Until it hit the headlines this week, few people outside the veterinary and intensive livestock farming sectors are likely ever to have heard of the antibiotic colistin. It’s not one your normal doctor would ever prescribe for you. But it’s suddenly become big news following the discovery of resistance to it in China.
The history of colistin
Colistin was one of the first antibiotics to be developed in the early 1950s, but it wasn’t used to treat serious infections in human medicine because it is very toxic. All antibiotics have side effects which affect different individuals to different extents, but few of them are as severe as those associated with colistin, which can cause kidney and neurological damage that is occasionally irreversible.
It’s hardly surprising, therefore, that drug companies originally assumed there would be no problem if colistin was developed for use in livestock production, as products like Coliscour and Colibird. One of its main uses has simply been to prevent or treat diarrhoea in piglets caused by E. coli bacteria which spread very quickly on intensive farms and especially in piglets weaned at 3-4 weeks of age, because their immune systems do not function fully until they are about 8 weeks of age.
But it is also used to treat and prevent E. coli and salmonella infections in veal calves and poultry. E. coli blood poisoning infections affect about 40,000 people a year in the UK every year and kill about 7,000 of them, including from time to time newborn babies which become infected in the birth canal.
The rise of antibiotic resistance
This gives an indication of why there is concern: resistance in farm animals can be in one of the same types of bacteria currently becoming the most difficult to treat in humans due to the rise of antibiotic resistance and the fact that no new antibiotics have been developed for such infections since the mid-1980s, and none are currently at an advanced stage of development.
But, in a sign of why antibiotic resistance is becoming such a problem, hospital doctors are now having to resort to colistin and a couple of other little-known antibiotics which also have significant side-effects, to treat some infections which are resistant to all other antibiotics. Use of colistin to treat human infections in the UK per 1000 people is the highest in Europe, and Ireland and Greece are the next two highest using countries. If you are otherwise fit and healthy, colistin may still save your life; if you are old or have a lot of health problems it might not. One study found that the ‘Adverse affects of colistin therapy contributed to the death of 13 (4.5%) of patients’.
The development of colistin resistance means that for those affected by a resistant strain, even colistin isn’t going to work. There is no clear evidence yet that this type of resistance has reached the UK. It has not yet been found in E. coli but it has been found in salmonella. Scientists are still unclear, however, if the strains involved are naturally resistant to colistin or have acquired this resistance. But with the volume of global travel and the international trade in meat, recent history with resistance to other types of antibiotics – less toxic ones previously seen as the antibiotics of last resort, teaches us that it will get here sooner or later, most probably carried unnoticed by someone returning from a visit to China who may not even become ill.
And that’s one of the unnerving things about some types of antibiotic resistance, the type that is carried on small pieces of DNA called plasmids which are separate from the chromosome. This type can spread and we can acquire it from completely harmless, or even beneficial, bacteria. The resistance can then pass (through a primitive form of sex between bacteria) to strains which cause life-threatening infections. There, it can survive for some time until, by chance, the circumstances arise where a pathogenic strain of E. coli is able to cause an infection – quite often initially just a urinary tract infection.
Colistin use in the UK and the rest of Europe
There are no published figures for the amount of colistin used on UK farms, but as an overall percentage of the antibiotics used the indications are that it is very small at about 0.1% of all farm antibiotic use. In the past the SFT has taken the position that it is reasonable for medically important antibiotics to be used to treat serious infections in farm animals if (and only if) it is known that no safer alternatives are available. However, we feel that because we really are at the very end of the line when it comes to colistin, that different considerations apply and that all use in farm animals should cease immediately.
In contrast to the UK, use on farms in the EU overall is very high, making colistin the 5th most widely used antibiotic on farms. In Spain, Portugal France, Estonia and Belgium colistin use in farm animals accounts for 13%, 9%, 6%, 5% and 3.5% respectively of all farm antibiotic use. And because of the number of people in the UK who spend time in other European countries each year, along with those who visit the UK each year, and because of the large amounts of meat and eggs imported into the UK, there is also a high probability that resistance could eventually spread to the UK from these countries.
Colistin, is also one of only four antibiotics which can be added to the drinking water of egg-laying hens suffering where there is no requirement to observe any withdrawal period at all. Eggs on sale can come from hens right in the middle of antibiotic treatment and chicken can be slaughtered for human consumption just 24 hours after being treated with colistin. One of the most disconcerting things about the regulation of farm antibiotics is that the legal withdrawal periods – the number of days from zero up to 40 (or more in some cases) after treatment when meat, milk or eggs are not supposed to enter the food chain, is based only on the level of antibiotic residues and takes no account the levels of antibiotic resistance.
These sorts of things are allowed because the amount of the antibiotic itself, or it’s metabolite, which ends up in the egg is considered to be below official safety limits. But because issues to do with antibiotics have not previously received the same level of public concern as pesticides, regulators have got away with publishing the results of residue tests which only list situations where residues are above, or close to, the official maximum residue limits. In contrast pesticide data on all detectable residues have long been made public.
The link with farms
The study, published in The Lancet Infectious Diseases, found that in China, where the resistance to colistin has just been discovered, over one in every five (21%) of E. coli samples from pigs and 15% from meat were found to be resistant to colistin, compared with just 1% in human infections. This suggests that some of the resistance at least is originating in farm animals and passing to humans. However, even if it were the other way round and originated in humans, there is evidence that farm animals can acquire resistance from people who look after them and from feed contaminated or affected by human sewage. And the problem there is that this would then rapidly spread amongst animals receiving colistin, greatly increasing the reservoir for further human infections.
All this illustrates why we still have a huge problem with the overuse of antibiotics on farms, a problem which the industry continues to brush under the carpet, with policymakers, journalists and the public still frequently misled into believing we only really need to reduce the use of antibiotics in human medicine.
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