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Two classes of commonly prescribed oral antibiotics are associated with the greatest risk for severe drug rashes that can lead to emergency department visits, hospitalizations and even death, according to a study by researchers at ,  and the University of Toronto.

The study, , found that sulfonamides (“sulfa drugs”) and cephalosporins were associated with the highest risk of reactions. The findings were based on a case-control study that used health-care data from ICES of adults 66 years or older who received a prescription for at least one oral antibiotic between 2002 and 2022 in Ontario.

Serious cutaneous adverse drug reactions (cADRs), or severe drug rash, are a group of rare but potentially life-threatening delayed reactions involving the skin and, often, internal organs. Some of these reactions carry mortality rates from 20 to 40 per cent. While many different classes of drugs can cause serious reactions, antibiotics are among the most commonly reported triggers.

The researchers say physicians should consider prescribing lower-risk antibiotics for patients when clinically appropriate.

“Clinicians have speculated that certain antibiotics carry greater risk for these severe reactions, but no study has ever confirmed these claims,” says Erika Lee, an allergist and a trainee with ICES and the Temerty Faculty of Medicine’s .

“Our objective was to explore the risk for cADRs in a population of older adults, who tend to receive disproportionately more antibiotic prescriptions than younger adults.”

Over the study period, 21,758 adults had an emergency department visit or hospitalization for a serious reaction following oral antibiotics and were matched with 87,025 controls who did not have a reaction.

“The good news is that most patients who visited the hospital with these reactions were discharged without being admitted, so that should be reassuring to providers and patients,” says Lee. “However, of those who were admitted to hospital with the most severe reactions, 20 per cent were treated in the ICU and five per cent of hospitalized patients died, which underscores the need for careful prescribing practices.”

The most commonly prescribed antibiotics were penicillins (29 per cent), followed by cephalosporins (18 per cent), fluoroquinolones (17 per cent), macrolides (15 per cent) nitrofurantoin (nine per cent) and sulfonamides (six per cent). Less commonly prescribed antibiotics were grouped together and accounted for seven per cent of prescriptions.

Other key findings include:

• There were two antibiotic reaction-related hospital visits for every 1,000 antibiotic prescriptions dispensed
• About one in eight patients who arrived at the emergency department with antibiotic-related reactions were hospitalized, likely because their reactions were more severe or because of concerns about potential complications
• Twenty per cent of hospitalized patients with the most severe forms of reactions were treated in a critical care unit, and five per cent of those patients died

“While rare, these severe drug reactions can be life-threatening. Patients should be aware of rash, fever and other symptoms, which can start weeks after a prescription has been started and even after the course of antibiotics has stopped,” says David Juurlink, a staff internist and head of the division of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre, senior core scientist with ICES and professor in  in the Temerty Faculty of Medicine.

“It’s also one more reason why antibiotics should be prescribed only when they’re truly needed.”