theGIST Issue 12

Science in the Spotlight
The antibiotic
resistance crisis:
Why researchers are going
back to the drawing board
There's an old adage that says 'it
takes two generations to forget'. This
is certainly true when it comes to infectious
diseases and remembering
a time before antibiotics. A diminishing
number of people are alive today
who experienced the penicillin therapeutic
revolution of the 1940s and
even fewer who witnessed the horrors
of infectious disease treatment
that came before.
The normalisation of successful infection
control has led to it not only
being taken for granted but expected.
A sort of desensitisation to the wonderful
therapeutic advancements
that are antibiotics. Advancements
that mean if you get a persistent
chest infection, you don't hunker
down in a sanatorium by the sea with
your last hope being to "take the sea
air". Instead, you can expect some
antibiotics from your GP and should
begin being relieved of your symptoms
within 48 hours.
It is clear that antibiotics are one
of the greatest success stories of
medical science. This is reflected in
their use at every level of the healthcare
setting from prescriptions in
primary care, to use prophylactically
in routine operations and intravenous
administration for medical emergencies
such as meningitis.
However, this broad use isn't
without its problems and has meant
antibiotics have become a victim of
their success. Ever since the introduction
of the first widely used antibiotic
penicillin, we
have been careless
with their administration
and
have adopted a
laissez-faire attitude towards antibiotic
consumption, safe in the assumption
that the next medical
science phenomenon is around the
corner to cushion our fall.
There are problems in paradise.
Antibiotic resistance arises from
'selection' of resistant bacterial
cells in a bacterial population. So, if
you administer an antibiotic at a
dose not high enough to kill the
population as a whole, those bacterial
cells with some resistance
are selected for; they survive and
thrive without competition. The
emergence of resistance was
something Alexander Fleming predicted
in his 1940 Nobel lecture,
warning that "there is the danger
that the ignorant man may easily
underdose himself and by exposing
his microbes to non-lethal quantities
of the drug make them resistant"
[1].
These resistant strains can then
pass on antibiotic survival information
in the form of a plasmid, which
allows other bacterial species to
become resistant and persist. For
example, in the case of Klebsiella
pneumoniae, its population can accumulate
these resistance plasmids
and act as a reservoir of
resistance; a sort of library for other
bacteria to acquire instructions
on how to survive clinically relevant
antibiotics. In recent decades, this
has led to the emergence of MDR
strains (multidrug-resistant), with
some presenting resistance to almost
all known antibiotics. In other
words, if you catch one of these,
there is little a doctor can do to treat
you and, alarmingly, the incidence of
these cases is increasing.
To make matters worse, pharmaceutical
companies have woken up
to the business plan screw up that is
antibiotic resistance. The average
cost of bringing a novel drug candidate
through clinical trials to bedside
is around $2.6 billion USD. Understandably,
recouping this in drugs
sales whilst the clinical environment
is riddled with resistance would
likely reduce profit margins on antibiotics
that become ineffective
quickly. As a result, pharmaceutical
companies have diverted research
and development efforts away from
antimicrobial drug discovery.
This becomes a two-pronged problem
in the clinic with no new classes
of antimicrobials entering the market
in the last 40 years and resistance
to the current drugs continuing
to gather pace. Therefore, there has
been a narrowing of treatment options
for some infections. The World
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