I am hoping that readers with access to antibiotic usage
data will be able to help here.
One of the legs upon which antimicrobial stewardship rests
is to assure that the most efficacious and safe antibiotics are used in the
appropriate dosage for the appropriate length of time in the context of any
given infection. Based on numerous discussions with infectious diseases
physicians, microbiologists and companies over the last 30 years, I believe
that this approach to the use of antibiotics is undermined by the pricing
within the antibiotics marketplace.
One can only (with some exceptions) use antibiotics that are
available within one’s institution or organization – that is – those that are
on formulary. Formulary committees vary somewhat in how they make decisions as
to which drugs to make available to physicians and patients, but most take into
account clinical data, pharmacoeconomic data, microbiology and price. They then try and make a value decision. Two
factors work against new antibiotics. Generics like colistin are cheap. Most
clinical data comes from non-inferiority trials. Pharmacoeconomics and
microbiology may act to counter negative factors, but then there is the overall
pharmacy budget. In institutions, regions,
and nations where the budget is tight, generics will be favored. Was linezolid
favored by antimicrobial stewards for the treatment of MRSA pneumonia – even
after it was shown to be superior to vancomycin? I don’t think so. (As I noted
in a previous blog,
there may have been a number of reasons for this).
One particular comment from a European expert sticks in my
mind. We were discussing the issue of value-based pricing for antibiotics. I was speculating on what the price for a new
drug specific for Acinetobacter, for example, would have to be to
provide a return on investment for its sponsor. The discussion was based on a 2013 meeting
held by Pew Charitable Trusts. When I mentioned prices ranging from $10,00 to
$30,000 per course of therapy, this expert recoiled in disgust saying that in
their country they would just continue to use colistin. This was in spite of
the fact that at the Pew meeting, insurers had expressed a willingness to cover
such costs depending on the data supporting the safety and efficacy of the
antibiotic in question. I was shocked – but also naïve. This opinion was
frequently stated by experts and pharmacists during market studies prior to the
launch of Avycaz.
Recently, two antibiotics were shown to be superior to
colistin both in terms of safety and efficacy – ceftazidime-avibactam
and plazomicin.
Of those, only Avycaz is currently marketed (plazo awaits regulatory
approval). A recent prospective observational
study of caz-avi demonstrated a 9% mortality in the caz-avi group vs 32% in the
colistin group – a 23% reduction in mortality when caz-avi was used as compared
to colistin. Most infections treated were pneumonia or bloodstream infections.
Renal failure was significantly more common the the colistin group and overall,
there was a 64% chance that caz-avi treatment would lead to a better outcome
compared to colistin. A third new
antibiotic, Vabomere (meropenem-vaborbactam), has shown superiority
to “best available therapy” (that often included colistin or polymyxin) in the
treatment of infections caused by carbapenem-resistant pathogens. It is
now being marketed by Melinta. 
Given that cetazidime-avibactam has now been available
globally for a period of time, and given good clinical practice and good
stewardship, it should be replacing colistin/polymyxin in terms of prescription
volume. But sales data for 2016 do not
yet bear this out. Apparently, the cost
of Avycaz in North America at around $8000 per course of therapy remains prohibitive. Vabomere is priced at about $5000-$10,000 or so per course of
therapy as far as I can tell. I have
been unable to examine prescription volumes for these drugs to further
substantiate my fear. But I strongly
suspect that the price perversion of the marketplace is leading to continuing
use of inferior antibiotics when new but much more expensive antibiotics would
be a better choice for patients.
I hope that one of you out there can help research this
topic by examining prescription volumes (or by other methods) . . .
I think that all physicians and patients would agree that inferior
therapy should not be used for potentially life-threatening infections. The
question is – which price are we willing to pay – the price in dollars or the
price in lives?
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