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Posted: Friday 14 July, 2017 at 9:07 AM

Antibiotic Resistance

By: James Milnes Gaskell, Syndicated columnist

    If you are certain that neither you nor any of your loved ones will ever acquire an infection, you might think that antibiotic resistance need not concern you and anyway that it is a matter solely for the medical profession.  Wrong on both counts.

     

    Over 70 years ago infection and trauma were leading causes of death.  Then the antibiotic era began, the sulphur drugs in the 1930’s, penicillin and many others in the 1940’s and onwards.  Antibiotics saved millions who in former times would have succumbed to an infection.  Sadly, seriously and negligently we have squandered this resource.

    Let us go back to the beginning to see what might be the significance of this.  Just under 4 billion years ago, single celled life, bacteria, began on earth.  These creatures reproduce by dividing their cell.  This can happen in as little as 20 minutes. In any new generation there will be some whose modified genetic structure has produced a cell better adapted to the latest conditions of life, and this, as we will see, is essential to what we call antibiotic resistance.  Since the beginning and ever afterwards bacteria have been fighting each other for available space and energy/nutrients.  They develop weapons against other bacteria, and those under attack evolve defences.  Those defences may be called antibiotics.  Such a word is not limited to a prescription pill from a doctor’s office.  Bacteria have defended themselves throughout their existence.  They have colonised every part of the planet, their number is as near to infinity as not to matter.  There are innumerable species relating to their surroundings in different ways.  We are concerned with their relationship to human kind.  In our gut, lining the intestinal tract, there may be 100 trillion bacteria of up to 1000 different species, the total weight of which is about three pounds.  They digest our food for us, and fight invading microbes.  Without them we could not exist.  Many bacteria live on the skin and including those that emerge from the lungs or excreta, are sometimes transferred between people by skin contact.  Whilst we could not live without our friendly bacteria there are many harmful ones (pathogens) which cause different kinds of infection, and which we must try to avoid or defeat.  Antibiotics manufactured mainly by the big drug companies (Big Pharma) have helped us to overcome many infections and diseases.  However, continuously over this period pathogenic bacteria have been evolving defences and now many of our formerly powerful antibiotics are ineffective.  This is seriously bad news world wide, and because there is so much international travel strains of resistant bacteria evolving in one country are soon transferred to people in other places.

    For the first 30 or so years from the first use of penicillin in the early 1940’s, several classes of antibiotics were developed.  Resistance, not yet global, has evolved against all of them, even the carbapenims and colistin, the drugs of last resort.  Clearly, we need many new classes of antibiotics now if we are to be able to continue modern surgery safely and deal effectively with infections.  The problem is well recognised at the top level.  It was on the agenda at the G20 meeting in Hamburg.  The World Health Organisation has given repeated warnings about the appearance of multidrug resistant superbugs (see later).   In the US the figure given for drug resistant infection deaths is 23,000 per year, out of around 2 million hospital acquired infections.  A striking and alarming feature is that a nasty and life threatening infection, carbapenim resistant enterobacteriaceae [ CRE ] occurred in 65000 cases in 2015.   Calculations are that these infections double every two years.  So we expect 130,000 persons in the US to be infected this year and 260,000 in 2019.  These are dangerous infections giving rise to a range of different symptoms including urinary tract infections, pneumonia and sepsis (which used to be called blood poisoning).  40-50% of those with sepsis die of it.  Another frightening aspect of CRE is that their multiple drug resistance can be genetically transferred to other types of pathogen, by physical or near physical contact.

    The totality of the problem is well set out in excerpts from a speech by Dr. Margaret Chan, then Director General of WHO in 2016 as follows:
    ‘The rise of antimicrobial resistance is a global crisis, recognised as one of the greatest threats to health today…  Superbugs haunt hospitals and intensive care units all around the world…  Even with the best of care only around 50% of resistant tuberculosis can be cured…  With few replacement products in the research and Development (R & D) pipeline the world is heading towards a post-antibiotic era in which common infections will once again kill…

    This may even bring the end of modern medicine as we know it.  Compelling evidence shows that resistance is driven by the total volume of antibiotics used, also in food production.  …    What we need right now is to use the power that comes from political leaders…  We need national action plans that amplify the global action plan…  We need ways to target all behaviours that contribute to the misuse of these fragile medicines…  Antimicrobial resistance is a slow-motion tsunami.’

    What does she mean by misuse?  The more antibiotics you take over a lifetime, the more likely it is that you will develop drug resistant bacteria.    Calculations are that 30% of all antibiotic prescriptions are unnecessary, either because they are aimed at a viral infection, such as a cold or ‘flu, that cannot be touched by antibiotics or because the wrong antibiotic is given.  There are broad range antibiotics which target many different kinds of pathogen and narrow range that kill specific bacteria.  Doctors, in the absence of knowledge of the identity of the pathogen tend to use a broad range drug.  The disadvantage of this is that the broad range kills off more friendly bacteria allowing for an increased chance of developing resistant bacteria.

    Sick people tend to congregate in hospitals and that is, obviously, where most resistant infections begin and are transferred to others.  Hygiene and especially thorough soap and water hand washing has a big part to play in prevention.

    Dr. Chan mentions food production.  In the US 70% of all antibiotics are sold for use on livestock and poultry.  More than 96% of those drugs are routinely distributed en masse in feed or water, often to animals that are not sick to speed up growth and help animals survive the crowded, insanitary conditions of industrial farms.  Government testing has shown residues of antibiotics important for human medicine in the tissue of meat, poultry and farmed fish for sale.  In America there is no political will to enact legislative control.  The system is corrupted by the influence of powerful industry lobby groups.  Congress woman Louise Slaughter has in every session since 2006 introduced a Bill to limit the use of antibiotics in livestock feed to counter the threat of antibiotic resistance.  This would phase out eight major classes of antibiotic in healthy food producing animals, while allowing their use for sick animals.  This sensible bill has no chance of receiving the required support.

    Remember that Dr. Chan said that there were few replacement products in the R & D pipeline. Why is this?  It is because the directors of the Big Pharma companies, those that have the research capacity and the funds have decided that antibiotics which may be used by patients just for a short time, and against which resistance may rapidly develop are no longer worth the application of funds or research.  Indeed Pfizer closed its antibiotic research facility in 2011 and others have taken similar action.  Far more profitable they consider is to develop drugs for conditions that people will have for a long time, for example diabetes, blood pressure, arthritis and cancer medications.  It may take 10-15 years to bring a new drug to market through all the tests and regulated trials and cost up to a billion dollars.  Much money can be lost when a drug fails its trials.  And if a patent lasting 21 years has been obtained at the beginning then the drug, if a long time in development, will have only a short time in which to enjoy its patent protection and recoup the investment. This was recognised when the US passed the ‘Generating Antibiotics Now Act’ in 2012, whereby some patents may be extended for limited periods.  It has had little effect.

    Unless some large governmental funding guarantees are forthcoming it seems that Big Pharma is not interested, so we may have to rely on smaller innovative biotech companies, but their difficulty is the funding.  They may have a product which looks successful in the laboratory, but they then have to persuade investors to fund the trials.  Not easy at all.

    A novel approach that I am following is that of Helperby Therapeutics, [where I declare a family interest] headed by Professor Anthony Coates of St. George’s Hospital University, London.  This company has a range of products differing from others in that they are aimed at pathogens in the dormant stage.  This may be crucial to the prevention of early resistance.  Bacteria go in and out of active and dormant phases.  Existing antibiotics are only effective against the active phase. So, if the antibiotic has been dissipated in the body by the time the dormant ones wake up, there may be nothing but the body’s immune system to deal with the newly active bacteria.  This is why it is important to finish a course of antibiotics even though you may be feeling much better.  Some of Helperby’s drugs have been paired in successful human trials with existing antibiotics,against which resistance has arisen which they rejuvenate and make effective again.  This means that they are antibiotic resistance breakers.  The media, eyes set upon Superbug Armageddon, has not picked up these promising results, some achieved under FDA Fast Track guidance.

    ‘We take it for granted that science has a social responsibility ‘ J.Bronowski.  Unfortunately Big Pharma abandons their duty of antibiotic R & D and demands such large sums from governments that those institutions do not provide them.  Instead, governments should develop ways of backing the smaller biotech companies at least after a successful phase one human trial, as that is the point at which the remaining trials become too expensive for the smaller unit.  

    We now anticipate a period of unknown duration, until new and effective drugs are marketed, during which the overall situation will become progressively worse.  All that we can do in our small islands, on a personal level, is to live a healthy lifestyle, try to stay out of hospital, practise good hygiene, avoid physical contact with infected persons, complete any prescribed course of antibiotics, and perhaps ask our doctor to prescribe the narrowest range antibiotic that he considers will be effective.  We can also expect that if and when new antibiotics are available, that we shall have to pay much more for them.  This article if not medical advice.  It is for information only.  Always consult your doctor.
     
    Do we have a National Action Plan as advocated by the WHO? Can we be told about this please.
     

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