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. 2016 Jul 27;11(7):e0158407.
doi: 10.1371/journal.pone.0158407. eCollection 2016.

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

Li-Ju Chen  1   2 , Fei-Yuan Hsiao  1   2   3 , Li-Jiuan Shen  1   2   3 , Fe-Lin Lin Wu  1   2   3 , Woei Tsay  4 , Chien-Ching Hung  4 , Shu-Wen Lin  1   2   3
Affiliations

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

Li-Ju Chen et al. PLoS One. .

Abstract

Objective: 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.

Design: A nationwide nested case-control study.

Setting: National Health Insurance Research database.

Participants: 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).

Results: 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 (<3 DDDs, aOR 1.62; 3-5 DDDs, aOR 1.78; and >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.

Conclusions: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart describing the enrollment of the study cohort, the cases and
the controls.
See this image and copyright information in PMC

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