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Rise of the Microbes

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On receiving the 1945 Nobel Prize in Medicine for discovering penicillin, Alexander Fleming finished his lecture with a warning: ‘There is the danger,’ he said, ‘that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.’ Antibiotic resistance is now one of the biggest threats to global health, food security and development. It could kill as many as 10 million people a year by 2050.

According to the World Health Organisation’s 2017 Global Tuberculosis Report, there were almost half a million cases of multiple-drug resistant TB in 2016 – cases that are resistant to the two most powerful drugs. Only one in five patients were started on treatment and only half of them were cured.

Antibiotics are routinely given to patients undergoing common surgical procedures (including caesarean sections and hip replacements) to prevent them from getting infections during and after surgery. But rising resistance to the drugs normally doled out before operations is threatening the safety of such procedures. A 2015 Lancet study found that in the United States, 39 per cent of surgical site infections after caesareans are caused by organisms that are resistant to the standard antibiotics given to the patient before the procedure.

Such common infections as gonorrhoea, pneumonia and TB, once easily treated with penicillin, are becoming increasingly difficult to cure. That means more reliance on last-line antibiotics. But sometimes even last-line drugs don’t work and we simply run out of options. John Turnidge, an Australian expert on gonorrhoea antibiotic resistance, told me that the country was considering going back back to an old drug called spectinomycin, which has some toxicity. ‘Everything else is experimental,’ he told me.

Colistin, discovered in Japan in 1949, was one of the first antibiotics to be effective against gram-negative bacteria such as Pseudomonas aeruginosa which can cause pneumonia and surgical site infections. It went out of fashion for human use in the 1970s because of its high toxicity and associated kidney problems. But it has made a comeback in recent years and is now used as a last resort therapy for multiple-drug resistant gram-negative bacteria.

British and Chinese scientists have recently reported, however, that the colistin-resistance gene MCR-1, first identified in E. coli in Chinese pigs in 2015, has since been discovered in farm animals and people in more than thirty countries across five continents. The findings ‘pose a significant public health threat’.

Research into new antibiotics isn’t a priority for the pharmaceutical industry; it’s a lot less lucrative than cancer therapies, for example. But it does go on, and earlier this year scientists in Italy discovered a new antibiotic that is highly effective against bacteria resistant to known antimicrobials. Pseudouridimycin, found in soil collected from under a cypress tree in Tuscany, appears to combat infections in mice.

Clinical trials will probably start in the next three years; it will be some time before it’s available on the market. It’s also likely to be far more expensive than the drugs we have today, raising questions about who will have access to new antibiotics in the future. In any case, a new antibiotic is only ever a temporary fix, because bacteria will eventually develop resistance – sooner rather than later if current practices continue.

As Ramanan Laxminarayan, the director of the Center for Disease Dynamics, Economics and Policy in New Delhi, recently told me, ‘the current problem really is the fact that people don’t take it into account that their overuse is hurting everyone else’ – it’s a tragedy of the commons. ‘Some people not doing the right thing in respect to antibiotics is drawing away from the global stock of effectiveness,’ Laxminarayan said.

The answer isn’t to restrict access to the drugs, but to ensure they are used responsibly. Doctors who prescribe unnecessary antibiotics, pharmacists who dispense them, and patients who demand them, all bear some responsibility for the rise in antimicrobial resistance. But the burden doesn’t only fall on individuals: it’s also a matter for health services, the pharmaceutical, agricultural and food industries, and the governments that regulate them.

Comments

  1. thebears says:

    Antibiotic resistance is a massive problem, and individuals (and doctors) do have a responsibility. But I can’t help suspecting that misuse by patients is smaller scale than mass dosing of farm animals – which is often a default rather than a specific treatment? It’d be interesting to see a specialist comment on this.

    • Graucho says:

      To make matters worse, the well known side effect of antibiotics fattening animals has only encouraged overuse.
      https://www.scientificamerican.com/article/antibiotics-linked-weight-gain-mice/

    • whisperit says:

      The critical feature of bacterial resistance is that the genes that convey resistance are often contained on circular loops of DNA called plasmids. Plasmids can be absorbed and shared by many species, so that resistance can be spread through populations and across species very rapidly. To that extent, the clear distinction that we see between “animals” and “humans” is of little concern to bacteria.

      A recent paper in the Lancet (Tran-Dien et al) highlights, through one example, how the widespread use of antibiotics to promote animal growth in the 50s and 60s probably led to the explosive spread of the gene for ampicillin resistance in some Salmonella strains.

      This year, the FDA prohibited the use of medically important antibiotics solely for growth promotion in animals. Unfortunately, vets can still prescribe their widespread prophylactic use, even when no infection is present.

      Its a situation where the commercial interests of the pharmaceutical industry may not be unequivocally aligned with human welfare.

  2. MajorBarbara says:

    Another issue not often considered is that, especially at the lower-income working level, there is a mighty incentive for the patient to demand antibiotics.
    Say you are a worker with some kind of respiratory infection. The doctor tells you it’s viral, and therefore antibiotics will do no good, you just have to rest at home until it passes. However, your employer’s policy is, if you don’t come in today, don’t bother coming back at all. Or even if it isn’t, if your boss walks by your unoccupied desk or work station, he’s likely to think it might well remain unoccupied at a cost savings and little or no loss to the company.
    Under such circumstances, and I’ve lived them, the worker is likely to demand antibiotics anyway, on the off chance that even if it won’t kill the virus, it may kill off an opportunistic secondary infection. Or at least when he drags himself back to his post, he can present his prescription and pill bottle to his boss as evidence he wasn’t slacking, and moreover isn’t all that sick (and therefore needn’t be replaced by a younger, presumably healthier, cheaper worker somewhere in the Third World).
    To tell this man that his short-term individual life doesn’t matter as much as the long-term welfare of the species or the planet will ring hollow. He’s heard all his life that he’s merely a means to an end. He will grasp at whatever he thinks may work to his benefit. Even if you tell him he, himself, may eventually fall prey to one of the resistant infections his individual choice is promoting, he will answer that no one lives in ‘eventually’ and he must pay his bills now.
    I see no way around this dilemma that doesn’t involve coercion.


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