Antimicrobial resistance (AMR) may lead to antibiotics used to treat infections in humans not working. This is because we are using them too frequently and for too long, so bacteria develop ways to avoid attack from antibiotics. Scientists have predicted by 2050, 10million people/year will die because antibiotics wont work.
Antibiotics, tablets and skin applications (e.g. creams), are commonly used to treat of acne or spots in primary-care, sometimes for months at a time. Acne is common, affecting almost everyone to some degree, however it is moderate to severe in 20% of adolescents and it is those people who are prescribed antibiotics. Guidelines recommend that courses of antibiotics are repeated, each course duration being 3-6 months. Treatment courses can be given over many years intermittently. Most find antibiotics work for their acne, but this is not because acne is an infection, but because antibiotics lessen the redness of spots (anti-inflammatory). This approach does not stop spots coming back again in the future.
Antibiotics are recommended in all treatment guidelines for acne. We know from international studies that antibiotics are used frequently to treat acne, so there is a concern that they may be contributing to the problem of AMR. To fully understand the scale of antibiotic prescribing for acne in the UK, it is necessary to explore how these drugs are used by looking at antibiotic prescriptions over five-years, to determine the antibiotic prescribed, the duration of each individual course of antibiotic and the number of repeat courses.
The World Health Organisation declared the threat of Antimicrobial Resistance (AMR) a most urgent crisis. Without intervention, it is expected up to 10 million deaths/year from infections will occur by 2050 and the cost could reach 100 trillion USD. The overuse of antibiotics is a known driver of AMR as repeated and sustained exposure allows microbes to develop mechanisms to avoid the effects of drugs designed to defeat them.
Acne vulgaris is a chronic skin disorder with onset predominantly in adolescence. Prevalence studies show that 80-100% of adolescents have acne and 20% are moderately-severely affected. Duration is variable with 5% of people in their 50s with acne. Topical/oral antibiotics are commonly prescribed for the treatment of acne for several months. Tetracyclines and macrolides are the two most common oral antibiotic classes prescribed with dihydrofolate-reductase inhibitors (trimethoprim) prescribed second-line.
The pathophysiology of acne is multifactorial and although Cutibacterium acnes is associated in the development of acne, acne is not an infection, and antibiotics are used predominantly for their anti-inflammatory effects over antimicrobial. We do not understand how long-term antibiotics for acne attenuate flora elsewhere, nor how they influence the ability of bacteria at other infective sites to withstand their effects, which may contribute to AMR. Antibiotic prescribing is not generalisable across countries, as practices vary, therefore studies investigating antibiotic use elsewhere may not be applicable to the UK. While a previous study aimed to establish how acne medications are prescribed in the UK, follow up was restricted to one year. Given the chronicity of acne and the common practice of using antibiotics intermittently over several years, further study over a longer period is warranted. The overall aim of this study is to use the CPRD to elucidate how people with acne are managed with long-term oral/topical antibiotics in primary care for up to five-years follow-up.
This is a drug utilisation study aiming to identify how topical and oral antibiotics for acne are prescribed over the course of this chronic disease.
Outcomes will therefore be defined as:
1) Initiation of an oral or topical antibiotic for acne.
2) Substituting/switching a topical or oral antibiotic for another between classes.
3) Addition of an antibiotic to existing antibiotic treatment
4) Discontinuation of a topical or oral antibiotic.
5) Duration of antibiotic treatment including median duration.
6) Re-initiation of an antibiotic this is defined as a further prescription of an antibiotic after having previously been prescribed an antibiotic for a minimum of 4 weeks for acne, regardless of class, if there is no antibiotic prescription covering the previous 60 days.
Definitions to be used:
Treatment initiation (figure 1):
A new topical or oral antibiotic prescribed for at least 28 days preceded by 365 days of no antibiotic use. As there are no Daily Defined Doses (DDDs) for topicals, 0.5g per day will be amount used to define a daily dose as has been used by other studies.(1, 2) For the purposes of analysis, people with an antibiotic prescription for acne for less than 28 days will be excluded.
Treatment switching (figure 2):
Treatment switching is defined as the addition of a second antibiotic class (for acne) without the continuous use of the initial first antibiotic. The new antibiotic is used in place of the previous antibiotic treatment. Therefore, if a second drug is added, but with less than 30 overlapping days supply, this will be defined as a treatment switch between antibiotics. Second, third and fourth antibiotic initiation will only be considered treatment switches if there are 30 or less days supply from the prescription of the previous antibiotic.
Treatment addition (figure 3):
If there are overlapping days supply for the first and second antibiotic for 30 days or more then this is defined as a treatment addition of the second antibiotic, (and for subsequent antibiotic additions thereafter defined as the third and fourth additions etc).
Treatment discontinuation (figure 4):
This is defined as no available days of antibiotic supply 30 days after the last covered day.
Treatment re-initiation (figure 5):
This is defined as an antibiotic prescription in those who have previously received antibiotics for their acne with a treatment gap of at least 30 days.
We will stratify drug utilisation across age categories, geographic location (if possible), calendar year, quintiles of Index of Multiple Deprivation (IMD), Ethnicity and sex to understand prescribing in separate populations.
Sinead Langan - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Ketaki Bhate - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Clemence Leyrat - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Laura Shallcross - Collaborator - University College London ( UCL )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Nicholas Francis - Collaborator - Cardiff University
Richard Stabler - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Sarah-Jo Sinnott - Collaborator - Not from an Organisation
Susan Hopkins - Collaborator - Public Health England
Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation