Common antibiotics linked to serious skin reactions

Several classes of commonly prescribed oral antibiotics appear to carry an increased risk of serious cutaneous adverse drug reactions (cADRs), according to a study.

Analysis of 20-year data involving 3,257,181 older adults with an outpatient antibiotic prescription showed that the odds of serious cADRs within 60 days of antibiotic exposure were more than twofold higher with sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9, 95 percent confidence interval [CI], 2.7–3.1) and cephalosporins (aOR, 2.6, 95 percent CI, 2.5–2.8) when compared with macrolides. [JAMA 2024;332:730-737]

Associations with serious cADRs were also evident with nitrofurantoin (aOR, 2.2, 95 percent CI, 2.1–2.4), pennicillins (aOR, 1.4, 95 percent CI, 1.3–1.5), and fluoroquinolones (aOR, 1.3, 95 percent CI, 1.2–1.4).

Crude rates

A total of 34,114,254 courses of antibiotics were associated with 72,449 serious cADR-related ED visits or hospitalization within 60 days following exposure, translating to a crude rate of 2.12 antibiotic-associated serious cADRs per 1,000 prescriptions.

Cephalosporins carried the highest absolute risk of serious cADRs (crude rate, 4.92 per 1,000 prescriptions), followed by sulfonamide antibiotics (crude rate, 3.22 per 1,000 prescriptions).

Hospitalization outcomes

Hospitalization for serious cADRs was documented in 2,852 patients (median age 80 years, 61.2 percent female). Of these, 50 (1.8 percent) had Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).

The median length of stay in the hospital was 6 days, and close to three-fourths of patients (74.1 percent) were discharged home. A total of 273 (9.6 percent) hospitalized patients, including 10 (20.0 percent) with SJS/TEN, required treatment in a critical care or burn unit. In-hospital mortality rate was low for serious cADRs overall (n=150, 5.3 percent) but elevated for the SJS/TEN subtype (n=10, 20.0 percent).

Judicious prescribing

“Overall, these findings strengthen understanding of hospital-related outcomes for serious cADRs and highlight the morbidity and mortality related to severe drug reactions following antibiotic therapy,” the investigators said.

What was unexpected was the association between serious cADRs and use of nitrofurantoin, they continued. Nitrofurantoin is commonly prescribed as a first-line treatment for uncomplicated urinary tract infections in older adults. Hence, the finding on this antibiotic class points to a potential novel risk at a population-based level and should be verified in other populations to confirm this association, according to the investigators. [CMAJ Open 2017;5:E878-E885; Clin Infect Dis 2011;52:e103-e120; Aging health 2013;9]

“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,” they said.

The analysis included 21,758 older adults (median age 75 years, 64.1 percent female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy (case group) and 87,025 matched controls who did not. The median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days, and the median duration of antibiotic prescription overall was 7 days. Most participants in the case group visited the ED only (n=18,906, 86.9 percent), while the remainder were hospitalized for serious cADRs (n=2,852, 13.1 percent).