Identification of risk factors and development of a predictive model in patients using cefmetazole for international normalized ratio elevation
Takaya Namiki, Yuta Yokoyama, Motonori Kimura, Shogo Fukuda, Shoji Seyama, Osamu Iketani, Masaru Samura, Haruki Ishikawa, Aya Jibiki, Hitoshi Kawazoe, Hisakazu Ohtani, Naoki Hasegawa, Kazuaki Matsumoto, Hideki Hashi, Sayo Suzuki, Tomonori Nakamura
Abstract
Patient risk factors related to coagulopathy and bleeding when using cefmetazole (CMZ) have not yet been identified, and no models exist to predict side effects during CMZ treatment. Moreover, reports that examine which patients should be careful when using CMZ to ensure safety are lacking.
Introduction
Extended-spectrum β-lactamase-producing enterobacteria (ESBL-E) have become a major public health challenge owing to increasing number of patients affected by antimicrobial-resistant bacteria between 2012 and 2017, leading to increased morbidity and mortality rates [1,2]. ESBL-E strains are usually treated with carbapenems [3], but the emergence of carbapenem-resistant Enterobacteriaceae due to increased use of carbapenems remains a point of concern [4].
Materials and method
Patient information
This retrospective observational study was conducted on patients who were being administered CMZ at Tokyo Bay Urayasu Ichikawa Medical Center and Keio University Hospital between January 2019 and October 2022. This study was reviewed and approved by the central comprehensive review of the Keio University School of Medicine Ethics Committee (Approval date: January 16, 2023, approval Number: 20221159).
Results
Patient data
The study covered 4,877 patients who used CMZ, with 565 intermediate target patients, for a final total of 429 patients after applying the exclusion criteria (61 in the elevated group and 368 in the non-elevated group) (Fig 1). The median age of the final target patients was 72 (interquartile range [IQR]: 60–82), and 74 (IQR: 65–83) and 72 (IQR: 60–82) years in the INR-elevated and non-INR-elevated groups, respectively. The proportion of males among the final target patients was 57.3% in the final target patients and 59% and 57.1%, in the INR-elevated and non-INR elevated groups, respectively (Table 1).
Discussion
Risk factors INR elevation in patients using CMZ were liver disorder, nutritional risk, no-diabetes mellitus, and concomitant administration of warfarin. In addition, we presented the probability of elevated INR for each risk score in patients with these risk factors, which we believe will contribute to the safe use of CMZ.
Acknowledgments
The authors thank Hiromi Shikano and Izumi Nishisaka at the Division of Supporting Services, Tokyo Bay Urayasu Ichikawa Medical Center. The authors thank everyone at the Department of Hospital Information System Department, Keio University Hospital. We also thank Takanori Ogawa at Certara GK for advice regarding the analysis. We would like to thank Editage (www.editage.com) for English language editing.
Citation: Namiki T, Yokoyama Y, Kimura M, Fukuda S, Seyama S, Iketani O, et al. (2025) Identification of risk factors and development of a predictive model in patients using cefmetazole for international normalized ratio elevation. PLoS One 20(7): e0322909. https://doi.org/10.1371/journal.pone.0322909
Editor: Mehmet Baysal, Tekirdag Namik Kemal University: Tekirdag Namik Kemal Universitesi, TÜRKIYE
Received: May 20, 2024; Accepted: July 10, 2025; Published: July 28, 2025
Copyright: © 2025 Namiki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: We have made the data available in a public repository on Figshare. You can access the data through the following private link URL: https://figshare.com/s/a7cc966004fa34980f25.
Funding: The author(s) received no specific funding for this work.
Competing interests: Dr. H. K. received research funding from Eli Lilly outside of the submitted work. Dr. K. M. received grants from Meiji Seika Pharma, Sumitomo Pharma and Shionogi outside of the submitted work. T.N. received research funding from Chugai, Daiichi Sankyo, Kyowa Kirin, Otsuka Pharmaceutical, Sanofi, and Shionogi outside of the submitted work. Conflicts that the editors consider relevant to the manuscript content have been disclosed. There are no conflicts of interest to declare. Although Dr. H. K, Dr. K. M, and Dr. T. N have received funding outside of the research, this does not alter our adherence to PLOS ONE policies on sharing data and materials. We have submitted to ICMJE.
