WHO Essential Medicines List update: Thoughts from an expert
Last month, the World Health Organization (WHO) updated its Essential Medicines List, the list of medicines it recommends for treating priority conditions worldwide. The update saw the biggest revision to its guidelines on the use of antibiotics in the list’s 40-year history.
We asked Professor Mike Sharland, one of Europe’s leading experts in antimicrobial prescribing, resistance and healthcare associated infection in children, to talk us through the update and what this means for clinicians. Mike was a member of the Essential Medicines List panel and helped to develop the new classification system for antibiotics.
The WHO Essential Medicines List has just released the biggest update to its antibiotics section in 40 years. Can you talk us through what’s changed?
Previously the list has always been just a list, with around 25 different antibiotics included (such as amoxicillin and penicillin). And that’s been helpful; for example, if you wanted to know which antibiotics you should order into your hospital, the list could tell you. Previously, however, no-one had tried to classify the antibiotics into different groups or give any guidance on their use. So this update is trying to do both of those things.
Firstly, we looked at different clinical infection syndromes and to specify first and second choice antibiotics for those. So, the WHO now includes guidance on which antibiotics you should be using, particularly narrow spectrum antibiotics at the first phase, and this was the first part of the work.
The second part was using that first and second choice methodology to then develop a categorisation of the antibiotics that are on the Essential Medicines List.
What do these new updates mean for clinicians day-to-day?
We see this list assisting stewardship and supporting local and national guidelines. When you are trying to implement a hospital, district or community guideline, these are the core antibiotics you should be trying to recommend wherever possible. You can also look at trends in your use over time; are you using more of these core access antibiotics? Are you using more of the watch group?
For an individual doctor, frequently many adults and children are treated, inappropriately, with very broad spectrum antibiotics, where there is no evidence that actually they are better in any way. For instance, there’s a high use of cephalosporins and quinolones where there’s no clinical evidence and benefit for simple respiratory tract infections. The Essential Medicines List will hopefully be another way of trying to guide people towards using more narrow spectrum antibiotics, in appropriate dosing and duration.
The WHO is also planning to reformat this into a traffic light system: so these are your green antibiotics, these are your amber and these are your red, which is easier to remember, and this can then be taken and developed into local educational and stewardship tools. That is, at the least, how we hope that it will be used in the future.
Antibiotics are now grouped into three distinct categories. Could you talk us through these categories and what each means in practice?
The first category is ‘access’. One of the concerns internationally is whether both children and adults actually have access to antibiotics in the first place. There’s still a very high mortality rate for children with pneumonia and other infections in certain countries where often, if you’re poor, there’s no availability. There are stock-outs of a lot of older antibiotics, where there’s no company manufacturing them, and there is a very serious problem with access.
So the rationale of the ‘access’ category is that there are around a dozen antibiotics that we think everybody should have access to for these different specific common clinical infections, such as urinary tract infections and pneumonia.
The idea is that they’re broadly the first choice narrow spectrum antibiotics and they should always be available to anybody, anywhere in the world, at an affordable cost, in an appropriate formulation and an appropriate dose and duration. So ‘access’ contains core named antibiotics, which by definition tend to be narrow spectrum antibiotics, such as amoxicillin and penicillin, and these are the ones that tend to have less likelihood of producing resistance.
Those are also the antibiotics that ideally we’d like to encourage countries to include in their own guidelines as well, so if they are producing guidelines for treating ear infections, throat infections or other common infections, then the encouragement would be for countries to include these medicines as their first-line antibiotics for common infections.
The ‘watch’ category is different. Watch antibiotics are those that are quite widely used, such as cephalosporins and quinolones, but ‘watch’ means that those antibiotics tend to have a higher likelihood of driving resistance, which is a problem. They tend to have more side effects and more toxicities associated with them, and often come at a higher cost as well.
So they are antibiotics that are used, but you need to keep an eye on their use and ideally not give them as first-line choices.
From a prescribing point of view, does this mean you’d potentially want to try something else first and not default to those?
That’s right. The great majority of prescribing for the common clinical infections can all be done with ‘access’ antibiotics. So from ear infections, to throat infections, to chest infections, to urine infections, to skin infections...the great bulk of antibiotics prescribing, 80-90%, can and should be done with the access group of antibiotics. That’s not to say the watch group can’t be used and shouldn’t be used, but they should all be conserved where possible.
The ‘reserve’ group is more the antibiotics of last resort, such as colistin. Again, if you’ve got a severe multi-resistant infection, that is only sensitive to colistin, then of course you use it. But ideally they should be reserved to where they are very much needed. So, when patients have got a resistant infection with particular, specific and rare scenarios, that’s where they should be used.
The Washington Post called the creation of the reserve list ‘controversial’. What are your thoughts on this?
I think there’s two parts to this. One of the problems with a lot of older, off patent antibiotics is that they are frequently unavailable, they’ve got a very limited number of manufacturers globally, and there are often stock-outs, where areas run out of the antibiotics. At the moment there’s a global shortage of piperacillin/tazobactam, and there are also issues about the sort of price associated with a lot of those older antibiotics.
So in some sense you could be concerned that by putting them on a reserve list, it might be a disincentive for manufacturers. But the use of most of those antibiotics on the reserve list is going up globally, because of increasing problems with antimicrobial resistance.
Also, the list is carefully worded to say that it’s not that you shouldn’t be using those antibiotics at all, but that they should be used rationally, with appropriate restrictions and stewardship, as you don’t want your last-ditch antibiotics being widely used where they are not necessary, and it’s actually very inappropriate for them to be used.
Though there are obviously newer antibiotics coming through, there are serious restrictions with many of the ones in development. For example, virtually all of the new antibiotics being developed are intravenous and there are very few oral antibiotics. There are also virtually no oral antibiotics in the pipeline to treat multi-drug-resistant gram negative infections.
Mike Sharland is Professor of Paediatric Infectious Diseases at St. George’s University of London, Lead Consultant Paediatrician at St George's University Hospitals NHS Foundation Trust, and one of the UK and Europe’s leading experts in antimicrobial prescribing, resistance and healthcare associated infection in children. Mike is also Co-Chair of the Longitude Prize Advisory Panel.