TACKLING DRUG-RESISTANT INFECTIONS GLOBALLY FINAL REPORT AND RECOMMENDATIONS

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A case study using gonorrhoea
The 70-year history of antibiotics has been marked by the
continual and seemingly inevitable rise of antibiotic resistance.
Gonorrhoea, a sexually-transmitted bacterial infection,
illustrates very well our constant ‘battle’ to overcome resistant
bacteria and so treat drug-resistant infections. Penicillin was
first used to treat gonorrhoea in 1943 and was highly effective,
but even by 1955 doctors had to increase their dosage 10 fold
in order to combat growing resistance. By the mid-1960s
tetracyclines had started to replace penicillin as resistance
continued to increase. In the 1980s and 90s doctors began
to switch again to fluoroquinolones such as ciprofloxacin.
However these too eventually could not be used because of
rising resistance rates, leading to the recommendation from
the WHO in 2004 that cephalosporins should be used in all
cases66. Currently the recommendation is for ‘last-resort’ dual
therapy with injectable ceftriaxone and oral azithromycin. We
have no obvious drugs left to use against gonorrhoea if these
fail, and because of this it is internationally considered to be
an urgent priority as resistance to both of these agents heralds
potentially untreatable infections.
While doctors have stopped prescribing many older drugs
due to resistance, this does not mean that these drugs
would never work. On the contrary as of 2013, 70 percent of
gonorrhoea cases in England and Wales were treatable with
oral ciprofloxacin and over 80 percent with penicillin. But a 20
or 30 percent chance that the treatment would fail is too high
for doctors to give these drugs to their patients; instead they
normally stop prescribing first-line drugs for gonorrhoea once
resistance rates exceed five percent. Given the combination
of the shortage of new drugs for gonorrhoea, old drugs that
would often work if we could use them, and existing molecular
diagnostics that are relatively widely used, we felt that it would
make for a good case study of the impact that a new rapid
diagnostic for predicting resistance could have.
There are three benefits to introducing a new diagnostic in this
area. The first is that patients would be diagnosed and treated
appropriately faster than they are at present. Secondly, this
would reduce transmission because people would be infected
for shorter lengths of time. Finally, we could begin re-using
old drugs, which would increase the size of our arsenal and
simultaneously reduce the selective pressure for resistance to
ceftriaxone, prolonging its effectiveness.
In order to best understand this we asked Dr Katy Turner
from the University of Bristol67 to examine the benefits of a
diagnostic for gonorrhoea, quantifying them where possible.
She found that rolling out a rapid diagnostic would reduce the
average time it takes for patients to receive treatment in the
UK by over two days. This would improve medication rates as
doctors could prescribe appropriate treatment on the spot,
and would reduce transmission as people would more often
be treated successfully before they had unprotected sex again.
Secondly a diagnostic that could predict resistance to older
agents could reduce the number of ceftriaxone courses by more
than 66 percent as most people would be given either penicillin
or ciprofloxacin. This would reduce selective pressure on
ceftriaxone, which would likely have huge benefits in fighting
resistance, although it is more difficult to quantify how this
would play out over time.
Finally, Dr Turner found that while there would be some cost
savings from bringing in the resistance diagnostic, due to
fewer appointments for patients, such savings were likely to
be lower than the cost of the diagnostic. This diagnostic does
not currently exist, so we can only guess how much it would
cost, but if priced at 50 GBP (75 USD) per test, it would cost
the UK an additional 70 million GBP (100 million USD) per
year to introduce the diagnostic. Whilst the price of testing for
resistant gonorrhoea is high, because the overall proportion of
infection in those tested is low, the benefit from preventing
or even slowing increases in resistance to ceftriaxone is
nonetheless substantial, since the costs of developing new
antibiotics are huge and, more importantly it takes around 10
years for new drugs to reach market.
This example highlights the paradoxical problem of new
diagnostics; in the short-term it is often cheaper for healthcare
providers and commissioners to rely on the current methods
of diagnosis rather than to adopt new strategies. However,
if we accept the financial ‘hit’ and introduce the new tests,
by preserving useful treatments for gonorrhoea and lowering
infection rates, the longer-term payoff to society would be
large. This is why we believe it makes sense for governments
to intervene in the market so that the external benefits of
diagnostics are properly captured.
66 Barry P, Klausner J, The use of cephalosporins for gonorrhea: the impending problem
of resistance, Expert Opinion on Pharmacotherapy, 2009, 10, 4.
67 Turner K, Christensen H, Adams E, McAdams D, Fifer H, McDonnell A, Woodford N,
Analysis of the potential impact of a point-of-care test to distinguish gonorrhoea
cases caused by antimicrobial-resistant and susceptible strains of Neisseria
gonorrhoeae, (In preparation), 2016.