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So what's in your medicine cabinet?
A McDonnell Foundation Workshop

“A 43-year old policeman in Oxford, England was admitted to the hospital in early October of 1940, with disseminated Staphylococcus aureus and Streptococcus pyogenes infection. His disease began as a sore at the corner of his mouth. He failed all local drainage therapy... When the penicillin was begun on February 12, 1941, the infection had already spread to involve most of his face, both orbits, his lungs, and his right arm. Between the dates of February 12-17 the patient was administered 4.4 grams of penicillin. This caused dramatic improvement. Infection of the face and arm disappeared, and the policeman’s fever subsided. His white blood cell count fell from 20,000 at the start of the therapy to 8,400 at the end.”

This excerpt from the Lancet in 1941 describes the trial use of intravenous penicillin in the treatment of a policeman suffering from an invasive infection that had begun with a simple thorn scratch on his cheek. As difficult as it is to imagine today, our ability to treat common bacterial infections goes back only 65 years. Yet, the rapid rate of emergence of pathogens resistant to these wonder drugs has already returned us to an era where community acquired, untreatable strains of Staphylococcus aureus are increasingly common and a simple scratch from a rose bush could lead to painful death.

Yet, there is insufficient movement towards a coordinated response to this problem to match the attention to other emerging threats, such avian influenza. The explanation is complex. In part, it has to do with the irrational ways people weight different risks; in part it has to do with the fact that the emergence of antibiotic resistance involves problems of the Global Commons; and in part, it has to do with the ways that accepted wisdom spreads, and the role of social norms and a litigious society in guiding medical practice in the face of uncertain scientific information.

There are two major gaps in our understanding of drug resistance and this is a major impediment to a forceful societal response. The first gap is in our understanding of the ecology of resistance. Much of what we know about the impact of compliance and dosing on resistance comes from just one disease, tuberculosis. Furthermore, it is unclear how risk factors for emergence of resistance relate to risk factors for the spread of resistant pathogens from one patient to another. The second gap is in our understanding of incentives (or lack thereof) that prevent patients, physicians and health care facilities for using antibiotics with a more careful eye towards resistance. These gaps are inter-related – for example, a better understanding of compliance on the evolution of resistance, is useful in assessing the importance of missing incentives for patients to comply with antibiotic treatment. A third gap is in our understanding of how to develop novel classes of drugs that will fill the holes left as existing drugs gradually become useless due to resistance.

We propose to convene a small, yet diverse, gathering of thinkers with the goal of discussing the key issues involved in interfacing economic and behavioral considerations in understanding how resistance emerges and spreads. Scientific uncertainty is a central point for discussion, because standard wisdom on issues such as compliance must be evaluated within that context. The emergence and persistence of drug resistance is a complex phenomenon driven not just by biological and medical factors but also by economic and behavioral factors that influence how physicians determine antibiotic treatment, how patients demand these drugs and how hospitals determine how much to invest in keeping these pathogens under check. The problem of resistance is at the point of contact between these two complex systems- and any attempt to craft solutions based on an understanding of just one will be incomplete and likely to fail without knowledge of the other. In addressing these issues, we will build heavily on the progress made in the previous two contributions of the McDonnell Social Norms Group (see attached).

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