Medics need to be fleet of foot when it comes to determining whether they are dealing with something tame or wild, but the traditional route to identifying bacteria takes time. Now a team of Harvard researchers is coming to their aid in the fightback against drug resistance, HELEN COMPSON learns.
Time is of the essence, of course. Faced with an unconfirmed illness, a medic on the frontline yet needs to choose a course of action.
And in terms of today’s desperate bid to halt the spectre of antibiotic resistance, the weight of responsibility has never been heavier.
But good news, help is on its way. A Harvard University research team is about to trial a new approach to analysis and prescription that one among its ranks says turns received wisdom on its head.
Actually, the way Bill Hanage, Associate Professor of Epidemiology, really put it was “we’ve taken a different approach to pretty much everybody else working in this field.
“The old school way of doing things was to take a sample, grow it on an agar plate, purify it, figure out it was exactly what you thought it was and then send it for testing all the way down the line, when what you want to know about is a specific pathogen and its antibiotic resistance determinants and to figure out the genome, so the approach is arse backwards.”
It takes time to get back the lab results that confirm diagnosis and precisely identify drug-resistant bacteria and all the while the illness can be galloping off into the distance.
Now, the Harvard team aims to arm medics with a new method, christened ‘genomic neighbour typing’, whereby the type of bacteria most likely at work in their patients is inferred within minutes of sequencing.
Simply put, metadata distils the identity of the bacteria’s closest relatives in a database of genomes.
Or as Bill Hanage explains it, “If you are walking in the jungle and there is huge feline with stripes, jaws and big teeth moving in the undergrowth near you and it starts growling, you don’t wait until you have sequenced its DNA before taking evasive action.
“All of the indicators are is that it’s a tiger and in the same way, if you look at all the information before you, you often find features that are correlated with drug resistance.”
All bacteria were not created equal – some were more prone to creating resistance than others. What genomic neighbour typing did was help medics make informed decisions about what they were dealing with.
“We know a lot about the world, we know what the resistance threats are,” said Bill. “What we have done is devise an approach whereby the doctor says, ‘hey, have I got a tiger in my sample?
“That’s a different question to ‘what are the antibiotic resistance characteristics of the sample?’
“You are just asking ‘have I got a tiger?’ You can send the samples to somebody else to count the stripes.”
Drug resistance is often described in apocalyptical terms: one of the biggest threats to human health which, by 2050, could be claiming ten million lives a year due to the inability to treat infection. The lives of our children and grandchildren are at stake …
Bill, who employs a mix of theoretical and laboratory work to research the evolution and epidemiology of infectious disease, takes a more measured view. “You hear it said that drug resistance is getting progressively worse, but that is false,” he said. “It is more complicated than that.
“Sometimes it does seem to be getting worse, but sometimes it appears to be getting better and it’s not clear what the factors are that determine that.
“However, what is true is the chance of someone you care about dying from drug-resistance infection is higher today.”
And that was a huge source of concern all over the world, particularly in places already facing a spectrum of increasingly untreatable infections. “It is a big deal,” he said. “The Bill and Melinda Gates Foundation has given funding to develop research.
“As a doctor, you are seeing people fall ill with infections you used to be able to treat and now you cannot.
“Sometimes those people die or they are in hospital longer, where they are at risk of other complications and taking up beds.”
In helping medics prescribe more precisely and efficiently, the genomic neighbour typing method will reduce the reliance on broad-spectrum antibiotics.
“When a doctor sees a patient, initially they know nothing about what is causing the disease,” he said. “They probably know that what they are seeing is a urinary tract infection, judging from the symptoms presenting, but they don’t know the cause.
“So when it comes to prescribing antibiotics, that is based on previous experience and a best guess.”
While broad spectrum antibiotics, so called because they cover a lot of the bases, are a reliable fall-back, their usage produces tremendous selective pressure not only on the potentially dangerous pathogen, but also on all the other bacteria in the body to evolve resistance, because they are all being targeted.
What the new method does is help the doctor on the hospital floor to recognise, ‘this is the same condition that was affecting patient ‘x’ we treated successfully last week using this drug’.
Bill said: “This could enable doctors to use narrow spectrum antibiotics, the specifically-targeted silver bullets, with the same confidence they currently use broad-spectrum antibiotics.
“It will allow us to take some old drugs that have been abandoned as too narrow spectrum back off the shelf and start using them again.”
Thereby bolstering the armoury being used in the battle with drug resistance.