Common antibiotics carry a small but serious risk of life-threatening drug reactions, but some are safer than others

Two classes of commonly prescribed oral antibiotics are associated with the highest risk of serious drug reactions that can lead to emergency room visits, hospitalizations and even death, according to a new study.

Researchers from ICES, the Sunnybrook Research Institute and the Department of Medicine at the University of Toronto’s Temerty School of Medicine suggest that prescribers should consider using antibiotics with lower risk to their patients when clinically appropriate.

Serious cutaneous adverse reactions (cADRs), or serious drug reactions, are a group of rare but potentially life-threatening delayed adverse reactions involving the skin and often internal organs. Some of these reactions carry a mortality rate of 20 to 40%. Although many different classes of drugs can cause serious cADRs, antibiotics are among the most common triggers for these reactions.

“Physicians have speculated that certain antibiotics have a higher risk of these serious reactions, but no study has ever confirmed these claims,” ​​says Erika Lee, an allergist and trainee at ICES and Temerty Medicine’s Eliot Phillipson Clinician-Scientist Training Program. “Our goal was to examine the risk of cards in a population of older adults, who tend to receive disproportionately more antibiotic prescriptions than younger adults.”

The study, “Oral Antibiotics and the Risk of Serious Cutaneous Adverse Reactions,” was published in JAMA. The benchmark study used health care data from ICES on adults aged 66 years or older who received a prescription for at least one oral antibiotic between 2002 and 2022 in Ontario, Canada.

During the study period, 21,758 adults were admitted to the emergency department or hospitalized for a serious cADR following oral antibiotics and were matched with 87,025 nonresponder controls.

The highest risk for two classes of antibiotics

“The good news is that most patients who visited the hospital with these reactions were discharged without being admitted, so that should be reassuring for providers and patients,” says Lee. “However, of those hospitalized with the most severe reactions, 20% were treated in the intensive care unit and 5% of hospitalized patients died, highlighting the need for careful prescribing.”

The most common antibiotics prescribed were penicillins (29%), followed by cephalosporins (18%), fluoroquinolones (17%), macrolides (15%), nitrofurantoin (9%) and sulfonamides (6%). Less frequently prescribed antibiotics were grouped together and accounted for 7% of prescriptions.

The main results are:

• All antibiotics were associated with a higher risk of serious cADRs compared to macrolides, but sulfonamides (“sulfa drugs”) and cephalosporins were associated with the highest risk.

• About one in eight patients presenting to the emergency department with antibiotic-related cADRs were admitted to the hospital, likely because their reactions were more severe or because of concerns about potential complications.

• 20% of hospitalized patients with the most severe types of cADR were treated in the emergency department, and 5% of them died.

Need more awareness

“Although rare, these serious drug reactions can be life-threatening. Patients should be aware of rashes, fever, and other symptoms, which can occur weeks after starting a prescription and even after antibiotics have stopped,” says David Juurlink, an internist. and Chief of the Division of Clinical Pharmacology and Toxicology at Sunnybrook Health Sciences Center, Chief Core Scientist at ICES, and Professor of Medicine at Temerty Medicine.

“It is also another reason why antibiotics should be prescribed only when they are really needed,” he adds.