Antibiotic-associated eosinophilic and occlusive arteritis in calves complicating preclinical studies of left ventricular assist devices

• Published in: Toxicologic pathology Vol. 41; no. 3; p. 519
• Main Authors: Cooper, Timothy K, Griffith, James W, Reibson, John, Peterson, Rebecca, Roush, Evan P, Zhong, Qing, Weiss, William J, Rosenberg, Gerson
• Format: Journal Article
• Language: English
• Published: United States 01.04.2013
• Subjects: Animals; Anti-Bacterial Agents - adverse effects; Arteritis - chemically induced; Arteritis - etiology; Arteritis - physiopathology; beta-Lactams - adverse effects; Blood Pressure; Cattle; Clinical Trials as Topic; Eosinophilia - chemically induced; Eosinophilia - etiology; Eosinophilia - physiopathology; Eosinophils - cytology; Eosinophils - drug effects; Heart-Assist Devices; Infarction - pathology; Kidney - blood supply; Kidney - pathology; Kidney Cortex - blood supply; Kidney Cortex - pathology; Leukocyte Count; Lung - blood supply; Lung - pathology; Male; Pulmonary Artery - pathology
• ISSN: 1533-1601
• DOI: 10.1177/0192623312450630

Repeated bolus intravenous (IV) administration of large doses of beta-lactams and aminoglycosides has previously been associated with the development of eosinophilic and occlusive arterial lesions limited to the lungs in calves. Reviewing 13 years worth of records from left ventricular assist device implantation studies, morphologically identical segmental arterial lesions were present in 32 of the 56 calves receiving IV antibiotics, affecting lungs (6/50), kidneys (12/56), or lungs and kidneys (14/50). In 16 of these calves, renal arterial lesions spatially colocalized with renal cortical infarctions. Lesions were noted in additional abdominal organs in 4 of the 50 calves and were exclusively present in the liver in a single calf. Similar arterial lesions were also noted in the lungs (3/4), kidneys (1/4), liver (1/4), and spleen (1/4) of unimplanted calves receiving similar IV antibiotic regimens for bacterial infections. Lesions were observed with therapeutic IV doses of cephalosporins with or without aminoglycosides over shorter intervals than previously implicated. Lesions were significantly associated with increased peripheral eosinophil counts and mildly elevated, not reduced, arterial pulse pressures. This report documents the features of an idiosyncratic drug reaction with features strongly suggestive of an acute type-I hypersensitivity in this species.