Antimicrobial (antibiotic) resistance

The control of infectious disease in the 20th century was very largely due to public health measures, such as vaccination programmes in the population, and to the use of antibiotics in the individual. In the past, lobar pneumonia was a major killer of otherwise healthy you adults; and the progression of this illness was often inexorable, unless with a rising temperature and rising delirium, the patient came to a ‘crisis’ with a sudden, marked improvement—the ‘crisis’ had passed. I have only ever seen historical records of this, but the rapid fall of temperature is quite remarkable. A forbear of mine had a lobar pneumonia in the 1930s, though he was one of the first to be treated by the early sulpha drug, M&B 693. Without it he would probably have died, like his brother; and I wouldn’t be here. Even so, he needed a considerable period of convalescence.

Infectious diseases are caused by microbes such as bacteria, as well as by viruses and other micro-organisms (and by prions). Antibiotics, such as the penicillins, are compounds derived from micro-organisms which interfere with the ability of other bacterial micro-organisms to replicate. Antimicrobials include these compounds as well as others which are entirely synthetic, such as the sulphonamides. This distinction is technical, and is often ignored, the terms being used interchangeably. Some viral infections can be halted with antiviral drugs; viral infections cannot be cured with antibiotics. Antiseptics are quite different; their action is chemical rather than biological, and the compounds are far too toxic for internal use.

The first antimicrobials were Salvarsan, an arsenic compound introduced in the first decade of the 20th century and used in the treatment of syphilis, and the sulpha drugs, starting with the ‘dye’ Prontosil Rubrum in the 1930s. Only some bacteria were sensitive to these drugs. Though discovered in 1928, penicillin did not become available in quantity until the 1940s. Since then, many other families of drugs have been discovered and brought into commercial use. However, no new class of antibiotic has been introduced in the last 15 years.

Drug resistance was soon apparent but generally overcome by alterations to the chemical structure, producing novel compounds; this wasn’t a long term solution.

MRSA is methicillin resistant Staphylococcus aureus. S aureus is the bug often found in boils and living quietly in the nose, and methicillin is a variant of the original penicillin. Unfortunately, although there have been further modifications to the basic penicillin structure, if an organism is methicillin resistant, it will be resistant to more modern variations. It’s become a very widespread and difficult problem, as has Clostridium difficile, often an opportunistic infection following treatment for unrelated problems.

Microorganisms become resistant because of changes to their genetic material, sometimes introduced by other organisms, or because they were ‘mutants’, and had always been resistant. Such emerging resistance can be seen as a natural response to a threat. In a germ population, such resistant organisms will come to dominate as their ‘weaker’ brethren are eliminated.

Bad practice also contributes to antibiotic resistance. As antibiotics have no effect on viral illnesses, giving them for such illnesses only tends to eliminate those bacteria which we all carry around; and their replacements may well be resistant. Further, incomplete courses of antibiotics also tend to produce resistant strains. In some places, antibiotics are used as ‘growth promoters’ in food production, particularly in livestock. Again, this tends to favour the emergence of resistant strains; and there are also the problems that the soil and watercourses can become contaminated with the drugs, and that the antibiotics enter the food chain.

Antibiotic resistance is now a serious problem. There are strains of tuberculosis that are resistant to most or almost all antibiotics. There is no other effective treatment for this disease. There are strains of gonorrhoea which are only sensitive to a single antibiotic; when they gain resistance to this, there will be no effective treatment.

It’s not just the treatment of infections which is threatened. In many operations, antibiotics are given to prevent infection, even in such apparently straightforward procedures as removal of the gall-bladder. In implant surgery, such as a replacement hip operation, deep infection around the metallic prosthesis may require removal of the metal at a further operation. It may not be easily possible to ‘re-do’ the original operation later. There are similar problems with cardiac surgery and the replacement of heart valves. Patients receiving transplants have to have their immune system depressed to avoid organ rejection; such people are particularly susceptible to infection.

Antibiotics have traditionally been developed and brought to market by pharmaceutical firms, or ‘big pharma’. This is extremely expensive and difficult. Firms have tended to make products more suitable for long-term problems, rather than those for ‘one-off’ use; the firms exist, after all, to make a profit for their stakeholders, they are not altruistic, charitable enterprises, even if they ought to have a moral compass.

The serious problems with drug resistance have recently been highlighted by the Guardian (also here) and was also the subject of a Panorama documentary on BBCTV. It’s vital that new antibiotic classes are developed, otherwise much of modern medicine that we now take for granted will become impossible. The Guardian article discusses new funding streams, and it’s vital that these are taken extremely seriously.

  • Sergiogiorgio

    The biggest problem in development of new antibiotics is that it is not economically viable for the Pharma companies. The commercial return does not meet the development costs. The only way through this is for governments to either fund the Pharma companies or allow higher prices at the back end. The governments and pharma companies are waiting to see who blinks first.

  • chrisjones2

    Mmmmm it may be worse than that. The problem is that the profession for natural sensible and professional reasons want to hold back new antibiotics as ‘last resort’ ie low volumes drugs This means that in the short term they aren’t profitable but in long term they may be

    Just last week Jim ONeills review for the UK Government recommended that Governments establish a $2bn fund to bankroll the development costs – in effect guarantee a baseline price for new drugs that work. This is perhaps one of those areas where Government can play a real and positive role in developing a social good – so why does UK PLC not do it and share the patent with the developers to sell to the Americans later?

  • Sergiogiorgio

    Chris – there’s just not a lot of appetitive to develop antibiotics and antivirals at the minute because of the relatively high cost of goods versus the market price. For an influenza vaccination I’d guess a COGs of maybe 50p a unit (a sterile filled liquid into a vial) and a sell price of a few quid. When you compare this to some oncology or orphan drug indications with a COGs of say £2 and a sell price of thousands, sometimes 10’s of thousands, the numbers don’t stack up. Believe it or not $2B wouldn’t cover the development costs of one antibacterial or antiviral from scratch. And the madness is that the government regulators set this price. Go figure!