Friday, February 5, 2021

AMR - a Holistic Approach


A very important report on the state of antibiotic use and resistance globally has just been release by The Center for Disease Dynamics, Economics & Policy (CDDEP).  Before delving into this topic, I want to explain my long absence from my blog.  I have been ill but am rapidly recovering and am now ready to continue thinking and writing about AMR. 


 The report focuses on the relationship between antibiotic use and resistance with a tool that provides an index or score for a given country.  A number of countries are included as examples in a digital dashboard. This tool and dashboard will be helpful for national and international agencies to evaluate and develop policies to address problems of resistance.  The report also notes that among some LMICs, there is a clear issue of access such that patients suffer and die from simple lack of antimicrobial therapy or vaccines more than from resistant infections. A webinar by CDDEP with Ramanan Laxminarayan and Dame Sally Davies and others discussing the report is also available. 


While I cannot agree more wholeheartedly that a greater understanding of the “you use it, you lose it” law of antimicrobial resistance is important, it is not the whole story.  As implied, even carefully monitored and appropriate use of antibiotics will still select for resistant variants within microbial populations. There are many examples of this from our experience in hospitals with strong antimicrobial stewardship policies, even given the fact that these hospitals exist within a larger global community. What this means is that, even if we alter our policies and focus our antimicrobial use in animals and in humans to only what is needed, we will still face the problem of resistance.  It is likely that under those circumstances resistance will evolve and grow more slowly – but it is still going to be inevitable. 


Therefore, in a holistic approach to resistance, we have to anticipate resistance even to our last line antibiotics. This means that our current antibiotics will yield to resistance over time and that we will need new antibiotics (or possibly other approaches) to deal with these resistant infections. And today, we are nowhere near ready for that eventuality given the perilous state of our antimicrobial pipeline. 


Our pipeline depends on the ability of sponsors (for profit or not) to discover, develop, manufacture and distribute new, effective drugs for the treatment of resistant infections. While there is more and more support for discovery and early development, and even some new support for late-stage development, without an ability to manufacture and distribute these putative new products globally, the entire endeavor collapses like a house of cards. And that is exactly what has been happening over the last decade. The clear evidence for this is in the bankruptcy of multiple small companies who engaged in the commercialization of new antibiotics active against resistant infections. To compound this, a number of sponsors have been unable to market their new antibiotics in Europe given burdensome and expensive regulatory requirements or inadequate national pricing proposals. Even if, as some argue, that these products deserved their fate, private investment in antibiotics is getting more and more difficult. 


Recent economic analyses by John Rex and Kevin Krause at a meeting of the National Academies (see links here) shed some light on the costs of commercialization – and they are considerable. The problem is that we know what we must do to address the problem.  We have to pay! While some countries (e.g. UK) are trying this by an effort to “pay their share” – this is clearly insufficient by itself. Either we need a more global approach, or some country or region must take a leadership position and provide much more than their “share.” I’m looking at you US and EU! 


Without addressing this other end of the AMR problem, our inadequate pipeline, stewardship will only delay the inevitable. 





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