Comparative clinical features of antibiotic-associated Kounis syndrome and non-Kounis allergic coronary events: a disproportionality analysis using U.S. Food and Drug Administration Adverse Event Reporting System

BACKGROUND: Kounis syndrome (KS) is an acute coronary syndrome (ACS) triggered by allergic reactions and is frequently associated with antibiotic exposure. However, patient characteristics of antibiotic-associated KS cases are not well described. Some cases with KS-consistent symptoms may instead be reported as antibiotic-associated allergic coronary events (non-KS) without proper diagnosis. Characterizing these non-KS events may improve the accurate diagnosis of KS. This study explores the clinical features of antibiotic-associated KS and non-KS allergic coronary events in the FDA Adverse Event Reporting System (FAERS) and generates hypotheses regarding potential underdiagnosis and improved recognition of KS. METHODS: FAERS reports (September 2012-December 2024) were screened for allergic symptoms (SMQ: Anaphylactic reaction; Hypersensitivity) and ACS (SMQ: Acute myocardial infarction) with antibiotics listed as suspected drugs. After exclusions, 459 cases (KS: 205; non-KS: 254) were included. Extracted variables included demographics, comorbidities, drug use (ATC classification), and outcomes. Logistic regression identified factors independently associated with non-KS classification. RESULTS: Non-KS group exhibited higher rates of cardiac comorbidities, diabetes, and mortality (all p < 0.05). Among suspected antibiotics, penicillins were the only class more frequently reported in KS cases (42% vs. 30%, p = 0.010). In the multivariable analysis, factors independently associated with non-KS classification included female sex (odds ratio [OR] = 1.804), fatal outcomes (OR = 4.320), and use of quinolones (OR = 11.108), aminoglycosides (OR = 3.480), renin-angiotensin agents (OR = 2.608), analgesics (OR = 2.055), and polypharmacy (OR = 3.314) (area under the curve = 0.815). CONCLUSIONS: These exploratory findings indicate that non-KS allergic coronary events, characterized by higher comorbidities, mortality, and proportion of cases reporting the use of quinolones or aminoglycosides, may suggest a potential relationship between non-KS coronary events and KS underdiagnosis, warranting further prospective investigation.