Efficacy of meropenem and amikacin combination therapy against carbapenemase-producing Klebsiella pneumoniae mouse model of pneumonia

• Material Type: 博士論文
• Title: Efficacy of meropenem and amikacin combination therapy against carbapenemase-producing Klebsiella pneumoniae mouse model of pneumonia
• Author/Editor: 太田, 賢治
• Author Heading: 太田, 賢治
• Publication, Distribution, etc.: Elsevier Ltd.
• Publication Date: 2021-09-01
• Publication Date (W3CDTF): 2021-09-01
• Alternative Title: カルバペネマーゼ産生Klebsiella pneumoniae肺炎マウスモデルにおけるメロペネムとアミカシン併用療法の有効性評価
• Periodical title: Journal of Infection and Chemotherapy
• No. or year of volume/issue: 26 12
• Volume: 26
• Issue: 12
• Pages: 1237-1243
• ISSN (Periodical Title): ISSN : 1341-321X; ISSN : 1437-7780
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2021-09-01
• Dissertation Number: 甲医歯薬第1363号
• Degree Type: 博士(医学)
• Text Language Code: eng
• Target Audience: 一般
• Note (General): Background: The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) is a global health problem due to its high mortality and limited treatment options. Combination antimicrobial therapy is reported to be effective against CRE in vitro; however, its efficacy in vivo has not been thoroughly evaluated. Thus, this study assessed the efficacy of combination therapy of meropenem (MEPM) and amikacin (AMK) in a carbapenem-resistant Klebsiella pneumoniae (CR-Kp) mouse model of pneumonia.Materials and methods: Agar-based bacterial suspension of CR-Kp clinical isolates was inoculated into the trachea of BALB/c mice. Treatment was initiated 6 h post infection, with 100 mg/kg MEPM every 6 h, 100 mg/kg AMK every 12 h, or in combination; survival was evaluated for 7 days. The number of viable bacteria in the lungs, lung histopathology, and neutrophil counts in broncho-alveolar lavage fluid (BALF) were evaluated 42 h after infection.Results: All mice in the untreated control group died in 48 h, while all the mice in treatment groups survived past 7 days following infection. The bacterial count in the lungs (log10 CFU/mL, mean ± SEM) in the combination group (2.00 ± 0.00) decreased significantly compared to that in control (10.19 ± 0.11, p < 0.0001), MEPM (6.38 ± 0.17, p < 0.0001), and AMK (6.17 ± 0.16, p < 0.0001) groups. BALF neutrophil count reduced only in the combination therapy group. Combination therapy prevented the progression of lung inflammation, including alveolar neutrophil infiltration and hemorrhage.Conclusions: This study demonstrates in vivo efficacy of MEPM and AMK combination therapy against CR-Kp pneumonia.; 長崎大学学位論文 学位記番号:博(医歯薬)甲第1363号 学位授与年月日:令和3年9月1日; Author: Kenji Ota, Norihito Kaku, Katsunori Yanagihara; Citation: Journal of Infection and Chemotherapy, 26(12), pp. 1237-1243; 2020; identifier:Nagasaki University (長崎大学), 博士(医学) (2021-09-01)
• Source: https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27096&item_no=1&attribute_id=70&file_no=1 （fulltext）; https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27096&item_no=1&attribute_id=70&file_no=1
• Access Restrictions: インターネット公開
• Rights (production): © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
• Related Material: http://hdl.handle.net/10069/00040950
• Related Material (DOI): 10.1016/j.jiac.2020.07.002
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 長崎大学 : 長崎大学学術研究成果リポジトリ