Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Please can you give a brief introduction to amoxicillin?
Amoxicillin is a broad spectrum penicillin, and in the UK is one of the most frequently used antibiotics.
It is commonly used either on its own or, where there are particular concerns about resistance, in combination as Co-amoxiclav (as Amoxicillin-clavulanic acid) which extends its anti-bacterial spectrum.
What is amoxicillin typically prescribed for?
Most commonly it is prescribed for respiratory tract infections and upper respiratory infections such as rhinosinusitis, otitis media and lower respiratory tract infections (bronchitis/chest infections/pneumonia).
How did your research into the effectiveness of amoxicillin originate?
We have wanted to do a study like this for some time – it’s clear we did not have enough evidence overall, and certainly not for subgroups such as the fit elderly.
Various things then came together - the combination of funds being available through the European Commission, and a group of like-minded European researchers ranging from microbiologists, geneticists through to primary care physicians came together to put in the grant bid.
Why had there previously been conflicting results over the effectiveness of amoxicillin in patients with lower respiratory tract infections (LTRI)?
The problem had not been so much conflicting results but the relatively paucity of evidence, not only for amoxicillin, but for all antibiotics used in chest infections.
The evidence from placebo controlled studies for important symptoms is only from a few hundred people – for example less than 400 people for outcomes such as feeling unwell or limiting activities.
A key issue is also that it is not clear that the evidence is all from the typical settings where antibiotics are mostly prescribed (i.e. primary care) and no evidence for important subgroups like the fit elderly.
How many people must be included in a study for it to be considered comprehensive?
There is no simple answer to this, but clearly the study must be big enough to answer the particular research question.
In this case our desire to look at important patient subgroups (e.g. the older age group) meant a large sample was needed.
If by comprehensive you also include generaliseability, the more settings the study happens in the more likely the results are to be generaliseable to other settings hence the importance of our results across several health countries and health systems.
Why had this research previously been lacking?
Funders have traditionally not placed major priority on acute infections that are managed predominantly in primary care settings so it has been difficult to get sufficient funds
What did your research involve?
2061 patients across several European countries presenting to their primary care physician with a cough lasting less than 4 weeks - who the physicians judged to have an infective cause of their cough but who did not have pneumonia - were randomised to have a high dose of amoxicillin (1g three times a day) or placebo for 7 days.
The dose was chosen to overcome the vast majority of resistance organisms in Europe.
What did your research find?
The data from this study shows clearly that most of the patients that are currently getting antibiotics including the fit elderly are not likely to benefit from them (around ½ a day of helping significant symptoms for an illness lasting 3 weeks, and 3% of patients not developing worse or new symptoms).
Why do you think that most patients that are currently getting antibiotics are not likely to benefit from them?
Difficult to know, but probably there is little benefit because most infections are not bacterial and even when they are it may not be just the presence of bacteria that drives the symptoms, but also the inflammatory process.
Can taking amoxicillin be harmful?
Mostly it is well tolerated, but 5% more patients get rash, nausea or diarrhoea who would not have had it, and very occasionally a severe allergic reaction occurs (one patient had anaphylaxis in the antibiotic group of this study).
Over-using antibiotics when they don't work well will lead to really serious infections becoming potentially untreatable due to antibiotic resistance.
What impact do you think your research will have?
Hopefully physicians will prescribe fewer antibiotics for chest infections.
What do you think the future holds for the use of amoxicillin?
It will have a very useful future if it is not used too much: it is currently useful in patients with pneumonia and for selected patients with other infections (for example very young children with both ears affected by ear infections).
Are there any strategies in place to ensure that amoxicillin is not used too much?
This will vary between health systems but generally the answer is that most health systems have poor control of antibiotic prescribing and insufficient resources are made available to curb unnecessary antibiotic prescribing.
Where can readers find more information?
They can find our research paper here: http://www.thelancet.com/journals/lancetid/article/PIIS1473-3099%2812%2970300-6/abstract
About Prof Paul Little
Paul Little lives in Hampshire, UK, with his wife and two children. He was appointed to a personal chair as Professor of Primary Care Research at the University of Southampton in 2003.
He undertook medical training at Oxford University and Kings College hospital. He trained in general medicine, and after achieving the Membership of the Royal College of Physicians (MRCP) he then trained as a general practitioner (GP) in Southampton in 1990.
He was the first GP to be awarded a Wellcome Health Services Research training fellowship, and then a Medical Research Council (MRC) Clinician Scientist Fellowship, and has been a GP for the last 20 years in the Southampton area. He has worked on several funding Boards and several National Institute for Clinical Excellence (NICE) panels.
Professor Little is perhaps best known internationally for research on antibiotic prescribing strategies, which has addressed one of the major threats to public health - the danger of antibiotic resistance - and in the developing and trialling of complex interventions to support patient and practitioner behaviour change.