medwireNews: Sulfonamides, cephalosporins, nitrofurantoin, penicillins, and fluroquinolones all carry a higher risk for serious cutaneous adverse drug reactions (cADRs) than macrolide antibiotics in older people, say researchers.
Serious cADRs are a group of rare but potentially life-threatening drug hypersensitivity reactions that involve the skin and, very often, the internal organs, David Juurlink (Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada) and associates explain in JAMA. While these reactions may be induced by other drug types, “antibiotics are among the most commonly implicated triggers.”
To gauge the relative risks for serious cADRs across antibiotic classes, the researchers performed a population-based, nested case-control study. Data collated over a 20-year study period by several Ontarian administrative health databases were used to identify a group of people aged 66 years or older who had received at least one prescription for an oral antibiotic.
The team identified 21,758 people who had a serious cADR, defined as the need for emergency department (ED) care or hospitalization within 60 days of an antibiotic prescription. Each case was matched by age and sex with up to four individuals who did not have a serious cADR (n=87,025).
Overall, the median age of cases and controls was 75 years, 64% were women, and the median duration of the prescribed antibiotic course was 7 days. The most commonly prescribed antibiotics were penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), sulfonamides (6.2%), and “others” (6.9%).
Among those who needed to consult for a serious cADR, the median time between antibiotic prescription and a hospital visit was 2 weeks. Most (86.9%) people with a serious cADR only visited the ED, but 13.1% were admitted to hospital.
Multivariate analysis showed that sulfonamides and cephalosporins conferred the greatest risk for cADRs in the 60 days after starting treatment, with respective odds ratios (OR) relative to macrolides of 2.9 and 2.6, after adjusting for potential confounding factors such as malignancy, chronic liver disease, chronic kidney disease, and HIV.
Macrolides are “rarely associated with serious cADRs,” which is why they were used as the comparator, say the researchers.
An “unexpected finding,” however, was that nitrofurantoin also doubled the risk for serious cADR (OR=2.2). Such an association has not previously been reported and “highlights a potential novel risk at a population-based level” that “should be further explored in other populations to verify,” the researchers suggest.
Respective adjusted ORs for penicillins, fluroquinolones, and all other antibiotics were 1.4, 1.3, and 2.3.
Sensitivity analyses, which included looking at serious cADRs occurring within 30 days of antibiotic prescription, produced similar results, but with larger effect sizes.
The overall crude rate of serious cADRs occurring with antibiotic use was found to be “low” at 2.12 per 1000 prescriptions, the authors say. Crude rates per 1000 prescriptions for the various classes of antibiotics were 4.92 for cephalosporins, 3.22 for sulfonamides, 2.48 for fluroquinolones, 2.33 for nitrofurantoin, 1.94 for penicillins, 1.80 for macrolides, and 3.95 for all other antibiotics.
“We found that all commonly prescribed oral antibiotics were associated with an increased risk of serious cADRs leading to an ED visit or hospitalization, relative to macrolides, with sulfonamide antibiotics and cephalosporins posing the highest risk,” the researchers say.
They conclude that the findings “underscore the importance of judicious prescribing, with preferential use of those [antibiotics] associated with a lower risk when clinically appropriate.”
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