Cephalosporin triggered Kounis syndrome: Pathophysiological and clinical insights

Background: Acute coronary syndrome triggered by hypersensitivity to various natural, chemical, or pharmaceutical allergens is known as Kounis syndrome. Kounis syndrome is classified in three subtypes based on its pathophysiological mechanism and outcome. Among pharmaceuticals, cephalosporins are frequently implicated in allergic illnesses, with ceftriaxone being one of the most frequently reported causes. Based on literature reports and our own experience, we focused on the main clinical features regarding ceftriaxone triggered KS (CTKS). Methods. Medical records from all CTKS cases, as published by the end of December 2024, were retrieved and analyzed, including a patient admitted to our hospital after inadvertent twice ceftriaxone administration. Results: Clinical findings from 10 CTKS patients, mean aged 61 +/- 18 (range 24-85) years, 5 males, were studied. Type-I KS (coronary vasospasm) was found in 8 cases (80 %), whereas 2 more patients showed a type-II variant (atheromatous plaque thrombosis), with the right artery as the most involved coronary vessel. Apart from transient hemodynamic instability in 2 patients on admission, everyone was discharged in a good clinical condition. Conclusions: CTKS is a rare, but likely underrecognized, clinical condition that may occur regardless of gender, age, history of allergy or preexisting coronary artery disease. The predominant type-I variant indicates a transient coronary asospasm (and/or microcirculatory impairment) as the most likely pathogenic mechanism. Key pathophysiological, clinical, and prognostic aspects are discussed.