The Association Between Cephalosporin and Hypoprothrombinemia: A Systematic Review and Meta-Analysis

Gi Hyue Park, Seungyeon Kim, Min Soo Kim, Yun Mi Yu, Gun Hee Kim, Jeong Sang Lee and Euni Lee
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Gi Hyue Park: College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea
Seungyeon Kim: College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea
Min Soo Kim: College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea
Yun Mi Yu: Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon 21983, Korea
Gun Hee Kim: College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea
Jeong Sang Lee: Department of Thoracic & Cardiovascular Surgery, SNU-SMG Boramae Hospital, Seoul 07061, Korea
Euni Lee: College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea

IJERPH, 2019, vol. 16, issue 20, 1-14

Abstract: Cephalosporins that contain the N-methylthiotetrazole side chain (NMTT-cephalosporin) have been reported to be associated with coagulation-related adverse events; however, a comprehensive evaluation regarding the association is lacking. A systematic review and meta-analysis were conducted to assess the safety profile of NMTT-cephalosporins with respect to hypoprothrombinemia and bleeding. The MEDLINE, Embase, Cochrane, and RISS databases were systematically searched for clinical studies up to October 2018. The association between NMTT-cephalosporins and hypoprothrombinemia was estimated using an odds ratio (OR) with a 95% confidence interval (CI). A total of 15 studies on cefamandole, cefoperazone, cefotetan, cefmetazole, and moxalactam were identified and included in the meta-analysis. Hypoprothrombinemia (OR 1.676, 95% CI 1.275–2.203) and prothrombin time (PT) prolongation (OR 2.050, 95% CI 1.398–3.005) were significantly associated with NMTT-cephalosporins, whereas bleeding was not (OR 1.359, 95% CI 0.920–2.009). Subgroup analyses revealed that cefoperazone (OR 2.506, 95% CI 1.293–4.860), cefamandole (OR 3.247, 95% CI 1.083–9.733), and moxalactam (OR 3.367, 95% CI 1.725–6.572) were significantly associated with hypoprothrombinemia. An Antimicrobial Stewardship Program led by a multidisciplinary team could play a critical role in monitoring cephalosporin-related hypoprothrombinemia or PT prolongation in patients with underlying clinical conditions at risk for bleeding. The multidisciplinary team could also assist in communicating the potential safety concerns regarding NMTT-cephalosporin use with healthcare professionals to decrease the risk of adverse events.

Keywords: cephalosporins; hypoprothrombinemia; prothrombin time; bleeding (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2019
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