Elevated International Normalized Ratio associated with long-term azithromycin therapy in a child with cerebral palsy

Abstract

A case of coagulopathy in a pre-adolescent with cerebral palsy that developed after chronic prophylactic antibiotic use is reported. An 11-year-old boy with cerebral palsy was brought to the emergency department experiencing restlessness and decreased oxygen saturation. Evaluation of the patient revealed gallstone-related pancreatitis, with elevated serum amylase and lipase concentrations and abnormal liver function test results. At the time of the initial evaluation, the International Normalized Ratio (INR) was 6.54 (normal range, 0.8-1.2), and the activated partial thromboplastin time was 53.8 seconds (normal range, 24.4-34.8 seconds). The boy's medication history included use of azithromycin 200 mg every other day for about two years for antiinflammatory therapy. On confirmation of the elevated INR 2 hours after the initial evaluation, azithromycin was discontinued, and a single dose of phytonadione 2 mg was administered. About 14 hours after phytonadione administration, the INR had declined to 0.94; 43 hours later, the INR remained within the normal range without further phytonadione therapy. Using the probability scale of Naranjo and colleagues, this case was rated as a probable drug-related adverse event. Previous reports have linked the development of vitamin K deficiency and impaired coagulation to long-term antibiotic use, but not specifically to use of azithromycin or other macrolide antibiotics. An elevated INR in a child with cerebral palsy was evidently related to long-term therapy with azithromycin. The abnormal INR normalized after discontinuation of azithromycin and administration of one dose of phytonadione.