Candy floss, bacon butties, kiss-me-quick hats and seaside piers are hallmarks of Britain’s Victorian seaside resorts. For generations, Brits have gone to the seaside with their buckets and spades, built sandcastles with the kids and optimistically eaten ice creams under grey skies. Every year Britain’s politicians party in those same seaside resorts: spin and candy floss. In his finely observed account of coastal Britain, Notes from a Small Island, Bill Bryson caught the gist of these coastal communities.
Looking back at this week’s latest outbreak of election fever; the UK General Election, the British seaside spoke to its horizon. From John o’ Groats to Land’s End, the East coast voted 70% Conservative, while the West coast voted only 40% Conservative (X2 =12.17, p < 0.001). Could this have something do with the communities on the East coast looking out over the North Sea and the English Channel to EU neighbours, while the West Coast looks over Ireland to the more distant Americas?
But what about the candy floss resorts themselves: places where you can rely on proprietors of seaside boarding houses to speak their mind. Well, in the 2017 election mainland towns that are still blessed with a pier in England were overwhelmingly Conservative; 27 of the 33 (81%) available for assessment, compared to the one of six (17%) with piers in Scotland and Wales. You don’t need sophisticated stats to tell you that the Welsh and Scottish seaside resorts have a different outlook. But for those that worry about numbers, it is a significant difference (X2 = 7.67, p < 0.01). A pairing of maps makes this spatial correlation clear.
Seaside piers and 2017 UK election results
And here’s another piece of statistical candy floss: the number of parliamentary seats now held by Conservatives (R2=0.07) and Labour (R2=0.999) both correlate closely with the number of seaside piers per country within the UK (p=0.015 and 0.003, respectively).
So what on Earth has this to do with drug resistant infections and antimicrobial resistance (AMR)? If you’ve read this far, you’re likely to remember that the UK has led the global effort to get AMR on the political agenda. Yesterday’s retreat into Britain’s political tribal heartland, and a preoccupation with whether to separate from the EU for a stick of rock or a ball of candy floss, both risk losing the AMR plot. The drug resistant infection maps highlight the major international hotspots for MRSA, NDM1 and so on. The looming AMR crisis facing in health services may not yet be lapping at the edges of the UK’s seaside communities. But a loss of major groups of antibiotics could make a dose of sea air and a fat full of candy floss about as effective. If you take a look at the heat map for antibiotic prescribing in the UK’s coastal towns, many are doing their level best to catch up with the AMR profile of the major urban centres. These communities have yet to learn how to avoid making their antibiotic yesterdays turn into their drug resistant infection tomorrows.
FAST method for antimicrobial susceptibility testing
After a long lead-in, the first description of our FAST method has just stepped out of the shadows for all to see. FAST stands for flow-assisted antimicrobial susceptibility testing. It is an ultra-rapid method for one of the species on the World Health Organization’s top priority multidrug resistant bacteria hit list.
The FAST Lab team of bacterial flow cytometrists shortly after the 1st FAST method’s publication.
Introducing the lab team.
The FAST Lab team on the QE2 Medical Campus in Perth, Western Australia have been working on multi-drug resistant Klebsiella for several years now. They have witnessed an increase in carbapenem resistance. The mechanisms of resistance to carbapenems are getting increasingly complicated. This can make the pathology laboratory’s task a bit tricky, prolonging the time it takes to come up with a definitive antimicrobial susceptibility. This rapid method is our response to the challenge. It’s now up to the FAST Lab and our international partner labs to work out how to bring this rapid method into wider use.
See the FAST Lab team here.
The need for a faster AST method.
The FAST scanner. Thinking the task through from the pointy, clinical end, the overriding problem is that the antibiotic pipeline is very dry. It will take a decade or more to bring any major new antibiotic into widespread clinical use. That is why we need better, faster diagnostic methods to target our dwindling stock of antibiotics more effectively. At the moment, conventional antimicrobial susceptibility tests take 18-36 hours after initial detection of bacteria in a clinical sample. The internationally recognised Minimum Inhibitory Concentration (MIC) takes 24hr. MIOC tests start with a pure culture of the bacterial species in question and depend on culture. Our method takes around three hours because it uses an acoustic flow cytometer to detect early changes in antibiotic-exposed bacteria. As a flow cytometer is a very sophisticated automated microscope, you can imagine how much more efficient it is than the human eye.
Speed dating AMR
The race is on. Can FAST get even faster? At present, the first iteration of our method removes the delay caused by the second culture stage in the clinical lab process. True culture-independent antimicrobial susceptibility testing has to remove the primary culture stage as well if the treating physician is going to get antibiotic decision support at the point of care. The time it takes to complete the decision pathway is particularly important in sepsis. We may be fast, but we’re not yet on the inside track with severe drug resistant infections. There are some promising technologies that could lead to practical improvements, but you will have to wait a bit longer for the lab team to bring them to fruition.
Language! It sounds like something a teacher shouts across the school playground during a noisy recess. This week’s comment in the journal Nature calls us to task for our inconsistent, inaccurate and impenetrable use of language in connection with antimicrobial resistance (AMR). The authors rightly call out terms that do not communicate complicated ideas about resistance in digestible words and phrases.
Guilty, as charged.
Micrognome’s readers will be familiar with the language theme. These pages have spilled a lot of digital ink on the language of infection, its mechanisms and consequences. More recent entries have homed in on the language problems of AMR, not least the abstract nature of AMR and our need for a simple word or phrase to use in calling out its consequences; highly antibiotic resistant diseases.
Nature’s commentary gives us a good serving of bad language. We need to drop the complicated tongue twisters like antimicrobial resistance and multidrug resistant [insert your favourite bacterial name here]. How many frontline clinicians can accurately conjugate Graeco-Roman Linnean bacterial names? Even those bacterial names in common usage are often short forms that lack strict accuracy, so there is little scope for terminological pedantry. The commentary correctly identified the untreatable aspect of this phenomenon as a core feature. But if we take a look at just one common example, we can see that this is still a work in progress.
These figures shows bacteria growing on agar after incubating a sample of urine from a patient with a common urinary tract infection. These bacteria have then been cultured in a smooth lawn on a clear type of agar with disks that contain antibiotics.
E.coli growing on CLED agar, showing yellow colonies of concentrated bacteria.
Test for antibiotic resistance due to extended spectrum beta-lactamase (ESBL)
These disks are in pairs with (left) and without (right) a chemical that switches off a mechanism the bacteria from the urine specimen use to inactivate the antibiotics. If you have managed to follow the story so far you will notice how the circular halo of clearing around each disk is much larger on the left than the right. That is because the chemical added to the antibiotic protects the antibiotic against bacterial inactivation. Sometimes this approach can be used to treat a resistant infection. Complicated, isn’t it? For more information on antibiotic inactivating mechanisms read [here].
If you read this far you either live an unhealthy life away from natural sunlight in a clinical lab, or have an unusual level of fascination with the natural world. The rest of the global population don’t connect with the granular detail of AMR and its pathological consequences. Our experience of disease is usually couched in terms of illness or sickness, and does not stretch to the invisible biological processes that keep the Micrognome and his tribe gainfully employed. So if there is improvement to be made in the language of infection, it needs to be translated into the language of infectious disease. Drug resistant infection may thus need a bit of adjustment, to drug resistant disease. Happy editing.
2016 in review
A lot has happened this year. Sometimes it’s been like doing traffic duty during rush hour in the centre of Rome: lots of decisions, vehicles coming at you from all angles and no obvious coffee break on the horizon. It has left little time to review the bigger currents in the overall tide of events until now, when clinical demands continue to compete for time in the few days remaining. This review will be brief.
Antimicrobial resistant infections continue to dominate our work. The rise and rise of antimicrobial resistance grabbed the news headlines in August when the UN General Assembly debated the scale of the problem and the need for a global action plan; only the fourth time the UN has given a health issue this level of priority. As a result of securing support from the Bill and Melinda Gates Foundation for work on a new method for detecting antibiotic resistance, we had a presence at the Gates Foundation annual scientific meeting in London. It was a great opportunity to hook up with other impatient innovators and pool our efforts in the search for technology solutions to some of the world’s biggest health challenges. The conference was an important boost to our R&D programme in the last quarter, when most people are preparing for the long summer holiday. We end the year on a positive note, expecting some important news early in 2017. We’re going to have to keep readers in suspense until then.
Rambutan seller, on the road between Colombo and Peradeniya
Our itinerary took us to Sri Lanka for training twice in 2016. The first time was a Rotary Global Grant activity that trained a group of clinical laboratory scientists and doctors in molecular biology methods. The top trainees were selected for a vocational training team, which visited Western Australia for additional immersion training with PathWest and University of Western Australia staff. But before that visit could take place, molecular biology equipment was delivered to Sri Lanka, and installed in clinical laboratories in Central and Northern Provinces. Lab Without Walls members travelled to Sri Lanka twice this year to support the project, and are helping Sri Lankan colleagues complete the next stage of a surveillance project on the potentially fatal tropical infection known as melioidosis.
Real time thermocycler’s first run in Northern Province, Sri Lanka.
Laboratory support for patients with sepsis was the focus of our initial work on regional diagnosis of septicaemia, and continued in field trials of the FilmArray technology in regional pathology laboratories. That work has expanded into a health economic study and evaluation of a similar FilmArray method for meningitis. This work in regional Western Australia was presented at national meeting in Perth and Melbourne, and European meetings in Wurzburg, Munich and Prague.
Those who want to hook up with our lab team can have a closer look at current projects via ResearchGate.
In many ways 2016 has been a year of the internationally bad, the sad and the mad. One of the sadder losses we ought to note is the passing of Jack Woodall, founder of the ProMED alerts for emerging infectious diseases. The world needs much more of his brand of enthusiastic internationalism. Considering his passing puts the work we’ve done this year into perspective. As we gaze into the start of 2017, how can we seize the day, strive to be our best and close in on those elusive millennium development goals? Let’s aim to achieve more than a bit of order in the rush hour traffic.
Rumours of the Micrognome’s demise have been gathering for some time. So a search party was sent out to locate the missing gnome or confirm his fate. Fortunately our efforts have not been wasted. True, there were a few false trails, but we can now reveal that we have been able to verify recent sightings in northern Europe.
Frightened of resistance?
According to our gnomefinder-general, the Micrognome took to the woods at the news of resurgent antimicrobial resistance. At present Europe is at the forefront of the battle against resistance, bringing global attention to the subject. So no quiet retirement for the Micrognome, his colleague the MicroB, located on a mossy birch stump, or their friend the Lab Rat seen here boxed in at the Nobel Museum.
Taking AMR seriously
For those who have been waiting patiently for reassembly of our intrepid team, the wait is almost over. But there are a few skeptics out there who still don’t think antimicrobial resistance is anything worth bothering about. Well, our three bug-busters respectfully suggest they take a look at what the adults are saying about untreatable infection:
Tragedy of the commons
The Micrognome’s considered opinion is that there may be a consensus on AMR strategy, but there is still a long way to go on the application at ground level. We are missing a plan. Good ideas from the great and the good rarely percolate down from the lofty mountain heights to the the murky depths of pine forests and birchwoods where micrognomes are at home. The specific tasks to control, turn back and eventually eliminate AMR are going to take more than just the micrognome and friends to set in motion. It needs to be a giant effort to conserve the dwindling stock of effective antibiotics, reserve them for evidence based use so that their benefits are preserved for those in most need. Conserve. Reserve. Preserve. These will be the watchwords for the coming fight to overturn the AMR tragedy of the commons.
So don’t leave it to infection to test how much you’re missing on AMR. You really don’t want to end up like this interesting specimen.