Sunday, October 22, 2017
Emerging antibiotic resistance is not going away. MRSA is maybe less common today than it was 20 years ago – but MRSA infections occur in my small hospital population every week. Plasmid-mediated resistance (mcr) to colistin, our very last line and very toxic antibiotic that does not even work that well, continues to spread. The CDC is tracking mcr in the US and the picture is not encouraging. Carbapenem-resistant Enterobacteriaceae – those Gram-negative pathogens resistant to our last line safe and effective class of antibiotics – have now been reported from every state in the US except one, Maine. This is in spite of all of the work, all of the publications and all of the hand-wringing that has occurred over the last several decades.
We know what we have to do.
· Preserve the utility of the antibiotics we have through appropriate use including in animal husbandry.
o This also means regulating antibiotic use and antibiotic production in countries that do not currently do so.
o But even appropriate use will, ultimately, select out resistant strains.
· Provide for a robust pipeline of new antibiotics active against the continually emerging resistant pathogens.
o Solve the scientific problem of getting antibiotics to permeate into Gram-negative bacteria.
o Stop the continued loss of antibiotic discovery research through attrition of companies working in this domain.
o Train a new generation of antibiotic hunters.
o Fix the broken antibiotic market.
All of this has been the subject of numerous new articles, documentaries, and even, in the prior administration in the US, a part of the political debate. And yes, we have made and are making some progress on all these fronts EXCEPT the problem of the antibiotic market. If we don’t fix that, everything else is a house of cards that will collapse of its own weight.
The problem I have is that I know that I am already speaking to a population of interested parties. Maybe some of you are the converted, the true believers. I now have to ask all of you who read this blog to become more involved. I have in the past requested that you contact your representatives in government. I hope you did so. Now I must ask that you contact all of your family members, distant cousins, friends, acquaintances and anyone you can think of and ask them to do the same.
Some of you are involved in training professionals. Make this a learning topic.
I accept that I am getting older and that sooner rather than later I will end up in hospital risking that highly resistant infection that may take my life. But I have a hard time accepting that my children and grandchildren will have to deal with antibiotic resistant pathogens for which we have no or only very limited therapeutic options.
I hope that all of you feel the same way I do and that you will act!
Wednesday, October 4, 2017
Since the reboot of antibiotic development that the US Food and Drug Administration undertook in mid-2012, there has been a clear acceleration in the rate of approvals of new antibiotics. The graph below shows FDA approvals of New Molecular Entities of antibiotics over time – and it speaks for itself. Clearly, even after the reboot, we are not reaching the rates of approval we saw during the 80s and 90s – the heyday of antibiotic discovery and development. But there seems to be a clear improvement.
A close look at those approvals shows that two of the antibiotics approved in 2014 (dalbavancin and oritavancin) were holdovers discovered in the 90s that had previously been discontinued from development related to changing FDA regulations, to market considerations and to technical issues. Both are administered intravenously and target only Gram-positive pathogens. Nevertheless, the post-2012 approval rate remains encouraging. Will this continue?
I “borrowed” the analysis below from a public presentation by John Rex describing the DRIVE-AB recommendations for pull incentives. Here he analyzes the current pipeline focusing on resistant pathogens in terms of WHO priorities and the likelihood of approval of products currently in clinical trials. It looks like it is conceivable that today’s rate will continue over the next five years but that new antibiotics active against resistant strains of the gonococcus, Acinetobacter and Pseudomonas will remain rare for the foreseeable future. The forecast is much more favorable for antibiotics active against Enterobacteriaceae including those possessing extended spectrum B-lactamases and those active against Gram-positive pathogens.
The WHO has concluded that this pipeline is insufficient to meet our needs over the next decade and it is difficult to argue with that. Clearly, we need to stimulate additional research – hence the need for both push and pull incentives.