Diagnostics
Other examples of antimicrobial resistance include the so-called ‘super gonorrhea’ (drug-resistant gonorrhea) presenting a new sexual health threat, and the several ‘superbugs’ in hospitals already considered a notorious menace. Today, 700,000 people die a year from drug-resistant diseases – and that figure is almost certain to climb. The UN estimates that, by 2050, AMR could contribute to ten million deaths a year, the bulk of which will be in lower-income countries. Against this backdrop, it is abundantly clear that we shouldn’t be overusing antibiotics. The more a drug is used, the greater the odds that the pathogen being targeted – along with other bacteria in the body – will develop drug-resistant properties. According to the US Centers for Disease Control and Prevention (CDC), between one-third and half of all antibiotic use in humans is unnecessary or inappropriate – adding fuel to a fast-growing fire. If we want to dampen the blaze, we need widespread antimicrobial susceptibility testing (AST), a laboratory procedure designed to identify which drug is appropriate for which patient. “Antibiotic susceptibility testing allows you to ensure that you’re using the most appropriate antibiotic for that infection,” says Professor Matthew Avison, senior lecturer in microbiology at the University of Bristol. “At the moment, clinicians tend to err on the side of newer antibiotics, which are where rates of resistance are likely to be lower. Unfortunately, the more they use them, the more rates of resistance will go up. We want to encourage them to use the older ones where possible.” Although these older antibiotics might prove ineffective, AST should give you a definite answer either way. If they are in fact going to work, you should be able to prescribe them with confidence, keeping the newer ones in reserve. “Alternatively, when it’s not going to work, you should then use the thing that will work,” says Avison. “Those are the two main reasons why we would use a susceptibility test – to ensure the patient gets something that’s going to work and to ensure that the latest antibiotics aren’t wasted when they aren’t necessary.”
Time is of the essence
Professor Alex van Belkum, global director of microbiology research at diagnostics company bioMérieux, points out that resistance flourishes the moment that you treat your patients with the wrong combination of drugs. “If you use antimicrobials that are too broad spectrum, then you may be wasting them by applying them in large numbers to patients who could profit from some of the more focused therapeutic approaches,” he says. “Aside from that, AST can also be used to do epidemiological studies and monitor the resistance of bugs.” AST, then, is an important tool in our armoury against AMR. But unfortunately, the procedure hasn’t yet lived up to its billing. The AST process takes around 24–48 hours on average, meaning the patient will often have begun a
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course of antibiotics – and not always the right ones – before the result comes back. “The systems that are currently available do what they should do, but they take way too long,” says van Belkum.
“If you could do an antimicrobial susceptibility test like you do a urine test or haemoglobin test, in half an hour, you would be able to provide your patient with exactly the right antimicrobial targeted towards their specific infection.” It’s for that reason that researchers have been turning their focus to rapid AST – tests that could be performed almost at the point of care, or at the very least, in time to guide that patient’s course of treatment. If the lab could return results that same day, rather than a day or two later, GPs would be able to take advantage of ‘delayed prescribing’ and quash inappropriate prescriptions.
“By the time the patient goes to get the prescription filled that evening, or maybe the next morning, the chemist will have been given the information through the GP’s system,” says Avison. “The patient will receive the drug that actually is necessary, rather than just the best guess.” Further down the line, the test might be performed by the GP practice itself, with no need to send the patient’s sample to a lab. “Potentially, the patient could sit in the waiting room and then leave with the correct prescription,” says Avison. “But that's a little way away, for all sorts of commercial and other reasons.”
New approaches
Under existing methods, an antimicrobial is added to a living bacterial culture to see whether it continues to grow. Lab technicians work with a suspension culture that includes hundreds of thousands of cells and need to go through multiple replications – a time-consuming process. As a result, researchers are on the hunt for other approaches that don’t rely on detecting changes in bacterial populations.
“What has happened over the past decade or so is that there are a couple of single cell approaches that are very promising,” says van Belkum. “If you are capable of fishing out one cell from a clinical specimen, then you only need to visualise what happens to that cell in order to define whether or not it is susceptible to the antimicrobial.”
US company Accelerate Diagnostics was the first to commercialise such a technology. Its Accelerate Pheno system immobilises individual cells on a piece of glass, and traces them over time in the presence or absence of an antibiotic. Results arrive within about seven hours. But even this could be too long a wait in some cases, and several diagnostics startups are attempting to cut the time down to minutes, not hours. Swedish startup Astrego Diagnostics uses microfluidics and image analysis methods to perform AST in less than 30 minutes. Similarly, UK-based Vitamica, a spin-off from the University of Bristol, is developing a rapid AST that
1–2 bioMérieux 13 50%
As much as half of all antibiotic use in humans is unnecessary or inappropriate.
CDC
Number of days the antimicrobial susceptibility testing process takes on average.
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