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. 2023 Feb 15;159(4):384–392. doi: 10.1001/jamadermatol.2022.6378

Worldwide Prevalence of Antibiotic-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

A Systematic Review and Meta-analysis

Erika Yue Lee 1,2,✉, Christopher Knox 3, Elizabeth Jane Phillips 4,5,6,7
PMCID: PMC9932945  PMID: 36790777

This systematic review and meta-analysis of 38 studies including 2917 patients evaluates the prevalence of antibiotics associated with Stevens-Johnson syndrome and toxic epidermal necrolysis worldwide.

Key Points

Question

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

Antibiotics are an important risk for SJS/TEN described worldwide, and sulfonamide antibiotics remain the leading association, highlighting the importance of judicious use of antibiotics and limiting the sulfonamide class to only specific indications and durations of therapy.

Abstract

Importance

Antibiotics are an important risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most severe types of drug hypersensitivity reaction with a mortality rate up to 50%. To our knowledge, no global systematic review has described antibiotic-associated SJS/TEN.

Objective

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 that described SJS/TEN risks since database inception to February 22, 2022.

Study Selection

Included studies adequately described SJS/TEN origins and specified the antibiotics associated with SJS/TEN.

Data Extraction and Synthesis

Two reviewers (E.Y.L. and C.K.) independently selected the studies, extracted the data, and assessed the risk of bias. A meta-analysis using a random-effects model was performed in the studies that described patient-level associations. Subgroup analyses were performed to explore the heterogeneity. The risk of bias was assessed using the Joanna Briggs Institute checklist, and the certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

Main Outcomes and Measures

Prevalence of antibiotic-associated SJS/TEN was presented as pooled proportions with 95% CIs.

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 of evidence. Among antibiotic-associated SJS/TEN, the 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 a statistically significant heterogeneity in the meta-analysis, which could be partially explained in the subgroup analysis by continents. The overall risk of bias was low using the Joanna Briggs Institute checklist for case series.

Conclusion and Relevance

In this systematic review and meta-analysis of all case series, antibiotics were associated with more than one-quarter of SJS/TEN cases described worldwide, and sulfonamide antibiotics remained the most important association. These findings highlight the importance of antibiotic stewardship, clinician education and awareness, and weighing the risk-benefit assessment of antibiotic choice and duration.

Introduction

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe drug-associated reactions with mucosal erosion, epidermal detachment, and necrosis that affect 1 to 10 individuals per million population per year.1,2,3 Short- and long-term morbidity and mortality include visual impairment and adverse effects on mental health and quality of life.4,5,6 Stevens-Johnson syndrome is defined as less than 10% body surface area (BSA) detached, SJS/TEN overlaps 10% to 30% BSA detached, and TEN is defined as 30% or more BSA detached.4

Stevens-Johnson syndrome/TEN can occur in any age group, and the most common association is drugs.5 Symptom onset is usually within 4 to 28 days of continuous exposure to a culprit drug. Commonly implicated drugs have been unchanged over the past 3 decades and include allopurinol, aromatic anticonvulsants, antibiotics, and nonsteroidal anti-inflammatory drugs.1,7 Infection is also a recognized risk for SJS/TEN, particularly in children and young adults, most of whom go undiagnosed.8 Up to 33% of cases do not have a clear trigger, especially in children.9

Stevens-Johnson syndrome/TEN is mostly a clinical diagnosis based on detailed history and compatible skin findings such as a prodromal syndrome followed by atypical targetoid lesions with dusky center, evolution of vesicles or bulla, positive Nikolsky sign, and mucosal erosions.5 Skin biopsy can be helpful but not necessary.10 An ALDEN (algorithm of drug causality for epidermal necrolysis) score can be used to identify the most likely culprit drug(s) of SJS/TEN, especially when there are multiple drugs involved.9

Drug-associated SJS/TEN is considered the most severe type of drug hypersensitivity reaction and carries a mortality rate of up to 50%.5,11,12 Prompt cessation of culprit drugs is associated with a decreased risk of death compared with SJS/TEN of unknown cause.13 Antibiotics are a common risk for SJS/TEN; however, how this has changed over time is unclear. Ongoing efforts should be made to avoid inappropriate and unnecessary use and reduce the risk of life-threatening adverse drug reactions.14

We conducted a systematic review of all observational and experimental studies that described the risks for SJS/TEN in any age group from any country. We also performed a meta-analysis on the appropriate studies to determine the prevalence of antibiotics associated with SJS/TEN and the relative prevalence of each antibiotic class triggering antibiotic-associated SJS/TEN.

Methods

Search Strategy

We searched Embase and MEDLINE databases for original and peer-reviewed articles. Articles published in English since 1946 for Embase and since 1964 for MEDLINE were included; the last search was conducted on February 22, 2022. The search terms used were either subject headings (Embase) or Medical Subject Headings (MEDLINE) and included “Stevens-Johnson syndrome,” “toxic epidermal necrolysis,” “anti-infective agents,” “anti-inflammatory agents,” and “anticonvulsants.” We excluded case reports, surveys, conference abstracts, editorials, and reviews. The details of the search strategy are summarized in eTable 1 in Supplement 1. The protocol on the systematic review and meta-analysis of antibiotic-associated SJS/TEN was registered in the PROSPERO database on May 10, 2022 (CRD42022303846). Ethics approval and patient informed consent were not required for this review because it included only previously published research. The review was performed in accord with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.

Inclusion and Exclusion Criteria

Among all of the experimental and observational studies that described SJS/TEN associations, we assessed the studies based on the following eligibility criteria: (1) clearly described study setting; (2) SJS/TEN clearly diagnosed on clinical and/or histopathologic criteria15,16; (3) sufficient description of culprit drugs associated with SJS/TEN; (4) specific information on antibiotic triggers provided; and (5) at least 30 patients with SJS/TEN recruited consecutively over a minimum of 1 year. A sample size of 30 or more was used because it would permit the assumption of normal distribution based on the central limit theorem.17 The detailed inclusion and exclusion criteria used for each stage of screening are summarized in eTable 2 in the Supplement.

Data Collection

Two reviewers (E.Y.L. and C.K.) independently screened records using Covidence (Veritas Health Innovation) and extracted data. If more than 1 study came from the same center with overlapping study periods, we included the study with the longer duration to avoid double counting patients. The literature search and final study selection were summarized using the PRISMA diagram (Figure 1). It was prospectively planned that conflicts from screening or extracting stages that could not be resolved between the 2 reviewers would be then discussed with the third reviewer (E.J.P.) to reach a consensus.

Figure 1. PRISMA Diagram for Study Selection.

Figure 1.

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The following information was extracted from the studies using a prespecified data extraction template. Study characteristics included publication year, study design, study duration, country, and name of hospitals. Patient demographics included total number of patients, number of female patients, ethnicity, age, latency period (ie, time from starting the drug to onset of symptoms), length of stay in hospitals, and mortality. The SJS/TEN characteristics included types of SJS/TEN based on the percentage of affected BSA, how the diagnosis was made, and triggers identified through use of predefined criteria or algorithms. Information on risks included number of culprit drugs, number and class of culprit antibiotics, infections identified as the cause, and unknown causes.

Meta-analysis and Outcomes of Interest

The studies described in the systematic review were included in the meta-analyses if the SJS/TEN cause was counted at the patient level. As such, studies that counted each trigger separately in patients with multiple triggers were excluded so that the number of triggers matched the number of patients with SJS/TEN at the study level. In addition, in studies that had overlapping patients, we included the studies with the most comprehensive information.

Among the studies included in the meta-analyses, the primary outcomes were the proportions of antibiotics associated with SJS/TEN and relative proportions of each antibiotic class triggering antibiotic-associated SJS/TEN. The secondary outcome was the proportion of antibiotics triggering drug-associated SJS/TEN, excluding patients with SJS/TEN associated with infections or unknown causes.

Quality Assessment

We assessed the risk of bias for the included studies using the Joanna Briggs Institute (JBI) critical appraisal checklist and calculated the score sum for each study.18 We assessed the certainty of evidence for each study using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.19 Any disagreement was resolved through discussion either between the 2 reviewers (E.Y.L. and C.K.) or with the third reviewer (E.J.P.).

Subgroup and Sensitivity Analysis

To explore the potential sources of heterogeneity, we performed 2 planned subgroup analyses on the primary outcomes by age groups and by continents. Two sensitivity analyses were performed using studies with the median and higher JBI score, as well as studies that specified drug association using predefined criteria or established algorithms such as ALDEN score.

Statistical Analysis

We performed statistical analyses in R, version 3.6.1, using the meta package, version 4.12-0 (R Foundation for Statistical Computing). We calculated the proportions of antibiotics associated with SJS/TEN in each study and used the Clopper-Pearson method to compute the 95% CIs. Given the considerable differences among studies related to geography and patient characteristics, we used the random-effects model by applying the DerSimonian and Laird method to pool the proportion estimates to generate the overall antibiotic prevalence. The studies were weighted by the inverse-variance method. Results were presented in forest plots. Heterogeneity was examined using the I2 statistic, τ2, and Q test; P < .05 represented statistically significant heterogeneity beyond chance. Publication bias was assessed using a funnel plot. Bonferroni correction was applied for multiple comparisons whenever appropriate.

Results

Study Selection

The literature search resulted in 4831 studies, and 364 of them were duplicates and thus removed. The remaining 4467 studies were screened for title, abstract, and full text, and 64 potentially relevant studies were identified. Of the 64 studies that underwent data extraction,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83 3 studies described the same study population and were excluded from the meta-analysis. Furthermore, there were 23 studies that did not count the SJS/TEN associations at the patient level and thus were excluded.

In the end, the meta-analysis included 38 retrospective observational studies with 2917 patients from more than 20 countries.20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57 There were 16 studies from Asia (1298 patients), 14 studies from North America (932 patients), 4 studies from Europe (208 patients), 3 studies from Africa (437 patients), and 1 study from Australia (42 patients). Only 2 of the studies included patients from more than 1 country. Almost all of the studies provided aggregate data on patient demographics and SJS/TEN types and associations. Information on ethnicity, latency period, and length of stay in hospitals was only available in some studies and thus not shown. The study demographics are summarized in eTable 3 in Supplement 1.

Assessment of Study Quality

All of the studies included in the meta-analysis met the definition of case series, so the JBI checklist for case series was used to assess the risk of bias, and a score out of 10 was calculated for each study.18,84 Overall, the risk of bias was low, with a median (IQR) JBI score being 7.00 (5.75-7.00) (eFigure 1 in Supplement 1). Using the GRADE approach, the certainty of evidence was deemed moderate due to the serious inconsistency from heterogeneity detected in the primary outcomes (eTable 4 in Supplement 1).

Risks for SJS/TEN

The triggers for SJS/TEN are summarized at the study level in eTable 5 in Supplement 1. A single drug was associated with 86% (95% CI, 80%-92%) of all SJS/TEN cases; the remaining 14% (95% CI, 8%-20%) were associated with multiple potential drug triggers, unknown drug names, infections, or unknown causes. All studies, except for one21 described antibiotics as one of the triggers for SJS/TEN. The other common triggers were anticonvulsants, allopurinol, and nonsteroidal anti-inflammatory drugs. Infection was an uncommon trigger in both adult and pediatric patients with SJS/TEN. All studies were able to identify most SJS/TEN triggers.

Prevalence of Antibiotic-Associated SJS/TEN

The pooled proportion of antibiotics associated with SJS/TEN (38 studies; 2917 patients) was 28% (95% CI, 24%-33%), with moderate certainty of evidence (Figure 220,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57). There was no evidence of publication bias (eFigure 2 in Supplement 1). The pooled proportion of antibiotics triggering drug-associated SJS/TEN (38 studies; 2425 patients) was 35% (95% CI, 29%-40%) (eFigure 3 in Supplement 1). The pooled proportion of sulfonamide antibiotics triggering drug-associated SJS/TEN (38 studies; 2425 patients) was 11% (95% CI, 7%-16%).

Figure 2. Proportion of Antibiotics Associated With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

Figure 2.

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We also analyzed antibiotic-associated SJS/TEN by antibiotic class, and only classes with nonzero proportions were presented. The pooled proportion of β-lactams–causing antibiotic-associated SJS/TEN was 39% (95% CI, 30%-48%), and this was dominated by penicillins (22%; 95% CI, 17%-28%) and cephalosporins (11%; 95% CI, 6%-17%). The relative proportions of the top 5 classes triggering antibiotic-associated SJS/TEN are summarized in Table 1. Sulfonamide was responsible for 32% (95% CI, 22%-44%) of antibiotic-associated SJS/TEN, whereas the macrolide class was the least common class causing antibiotic-associated SJS/TEN (2%; 95% CI, 1%-5%).

Table 1. Relative Proportions of Antibiotic Classes Associated With Antibiotic-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Among Patients (n = 985).

Antibiotic class Studies, No. Proportion (95% CI), % I2, % τ2 P valuea
Sulfonamides 38 32 (22-44) 91 0.112 <.001
Penicillins 38 22 (17-28) 63 0.019 <.001
Cephalosporins 38 11 (6-17) 77 0.038 <.001
Fluoroquinolones 38 4 (1-7) 69 0.025 <.001
Macrolides 38 2 (1-5) 43 0.009 <.001
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a

Test of heterogeneity.

Subgroup Analyses

The first subgroup analysis was conducted using studies that contained adults only (10 studies; 1028 patients) and those that contained children only (5 studies; 208 patients). There was no difference in the proportion of antibiotics associated with SJS/TEN between adult and pediatric groups (eFigure 4 in Supplement 1). However, the relative proportions of antibiotics associated with antibiotic-induced SJS/TEN by age group are summarized in eTable 6 in Supplement 1. While the relative proportions for penicillin class were similar in both adults and children, they were significantly higher for cephalosporins and fluoroquinolones but appeared lower for macrolides and sulfonamides in adults than in children (eTable 6 in Supplement 1).

The second subgroup analysis was stratified by continents, and there was a statistically significant difference in the proportion of antibiotics. Asia was further divided into regions physiographically given the large number of studies and genetic heterogeneity. The relative proportions of antibiotic classes triggering antibiotic-associated SJS/TEN by continents were not performed due to fewer than 2 studies taking place in many continents. These results are summarized in Table 2.

Table 2. Subgroup Analysis on the Proportions of Antibiotics Associated With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis by Continent.

Continent Studies, No. Patients, No. Proportion (95% CI), % I2, % τ2 P valuea
Australia 1 42 43 (28-58) NA NA NA
North America 14 932 37 (30-45) 75 0.011 <.001
Africa 3 437 33 (6-68) 88 0.013 <.001
Europe 4 208 30 (16-48) 58 0.007 <.001
Asia, south 4 276 26 (11-44) 71 0.009 <.001
Asia, east 7 688 17 (10-25) 79 0.099 <.001
Asia, southeast 5 334 16 (1-44) 93 0.055 <.001
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Abbreviation: NA, not applicable.

a

Test of heterogeneity.

Sensitivity Analyses

The first sensitivity analysis used studies that described the criteria for drug associations (14 studies; 948 patients), and the pooled proportion of antibiotics associated with SJS/TEN was 27% (95% CI, 17%-39%) (eTable 7 in Supplement 1). The second analysis used studies with a JBI score 7 and above (21 studies; 1380 patients), and the pooled proportion of antibiotics associated with SJS/TEN was 24% (95% CI, 17%-31%) (eTable 7 in Supplement 1). Therefore, the sensitivity analyses were similar to the primary outcome.

Discussion

This systematic review and meta-analysis is, to our knowledge, the first to examine the prevalence of antibiotics associated with SJS/TEN in all age groups worldwide. The pooled proportion of antibiotics associated with SJS/TEN in 2917 patients was 28%, and this estimate was based on moderate certainty evidence. The prevalence of antibiotics triggering drug-associated SJS/TEN was higher at 35%. Furthermore, among the antibiotic-associated SJS/TEN, sulfonamide antibiotics remain the leading cause, whereas macrolides were the least frequent cause among the top 5 globally prescribed antibiotic classes.85

Drugs remain the most important risk for SJS/TEN and are an iatrogenic cause where early discontinuation and intervention improves patient outcomes.13 One systematic review, including 9 studies that described the risks for SJS/TEN over 20 years in Thailand, showed that drugs were associated with 100% of causes in adults and 97% in children.86 There was likely case selection or referral bias because up to one-third of SJS/TEN cases do not have a clear trigger.8 The present study showed that 86% of SJS/TEN cases could be associated with drugs, but this proportion could be underestimated. This study also included only single drug triggers in the numerator, while multidrug triggers or unknown drug names were put in the denominator. Furthermore, the prevalence of antibiotic-associated SJS/TEN has been examined regionally. One meta-analysis, including 25 studies on severe cutaneous adverse reactions (SCARs), showed that antibiotics were associated with 25% to 28% of SJS/TEN cases in China.87 This is similar to the worldwide prevalence of antibiotic-associated SJS/TEN observed in the present study. Thus, antibiotics remain one of the most common culprit drugs for SJS/TEN in both adults and children worldwide.

Among antibiotic-associated SJS/TEN, sulfonamide antibiotics are the most commonly involved group. A systematic review on all SJS/TEN cases in Thailand showed that sulfonamide antibiotics, which were all cotrimoxazole, were associated with 22% of SJS/TEN cases overall.86 This study showed that sulfonamide antibiotics were associated with 11% of drug-associated SJS/TEN, possibly due to a more heterogeneous population, whereas certain human leukocyte antigen (HLA) class 1 risk alleles predisposing to sulfonamide antibiotic-associated SJS/TEN have been described in South and East Asian populations.88,89,90 There has also been an increasing awareness of restrictive use of sulfonamide antibiotics.91,92 In fact, global sulfonamide antibiotic use has been decreasing since 2000 despite an ongoing upward trend of use in other antibiotic classes.85

Stevens-Johnson syndrome/TEN is considered the most severe form of drug hypersensitivity reaction, and antibiotics are an important risk. The top 5 common classes of antibiotics used worldwide in 2018 were penicillins, macrolides, tetracyclines, other β-lactams, and fluoroquinolones.85 This list almost corresponded to the top 5 common causes of antibiotic-associated SJS/TEN shown in the present study, except that sulfonamide antibiotics replaced tetracyclines. The study supports the ongoing effort to avoid unnecessary antibiotic use and restrict sulfonamide antibiotics to only specific indications to prevent SJS/TEN.91,92,93

There was considerable heterogeneity in the meta-analysis, which was not explained by the subgroup analysis using age group. This may not be surprising because drug use is the most important risk for SJS/TEN regardless of the age group. However, the heterogeneity could be partially explained by the subgroup analysis using continents. The difference in the proportions of antibiotics associated with SJS/TEN among the continents could be due to the variation in antibiotic use at physician, hospital, and regional levels, as well as differences in comorbidities such as HIV. The HLA alleles that are more prevalent in specific populations have more recently been described with sulfonamide antibiotics.89,90 For example, both HLA-A*11:01 and HLA-B*13:01 were identified to increase the risk of sulfonamide-associated SCARs in several Asian populations.89,90 One important future direction is to identify additional HLA and non-HLA risk alleles associated with SCARs in other populations in the hope that they can be implemented into clinical practice to predict individuals at risk and prevent potentially fatal SCARs.

Strengths and Limitations

Strengths of this study include vigorous inclusion and exclusion criteria. As such, we had to exclude studies based on large registry data or pharmacovigilance because each SJS/TEN case could not be ascertained. This likely explained why the overall risk of bias was low and that there was a lack of publication bias due to the homogeneous study designs. In addition, we included studies that counted triggers at the patient level so that the reported antibiotics were all single drug triggers of SJS/TEN. This ensures directness and precision, and thus likely contributed to the GRADE assessment being “moderate certainty evidence” despite all the studies being case series.

On the other hand, there are several major limitations in this study that merit consideration. First, the stringent eligibility criteria led us to exclude more than three-quarters of the studies at the full-text review stage and an additional 40% of the studies for meta-analysis so that only drug triggers identified at the patient level were included. This could have selected for studies that had associations identified and overestimated the proportion of SJS/TEN cases that had drug-associated causes. Second, most of the studies provided aggregated data for relevant patient and clinical characteristics, so meta-regression was not performed on the primary outcomes to further explore the heterogeneity. The aggregated data also restricted use of SJS/TEN as 1 entity instead of 3 separate entities, even though each subtype has different severity and mortality. This is noteworthy because nondrug-associated disease, more common in children and young adults, is more likely to have more mucosal and less cutaneous involvement and be classified as SJS. Third, we limited the search to English literature only. Finally, although we can look at patterns of antibiotic use, we cannot interpret how likely specific drugs are to trigger SJS/TEN. For instance, the relative risk of SJS/TEN associated with β-lactams related to their overage use is still extremely small. We also used the top 3 most common classes of drugs associated with SJS/TEN in the search strategy, assuming at least 1 of the classes would be listed as keywords in the studies that described SJS/TEN.

Conclusions

This systematic review and meta-analysis showed that antibiotics may be associated with more than one-quarter of SJS/TEN cases worldwide and that sulfonamide antibiotics remain the leading risk for antibiotic-associated SJS/TEN. The study highlights the importance of using antibiotics judiciously and limiting sulfonamide antibiotics to only specific indications and durations, as well as early recognition and prompt discontinuation of the implicated drugs to reduce morbidity and mortality associated with SJS/TEN. Future directions may look at the prevalence of other high-risk medications associated with SJS/TEN worldwide and the prevalence of antibiotics triggering other types of severe cutaneous adverse reactions.

Supplement 1.

eTable 1. Search strategies

eTable 2. Eligibility criteria

eTable 3. Demographics of the studies included in the meta-analysis

eTable 4. GRADE analysis

eTable 5. Outcomes of the studies included in the meta-analysis

eTable 6. Subgroup analysis on the relative proportions of antibiotic classes causing antibiotic-induced SJS/TEN by age group

eTable 7. Summary of sensitivity analyses

eFigure 1. Risk of bias assessment for the studies included in the meta-analysis

eFigure 2. Funnel plot for primary meta-analysis

eFigure 3. Proportion of antibiotics causing drug-induced SJS/TEN

eFigure 4. Subgroup analysis on the proportions of antibiotics causing SJS/TEN by age group

Click here for additional data file. (1.7MB, pdf)
Supplement 2.

Data Sharing Statement

Click here for additional data file. (15.8KB, pdf)

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplement 1.

eTable 1. Search strategies

eTable 2. Eligibility criteria

eTable 3. Demographics of the studies included in the meta-analysis

eTable 4. GRADE analysis

eTable 5. Outcomes of the studies included in the meta-analysis

eTable 6. Subgroup analysis on the relative proportions of antibiotic classes causing antibiotic-induced SJS/TEN by age group

eTable 7. Summary of sensitivity analyses

eFigure 1. Risk of bias assessment for the studies included in the meta-analysis

eFigure 2. Funnel plot for primary meta-analysis

eFigure 3. Proportion of antibiotics causing drug-induced SJS/TEN

eFigure 4. Subgroup analysis on the proportions of antibiotics causing SJS/TEN by age group

Click here for additional data file. (1.7MB, pdf)
Supplement 2.

Data Sharing Statement

Click here for additional data file. (15.8KB, pdf)

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