Key points What is the prevalence of antibiotics associated with Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) worldwide? Findings In this meta-analysis of 38 studies including 2917 patients, the proportion of antibiotics associated with SJS/TEN worldwide was 28%. Among antibiotic-associated SJS/TEN, the sulfonamide class was associated with 32% of cases, followed by penicillins (22%), cephalosporins (11%), fluoroquinolones (4%), and macrolides (2 %). Meaning that antibiotics are a major risk for SJS/TEN described worldwide, and sulfonamide antibiotics remain the main association, highlighting the importance of judicious use of antibiotics and limiting the sulfonamide class to only Specific indications and durations of therapy. |
Importance
Antibiotics are a major risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most serious types of drug hypersensitivity reaction with a mortality rate of up to 50%. To our knowledge, no global systematic review has described antibiotic-associated SJS/TEN.
Aim
To evaluate the prevalence of antibiotics associated with SJS/TEN worldwide.
Data sources
The MEDLINE and Embase databases were searched for experimental and observational studies describing the risks of SJS/TEN from database inception to February 22, 2022.
Study selection
The included studies adequately described the origins of SJS/TEN and specified the antibiotics associated with SJS/TEN.
Data extraction and synthesis
Two reviewers (EYL and CK) independently selected studies, extracted data and assessed risk of bias. A meta-analysis with a random effects model was performed on studies describing patient-level associations.
Subgroup analyzes were performed to explore heterogeneity. Risk of bias was assessed using the Joanna Briggs Institute checklist, and certainty of evidence was graded using the GRADE ( Grading of Recommendations Assessment, Development and Evaluation ) approach.
Main results and measures
The prevalence of antibiotic-associated SJS/TEN was presented as pooled proportions with 95% CI.
Results
Among the 64 studies included in the systematic review, there were 38 studies that described patient-level associations; the meta-analysis included these 38 studies with 2917 patients to determine the prevalence of single antibiotics associated with SJS/TEN.
The pooled proportion of antibiotics associated with SJS/TEN was 28% (95% CI, 24%-33%), with moderate-certainty evidence.
Among antibiotic-associated SJS/TEN, sulfonamide class was associated with 32% (95% CI, 22%-44%) of cases, followed by penicillins (22%; 95% CI, 17%-28%). ), cephalosporins (11%; 95% CI, 6%-17%), fluoroquinolones (4%; 95% CI, 1%-7%), and macrolides (2%; 95% CI, 1%-5%).
There was statistically significant heterogeneity in the meta-analysis, which could be partially explained in the subgroup analysis by continent.
Conclusion and relevance
In this systematic review and meta-analysis of all case series, antibiotics were associated with more than a quarter of SJS/TEN cases described worldwide, and sulfonamide antibiotics remained the most important association.
These findings highlight the importance of antibiotic stewardship, physician education and awareness, and weighing the risk-benefit assessment of antibiotic choice and duration.
