Sulfonamides and cephalosporins carried the highest risk.

Serious cutaneous adverse drug reactions (cADRs) can lead to life-threatening conditions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis and drug-induced hypersensitivity syndrome. Diagnosing these rare syndromes can be challenging, as most reactions are delayed, and relative risks for severe cADRs associated with various antibiotic classes are not well understood. To evaluate this risk, researchers in Canada used a large database that contained 20 years of outpatient antibiotic prescribing in older patients (age, 66 years and older). Each patient who received oral antibiotics within 60 days of emergency department presentation or hospitalisation for a serious cADR was compared with one to four age- and sex-matched controls who received antibiotics in the same 60-day period but who did not have cADRs.

Almost 22,000 patients (0.7% of older patients who received outpatient antibiotic prescriptions) experienced serious cADRs. Median antibiotic course was seven days, and median interval to presentation for serious cADRs was 14 days. Sulfonamides and cephalosporins were associated most strongly with serious cADRs, with adjusted odds ratios (ORs) of 2.9 and 2.6, respectively, compared with macrolides. Excess risks for serious cADRs also were noted for nitro-furantoin, penicillins and fluoroquinolones (adjusted ORs: 2.2, 1.4 and 1.3, respectively). Among 2850 patients hospitalised with serious cADRs, overall mortality was 5%, but it was as high as 20% for patients who developed Stevens-Johnson syndrome/toxic epidermal necrolysis.

Comment: This study highlights that serious cADRs occur with many oral antibiotics, particularly sulfonamides and cephalosporins. The authors estimate that for every 1000 antibiotic prescriptions, two serious cADRs will occur, which will require emergency department visits or hospitalisations. Although that small absolute risk might not be relevant when a patient has strong indications for an antibiotic, it joins the many other potential harms resulting from inappropriate antibiotic prescribing.

David S. Weisman, DO, FACP, Associate Professor of Medicine Clinician Educator, Georgetown University Medical Center, Washington, DC; Associate Program Director in Internal Medicine, MedStar Health, Baltimore, USA.

Lee EY, et al. Oral antibiotics and risk of serious cutaneous adverse drug reactions. JAMA 2024 Aug 8; e-pub (https://doi.org/10.1001/jama.2024.11437).

This summary is taken from the following Journal Watch titles: General Medicine, Infectious Diseases, Ambulatory Medicine, Hospital Medicine.