Kounis syndrome due to antibiotics: A global overview from pharmacovigilance databases.
BACKGROUND
Kounis syndrome (KS) is characterized by concurrent presence of anaphylactic and cardiac components. Available evidence suggests that antibiotics are frequently associated to KS. We therefore analyzed KS cases associated with antibiotics use from the two largest pharmacovigilance databases.


METHODS
Two pharmacovigilance databases, EudraVigilance and VigiLyze, were searched for cases reporting the adverse reaction "Kounis Syndrome" with antibiotics as suspected active substance. We analyzed the period from December 1st, 2001 to February 16th, 2016. For the most reported active substance, proportional reporting ratio (PRR) was calculated.


RESULTS
A total of 10 cases of KS associated with antibiotic use were retrieved from EudraVigilance database. Mean patients' age was 58.2years and 70% were male. The most frequently reported suspected antibiotic was the combination amoxicillin/clavulanic acid (four cases). VigiLyze database reported 13 KS cases associated to antibiotics. Mean age was 56years and 61% of patients were male. The most frequently reported antibiotic was again the combination amoxicillin/clavulanic acid (five cases). Seven duplicate cases were identified, leaving a total of 16 cases of KS, with six of them associated to amoxicillin/clavulanic acid use. The PRR value for amoxicillin/clavulanic acid against other kinds of antibiotics was 2.62 considering EudraVigilance data and 1.61 considering VigiLyze data.


CONCLUSIONS
This analysis provided a complete picture of the cases of KS associated with antibiotic use and identified a possible association between amoxicillin/clavulanic acid and KS. Since the number of cases is low, especially considering its wide use, further analyses are needed to confirm the association.
Italian Medicines Agency, Rome, Italy.
Francesca
F
Renda
Italian Medicines Agency, Rome, Italy.
Elena
E
Marotta
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: landoni.giovanni@hsr.it.
Giovanni
G
Landoni
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Alessandro
A
Belletti
Italian Medicines Agency, Rome, Italy.
Virginia
V
Cuconato
Italian Medicines Agency, Rome, Italy.
Luca
L
Pani
D054058:Acute Coronary Syndrome / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects*; D000707:Anaphylaxis / Q000139:chemically induced / Q000150:complications / Q000175:diagnosis / Q000628:therapy; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D003329:Coronary Vasospasm; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006633:Histamine Antagonists / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060735:Pharmacovigilance; D035583:Rare Diseases; D013577:Syndrome
D000900:Anti-Bacterial Agents; D005938:Glucocorticoids; D006633:Histamine Antagonists; D019980:Amoxicillin-Potassium Clavulanate Combination
Acute coronary syndrome; Antibiotics; Coronary vasospasm; Drug hypersensitivity; Myocardial infarction; Rare diseases