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

Q: What are the key findings of this study?

Non-Kounis allergic coronary events were independently associated with higher fatal outcomes (OR 4.320, p=0.002), quinolone use (OR 11.108), and aminoglycoside use (OR 3.480) vs Kounis syndrome.

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Antibiotic-associated Kounis syndrome and non-Kounis allergic coronary events (n=459). Intervention: Non-Kounis syndrome allergic coronary event classification vs. Kounis syndrome classification. Primary outcome: Fatal outcome associated with non-Kounis syndrome classification (OR 4.320, 95% CI 1.674-11.147, p=0.002).

Ichiro Nakakura; Yutaro Mukai; Atsuki Hosoda; N O'Hara; Kaori Yamanishi; Takaya Uno; Satoshi Yokoyama; Kouichi Hosomi; Yoshiko Une

doi:10.1186/s40780-026-00545-7

February 3, 2026Journal of Pharmaceutical Health Care and SciencesOpen Access

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

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Key result

Non-Kounis allergic coronary events are linked to ~4.3-fold higher mortality compared to Kounis syndrome.

OR 4.320
95% CI 1.674-11.147
P=0.002
n=459

Key Points

To compare clinical characteristics of antibiotic-associated Kounis syndrome and non-Kounis allergic coronary events in the FAERS database to identify factors linked to potential underdiagnosis.
Retrospective disproportionality analysis of FAERS reports from September 2012 to December 2024 screening for allergic reactions and acute myocardial infarction with antibiotics listed as suspected agents.
Included 459 cases categorized into Kounis syndrome (n = 205) and non-Kounis allergic coronary events (n = 254).
Multivariable logistic regression was performed using demographic characteristics, comorbidities, and ATC-classified drug exposures to identify independent factors associated with non-Kounis classification.
Penicillins were more frequently reported in Kounis syndrome than non-Kounis cases (42% vs. 30%, p = 0.010), whereas non-Kounis cases had higher rates of cardiac disorders (13% vs. 3%, p < 0.001), diabetes (13% vs. 2%, p < 0.001), and fatal outcomes (17% vs. 3%, p < 0.001).
Multivariable analysis identified independent associations with non-Kounis classification for fatal outcomes (OR = 4.320, 95% CI: 1.674–11.147, p = 0.002), quinolones (OR = 11.108, 95% CI: 1.376–89.705, p = 0.024), and aminoglycosides (OR = 3.480, 95% CI: 1.923–6.224, p < 0.001).
Additional independent factors associated with non-Kounis classification included polypharmacy (OR = 3.314, 95% CI: 1.779–5.450, p < 0.001), renin–angiotensin agents (OR = 2.608, 95% CI: 1.135–5.993, p = 0.024), analgesics (OR = 2.055, 95% CI: 1.097–3.850, p = 0.025), and female sex (OR = 1.804, 95% CI: 1.141–2.851, p = 0.012), with a model AUC of 0.815.

Study Design

Type

Observational (n=459)

PICO

P

Population

459 patients with antibiotic-associated allergic acute coronary events (205 Kounis syndrome and 254 non-Kounis syndrome) identified from the FAERS database between September 2012 and December 2024.

E

Exposure / Comparator

Non-Kounis syndrome allergic coronary event classification vs Kounis syndrome classification

O

Primary Outcome

Fatal outcome associated with non-Kounis syndrome classification — OR 4.320 (1.674-11.147), p=0.002

Main Result

Odds Ratio: 4.32 (95% CI 1.674–11.147)

Absolute Event Rate: 17% vs 3%

p-value: p=0.002

Limitations

Inherent biases of spontaneous reporting systems such as underreporting and selective reporting
Inability to verify diagnostic accuracy of individual cases due to lack of detailed clinical information (e.g., ECGs, coronary angiography, allergy test results)
Potential selection bias from excluding cases with missing sex, age, and reason for use
Inability to systematically identify interacting co-medications in the FAERS Public Dashboard
Modest sample size increase in sensitivity analysis may have reduced statistical power

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Implication

Comparative analysis identifies distinct characteristics in Kounis and non-Kounis allergic coronary events, suggesting underdiagnosis issues.

Abstract

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.

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Cite This Study

Nakakura et al. (2026) conducted an observational in Antibiotic-associated Kounis syndrome and non-Kounis allergic coronary events (n=459). Non-Kounis syndrome allergic coronary event classification vs. Kounis syndrome classification was evaluated on Fatal outcome associated with non-Kounis syndrome classification (OR 4.320, 95% CI 1.674-11.147, p=0.002). Non-Kounis allergic coronary events were independently associated with higher fatal outcomes (OR 4.320, p=0.002), quinolone use (OR 11.108), and aminoglycoside use (OR 3.480) vs Kounis syndrome.

synapsesocial.com/papers/698435fff1d9ada3c1fb5720 https://doi.org/10.1186/s40780-026-00545-7

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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

Key Points

Study Design

PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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

Key Points

Study Design

PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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