10/15/2005

Superbugs - the problem of antimicrobial resistance

Superbugs – the problem of antimicrobial resistance
by Roger Buxton

"We can close the book on infectious disease". U.S. Surgeon General testifying before Congress, 1969...

"Following a car accident Ed Hill was taken to the local hospital and was in intensive care for nine days. He seemed to be recovering well and was then transferred to another ward where he deteriorated. Ed became confused and at some points he lost consciousness. Eventually he was found to have MRSA [methicillin-resistant Staphylococcus aureus]. He was put on a course of Vancomycin and kept in hospital for another two weeks". BBC News report, 2000.

Nine out of one hundred patients in Britain acquire an infection whilst in hospital resulting in the loss of five thousand lives and a cost to the National Health Service of one billion pounds a year. The most worrying aspect of this is that many of these infections can no longer be treated with the usual antibiotics because the bacteria that cause them have become resistant to antibiotic attack...

What has gone wrong since the optimistic statement of the U.S. Surgeon General in nineteen sixty-nine? In general the answer is that we are using too many antimicrobial drugs for the wrong reasons. The biggest single factor in the spread of antibiotic resistance is the huge quantity of antibiotics used in human medicine and agriculture.

How do antibiotics work and why are they such a special form of treatment against bacterial infections? After all it is not difficult to kill most forms of bacteria, you can just soak them in bleach. The problem is that bleach will kill you along with the bacteria. Antibiotics, however, are substances produced by living organisms that kill bacteria but leave the patient alive. The reason for this apparently amazing selectivity is really very simple. It is because many of the chemical processes in bacteria are so very different from those in man or indeed in any animal. Penicillin for example, works by interfering with the growth of the wall that surrounds bacterial cells. This wall is made of a substance quite unlike anything in animals or plants. Other antibiotics work by interfering with other parts of the bacterial biochemistry that are also distinct from animal processes...

Within a couple of years of the first use of antibiotics, however, resistant bacteria were found and they have continued to spread. The reasons for this are linked to two special properties of bacteria: their ability to exchange genetic material with other bacteria and their incredibly fast growth. Antibiotic resistance arises either through changes called mutations in their genetic material, DNA, or by the acquisition of mutant DNA from other organisms by transfer of genetic material. In the case of new mutations, bacteria are at an immense advantage since they grow so fast. A standard laboratory bacterium divides into two new cells in the course of twenty to thirty minutes, and these two cells are each immediately ready to grow and divide into two more cells in the next twenty minutes. A single bacterium therefore can produce more than a million cells in the course of twelve hours. If an antibiotic is present in the growth medium then only the rare bacterium that has acquired a mutation making it resistant to the antibiotic will be able to grow.

Knowledge of how and why bacterial antibiotic resistance mutations occur helps us to identify practices in the use of antibiotics which have increased the spread of resistance. Spread has not been uniform in all countries of the world. In Denmark for example, only zero point two percent of Staphylococcus aureus bacteria are resistant to methicillin, but this rises to forty percent in Greece and eighty percent in Japan. Parts of the former Soviet Union also have a high rate of resistance. Undoubtedly these differences are related to both the availability of antibiotics and their method of use. In many of the countries with high rates of methicillin resistant Staphylococcus aureus, antibiotics can be freely purchased without a doctor’s prescription. They may then be used for incorrect periods of time and in inappropriate situations. Mutations leading to antibiotic resistance are much more likely to occur if the bacteria are exposed to low doses of drug since the bacteria can then accumulate a series of mutations gradually. Similarly, if the antibiotic is taken for too long, the chance of resistance developing increases, and on the other hand, if a treatment course is not completed, drug-resistant organisms may more easily survive. The same can happen if the course of treatment involves more than one antibiotic, as does the current therapy for tuberculosis. If the drugs are taken one after the other, rather than all at once, an antibiotic-resistant organism can emerge which can then accumulate further mutations when it is exposed to the next antibiotic. On the other hand if the antibiotics are taken together, the chance of a mutation giving resistance to all the antibiotics at the same time is vanishingly small.

Antibiotics should therefore be more and more regarded as precious drugs requiring careful regulation. Even in Britain antibiotics are often prescribed unnecessarily for infections that are caused by viruses rather than by bacteria. Upper respiratory tract infections or bronchitis, which are mostly viral in origin, account for more than one fifth of all antibiotic prescriptions, and it has been estimated that between ten and fifty percent of outpatient antibiotic prescriptions are unnecessary. Improved diagnostic procedures would help to alleviate this over-prescribing since doctors sometimes write a prescription "just in case" bacteria are involved in a disease. Increasing patients' understanding of these problems would also help to dampen down expectations that an antibiotic will always be prescribed.

Perhaps more controversial is the use of antibiotics in agriculture and veterinary practice. Besides being given to combat specific disease conditions, antibiotics are given at high doses to prevent infections occurring. This provides strong selective pressure for resistant organisms, especially in the conditions of close animal proximity common in many modern farming practices. Lower doses are also given to enhance food conversion. The appearance of Enterococcus faecium resistant to the antibiotic vancomycin, the "antibiotic of last resort" for the treatment of methicillin resistant Staphylococcus aureus, is a particularly ominous example of a resistant bacterium appearing in animals that subsequently was transferred to humans; its emergence in food can be traced to the widespread use of a type of vancomycin in livestock. However, since antibiotics are of such financial benefit to agriculture it is most unlikely that their use will be eliminated. But prudence demands that, as is the case in Britain, only antibiotics not used in human medicine or those which do not select for cross resistance with antibiotics used in humans are used for this kind of performance enhancement.

NIMR :: Mill Hill Essays 2001 :: Superbugs - the problem of antimicrobial resistance

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