Risk of serious cutaneous adverse drug reactions with oral antibiotics in older adults

Antibiotics are a known cause of serious cutaneous adverse drug reactions (ADRs), including potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. These reactions ate typically delayed in onset and include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)—the most severe cutaneous ADR, which has a mortality rate of 20%-to-40%. The relative risk of these reactions across antibiotic classes has not been well studied. To address this issue, Ontario researchers examined the risk of serious cutaneous ADRs associated with commonly prescribed oral antibiotics in older adults. They also characterized the outcomes of patients hospitalized for these reactions.The nested case-control study used Ontario population-based linked administrative datasets for adults (age ≥ 66 years) who received at least one oral antibiotic between 2002 and 2022. Patients who had an emergency department visit or hospitalization for a serious cutaneous ADR within 60 days of receiving an antibiotic prescription were matched with up to four controls who did not experience a cutaneous ADR.Conditional logistic regression was used to estimate the association between different classes of oral antibiotics and serious cutaneous ADRs, using macrolides as the reference group.Results showed the following:During the 20-year study period, 21,758 older adults (median age, 75 years; 64.1% female) had an emergency department visit or hospitalization for a serious cutaneous ADR following antibiotic therapy. They were matched with 87, 025 controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95%CI, 2.7–3.1) and cephalosporins (aOR, 2.6; 95%CI, 2.5–2.8) were most strongly associated with serious cutaneous ADRs relative to macrolides. Additional associations were seen with nitrofurantoin (aOR, 2.2; 95%CI, 2.1–2.4), penicillins (aOR, 1.4; 95%CI, 1.3–1.5) and fluoroquinolones (aOR, 1.3; 95%CI, 1.2–1.4).The crude rate of emergency department visits or hospitalization for cutaneous ADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95%CI, 4.86–4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95%CI, 3.15–3.28). Among the 2,852 case patients hospitalized for cutaneous ADRs, the median length of stay was six days, 9.6% required transfer to a critical care unit, and 5.3% died in the hospital.The authors conclude that commonly prescribed oral antibiotic classes are associated with an increased risk of serious cutaneous ADR compared with macrolides. Sulfonamides and cephalosporins carry the highest risk. The absolute risk of antibiotic-associated serious cutaneous ADRs was relatively low, with two cutaneous ADR-related hospital visits for every 1,000 antibiotic prescriptions dispensed to older adults. However, these results underscore the importance of judicious prescribing, with preferential use of lower-risk antibiotics when clinically appropriate.Reference:Lee EY, Gomes T, Drucker AM, et al. Oral antibiotics and risk of serious cutaneous adverse drug reactions. JAMA 2024; published online August 8, 2024. (accessed August 8, 2024).

Risk of serious cutaneous adverse drug reactions with oral antibiotics in older adults

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