World Antibiotics Awareness Week took place on 13 – 19 November this year to help raise awareness of the importance of antimicrobials and resistance.
Five experts were online for an hour to answer questions from a varied audience on an eclectic and thought-provoking range of subjects about antimicrobials and resistance.
The experts on the day were Dr Clare Taylor, Dr Jon Otter, Lisa Morgans and Dr Patricia McGettigan and I. The impressive number of tweets led to my phone giving up on sending notifications about 20 minutes into the one hour chat.
What struck me as particularly interesting was the fact that the questioners had looked beyond antibiotics. There was a genuine interest in resistance to other antimicrobials, antiseptics and disinfectants, including the potential for cross-resistance to other antimicrobials.
This, I believe, is an under-appreciated aspect of the global issue that is AMR and was thrilled to be able to express my opinions about this in particular.
The first question (actually, two questions) set the scene nicely: What is the global approach [to AMR] in the UK? Isn’t tackling AMR pointless unless we have global intervention?
The points were made that the One Health strategy advocated by the WHO, among others, is vitally important and that the UK government is taking a global lead in combatting AMR, as evinced by the recent O’Neill Report.
Individual contributions were also highlighted, including wise use of antibiotics, ensuring access to antibiotics in resource-limited settings and adopting good hygiene practices. As JustAPharmacist wisely tweeted ‘Prevention is better than cure’.
Question two referred to the recent controversial paper in the BMJ questioning whether ‘The antibiotic course has had its day’ and asking whether patients should stop taking antibiotics when they feel better rather than completing their prescription.
This met with a unanimous response from the experts that patients should do as their healthcare professional advises, as there is insufficient scientific evidence that not completing the course is the better option.
A few additional points were also made, such as, that over-the-counter use of antibiotics (with no professional advice at all), and that the use of counterfeit drugs and under-dosing of antibiotics are important considerations.
The under-dosing of antibiotics (including the use of counterfeit antibiotics containing little or none of the purported antibiotic) could lead to microbes being exposed to sub-optimal concentrations and facilitating increases in AMR.
The third question, and my favourite, was ‘Is antimicrobial resistance limited to bacteria?’ whilst antibiotic resistance and bacterial infections have largely dominated the ‘headlines’ in the realm of AMR, it was gratifying to see that people are considering other infectious diseases and the problems of resistance encountered while attempting to treat infections caused by fungi, viruses and other parasites.
The problem of antifungal resistance was exemplified by Candida auris, an emerging fungal pathogen resistant to a number of antifungals (thank you @marthacpowell) and azole-resistant Aspergillus fumigatus, where there is evidence that resistance originated in the environment from fungicide-treated fields. Additionally, the problems associated with antiviral and anthelmintic resistance was also highlighted, and often due to inappropriate drug use.
Farm to fork
Question four enquired how antibiotic resistance moves from farm to fork, a subject about which not nearly enough research has been carried out, especially in the context of the horizontal transfer of antibiotic resistance genes.
This was also the question that generated the most ‘discussion’ between the experts and with agreement that farming practices in disparate parts of the world are likely to make very different contributions to AMR and that each needs a tailored approach to solving the problem.
Again the point was made that this problem extends beyond livestock and that the use of fungicides in agriculture is creating problems with antifungal resistance. Let’s hope that the OH-STAR project can begin to provide some more answers to this important question!
Questions five and six appeared to be linked by references to antiseptics and AMR, in that can antiseptic mouthwashes create resistant oral bacteria and does the disinfectant Triclosan have serious side-effects, potentially including resistance? Whilst there is laboratory evidence that chlorhexidine (a common mouthwash antiseptic) resistance can cause cross-resistance to colistin, there is no evidence that this can occur elsewhere and is a single example that I am aware of. With respect to Triclosan, all experts agreed that this antiseptic was unsafe, as do the European Commission and US Food & Drug Administration and that there are links between Triclosan use and AMR, albeit with more research required.
Biocide usage and antibiotic resistance. Biocides such as triclosan and chlorhexidine exert their antimicrobial activity through non-specific interactions with cellular targets. Bacterial defence to such toxic compounds includes up-regulation of multidrug efflux pumps, such as qacA in S. aureus and mexAB-oprM in P. aeruginosa. Once expressed, these efflux pathways can not only export biocides, but also antibiotics, antiseptics, heavy metals and dyes, resulting in the development of multidrug resistance (Venter, et al, 2017, Essays in Biochemistry, 61(1):1-10).
Fighting for the future
The final question, and I thought the most difficult to answer, was ‘Can researchers use information gained about AMR organisms for good?’ The obvious answer to this is ‘Yes, of course!’, but then I struggled to think of specific examples.
Fortunately, my fellow experts were quick to answer. Probably the clearest use of AMR research for good is that it provides us with a greater understanding of how AMR is transmitted, and that knowledge can, in the future, be applied to preventing transmission.
Also, understanding mechanisms of resistance will help with the design of future generations of antimicrobials, hopefully avoiding, or at least postponing for as long as possible, the development of AMR. Another example of ‘good’ coming from this research is that the more we understand about AMR and mechanisms then this knowledge can be used to facilitate not only the diagnosis of the infecting microorganism, but also its resistance mechanisms, thus better guiding the most appropriate use of antimicrobials in the clinic for the greatest patient benefit.
Derry K. Mercer serves as Principal Scientist at Novabiotics Dr. Mercer is a biological scientist with more than 20 years of experience within the areas of microbiology, molecular biology, protein biochemistry, cell biology and bioinformatics.
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