In vitro Combined Inhibitory Activities of β-Lactam Antibiotics and Clavulanic Acid Against bla (KPC-2)-Positive Klebsiella pneumoniae.
In vitro Combined Inhibitory Activities of β-Lactam Antibiotics and Clavulanic Acid Against bla (KPC-2)-Positive Klebsiella pneumoniae.
复制标题
β-内酰胺类抗生素和克拉维酸对 blaKPC-2 阳性肺炎克雷伯菌的体外联合抑制活性
DOI：
10.2147/idr.s292612
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发表时间：
2021
影响因子：
3.9
通讯作者：
Hu F
中科院分区：
文献类型：
--
作者：
Peng M;Han R;Guo Y;Zheng Y;Yang F;Xu X;Hu F
产KpC的肠杆菌科细菌的传播已引发全球公共卫生关注，其中KpC-2阳性菌株在中国中最流行。因此，我们研究了三种β-内酰胺类抗生素和不同浓度的克拉维酸在体外对blaKPC-2阳性肺炎克雷伯菌的联合抑菌活性，以探讨它们的抗菌特性和对blaKPC-2阳性肺炎克雷伯菌感染的替代治疗方案。本研究收集了2016年至2018年中国地区19个省的153株肺炎克雷伯菌临床分离株，其中革兰氏阳性克雷伯菌为KPC-2阳性。采用微量肉汤稀释法对亚胺培南/克拉维酸、美罗培南/克拉维酸、头孢他啶/克拉维酸及单独用药进行药敏试验。β-内酰胺类抗生素与克拉维酸的浓度比分别为1：1、1：2、1：4、1：8、1：16、1：32。根据肠杆菌科CLSI指令确定的亚胺培南、美罗培南和头孢他啶的耐药点来确定这三种药物的药物敏感性。随着克拉维酸在化疗方案中所占比例的增加，三种药物的MIC值均逐渐下降，其中以美罗培南/克拉维酸浓度比为1：1(美罗培南/克拉维酸为1：2)的MIC50和MIC90下降最为显著。当克拉维酸浓度控制在4 mg/L时，亚胺培南MIC2~4 mg/L、美罗培南MIC2~8 mg/L或头孢他啶MIC8 mg/L可使70%以上的菌株恢复对上述方案的敏感性，但当初始MIC水平较高时，敏感率降至30%~40%。β-内酰胺类抗生素/克拉维酸在低浓度比下对革兰氏阳性肺炎克雷伯菌的联合抑菌活性最高，可能为优化这些抗菌方案的效果提供了一条新的途径。
The spread of KPC-producing Enterobacteriaceae has triggered a global public health concern, with KPC-2-positive strains being the most prevalent in China. We hereby studied the in vitro combined inhibitory activities of three kinds of β-lactam antibiotics and clavulanic acid at different concentrations against blaKPC-2-positive Klebsiella pneumoniae to explore the antimicrobial characteristics of these combinations and alternative therapeutic regimens for infections caused by blaKPC-2-positive K. pneumoniae strains. In this study, 153 clinically isolated blaKPC-2-positive K. pneumoniae strains from 19 provinces in China were collected from 2016 to 2018. Antimicrobial susceptibility testing of imipenem/clavulanic acid, meropenem/clavulanic acid, ceftazidime/clavulanic acid, and each antimicrobial agent alone was performed by broth microdilution technique according to the CLSI guidelines. The concentration ratios of β-lactam antibiotics to clavulanic acid were as follows: 1:1, 1:2, 1:4, 1:8, 1:16, 1:32. The antimicrobial susceptibility of the combinations was determined according to the breakpoints of Imipenem, meropenem, and ceftazidime established by the CLSI directives for Enterobacteriaceae. The MICs of all three combinations gradually declined with increments in the proportion of clavulanic acid in the regimens, and the most significant decline in the MIC50 and MIC90 was seen in combinations at the concentration ratio of 1:1 (also 1:2 for meropenem/clavulanic acid). When the concentration of clavulanic acid was restricted to 4 mg/L, the susceptibility of more than 70% of the isolates to the regimens could be restored with imipenem MIC 2–4 mg/L, meropenem MIC 2–8 mg/L or ceftazidime MIC 8mg/L. However, the percentage decreased to 30 to 40% when the initial MIC level was higher. The highest combined inhibitory activity of β-lactam antibiotics/clavulanic acid at low concentration ratios against blaKPC-2-positive K. pneumoniae may offer a new way to optimize the effects of these antimicrobial regimens.