I am writing this blog on the last day of the Interscience
Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San
Francisco. As someone whose living
depends on the pipeline of new antibiotics coming through, I am depressed. I always attend the poster review
session the first day of the meeting where the 10 best data sets on new
products are briefly reviewed. This year, as in the past few years, there have been precious
few gems among the 10 best. The
two most interesting to me were the presentations by Rempex where they are
developing a combination (Carbavance) between an old Japanese carbapenem, biapenem, and a
new B-lactamase inhibitor, RPX7009 – a boronate. Although this class of inhibitors has a bad reputation from
the past, the data on this molecule and on the combination look
encouraging. Merck – you may get a
run for your money!
The other
interesting presentation was from Trius on a topoisomerase inhibitor with a
very broad antibacterial spectrum.
It targets Gyrase B and ParE and is a completely novel class. Its actual binding site is the ATP
site. Unfortunately, many
compounds targeting this site have died a toxic death – so the jury is still
out – but the data are encouraging so far. The remaining presentations were
quinlones or quinolone relatives offering no particular advantage to existing
products either marketed or in late stage development. It seems unlikely that any of these
will get off the ground even though at least one has serious investor money
behind it. So – two out of the 10
best . . .I’m depressed.
On a totally separate note, an interesting study of
antibiotics in the treatment of exacerbations of bronchitis was recently published.
(A caveat – I was unable to get access to the actual article since I would have
to pay $$$ – so I am relying on the abstract and news reports for my
information). The investigators in
Spain, Dr. Lior and colleagues, studied over 300 patients with diagnosed
chronic obstructive lung disease who had acute worsening of their symptoms
(exacerbations). These patients
were only moderately ill. The
point of the study is that while it is clear that such patients with severe
exacerbations benefit immensely from antibiotics with reduced mortality rates,
it is not at all clear that those with milder disease benefit. This study
attempted to answer that question.
Half of the patients were treated with an antibiotic,
amoxicillin-clavulanate, and the other half received placebo in a blinded
fashion. Those that received
antibiotics were 14% more likely to achieve cure of their symptoms within 8
days and showed a longer time to their next episode – 233 days vs. 160 days. The study provides strong evidence for a
treatment effect of antibiotics in moderate exacerbations. I believe that by altering the design
of the study focusing on those most likely to have new bacterial pathogens as
the cause of their exacerbation would have led to an even more impressive
treatment effect. This is
important because both in Europe and the US, to
study a new antibiotic in the treatment of this disease, we would have to run
such a placebo controlled trial.
But, as
was the case for otitis media in children, equipoise may be lost. It may no longer be ethical to run such
a trial and, it is going to become harder to convince physicians and patients
to participate (rightly so!).
I know that I am running up against the pundits who only
want us to develop antibiotics for “serious” infections who believe that misuse
and abuse in the community breeds resistance. And I agree with their view in this regard. But at the same time, new antibiotics for
community acquired pneumonia should be developed – most of us agree on that. So the only thing that will happen is that they will be used “off-label” for "milder" infections like bronchitis. (By the way - if you are the patient with lung disease experiencing such an exacerbation - I wonder if you would consider the disease to be mild). Further, if
antibiotics work, which I think they do for some patients, and I think we can
identify those patients, we should be able to develop new antibiotics and get
them approved for use in this condition.
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