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

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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.
Original languageEnglish
Pages (from-to)2907–2915
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume73
Issue number11
Early online date25 Jul 2018
DOIs
Publication statusPublished - 1 Nov 2018

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