Abstract Objective To compare the Liverpool Causality Assessment Tool versus Naranjo Scale for screening suspected adverse drug reaction (ADR) cases. Methods We retrospectively reviewed patient charts with a history of suspected ADR, scored using both instruments and determined how each correlates with laboratory and other investigations. 924 charts from the Clinical Pharmacology Clinic at the London Health Sciences Centre were reviewed and 529 charts contained objective findings to support or against the diagnosis of ADR. The participant age ranged from 1 month old to 93 years. We determined the sensitivity and specificity of Liverpool and Naranjo tools for predicting ADRs with scores ranging from “Possible” to “Definite” were considered positive and “Unlikely/Doubtful” as negative for ADR. These results were confirmed by laboratory or clinical (re-challenge) testing in 529 cases. Results Liverpool causality tool had sensitivity (SN) of 97.2% ± 2.4% and specificity (SP) of 2.3% ± 1.57%. The positive (PPV) and negative predictive values (NPV) were 34.1% and 61.5%, respectively. The Naranjo scale had SN of 81.2% ± 5.69% and SP of 13.2% ± 3.56%. PPV and NPV were 32.7% and 57.5%, respectively. Conclusions The Liverpool Causality Assessment Tool is a more sensitive tool than the Naranjo Scale in the assessment of possible ADRs but both tools have poor specificity. The Liverpool Tool can be a useful screening tool in settings where other tests may not be readily available. However the low PPV and NPV of both instruments suggests pursue further testing is needed to confirm or deny an ADR.

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 Demographic data was collected form the patents and blood samples were withdrawn from all patients and from 19 healthy controls.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.