Efficacy of high-dose Meropenem (six grams per day) in treatment of experimental murine pneumonia induced by meropenem-resistant Pseudomonas aeruginosa
Efficacy of high-dose Meropenem (six grams per day) in treatment of experimental murine pneumonia induced by meropenem-resistant Pseudomonas aeruginosa
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大剂量美罗培南（每天6克）治疗耐美罗培南铜绿假单胞菌所致实验性小鼠肺炎的疗效
DOI：
10.1128/aac.02056-16
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Izumikawa K
中科院分区：
文献类型：
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作者：
Oshima K;Nakamura S;Iwanaga N;Takemoto K;Miyazaki T;Yanagihara K;Miyazaki Y;Mukae H;Kohno S;Izumikawa K
大剂量美罗培南（MEPM; 6 g/天）已被批准用于治疗化脓性脑膜炎;然而，关于其在难治性下呼吸道感染中的体内疗效知之甚少。本研究的目的是评价MEPM（6 g/天）在MEPM耐药铜绿假单胞菌引起的重症肺炎小鼠模型中的疗效。由耐MEPM的铜绿假单胞菌诱导的实验性肺炎用正常剂量MEPM（150 mg/kg体重，模拟人体中的3-g/天方案）或高剂量MEPM（500 mg/kg，模拟人体中的6-g/天方案）治疗。用高剂量MEPM治疗的小鼠显示出相对于未治疗小鼠的显著恢复的存活率，并且倾向于显示出高于用正常剂量MEPM治疗的小鼠的存活率。在用高剂量MEPM处理的小鼠中，肺中的活细菌计数（两种临床分离物）与未处理的小鼠（P< 0.001）或用正常剂量MEPM处理的小鼠（P <0.01和<0.05）相比显著降低。支气管肺泡灌洗液（BALF）中的炎性细胞数量也显着低于高剂量MEPM治疗的小鼠比未治疗的小鼠。在高剂量MEPM处理的小鼠中，上皮衬里液（ELF）中的游离MEPM浓度超过16 μg/ml持续85分钟，而在正常剂量MEPM处理的小鼠中则没有。我们的研究结果表明，高剂量MEPM（6 g/天）可能比正常剂量（小于3 g/天）提供更好的保护，防止由铜绿假单胞菌MEPM耐药菌株引起的肺炎。
High-dose meropenem (MEPM; 6 g/day) has been approved as a treatment for purulent meningitis; however, little is known regarding itsin vivoefficacy in refractory lower respiratory tract infections. The purpose of this study was to evaluate the efficacy of MEPM at 6 g/day in a murine model of severe pneumonia caused by MEPM-resistant Pseudomonas aeruginosa. Experimental pneumonia induced by MEPM-resistant P. aeruginosa was treated with normal-dose MEPM (150 mg/kg of body weight, simulating a 3-g/day regimen in humans) or high-dose MEPM (500 mg/kg, simulating a 6-g/day regimen in humans). Mice treated with high-dose MEPM showed significantly restored survival relative to that of untreated mice and tended to show a survival rate higher than that of mice treated with normal-dose MEPM. The viable bacterial counts (of two clinical isolates) in the lungs decreased significantly in mice treated with high-dose MEPM from those for untreated mice (P< 0.001) or mice treated with normal-dose MEPM (P, <0.01 and <0.05). The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was also significantly lower in mice treated with high-dose MEPM than in untreated mice. The free MEPM concentration in the epithelial lining fluid (ELF) exceeded 16 μg/ml for 85 min in mice treated with high-dose MEPM, but not for mice treated with normal-dose MEPM. Our results demonstrate that high-dose MEPM (6 g/day) might provide better protection against pneumonia caused by MEPM-resistant strains of P. aeruginosa than the dose normally administered (less than 3 g/day).