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Testing times for antimicrobial resistance

In a diagnosis of the global superbug threat today, economist Jim O’Neill includes a recommendation that doctors test patients to find out if their infection is bacterial before prescribing them antibiotics. MRC-funded researcher Dr Tariq Sadiq at St George’s Institute of Infection and Immunity writes here about his research to develop better diagnostic tests that will help us get these results faster so we can make better use of antibiotics.  Dr Sadiq explains the need to improve diagnostics in clinics and out in hard-to-reach populations around the world to combat widespread antimicrobial resistance.

Dr Tariq Sadiq in his lab

Medical advances undermined

How have we been able to make so many advances in medicine?  What’s made us so successful at treating cancer and performing heart surgery? Our ability to manage one of their most serious consequences: infection.

Antibiotic resistance undermines those advanc­­es and could mean infections that we thought we had defeated, become untreatable. Global deaths from drug-resistant infections are likely to continue to increase over the coming years if we don’t find new ways to tackle them, perhaps reaching 10 million by 2050, if there is no effective action. It is estimated that nearly half of them will occur in Asia.

Treating the pathogen, not the presentation

Pathogens are anything that cause a disease – including bacteria, fungi and viruses. Different pathogens can sometimes have similar ‘presentations’ or symptoms. Antibiotics only work on bacteria and for many infectious diseases it can be very difficult to know which virus, bacteria or other type of pathogen is causing the problem. Where good diagnostics are available they can take several days to provide a result. Even then we may need to conduct further tests to check if the antibiotic will work.

For sexually transmitted infections in particular, you so often have to treat patients when they first come to you – you can’t wait days for the results of an antibiotic susceptibility test. In more rural or lower-income settings you might be prescribing many miles away from a clinic with diagnostic capacity. If we can make better, faster, more portable diagnostics, we can get better at prescribing.

I’m working on developing tests that will tell doctors whether a patient has a particular infection, like gonorrhoea, and whether the strain they have is resistant to certain antibiotics – all in about 30 minutes. This will help doctors to choose the right antibiotic with a lot more certainty and speed than before. That might put less so-called ‘selection pressure’ on the broad-spectrum antibiotics that we currently use – we might not have to use them as frequently and we’d be able to go back to using ‘old’ antibiotics with real confidence that they will work.

Why recycle old drugs?

Until the recent discovery of Teixobactin, it had been 25 years since a new class of antibiotic was discovered. Overuse and misuse of antibiotics in agriculture and human medicine around the world has meant that a growing number of infections have developed resistance to the antibiotics we have and we can no longer use them.

If too much of any bacterial infection develops resistance to a drug, treatment guidelines will stop recommending the drug for that infection and doctors are meant to stop prescribing them. However, that same drug will still of course work for a proportion of cases – we just need good diagnostics to quickly tell us where.

Is a post-antibiotic dark age coming?

Widespread antimicrobial resistance would cause major increases in morbidity and mortality but I wouldn’t describe it as dark ages. We need to educate both the public and professionals to be more responsible about how we use antibiotics. Let’s look at it positively: we’ve identified the issue and there is currently a massive global effort to understand the policies and actions we need to implement to make a real difference. The right diagnostics are just one part of the answer and as they improve and we improve our knowledge of how best to deploy them, I believe we will really enhance our ability to stem the tide of antibiotic resistance.

Making it work at every level

At the moment we’re working on a four pathogen test to detect chlamydia, gonorrhoea, trichomoniasis and Mycoplasma genitalium, as well as a test that can detect antimicrobial resistance when the patient comes in.

But we want to do more than just develop a functional test – we want to know what patients and doctors prefer and how effective different configurations of the test would be. We can then build the test as close to those preferences as possible. We’ve been talking to these stakeholders about every aspect, for example, do they want a test that looks for one type of infection and finds the best drug to treat it? Or would they prefer a test that looks for several different infections but requires more tests to find the best drug to use? Those kinds of questions are important because we may not be able to build the perfect test straight away but whatever we do develop needs to get used otherwise it’s unlikely to have much impact, no matter how clever it is.

Our group includes clinicians, public health physicians, epidemiologists and basic scientists. We work closely with academic institutions, industry and with clinics around the country. Funding from the MRC and the UKCRC Translational Infection Research Initiative has allowed us to put in procedures enabling the navigation of the diagnostic ethics and regulation landscape to conduct effective evaluations of diagnostics much more quickly.

Keeping up with the bugs

Antimicrobial resistance evolves. That means the markers we use to detect antibiotic resistance will change. While we develop these tests we have to carefully consider how we build the technology so that we can update it with new markers to keep up with the bugs. Otherwise we could end up with redundant technology in clinics that takes a long time to replace due to limited resources and the process of getting new diagnostics through regulatory bodies.

Beyond the clinic

We’re not just talking about clunky desktop machines, we’re talking about new diagnostics that offer testing more widely and cheaply to every community across the globe. Like handheld devices that you can take out into settings in resource-poor countries where patients might be hundreds of kilometres away from the nearest clinic and you need an answer quickly on how to treat them.

In collaboration with other groups, we have also developed a smart-phone app where people can check their own chlamydia result at home and use their phone to get an electronic prescription and quickly find treatment. We have shown it to be safe and acceptable in preliminary studies and this means they can go straight to a pharmacy without any need to see a GP or even a traditional sexual health doctor if it is safe to do so. That means, potentially, many more people can be treated faster. Plus the way we’ve developed it means that they can still come to the doctor if they need to as the results will still form part of their care record.

Tackling antimicrobial resistance will be about responsibility and action as well as innovation, that certainly means new antibiotics but it also means making the most of what we already have and finding new ways to keep finding, preventing and fighting infection.

As told to Sylvie Kruiniger

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