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See Dr Morton’s respect antibiotics and understand your prescription
The Prime Minister, David Cameron was voicing his concerns about antibiotic resistance this week and a leading general practitioner was being grilled by John Humphries on the radio this morning. Is in fact all the problem due to doctors, particularly GPs dishing out antibiotics willy-nilly, or is the problem deeper requiring large-scale adjustments to our society that will be uncomfortable for politicians to face, leaving the easy option of blaming the GPs? Well firstly, the topic is not new, indeed antibiotic resistance has been recognized by doctors since the very beginning of the antibiotic era.
Antibiotics work by interfering with the normal physiology of the bacterial cell. The processes targeted include bacterial physiology, cell-wall construction and bacterial genetic processes. Now, interestingly, antibiotics have been produced in the natural world since life began in order to give a competitive survival advantage to the species producing the substance. All the early natural antibiotics were derived from these products of moulds or soil dwelling organisms. In order to counter these effects other species of bacteria developed an awesome array of defences from physical barriers such as slimes, to enzymes that destroy the inhibitor or even evolving alternative physiological pathways that are not affected by the antibiotic.
In 1943 Abraham and Chain reported the existence of an enzyme that could destroy β-lactam ring of antibiotic molecules such as penicillin before these drugs were in wide clinical use. In fact in the natural world, even in remote soils of Alaska, bacteria either produce factors to disable antibiotics or develop alternative metabolic pathways that are not affected by the molecule, enabling survival despite the presence of these substances in their environment. In favourable circumstances, bacteria multiply quickly and are able to swap genetic information between themselves, (yes, even bacteria have sex) vis bacteriophage virus infections and even across species boundaries. This allows resistance mechanisms to spread rapidly and widely. It is thus not surprising that drug resistance to antibiotics developed within months of their introduction, and then rapidly spread around the globe. So antibiotic resistance is not new, it’s just more urgent because there are so few new products in the pipeline. All the easily discoverable drugs have been found, developed and used already.
The prohibitive cost of developing a new antibiotic that will mostly remain on the shelf as a drug of last resort is not going to encourage innovations in this field.
In order to understand this subject we have take a radically different view of ourselves, and our world.
Microbes were first observed as long ago as 1683 when Leeuwenhoek using his high-powered prototype microscope discovered teeming masses of life in plaque from teeth. We now know that there are vastly more microbes living on our surfaces than there are human cells composing the entire body (100 trillion human cells support 20 times that number of bacteria on each and every one of us). We need these wonderful single celled creatures to survive. They protect us from their dangerous cousins, they provide nutrients and stimulate the development of tissues in the gut and immune systems.
Interfering with this complex ecosystem presents several challenges, and for example many readers will be aware of the spread of fungi that often occurs following antibiotic use (thrush) or the devastating diarrhoea caused by overgrowth of toxin-producing bacteria in the gut, a major headache for hospitals. Furthermore, antibiotic use selects for bacteria that are resistant. These clones usually cause no harm to the host and reside as part of the normal flora such as Methicillin-resistant Staphylococcus Areus (MRSA). However, they may be can colonise other humans, and if they cause disease such as a wound-infection in hospital a dangerous situation may result. This is because the bacteria may have developed resistance to not just one but to many antibiotics and also along the way picked up a few genes that make it a particularly vicious customer. These include toxins and enzymes to dissolve host tissues. Of particular concern are those organisms that are resistant to every known antibiotic, and this nightmare situation has already arrived with the first few people suffering from totally untreatable infectious disease including lethal wound infections, gonorrhoea and more worrying tuberculosis. Whilst limiting the use of antibiotics by doctors, particularly general practitioners in the community, will help slow the spread of resistance to a small extent the issue of antibiotic resistance is a global not a local issue. Similarly, the response has to be global agreement, and sporadic local initiatives will have limited effect on the dissemination of these dangerous clones of bacteria.
Well by far the largest use of antibiotics is in agriculture and fish farming. Farms use double the amount of antibiotics than do humans. Although banned in Europe as growth promoters, they are still used in herds to treat infectious disease and have the beneficial side effect of increasing meat production; which can mean all the difference to farmers struggling to survive on low margins paid to them by major supermarket chains. About 300 mg of antibiotics go into the production of 1 kg of meat or eggs. In the US in 2009, 13,600 tonnes, that is 80% of the total antibiotic use, was for animals that weren’t even sick, but allowed higher protein production in often cramped and unsanitary conditions of modern industrial farming. At the other end of the chain, antibiotic producers dump 50 kg of ciprofloxacin a day into the rivers of Hyderabad. Oh and by the way what did you do with the remains of your last prescription found in the bathroom cabinet? Flushed away perhaps? Millions of others did. Isn’t it easy to criticize the GP who failed to give the child with flu-like symptoms antibiotics, but hours later developed a rash and then meningitis. Are we sure that we also want to join in the clamour to blame the same doctor for over-prescribing antibiotics for children with sore throats and ear infections? When did you last tuck into a nice prawn, salmon dish or roast? Did you think to ask whether antibiotics were used at any stage in the production? We cannot have it all ways. Cheap food, safe surgery, prophylaxis of dangerous bacterial infections, patient pressure on doctors, farmers’ pressure on vets, supermarket pressure on the farmers’, our pressure on the supermarkets. Easier to blame the GPs don’t you think. We need to wake up now, and fast to encourage international co-operation and standards to reduce this problem before it is too late. Finger pointing if required should be done in the mirror by the politicians, Mr Cameron, the journalists, Mr Humphries and I am afraid dear readers, by all of us, ourselves.
Have a lovely summer.
Professor Ayliffe’s Gresham College Lectures Return of the Microbes
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