Antibiotics linked to 28% of Stevens-Johnson syndrome, toxic epidermal necrolysis cases

More than one-quarter of Stevens-Johnson syndrome and toxic epidermal necrolysis cases worldwide were attributed to antibiotic use, according to a study.

“Antibiotics are a well-described cause of SJS/TEN, but the prevalence of this association was unknown,” Erika Yue Lee, MD, of the division of clinical immunology and allergy in the department of medicine at University of Toronto, told Healio.

Lee and colleagues said that as many as half of patients can die from this complication as it is among the most severe types of adverse drug interaction.

“To our knowledge, no global systematic review has described antibiotic-associated SJS/TEN,” they wrote.

Experimental and observational analyses from the Medline and Embase databases from inception through Feb. 22, 2022, were investigated to assess the prevalence of antibiotic-associated Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN).

Eligible data sets were assessed for bias risk and then included in the meta-analysis that employed a random-effects model to determine patient-level data. The researchers also conducted subgroup analyses.

Of 64 studies included in the initial review, 38 studies reported data on patient-level associations between antibiotic use and SJS/TEN. Information for 2,917 patients was assessed for these associations.

“The study uses the design of a systematic review and meta-analysis to estimate the worldwide prevalence of antibiotic-associated SJS/TEN to summarize the existing published results,” Lee told Healio.

Results from the pooled analysis showed that antibiotic-associated SJS/TEN comprised 28% (95% CI, 24%-33%) of cases globally. Importantly, the researchers noted that there was a “moderate” certainty of evidence for this statistic.

Among patients who experienced antibiotic-associated SJS/TEN, the most commonly used class of drugs was sulfonamides at 32% (95% CI, 22%-44%). Other associations were reported for penicillins at 22% (95% CI, 17%-28%), followed by cephalosporins at 11% (95% CI, 6%-17%), fluoroquinolones at 4% (95% CI, 1%-7%) and macrolides at 2% (95% CI, 1%-5%).

Statistically significant heterogeneity was reported for the findings of this analysis. “Antibiotics are associated with different risks of SJS/TEN,” Lee told Healio. “The prevalence of antibiotic-associated SJS/TEN also varied widely across different continents, which could be due to variation in prescription pattern and varying risk in genetic predisposition.”

Findings from the Joanna Briggs Institute checklist indicated a low bias risk in these findings.

“Antibiotics are consistently associated with more than a quarter of SJS/TEN cases worldwide, and sulfonamide class remains a leading cause,” Lee said. “Prescribers should be aware of the antibiotic-associated risk of SJS/TEN, use antibiotics judiciously, and limit sulfonamide antibiotics to only specific indications and durations.”