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Ireland's political and cultural magazine
38 November/December 2020
eective.
Because of that, WHO says health
professionals should only prescribe
antibiotics when necessary and
patients should make sure not to
share or use leftover antibiotics.
New treatments are needed, but
they are hard to come by, Dr Burke
says. Antibiotics take years to
develop, cost billions, and are only
taken for a few days by most patients
and so are not lucrative. Drus for
chronic diseases such as diabetes
are taken daily for years, and so are
far more profitable.
The incentive to develop new
antibiotics is also reduced by bacterial
resistance – since Bi Pharma cannot sell a
dru that no loner works. One of the most
promisin avenues, Dr Burke oes on, is the
use of phaes - viruses that naturally infect and
kill bacteria.
Colin Hill, Professor in the School of
Microbioloy at University Collee Cork, is a
leadin researcher in the field: “Phaes are the
most abundant bioloical entities on the
planet”, he says. There’s about ten quintillion
D
OCTORS GLOBALLY
worry daily about
fihtin Covid-.
However, some doctors
and medical experts now
worry not just about the damae the
virus can cause, but about the
medical battles that will follow in its
wake.
Under uidelines produced in
April by the Health Service
Executive’s Antimicrobial
Resistance and Infection Team,
antibiotics are to be iven to Covid-
in-patients with symptoms of
bronchitis or pneumonia, or who
produce coloured sputum when they couh.
The uidelines also stated that “frail elderly
patients” are at reater risk of death from
infections and, so may need to be prescribed
with antibiotics far earlier than doctors miht
otherwise do with patients of that ae.
While often necessary to save lives, the lon-
term result of a rowth in the already hih use
of antibiotics worries some healthcare
professionals, includin Dr Liam Burke, a
bacterioloy lecturer and researcher at the
Centre for One Health at NUI Galway.
“With Covid, the whole world is usin tons of
antibiotics to protect people from secondary
bacterial infections”, Dr Burke says. “That’s
oin to have a hue knock-on eect on the
levels of antibiotic resistant bacteria after this
is all over”.
“There’s a lot of antibiotic resistance in
Ireland, enerally, includin in some of those
bacteria that live in our nose or our throat and
Accelerating the
three-billion-year-old dance
of phages with bacteria
by Shane Raymond
As Covid-19 and other diseases spawn resistance to over-used
antibiotics, phages - viruses that naturally infect and kill bacteria –
may be a long-term replacement
a doctor in ten years time might be able to
take a swab from an infected site, put it into
a machine and wait an hour. An algorithm
will look at the genomes and say: ‘use phage
number 17’.
normally don’t cause any problems at all. But,
when our immune system is down they can
cause an infection. The more antibiotics we
use, the more bacteria et resistant”, he
considers.
The World Health Oranisation (WHO) has
stated that antibiotic resistance is “one of the
biest threats” today, warnin that a host of
infections includin pneumonia, tuberculosis,
food poisonin and onorrhoea are becomin
harder to treat as antibiotics become less
Irish Reserch
POLITICS
November 2020 39November/December 2020 39
technology will predict whether an antibiotic
won’t work against an infection. “That’s
futuristic”, he says. “But a doctor in ten or
twenty years time might be able to take a swab
from an infected site, put it into a machine and
wait an hour. An algorithm will look at the
genomes and tell the doctor ‘use phage number
17’. But we’re not there yet”.
At the moment, phages have to be grown in
test tubes with the target bacteria. If you’re not
sure which will work, you can add a mix of them
and only the ones that can kill the bacteria will
multiply. Soon, there will be trillions of them.
In some countries, they skip the test tube.
“You can just give a patient hundreds of phages
in a single dose that covers the spectrum of
bacteria that might be present”, according to
Professor Hill.
“That’s what they’ve done in Russia and
Georgia. The likelihood is that one of those will
work. The problem is the US Food and Drug
Administration or the European Medicines
Agency - they don’t like having things where we
don’t really know what’s in it”.
These safety concerns halted plans to use
phages on a patient in Cork who had a joint
infection in a replacement knee. While
the phage could kill the target
bacteria in a lab, it would cost
€1.5 million to produce
each phage strain to the
required safety
standards, which the
researchers couldn’t
aord. The patient had to
have the knee joint
removed, Professor Hill
says.
“There would have to
be some kind of regulation
that says ‘we’re approving
phages as a body, not each
individual phage
independently’. When the
pressure from antibiotic
resistance becomes more
intense, that will probably
happen”.
The benefit of the variety and
specificity of phage treatments is
that, if the bacteria become resistant, you just
swap out the old phage for a similar one. Or, just
hit it with two or three at the same time, reducing
the chance that they can become resistant to
almost nothing.
“If phages were that good, they’d have simply
wiped out all the bacteria and then disappeared
themselves”, Professor Hill says. “For three
billion years, when a phage kills a bacterium, a
very small number of the bacteria will become
resistant to that phage and they will begin to
grow again. The phage will mutate to be able to
kill that new strain and the bacteria will have to
become resistant again. So there’s kind of a
dance that goes on for millions of years. We’re
merely accelerating that when we do phage
therapy”.
Professor Hill warns against overblowing the
benefits of phage treatments, which are often
featured in very dramatic stories about people
coming back from the brink after antibiotics fail.
“You only hear about the ones that work. You
never hear about anyone that got given a phage
and didn’t get better”, he says. There aren’t a lot
of randomised controlled trials on phage therapy
and successful studies show they work about as
well as antibiotics.
But Professor hill doesn’t see it as an either/
or choice. “It’s a way of conserving antibiotics”,
he says. “There’s an awful fear that bacteria will
emerge that are resistant to every antibiotic that
we have at our disposal. We’re not there yet, but
that’s always a doom-laden prophecy: people
say that we’re going to end up in the pre-
antibiotic era where surgeries weren’t possible,
where there were no treatments available. One
way of preserving antibiotics and using them
more cleverly is to have alternatives, and phages
will be one of those options”.
of them (that’s a one with zeros after it).
About half of all the bacteria on earth are
killed every hours by a phae, so they really
dominate in terms of the lifecycle and the
environment that bacteria live in”.
Discovered before antibiotics, phaes have
not been used in the battle aainst infection
so far because they have to be matched exactly
aainst the virus that doctors are tryin to
destroy: “For decades, the Holy Grail was
somethin that kills all bacteria”, he notes.
“So, a clinician doesn’t have to worry about
what you’re infected with. Here’s an antibiotic:
it will kill the infection no matter what it is - the
broader the better. Now we realise that that
wasn’t necessarily the riht way to o”.
Antibiotics are “blind”, Professor Hill says.
They try to kill every bu that lives in, and on,
humans, includin healthy ut microbes. The
microbes that survive antibiotics can develop
a resistance to them that is then spread onto
other strains of bacteria nearby.
These immune strains now livin in the body
are often benin until a disease like Covid-
hits and the immune system stops workin.
Then, as the environment they live in oes
haywire, they can turn fatal.
Professor Hill warns that when usin phaes:
“It’s not enough to know that your infection is
caused by a Methicillin-resistant Staphylococcus
aureus (MRSA), you literally need to isolate the
strain.
You can only find the right phage once you
isolate the bacterium and absolutely confirm
what it is.
When the phages infect the bacterium, they
multiply within it. It bursts and releases all these
new particles - you can get two hundred new
phages for every infection, so they really
replicate explosively. Within a few
hours, one phage can multiply
into millions. And, when
the bacteria are gone,
they have nothing to
grow on anymore, so
they disappear
eventually too”, he
claims.
“It’s not like an
antibiotic where you
have to deliver the
killing dose throughout
all of the body at one time.
Dose isn’t that important.
You can add the phage and
more or less leave them to it.
But, of course, finding the
right strain takes time and
money and eort”.
Professor Hill says that it’s
already possible to sequence all
the bacteria from a sample using
a small device hooked up to a
smartphone. He hopes that, one day, this
In Russia and Georgia they skip the test tube. You can just
give a patient hundreds of phages in a single dose that
covers the spectrum of bacteria that might be present. The
likelihood is that one of those will work.
Phge on dish
