion of ampicillin-resistant bacteria is around 50–80% (data from EARS-Net —European Resistance Surveillance System[1]). For example, the use of antibiotics in the pork industry has multiplied thousand fold; methicillin-resistant staphylococcus aureus (MRSAs) are increasingly found in slaughterhouses. Furthermore, an explosion of the presence of MRSA’s has been shown in blood cultures in the UK since 1989–2002, (data from EARS-Net), and many similar statistics have been reported in Europe.

These new resistant germs have been spreading exponentially, thanks to the movement of people in the modern society (migration, tourism, etc.). The speaker gave the example that up to the 80% of travellers in the Far East return with multi-resistant gram negative bacteria in their gut flora.

What are the consequences of antibiotic resistance expansion?

The first consequence is increased morbidity and mortality. This is because empirical therapy is uncertain and fails more often; hospital stays are prolonged, which negatively impacts health care organisations and cost.

Anti-infective therapy is also becoming less effective. Cheap, safe agents are abandoned in favour of more expensive agents with a broader spectrum, feeding a vicious circle with bacterial resistance. Older agents which were previously discarded because of their toxicity and poor performance have been brought back (vancomycin, colistin, Fosfomycin etc.). Very few alternatives are left to parenteral treatment, and, for some, patients there is no option for active antimicrobial therapy at all.

A global health threat

Resistance to antibiotics could bring about ‘the end of modern medicine as we know it.’ These were the words of Margaret Chan, the head of World Health Organization in 2012. The General Assembly of the United Nations dedicated a session in 2016 to this topic under the heading: ‘Drug-resistance infections pose the biggest threat to modern medicine.’

The correlation between antibiotic consumption and resistance is well documented, yet antibiotic consumption is still currently increasing in all countries (Klein et al., 2018). Some developed countries have made efforts to reduce consumption, and in Sweden for example, a slight reduction in this can be found. However, these measures remain insufficient to counteract the global levels of consumption.

Positive initiatives

To reduce the high levels of consumption, the UN, WHO and many national governments have started to put some of the following initiatives in place:

• surveillance programmes for antibiotic resistance and consumption
• public education on the issue
• restriction of the sale of antibiotics and their use in agriculture and livestock
• promoting correct indications in public and private health care systems
• EUCAST (European Committee on Antimicrobial Susceptibility Testing) in charge of standardising resistance definitions and susceptibility testing[2]

The pharma industry conundrum

There is a paradox in the pharma industry: policies are being put into place to reduce antibiotic consumption, but the public expects cheap medicines to be available. However, all of this makes it more and more difficult to develop new and successful drugs. For now, there is no promising new agent in the pipeline to face the resistance problem.

The solutions needed

• antibiotics should be sold only under prescription
• use in animal care should be regulated
• pollution of the environment by antibiotics should be ceased
• education must be undertaken so people understand that they do not always need antibiotics
• health care, vaccination programmes, clean water and sewage systems must be made available for all
• incentives for research and development of new antimicrobials could help
• control of the use and misuse of antibiotics, and of the dissemination of resistant organisms must be implemented.

If appropriate steps are not taken and the problem is not resolved, the human race will have to modify its expectations and prepare for a new era without antibiotics.

[1] European Centre for Disease Prevention and Control:  https://www.ecdc.europa.eu/en/about-us/partnerships-and-networks/disease-and-laboratory-networks/ears-net

[2] European Committee on Antimicrobial Susceptibility Testing (EUCAST): http://www.eucast.org