Meropenem penetration into epithelial lining fluid in mice and humans and delineation of exposure targets.
Meropenem penetration into epithelial lining fluid in mice and humans and delineation of exposure targets.
复制标题
美罗培南渗透到小鼠和人类的上皮衬里液中并描绘暴露目标。
DOI：
10.1128/aac.01559-10
复制
发表时间：
2011
影响因子：
4.9
通讯作者：
Louie,A
中科院分区：
文献类型：
--
作者：
Drusano,GL;Lodise,TP;Melnick,D;Liu,W;Oliver,A;Mena,A;VanScoy,B;Louie,A
Pseudomonas aeruginosa pneumonia remains a most-difficult-to-treat nosocomial bacterial infection. We used mathematical modeling to identify drug exposure targets for meropenem in the epithelial lining fluid (ELF) of mice with Pseudomonas pneumonia driving substantial [2 to 3 log10(CFU/g)] killing and which suppressed resistant subpopulation amplification. We bridged to humans to estimate the frequency with which the largest licensed meropenem dose would achieve these exposure targets. Cell kills of 2 and 3 log10(CFU/g) and resistant subpopulation suppression were mediated by achieving time > MIC in ELF of 32%, 50%, and 50%. Substantial variability in meropenem's ability to penetrate into ELF of both mice and humans was observed. Penetration variability and high exposure targets combined to prevent even the largest licensed meropenem dose from achieving the targets at an acceptable frequency. Even a highly potent agent such as meropenem does not adequately suppress resistant subpopulation amplification as single-agent therapy administered at maximal dose and optimal schedule. Combination chemotherapy is likely required in humans if we are to minimize resistance emergence in Pseudomonas aeruginosa pneumonia. This combination needs evaluation both in the murine pneumonia model and in humans.
