Colistin-associated Stevens-Johnson syndrome and toxic epidermal necrolysis reactions: a retrospective case-non-case pharmacovigilance study

ABSTRACT

Background

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening skin reactions. Colistin is a last resort antibiotic with a historically poor safety profile. The association between colistin and SJS/TEN has not been previously quantified.

Research design and methods

We identified colistin and SJS/TEN adverse event reports from the Food and Drug Administration Adverse Event Reporting System (FAERS) and calculated effect estimates using OpenEpi.

Results

From January 2013 through March 2021, 964 adverse events were reported for colistin. Colistin was listed as a secondary suspect drug in 13 SJS/TEN adverse event reports (1.3%), with a reporting odds ratio of 29.6 (95% confidence interval [CI] 17.1–51.1), and proportional reporting ratio of 29.2 (95% CI 17.0–50.2). Limitations of any FAERS study include the voluntary nature of reporting, unclear causal relationship between drug and adverse reaction, underreporting, and wide confidence intervals for rare adverse events like SJS/TEN.

Conclusions

Colistin was not the primary suspect drug in any SJS/TEN adverse event reports. We did identify a statistically significant safety signal for SJS/TEN with colistin as a secondary suspect drug. SJS/TEN is not currently included in the colistin product label. This association should be further explored in other pharmacoepidemiologic drug safety studies.

KEYWORDS:

• Colistin
• FDA adverse event reporting system
• Stevens-Johnson syndrome
• toxic epidermal necrolysis

Acknowledgments

The views expressed are those of the authors and do not necessarily reflect the position or policy of the United States Department of Veterans Affairs. This material is based upon work supported, in part, by the Office of Research and Development, Department of Veterans Affairs.

Author contributions

All authors contributed to the study conception and design, material preparation, data collection, and analysis, writing, and revision of the manuscript, and reading and final approval of the submitted manuscript.

Declaration of interests

A Caffrey has received research funding from Pfizer, Merck, and Shionogi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Availability of data and material

The study utilized publicly available data from the FDA Adverse Event Reporting system.