No pill for these ills

Submitted by Matthew on 10 September, 2014 - 1:40 Author: Les Hearn

Few of us can remember a time when people could die from trivial injuries or infections which now respond to antibiotics. The World Health Organisation estimates that drugs like penicillin and streptomycin have added some 20 years to our life expectancy.

Yet antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) could end our complacency and make even routine operations hazardous. Already, hospital-acquired infections by MRSA and Clostridium difficile are a major difficulty. In fact, a scarier problem is that of multi-drug-resistant bacteria or “superbugs”.

In the worst cases, bacteria may be resistant to all common antibiotics, as is the case with some strains of tuberculosis. Some 5,000 people per year die in the UK because they are infected by resistant bacteria. In the US, some two million are infected each year, with 23,000 deaths.

The problem of resistance has been known since the birth of medical antibiotics. It was recently highlighted, by UK Chief Medical Officer Sally Davies in a report [1]. Fifteen months later, David Cameron announced an inquiry into the problem.

The new “Longitude Challenge” has chosen as its focus, after a public vote, the development of a cheap, accurate, rapid, easy-to-use test for infections, so that bacteria may be targeted quickly with the appropriate antibiotic.

But why do we need new antibiotics to keep being found or made? The answer is evolution.

Alexander Fleming, discoverer of penicillin 85 years ago, warned that, if misused, resistance would soon develop and it would become useless. If just one bacterium among a population of trillions mutates to become resistant, it will survive. If not dealt with by the immune system and doubling every hour, its descendants will number trillions again in less than two days. And we will need a different antibiotic as the previous one will not work.

The early antibiotics were naturally-occurring compounds produced by moulds or bacteria to inhibit competition from other bacteria. Bacteria did not stand idly by and mutations that conferred antibiotic resistance evolved and spread in nature.

Bacteria have an extra trick — drug resistance can spread not just “vertically” (from parent to offspring) but “horizontally” by exchange of fragments of DNA, within species and even between species. This allows resistance to spread much faster.

The chance of resistance developing is increased if insufficient antibiotic is used, because more bacteria survive and the chance of a resistant mutation is increased. As Fleming said in his 1945 Nobel Prize lecture [2], “if you use penicillin, use enough”. The first patient treated with penicillin died only because there was not enough then available to kill all the bacteria in his bloodstream [3]. Mass production began in 1943 and in only four years resistance began to appear. That was due partly to black market sales of penicillin, where the stolen drug was diluted to increase sales. Art was to imitate life with the 1949 Graham Greene book and film The Third Man [4].

There is also over-use of antibiotics. They are frequently prescribed for virus infections, such as colds and influenza, for which they are ineffective. They can also be bought over the counter in some countries and taken inappropriately. This allows resistance to develop among the body’s natural skin and gut bacteria.

Subsequent injury allows an infection to occur which can no longer be treated with the antibiotic. Also, if the whole course of treatment is not taken (often because the patient feels better), the remaining bacteria have a greater chance of a resistant mutation.

And enormous amounts of antibiotics are given to farm animals because they enhance rates of growth — more scope for resistance to develop.

We have the greatest global economy ever, with enormously successful pharmaceutical companies, yet no new class of antibiotic has been introduced since 1985. Surely the capitalist market will supply a product for which there is a demand? This is certainly the expectation of those incorrigible optimists at spiked!, the website founded by members of the erstwhile Revolutionary Communist Party.

Their correspondent Robin Walsh, a trainee doctor, accused CMO Sally Davies of “fearmongering”: new drugs would rapidly follow if the government would alter its payment policy to the drug companies [5] and boost demand.

Unfortunately, financial incentives are not necessarily going to solve the problem. Drug industry insider Derek Lowe who blogs and writes In The Pipeline for Chemistry World [6] points out that virtually all targets in bacteria have already been attacked and no new targets have come up. Knowledge of bacterial genomes which has increased, but yielded nothing of use in 20 years.

He ruefully admits that it’s easy to come up with drugs that kill all cells but difficult to find those that attack only bacteria. Finally, any new antibiotic would rapidly come up against the same problem of resistance. This is because we are exerting “the most concentrated Darwinian selection pressure on pathogens” which leaves survivors very well-equipped to defeat future attacks. Lowe doesn’t think that money is the problem: it’s more that resistant bacteria are a very hard target!

This is highlighted by another recent finding — looking at environments across the world, ranging from oceans to soil to human faeces, a French research team found resistance genes relevant to human and veterinary medicine everywhere [7].

In order to generate profits, companies need to sell more of their products at as high a price as possible. That works for chronic illnesses, male impotence, headaches, diseases of the well-off, and so on, but not for bacterial infections. The more antibiotics you use, the quicker resistance evolves in bacteria. Antibiotics need to be used as sparingly as possible — not a recipe for generating profits. And when resistance has developed, there is little incentive to look for new antibiotics when they will be only a temporary solution.

New Scientist magazine is confident that solutions can be found if the free market is replaced by “socially-motivated medicine makers”. This goes against the worship of the market by the main political parties and certainly against extending the role of the private sector in health, as even Labour has done.

Other solutions include much more sparing use of antibiotics in medicine, banning their use in farming, much more rigorous hygiene in hospitals, development of new vaccines, and quicker tests to identify bacteria so that more appropriate antibiotics can be used straight away.

There really isn’t “a pill for every ill”.

Notes

1 CMO’s 2011 Report, Part 2 (published 2013): www.gov.uk/government/publications/chief-medical-officer-annual-report-…

2 www.nobelprize.org/nobel_prizes/medicine/laureates/1945/

fleming-lecture.html

3 Reserve Constable Albert Alexander had developed septicaemia following a scratch from a rose thorn and was dying in an Oxford hospital in 1941. He started rapidly recovering when given penicillin but when it ran out he worsened again and died.

4 The anti-hero Harry Lime (Orson Welles) steals, adulterates and sells penicillin on the black market. Asked about the victims of his crimes, Lime dismisses them as insignificant as scurrying ants. Highly recommended (the film, not Lime’s views!).

5 www.spiked-online.com/newsite/article/13447#.U_IhhhbaaX0

6 www.rsc.org/chemistryworld/2013/03/derek-lowe-antibiotics-research-phar…

7 www.cell.com/current-biology/abstract/S0960-9822(14)00328-5

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