ANTIBIOTIC RESISTANCE - 31/5/98

Dr. Robert Upshall,

Whinfield Surgery,

DR_ROBERT_UPSHALL@whinfield.co.uk

For general information on antibiotic treatment go to ANTIBIOTICS

There are broadly four types of patient that receive antibiotics:

• Patients with severe and potentially life-threatening infections - e.g. meningitis, septicaemia, pneumonia.
• Patients with self-limiting viral infections.
• Patients with annoying and troublesome infections that without antibiotics are likely to be very slow to clear up - e.g.wound and skin infections.
• Patients with bacterial infections that although they respond to antibiotics will get better without in any case - e.g. strep. throat.

The first two categories are pretty uncontentious. Most people, medical and non-medical, would agree that the first category should be treated with antibiotics whilst for the second category antibiotic therapy is totally inappropriate. The third category is also fairly uncontentious and most would treat although some might try local treatments that don't require antibiotics. The fourth category is the most contentious by far and the most interesting in this context because it pits the interests of the community against that of the individual and I believe it warrants informed debate amongst intelligent individuals in general and not just doctors, pharmacists and health service managers.

What are the issues here?

• Is antibiotic resistance increasing? There is little doubt that it is increasing. Certain infections have become much more difficult to treat recently and a particularly troublesome example is the Methicillin Resistant Staphylococcus Aureus (MRSA). This organism is just like the ordinary Staph. Aureus which we've known about for a very long time and which causes skin infections and boils and much more rarely serious internal infections such as a particularly nasty type of pneumonia in debilitated individuals. Unfortunately it happens to be resistant to most of the antibiotics that knock out ordinary Staph. Aureus without any difficulty. It tends to inhabit hospitals and infect patients who are already ill with something else.
• Is antibiotic  resistance new and how does it occur? No it's not new, many antibiotics occur in nature and have been part of the chemical warfare between bacterial species or between bacteria and fungi. Some bacteria have always been resistant to certain antibiotics whilst no antibiotic has ever been universally effective against allcomers. Antibiotics work by targeting certain functions of the bacterial cell - penicillin attacks the formation of the bacterial cell wall whilst others attack, for example, reproduction. Bacteria are so diverse that the metabolism of one type bears little resemblance to another type so different drugs are required to target each. Bacteria develop resistance by changing their metabolism to adapt to the presence of the drug being used and this happens in two main ways:
  • Natural selection. Mutations are occurring all the time and because bacteria can double their population every 20 mins or so it is very easy for a resistant mutation to take hold and reproduce up to millions of individuals from one in a very short space of time. (Go to your calculator and multiply two by two and the result by two and so on until you get to a seven digit number - it doesn't take long).
  • Acquiring resistance. This is potentially the most worrying. Many bacteria contain bits of extra DNA called plasmids and these often confer protection against environmental substances such as antibiotics. We have "friendly" bacteria in our bowel, for example, and these may well contain bacterial resistance plasmids - especially if we've recently taken antibiotics. Unfortunately these plasmids can pass from one bacteria to another carrying the protection against the antibiotic with them and the two bacteria involved can be of different species!
• What can we do?
  • Use fewer antibiotics and be stricter about when to use them
  • Hold back important new antibiotics and not use them unless there is no alternative.
  • In some cases use more than one antibiotic. TB has traditionally been treated with three antibiotics initially reducing to two effective ones when the "sensitivities" come back fro the lab. It is much more difficult for bacteria to adapt to two drugs simultaneously than one. Because TB requires many weeks of treatment resistance would be quite likely to eventually develop in the patient if only one drug is used. In fact this is happening because patients would often like to take just one drug (which may be more pleasant) and many parts of the world (where there is a lot of deprivation and resources are scarce) supervision of treatment may be minimal and courses of treatment terminated before the eradication of the infection is complete. Resistant TB is probably the most serious drug resistance problem world-wide which is almost criminal because we did have sufficient effective drugs originally and the knowledge of how to protect their effectiveness.
• Is there hope? Yes I believe there is if everybody is responsible. Obviously as doctors we have a vital role to play in educating people not to expect antibiotics to be given when they are not needed and not to be tempted to give them "just in case". Patients have a role to play in not demanding them and instead taking advice. Drug companies must be responsible in promoting them - unfortunately the patent system encourages the companies to sell a lot of a new drug quickly because the drugs long term viability is of no commercial interest to them. Politicians and health service managers must take appropriate advice and devise policy accordingly. If we do this I believe there are several ways to overcome our problems:
  • Discovering (or rediscovering) alternatives to antibiotic treatment. Before Penicillin we did cope with many infections quite successfully. Improved hygiene and the use of antiseptics rather than antibiotics are two examples from the past, immunotherapy may lie in the future along with anti-bacterial viruses.
  • Developing new drugs. Really novel developments are perhaps not as common as in the early days of antibiotics but we have much better tools to understand bacterial metabolism now and design drugs accordingly.
  • Resting established antibiotics. Resistant bacteria often pay a price. Rather like the history of armour where heavy steel armour quickly went out of fashion when it no longer conferred much protection against the weapons of the day, bacteria have usually had to change their metabolism to cope with the antibiotic and given a level playing field with the native non-resistant bacteria they will eventually lose out. If the mutation slows their doubling time by even a few seconds or increases the numbers dying naturally by fractions of a percent this will eventually lead to the non-mutated form prevailing in direct competition.

 So I would be very interested to hear your response to the following question:

• If you had a bacterial infection such as a strep. throat which was bad enough to make you lose time from work but which you knew was going to get better eventually would you wish to be prescribed an antibiotic for it in the light of what you have read in this article even if the advantage was perhaps to shorten the illness by two days? Email me with your reply.

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