Feature: Resisting microbial resistance

The focus for the World Health Organization’s (WHO) World Health Day last April was antimicrobial resistance, carrying the slogan: “no action today, no cure tomorrow”. The main message was that drug resistance is not only a continuing and growing global problem, but also that now may be the last chance to act.

The same message was trumpeted this month at the Australasian Society for Microbiology meeting in Hobart on 4-8 July. Besides antimicrobial resistance featuring heavily on the scientific program, Society President Professor John Turnidge also delivered a public lecture on the use and misuse of antibiotics, and how we might avoid entering a “post-antibiotic era”.

The success of antimicrobials against disease-causing microbes is undoubtedly amongst modern medicine's great achievements. Antibiotics, in particular, are truly wonder drugs which, since their commercial availability in the 1940s, have saved countless lives and caused spectacular gains in human health and life expectancy. Common and deadly scourges such as leprosy, tuberculosis, wound infections and syphilis could now be cured.

However, as with all good things, there is a downside: antibacterials like penicillin and erythromycin, which used to easily overcome many bacterial species and strains, have become less effective due to increasing drug resistance.

And like the infections antibiotics are designed to treat, resistance is spreading to dangerous levels such that previously alarmist headlines such as ‘super’ or ‘drug-resistant’ bugs are no longer a media beat-up.

For example, the last few years have seen an increasing emergence of stubbornly antibiotic-resistant Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB), which for a long time was reasonably well controlled. The result is around 500,000 new cases of multi-drug resistant TB occurring worldwide each year.

Other bacterial infections of major concern with respect to increasing drug resistance include diarrhoeal diseases such as dysentery, sexually transmitted infections such as gonorrhoea, and hospital-acquired infections. Some of these are ancient foes that we recently thought on their way towards total defeat.

Antimicrobial resistance is, of course, not a new problem and has been around as long as the bugs the drugs are designed to fight. Indeed, it antimicrobial resistance is simply an example of the power of evolution at work.

One mutation that lends resistance is spread to subsequent generations and increases in frequency as the non-resistant strains die out. The resistance mechanism then becomes increasingly prevalent until the chemical or compound exerting the selective pressure is completely ineffective.

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For many years, science and medicine managed to stay ahead in the war between microbes and their resistance mechanisms through the ongoing development of potent new antibiotics. However, this process has slowed dramatically in the last few decades.

Over the same time, human factors related to the medical and agricultural use and misuse of antibiotics have accelerated and amplified the spread and emergence of antibacterial resistance.

Underlying this status quo was the assumption that new agents would always be appearing to replace those rendered ineffective – an assumption that is clearly not the case anymore; less than five per cent of products in the current R&D pipeline of pharmaceutical companies are antibiotic drugs.

The nature of the problem

According to the WHO: “the most important contributor to antimicrobial resistance is inappropriate use. Both overuse, which tends to occur in wealthier nations, and underuse through lack of access or funding, inadequate dosing, poor adherence, and poor quality drugs, play a role.”

Thus, both economic factors and human nature contribute to the problem of antibiotic resistance, and underdeveloped nations are, as usual, paying the highest price. Turnidge says that in developed countries like Australia, antibiotic resistance is not considered a pharmaceutical or economic issue, but more of a complex societal problem.

“We need to examine the psychology of both user and prescriber to change perceptions and behaviours.” he says.

According to Turnidge, we actually got it wrong from the start with antibiotics by saying that these agents are harmless to us and that anybody can use them.

“We are paying the price for that now because people don’t want to give up things they have had access to for a long period of time. The result in many countries, including Australia, is that too many people are prescribed these drugs and this has created a high expectation in the community that antibiotics are the fix-all, even for infections not due to bacteria.”

He thinks that this positive feedback-type psychology – whereby people go to the doctor expecting them to prescribe an antibiotic, and are often not disappointed – can cause a knock-on or delayed effect in terms of resistance.

Read part II of Resisting antimicrobial resistance.