Abstract
The speed at which bacteria develop antimicrobial resistance far outpace drug discovery and development efforts resulting in untreatable infections. The World Health Organisation recently released a list of pathogens in urgent need for the development of new antimicrobials. The organisms that are listed as the most critical priority are all Gram-negative bacteria resistant to the carbapenem class of antibiotics. Carbapenem resistance in these organisms is typified by intrinsic resistance due to the expression of antibiotic efflux pumps and the permeability barrier presented by the outer membrane, as well as by acquired resistance due to the acquisition of enzymes able to degrade β-lactam antibiotics. In this perspective article we argue the case for reversing resistance by targeting these resistance mechanisms – to increase our arsenal of available antibiotics and drastically reduce antibiotic discovery times – as the most effective way to combat antimicrobial resistance in these high priority pathogens.
Highlights
Henrietta VenterThe speed at which bacteria develop antimicrobial resistance far outpace drug discovery and development efforts resulting in untreatable infections
The World Health Organisation (WHO) recently published a list of antimicrobial-resistant (AMR) organisms for which the need of new therapies are the greatest (Figure 1)
Contributing factors to the lack of financial gain to be derived from antibiotic development are the short treatment times (1–7 days typically), stewardship and short-lived efficacy before resistance start to develop (1–4 years) while the development of antibiotic is under the same stringent regulatory requirements as more lucrative drugs [14,15]
Summary
The speed at which bacteria develop antimicrobial resistance far outpace drug discovery and development efforts resulting in untreatable infections. The organisms that are listed as the most critical priority are all Gram-negative bacteria resistant to the carbapenem class of antibiotics Carbapenem resistance in these organisms is typified by intrinsic resistance due to the expression of antibiotic efflux pumps and the permeability barrier presented by the outer membrane, as well as by acquired resistance due to the acquisition of enzymes able to degrade β-lactam antibiotics. In this perspective article we argue the case for reversing resistance by targeting these resistance mechanisms – to increase our arsenal of available antibiotics and drastically reduce antibiotic discovery times – as the most effective way to combat antimicrobial resistance in these high priority pathogens. Accepted Manuscript Online: 25 March 2019 Version of Record published: 12 April 2019
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