Use of Hypoprothrombinemia-Inducing Cephalosporins and the Risk of Hemorrhagic Events: A Nationwide Nested Case-Control Study

• Published in: PloS one 2016-07, Vol.11 (7), p.e0158407-e0158407
• Main Authors: Chen, Li-Ju, Hsiao, Fei-Yuan, Shen, Li-Jiuan, Wu, Fe-Lin Lin, Tsay, Woei, Hung, Chien-Ching, Lin, Shu-Wen
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibiotics; Anticoagulants; Biology and Life Sciences; Cancer; Case-Control Studies; Cefmetazole; Cefoperazone; Cephalosporins; Cephalosporins - administration & dosage; Cohort Studies; Complications and side effects; Confidence intervals; Data bases; Dosage and administration; Drug dosages; Drug therapy; Exposure; Female; Flomoxef; Health insurance; Hemorrhage; Hemorrhage - chemically induced; Hemorrhage - epidemiology; Hospitals; Humans; Hypoprothrombinemias - chemically induced; Insurance; Insurance claims; Internal medicine; Liver; Liver diseases; Male; Medicine; Medicine and Health Sciences; Metabolism; Middle Aged; Nutritional status; Patients; Pharmacy; Population studies; Risk analysis; Risk factors; Studies; Taiwan - epidemiology; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158407

Existing data regarding the risk of hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins are limited by the small sample size. This population-based study aimed to examine the association between exposure to hypoprothrombinemia-inducing cephalosporins and hemorrhagic events using National Health Insurance Research Database in Taiwan. A nationwide nested case-control study. National Health Insurance Research database. We conducted a nested case-control study within a cohort of 6191 patients who received hypoprothrombinemia-inducing cephalosporins and other antibiotics for more than 48 hours. Multivariable conditional logistic regressions were used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins (overall, cumulative dose measured as defined daily dose (DDD), and individual cephalosporins). Within the cohort, we identified 704 patients with hemorrhagic events and 2816 matched controls. Use of hypoprothrombinemia-inducing cephalosporins was associated with increased risk of hemorrhagic events (aOR, 1.71; 95% CI, 1.42-2.06), which increased with higher cumulative doses (5 DDDs, aOR 1.89). The aOR for individual cephalosporin was 2.88 (95% CI, 2.08-4.00), 1.35 (1.09-1.67) and 4.57 (2.63-7.95) for cefmetazole, flomoxef, and cefoperazone, respectively. Other risk factors included use of anticoagulants (aOR 2.08 [95% CI, 1.64-2.63]), liver failure (aOR 1.69 [1.30-2.18]), poor nutritional status (aOR 1.41 [1.15-1.73]), and history of hemorrhagic events (aOR 2.57 [1.94-3.41]) 6 months prior to the index date. Use of hypoprothrombinemia-inducing cephalosporins increases risk of hemorrhagic events. Close watch for hemorrhagic events is recommended when prescribing these cephalosporins, especially in patients who are at higher risk.