# 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

## TL;DR

This study compares antibiotic-related allergic heart events diagnosed as Kounis syndrome versus non-Kounis cases using FDA data, finding differences in comorbidities and drug use that suggest possible underdiagnosis of Kounis syndrome.

## Contribution

The study identifies clinical and drug-use patterns distinguishing antibiotic-associated Kounis syndrome from non-Kounis allergic coronary events using FAERS data.

## Key findings

- Non-Kounis cases had higher rates of cardiac comorbidities, diabetes, and mortality compared to Kounis syndrome cases.
- Quinolones and aminoglycosides were more frequently reported in non-Kounis cases, suggesting a potential link to underdiagnosed Kounis syndrome.
- Penicillins were more commonly associated with Kounis syndrome cases than non-Kounis cases.

## Abstract

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.

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.

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).

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.

The online version contains supplementary material available at 10.1186/s40780-026-00545-7.