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 titleJournal of Infection and Chemotherapy
Degree grantor/typeNagasaki University (長崎大学)
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)
http://hdl.handle.net/10069/00040950
DOIinfo:doi/10.1016/j.jiac.2020.07.002
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2022-03-06T04:54:00+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション