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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. 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Efficacy of meropenem and amikacin combination therapy against carbapenemase-producing Klebsiella pneumoniae mouse model of pneumonia
http://hdl.handle.net/10069/00040546
http://hdl.handle.net/10069/00040546fd2f7e35-3497-4c51-b521-86fc6050231f
名前 / ファイル | ライセンス | アクション |
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JIC26_1237.pdf (525.0 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-03-12 | |||||
タイトル | ||||||
タイトル | Efficacy of meropenem and amikacin combination therapy against carbapenemase-producing Klebsiella pneumoniae mouse model of pneumonia | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | CPE | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | CRE | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Pneumonia mouse model | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Antibiotic combination therapy | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | In vivo | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Ota, Kenji
× Ota, Kenji× Kaku, Norihito× Yanagihara, Katsunori |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. | |||||
書誌情報 |
Journal of Infection and Chemotherapy 巻 26, 号 12, p. 1237-1243, 発行日 2020-12 |
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出版者 | ||||||
出版者 | Elsevier Ltd | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1341321X | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.jiac.2020.07.002 | |||||
権利 | ||||||
権利情報 | © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Journal of Infection and Chemotherapy, 26(12), pp.1237-1243; 2020 |