Treatments using antibiotics should stop as soon as possible
to prevent patients passing the “tipping point” of becoming resistant
to their effects, new research has shown.

A team of researchers, led by Prof Robert Beardmore from the
University of Exeter, has uncovered new evidence that suggests reducing the
length of the antibiotic course reduces the risk of resistance.

For the study, the researchers examined how microbial
communities – groups of microorganisms that share a common living space in the
body – reacted to different antibiotic cycling patterns, which sees the
medication restricted or increased, under laboratory conditions.

They found that changes both in the duration and dose of
antibiotics used and in sugar levels (which mimics the variable sugar levels in
human patients) could push these microbial communities beyond a “tipping
point” – creating an irreversible shift to becoming drug resistant.

The researchers insist this new study demonstrates that
resistant species can increase within the body even after an antibiotic is
withdrawn – if a tipping point was unwittingly passed during treatment.

The study is published in leading journal Nature
Ecology & Evolution.

Prof Beardmore, a mathematical biosciences expert from the
University of Exeter, said: “It’s a sensible idea that when you take an
antibiotic away, resistance goes away too, but we wondered what kinds of
antibiotic treatments don’t behave like that. After all, in some clinical
studies, resistance didn’t disappear when the antibiotic did.”

Antibiotic resistance occurs when microbes develop the
ability to defeat the drugs designed to kill them, and so they multiply
unhindered. Antibiotics are the most effective treatment for a wide-range of
microbial infections, including strep throat and pneumonia.

For decades, patients have been instructed to complete
courses of antibiotics because the perceived wisdom had been that taking too
few tablets would allow bacteria to mutate and become resistant. However, more
recently it has been suggested that the longer microbes are exposed to
antibiotics, the more likely it is that resistance will develop.

Little research has been conducted to show how the length of
a course of antibiotics impacts resistance, which, despite differences in
patients, for example in their blood sugar levels, are recommended to be the
same for all.

In the new study, the researchers examined how microbial
communities containing Candida albicans and Candida glabrata reacted to
different doses of an antimicrobial when fed with sugar.

Both species are commonly found together in healthy people,
but are also opportunistic pathogens which can cause infection.

The study showed that as the antimicrobial was introduced,
the communities were reduced, while the removal of the treatment allowed them
to flourish again.

Crucially, the researchers showed that if sugar levels
dropped in the community, it could reach a “tipping point” whereby
resistance would persist even after the antimicrobial had stopped being used.

The new research opens up the possibilities for further
studies to better understand when the best time would be to stop antibiotic
treatment, to prevent resistance occurring.

Co-author Prof Ivana Gudelj added: “Our body is a
mother ship for microbial communities but we’ve still expected to understand
drug resistance by studying microbial species one at a time, in the lab.

“We show this can be misleading because microbes have
intricate relationships that the drugs make even more complicated, and yet our
theories of antibiotic resistance have ignored this, until now. So that’s the
first surprise: even sugars can affect antibiotic resistance.”


University of Exeter

Beardmore R, et al. Drug-mediated metabolic tipping between antibiotic
resistant states in a mixed-species community. Nature Ecology &
Evolution (2018). Published 9 July 2018.