TACKLING DRUG-RESISTANT INFECTIONS GLOBALLY FINAL REPORT AND RECOMMENDATIONS

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critical to ensure that efforts are coordinated so as to leave no
‘blind spots’, and to better align spending with global priorities
for R&D on AMR.
Low-cost and high impact measures are often overlooked:
the example of old antibiotics
Much of the focus on antimicrobial R&D is rightly on providing
incentives to develop new drugs to combat the problem of
AMR. However, discovering and developing novel antimicrobials
is an expensive and lengthy process even with the correct
economic incentives in place. There may be lower hanging fruit
to exploit today: namely, making sure we make use of all the
diversity of antimicrobials that are already available, and that
we use them correctly.
“Forgotten antibiotics.” Experts agree that using a diversity of
antibiotics helps slow down the rise of resistance. Yet a study
in 201290 found that in 38 high-income countries studied, two
thirds of the antibiotics surveyed were not available in more
than half of the countries. The main reason for this is that
drugs manufacturers and distributors discontinue the stock
where it is not profitable enough to maintain it. This situation
is likely to be much worse in low and middle-income countries,
which already bear the brunt of developing resistance. There
must be ways for public health authorities to collaborate and
address this problem, for instance by bringing advance orders
together, to make sure old and useful antibiotics remain in
stock and can be used against infections.
Knowing how to dose old antimicrobials. Another low
hanging fruit in the fight against drug resistance is to make
sure we use antimicrobials in the correct dosage. Using too low
a dose – so called "sub-therapeutic dosage”- can speed up the
development of drug resistance: it exposes the microbes to the
drug without killing them, allowing them to develop resistance,
multiply and spread. Yet incorrect dosages for antimicrobials
are surprisingly common, especially for children, as many drugs
are not available in paediatric dosages. A study in 2015 showed
that nearly half the children in the sample were treated with
sub-optimal dosages of commonly used antifungal agents91.
A key driver of this routine non-optimal dosing is the
lack of recent studies of the pharmacokinetics (PK) and
pharmacodynamics (PD) of antibiotics. More study would
enable a better understanding of how the drug is broken
down, absorbed and excreted. Understanding these things is
crucial to determining what dose is optimal. Many PK and PD
studies on antibiotics were carried out in the 1950s-60s when
these antibiotics were discovered. However, with improved
techniques and protocols for PK/PD studies, these antibiotics
need to be re-evaluated to ensure that they are being used in
the most efficient way possible. This type of research is not
being done nearly enough at the moment.
It makes economic sense to devote innovation funding and
research capacity to steps like this to rejuvenate old drugs and
ensure better usage and dosing. Commercial and not-forprofit
partners are ready to begin this type of work - which
could be done in countries like South Africa, India, Brazil, China
and Russia where the expertise and the patients exist and the
need is pressing. Public or charitable funding is required and
would have a relatively low cost for a high public health value,
especially when compared with the cost of finding new drugs.
90 Pulcini C, Bush K, Craig WA et al., Forgotten antibiotics: An inventory in Europe, the
United States, Canada and Australia, Clinical Infectious Diseases, 2012, 54, 2, 268-74.
91 Lestner JM, Versporten A, Doerholt K, et al., Systemic Antifungal prescribing in
neonates and children: outcomes from the Antibiotic Resistance and Prescribing in
European Children (ARPEC) study, Antimicrobial Agents and Chemotherapy, 59, 2.