Oral Antibiotics Tied to Higher Risk of Serious Skin Reactions: Sulfonamides and Cephalosporins Pose Greatest Threat, Study Finds

The study published in the JAMA Network indicates that many antibiotics have the safety issue of having serious cARDs leading to hospitalization or visits to the emergency department. Compared to macrolides, sulfonamide antibiotics, and cephalosporins are associated with the highest risk.

All commonly prescribed oral antibiotics are linked to a higher risk of severe cardiovascular adverse drug reactions compared to macrolides, with sulfonamides and cephalosporins presenting the greatest risk, the researchers reported. 

Antibiotics are antibacterial agents for fighting bacterial infections, but they also pose risks of having adverse reactions. These reactions range from mild side effects like diarrhoea, and nausea to more serious conditions, including anaphylaxis and serious cutaneous adverse drug reactions (cARDs).

Serious cARDs is a life-threatening adverse drug reaction that involves skin and internal organs. However, due to a scarcity of studies comparing the risks of serious cADRs across different antibiotic classes, researchers came together to investigate the risks associated with commonly prescribed oral antibiotics and to assess the outcomes of patients hospitalized due to these reactions.

Erika Y. Lee, Division of Clinical Immunology and Allergy, Department of Medicine, University of Toronto, Toronto, Ontario, Canada, and colleagues designed a population-based, nested case-control study where they enrolled 21 758 older adults with having median age, 75 years, 64.1% female who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada.

They include cases who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not.

conditional logistic regression were used to understand how different types of oral antibiotics might be linked to serious skin reactions. In this analysis, they compared each antibiotic class to a specific group called macrolides.

Study findings reveal:

• In primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9) and cephalosporins (aOR, 2.6) were most strongly associated with serious cADRs relative to macrolides.
• Further associations were observed with nitrofurantoin (adjusted odds ratio [aOR], 2.2), penicillins (aOR, 1.4) and fluoroquinolones (aOR, 1.3).
• The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins, with 4.92 incidents per 1,000 prescriptions, followed by sulfonamide antibiotics, with 3.22 incidents per 1,000 prescriptions.
• Of the 2,852 patients hospitalized for serious cutaneous adverse drug reactions (cADRs), the median hospital stay was 6 days (with an interquartile range of 3 to 13 days). Additionally, 9.6% of these patients needed transfer to a critical care unit, and 5.3% died in the hospital.

“When clinically appropriate, prescribers should opt for antibiotics with a lower risk of adverse reactions,” researchers concluded.

Reference: Lee EY, Gomes T, Drucker AM, et al. Oral Antibiotics and Risk of Serious Cutaneous Adverse Drug Reactions. JAMA. Published online August 08, 2024. doi:10.1001/jama.2024.11437