Fuentes F, Martín M M, Izquierdo J, Gomez-Lus M L, Prieto J
Department of Microbiology, Faculty of Medicine, Complutense University of Madrid, Spain.
Scand J Infect Dis. 1995;27(5):469-74. doi: 10.3109/00365549509047048.
Several pharmacodynamic parameters are being studied and applied to the design of dosage regimens. The thigh infection model in neutropenic mice has been used in this study to investigate the in vivo postantibiotic effect (PAE) of meropenem against S. aureus, E. coli and P. aeruginosa. The sub-minimum inhibitory concentration (sub-MIC) postantibiotic effect (PA SME) of 1/2, 1/4 and 1/8 x MIC was also determined in vitro on S. aureus and E. coli after pre-exposure of these microorganisms to 10 x MIC of meropenem. The in vitro PAE was also determined. In vivo killing curves using 2 different short dosage regimens were also studied to relate the lethal effect to the time that serum levels were above the MIC. No significant in vivo and in vitro PAEs were observed. The PA SMEs were higher for S. aureus than for E. coli. The 2 short dosage regimens, in vivo, were equally effective in killing S. aureus, but not E. coli. These results suggest that the pharmacodynamics of meropenem on Gram-negative strains may need further study to elucidate the mechanisms and characteristics of these parameters. On the other hand, we need to standardize a reliable in vitro method to monitor regrowth with a good correlation with the in vivo conditions.
目前正在研究几个药效学参数，并将其应用于给药方案的设计。本研究使用了中性粒细胞减少小鼠的大腿感染模型，以研究美罗培南对金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌的体内抗生素后效应（PAE）。在将这些微生物预先暴露于10倍MIC的美罗培南后，还在体外测定了金黄色葡萄球菌和大肠杆菌在1/2、1/4和1/8倍MIC时的亚最低抑菌浓度（sub-MIC）抗生素后效应（PA SME）。同时也测定了体外PAE。还研究了使用2种不同短疗程给药方案的体内杀菌曲线，以将致死效应与血清水平高于MIC的时间联系起来。未观察到显著的体内和体外PAE。金黄色葡萄球菌的PA SME高于大肠杆菌。两种短疗程给药方案在体内对金黄色葡萄球菌的杀灭效果相同，但对大肠杆菌无效。这些结果表明，美罗培南对革兰氏阴性菌的药效学可能需要进一步研究，以阐明这些参数的机制和特征。另一方面，我们需要标准化一种可靠的体外方法，以监测与体内条件具有良好相关性的再生长情况。
