Macrolides are a type of antibiotic that include erythromycin, clarithromycin, and azithromycin. They are commonly used by adults and children to treat some common infections. This type of antibiotic is known to cause allergic reactions in some patients, but it is not known how often they happen or if certain patients are more likely than others to have a reaction to these drugs. In this study we will measure how often macrolide allergic reactions happen overall and by type (such as rashes, difficulty breathing). We will compare how often people using macrolides have allergic reactions compared to people using other commonly used antibiotics (amoxicillin, quinolones, trimethoprim, and nitrofurantoin).
We will also look at whether macrolides affect whether patients develop allergic diseases (eczema, asthma, allergic rhinitis, food allergy) and autoimmune diseases (rheumatoid arthritis, psoriasis, multiple sclerosis, lupus) compared with other antibiotics.
This study will help patients and their doctors understand how often allergic reactions occur in people who take macrolide antibiotics, if some patients are more likely to have a reaction than others, and whether macrolides are more or less safe than other commonly used antibiotics.
Macrolide antibiotics are one of the most common antibiotic classes used among adults and children worldwide. While drug allergies have been documented for macrolides, the epidemiology of macrolide allergy is unknown. Macrolide antibiotics have been associated with a variety of immunologic effects but have not been assessed as a risk factor for allergic or autoimmune disease.
This study will report rates of and risk factors for allergic reactions to macrolide antibiotics compared to other commonly used antibiotics among treatment-naïve patients and assess the association between macrolide exposure and incident allergic and autoimmune diseases among new users.
Objective 1: Among a population of antibiotic users (erythromycin, clarithromycin, azithromycin, amoxicillin, ciprofloxacin, ofloxacin, trimethoprim, nitrofurantoin) whose CPRD records began at birth (treatment-naïve), we will calculate incidence rates (IRs) and 95% confidence intervals (CIs) for allergic reactions for each study antibiotic. We will calculate incidence rate ratios (IRRs) with 95% CIs for each antibiotic type and class compared to users of ciprofloxacin. We will use HES APC to increase capture of Stevens-Johnson syndrome and toxic epidermal necrolysis.
Objective 2: In patients with at least 3 years of registration before first antibiotic use (new users), we will conduct a nested case control study using conditional logistic regression to estimate odds ratios (ORs) with 95% CIs for each allergic and autoimmune disease outcome (atopic dermatitis, asthma, allergic rhinitis, food allergy, rheumatoid arthritis, psoriasis, multiple sclerosis, systemic lupus erythematosus) by specific antibiotic and class with unexposed patients as the common referent group.
For both objectives, we will use linked deprivation scores and rural versus urban residence to assess whether these factors are confounders of associations between macrolides and these outcomes.
This study will inform patients and clinicians on rates and risk factors for macrolide allergies and relative safety of macrolide antibiotics compared with other commonly used antibiotics.
Cutaneous allergic reactions; anaphylaxis; Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN); asthma; atopic dermatitis; allergic rhinitis; food allergy; rheumatoid arthritis, psoriasis, multiple sclerosis, systemic lupus erythematosus
Susan Jick - Chief Investigator - BCDSP - Boston Collaborative Drug Surveillance Program
Rebecca Persson - Corresponding Applicant - BCDSP - Boston Collaborative Drug Surveillance Program
Catherine Vasilakis-Scaramozza - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
Katrina Hagberg - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
HES Admitted Patient Care;Practice Level Index of Multiple Deprivation;Practice Level Rural-Urban Classification