Antibiotic hypersensitivity in hospitalized patients is a challenging dilemma, as sometimes a thorough history might not be sufficient to identify the culprit agents. Vulnerable conditions often hamper investigational in vivo tests. Meanwhile, the decision of which drugs to be further continued or substituted is urgently needed. Enzyme-linked Immunospot (ELISPOT) assay has previously shown effectiveness in detecting drug-specific T cell response. Thus, we conduct this study to assess the role of ELISPOT for management of antibiotic hypersensitivity in clinical setting.
Methods
The medical records of inpatients who were diagnosed or developed non-immediate allergic reactions to antibiotics and underwent Interferon-gamma ELISPOT assay at King Chulalongkorn Memorial Hospital, Bangkok between 2012 and 2015 were retrospectively determined.
Results
Total 60 patients were evaluated (mean age 55.7 years, range 7-96 years), 33 (55 %) were female. Twenty-eight patients (46.7%) had underlying diseases including hematologic malignancy, solid tumor cancer, HIV infection, or autoimmune diseases. Fifteen (25%) individuals were concurrently on systemic corticosteroids. The majority of subjects (49.1%) experienced maculopapular exanthems (MPE), while 36.7 % had severe cutaneous adverse reactions. The mean duration from drug intake to the onset of symptoms was 8 days and the mean interval from symptoms onset to the collection of peripheral blood mononuclear cells (PBMCs) was 9.5 days. In most cases, the number of drug-specific IFN-gamma secreting cells was later analyzed with ELISPOT by incubating PBMCs with the culprit drugs or potential alternative drugs. Beta - lactams occupied 70.8% of the analysis. Penicillins, cephalosporins and carbapenems were the most frequently suspected compounds. The number of drug-specific IFN-gamma secreting cells more than 20 spot-forming cells/106 (PBMCs) was considered a positive test. Among those examined for responsible drugs, 22 of 48 tests (45.8%) yielded positivity. The proportion of positive outcomes was 66.7% in acute generalized exanthematous pustulosis, 46.2% in MPE, 40.0% in drug rash with eosinophilia and systemic symptoms and lowest in Stevens Johnson syndrome (16.6%). Subsequently, twenty-four persons underwent drug challenges test. All were able to tolerate their alternative medications of which ELISPOT displayed negative results.
Conclusions
Providing excellent negative predictive value and favorable sensitivity in particular T cell-mediated reactions, IFN-gamma ELISPOT might be applicable to confirm antibiotic hypersensitivity in patients with a history of non-immediate reactions and reduce further allergic risk prior to receiving potential allergenic drug.