The 2018 Garrod Lecture: Preparing for the Black Swans of Resistance

Livermore, David (2018) The 2018 Garrod Lecture: Preparing for the Black Swans of Resistance. Journal of Antimicrobial Chemotherapy, 73 (11). 2907–2915. ISSN 0305-7453

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      Abstract

      The need for governments to encourage antibiotic development is widely agreed, with ‘Market Entry Rewards’ being suggested. Unless these are to be spread widely – which is unlikely given the $1 billion sums proposed– we should be wary, for this approach is likely to evolve into one of picking, or commissioning, a few ‘winners’ based on extrapolation of current resistance trends. The hazard to this is that, whilst the evolution of resistance has predictable components, notably mutation, it also has completely unpredictable ones, contingent upon “Black Swan” events. These include the ‘escape’ of ‘new’ resistance genes from environmental bacteria and the recruitment of these genes by promiscuous mobile elements and epidemic strains. Such events can change the resistance landscape rapidly and unexpectedly, as with the rise of Escherichia coli ST131 with CTX-M-ESBLs and the emergence of ‘impossible’ vancomycin-resistant enterococci. Given such unpredictability, we simply cannot say with any certainty, for example, which of four current approaches to combatting metallo--lactamases (MBLs) offers the best prospect of sustainable, prizeworthy, success. Only time will tell, though it is encouraging is that multiple potential approaches to overcoming these problematic enzymes are being pursued. Rather than seeking to pick winners, governments should aim to reduce development barriers, as with recent relaxation of trial regulations. In particular, once -lactamase inhibitors have been successfully trialled with one partner, there is scope to facilitate licensing them for partnering with other established -lactams, thereby insuring against new emerging resistance.

      Item Type: Article
      Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
      Depositing User: LivePure Connector
      Date Deposited: 13 Jul 2018 12:30
      Last Modified: 23 Jan 2019 14:10
      URI: https://ueaeprints.uea.ac.uk/id/eprint/67620
      DOI: 10.1093/jac/dky265

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