loading page

Pathogenesis of Beta-lactam-induced Serum Sickness-Like Reaction: The potential role of Reactive Drug Metabolites
  • +2
  • Abdelbaset Elzagallaai,
  • Awatif Abuzgaia,
  • Blanca Rosa Del Pozzo Magaña,
  • Eman Loubani ,
  • Michael Rieder
Abdelbaset Elzagallaai
Western University

Corresponding Author:[email protected]

Author Profile
Awatif Abuzgaia
Western University
Author Profile
Blanca Rosa Del Pozzo Magaña
Western University
Author Profile
Eman Loubani
Western University
Author Profile
Michael Rieder
University of Western Ontario
Author Profile


Aims: Drug-induced serum sickness-like reactions (SSLRs) are idiosyncratic drug-induced hypersensitivity reactions that occur in susceptible patients 1-3 weeks after exposure to the culprit drug. The pathophysiology of this type of reactions is not well understood and its diagnosis is difficult due to the lack of safe and reliable diagnostic tests for identifying the culprit drug. The lymphocyte toxicity assay (LTA) is an in vitro test used as a diagnostic and investigative tool for drug hypersensitivity reactions (DHRs). In this pilot study, we investigated the pathogenesis of SSLR using the LTA test to evaluate the potential role of reactive drug metabolites in the pathogenesis of SSLR. Methods: Nineteen patients (14 males and 5 females) were recruited to this study. Demographic data was collected form the patents and blood samples were withdrawn from all patients and from 19 healthy controls. The LTA test was performed on all subjects and data is expressed as percentage increase in cell death compared to control (vehicle without the drug). Results: There was a significant (p<0.05) concentration-related increase in cell death in cells isolated from patients as compared to cells from healthy controls when incubated with the drug in the presence of phenobarbitone-induced rat liver microsomes (MICs). Conclusion: This data suggests the initial bioactivation of the drug to a reactive metabolite followed by a toxic response is a key first step in -lactam antibiotic-induced SSLRs. Further research is needed to explore the implications of this data as to the pathogenesis of -lactam antibiotic induced SSLR.
06 Apr 2020Submitted to British Journal of Clinical Pharmacology
07 Apr 2020Assigned to Editor
07 Apr 2020Submission Checks Completed
08 Apr 2020Reviewer(s) Assigned
01 May 2020Review(s) Completed, Editorial Evaluation Pending
04 May 2020Editorial Decision: Revise Minor