New research shows that commonly prescribed oral antibiotics are tied to increased risk of severe skin reactions in older adults.
In a study published yesterday in JAMA, researchers in Toronto looked at two decades worth of data on hospitalizations and emergency department (ED) visits for serious cutaneous adverse drug reactions (cADRs) and found significant associations with the use of sulfonamides, cephalosporins, and other commonly prescribed classes of antibiotics.
cADRs are a group of drug hypersensitivity reactions that can start as rashes but develop into more serious and potentially life-threatening reactions involving internal organs. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the more severe examples.
"Our results highlight the risk of serious cADRs following commonly prescribed antibiotics and underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate," the study authors wrote.
Greater risk for older adults, who receive more antibiotics
For the case-control study, researchers with the University of Toronto, the Institute for Clinical Evaluative Sciences (ICES), and the Sunnybrook Health Sciences Centre analyzed administrative health databases in Toronto from April 2002 through March 2022, focusing on adults aged 66 years or older who had received at least one oral antibiotic. They then looked for case-patients who had an ED visit or hospitalization for a serious cADR within 60 days of an antibiotic prescription.
"Clinicians have speculated that certain antibiotics carry greater risk for these severe reactions, but no study has ever confirmed these claims," study co-author Erika Lee, MD, an allergist with the University of Toronto, said in an ICES press release. "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, the researchers identified 3,257,181 older adults with an outpatient antibiotic prescription, of whom 21,758 had an ED visit or hospitalization for a cADR within 60 days of the prescription. They matched them with 87,205 control patients who were similar with regard to demographics, comorbidities, and healthcare use but who'd had no hospital encounter related to a cADR.
Among the cases and controls, the most commonly prescribed antibiotics were penicillins (28.9%), cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%).
Our results highlight the risk of serious cADRs following commonly prescribed antibiotics and underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate.
Multivariable analysis found that sulfonamides were the antibiotic class most strongly associated with cADRs relative to macrolides, with almost triple the risk (adjusted odds ratio [aOR], 2.9; 95% confidence interval [CI], 2.7 to 3.1), followed by cephalosporins (aOR, 2.6; 95% CI, 2.5 to 2.8). But all other antibiotic classes were also associated with increased risk of serious cADRs, including nitrofurantoin (aOR, 2.2; 95% CI, 2.1 to 2.4), penicillins (aOR, 1.4; 95% CI, 1.3 to 1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2 to 1.4).
The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1,000 prescriptions; 95% CI, 4.86 to 4.99) and sulfonamide antibiotics (3.22 per 1,000 prescriptions; 95% CI, 3.15 to 3.28). Among the 2,852 case-patients (13.1%) who were hospitalized for cADRs, the median length of hospital stay was 6 days, 9.6% required transfer to a critical care unit, and 5.3% died in the hospital. Fifty patients were identified as having SJS/TEN, 10 (20%) of whom died.
The authors note that although the absolute risk of antibiotic-associated serious cADRs is low and most of the patients who went to the ED or hospital were discharged without being admitted, older patients taking oral antibiotics should pay attention to adverse reactions.
"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," said corresponding author David Juurlink, MD, PhD, head of the division of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre. "It's also one more reason why antibiotics should be prescribed only when they're truly needed."
