Yamazaki Koichi, Ogura Shigeaki, Ishizaka Akitoshi, Oh-hara Toshinari, Nishimura Masaharu
First Department of Medicine, Hokkaido University School of Medicine, Kitaku, Sapporo, Japan.
Am J Respir Crit Care Med. 2003 Dec 1;168(11):1304-7. doi: 10.1164/rccm.200301-111OC. Epub 2003 Aug 6.
Direct measurement of the concentration of antimicrobial agents in bronchial epithelial lining fluid (ELF) would allow for a more informed approach to appropriate dosing of antimicrobial agents for respiratory tract infections. In this study, we determined the time versus concentration profile in ELF after an oral administration of levofloxacin, using recently developed bronchoscopic microsampling probes. These probes could be repeatedly and safely inserted through the fiberoptic bronchoscope in normal healthy volunteers. The concentration of levofloxacin in ELF was 43.4% of the corresponding serum value at 1 hour, reached the same level at 2 hours, decreased in a similar manner as that in serum, and returned to undetectable levels at 24 hours. It exceeded minimal inhibitory concentrations of Staphylococcus aureus (0.25 microg/ml), Klebsiella species (0.5 microg/ml), and Haemophilus influenzae (0.06 microg/ml) after 6 hours. The experimental procedure was well tolerated, and no complications were observed. In conclusion, bronchoscopic microsampling is a feasible and promising method for measuring antimicrobial concentrations in the target sites of respiratory tracts directly and repeatedly.
直接测量支气管上皮衬液（ELF）中抗菌药物的浓度，将有助于更明智地确定呼吸道感染抗菌药物的合适剂量。在本研究中，我们使用最近开发的支气管镜微量采样探头，测定了口服左氧氟沙星后ELF中的时间-浓度曲线。这些探头可通过纤维支气管镜在正常健康志愿者体内反复安全插入。ELF中左氧氟沙星的浓度在1小时时为相应血清值的43.4%，2小时时达到相同水平，随后与血清中的浓度以相似方式下降，并在24小时时降至检测不到的水平。6小时后，其浓度超过了金黄色葡萄球菌（0.25微克/毫升）、克雷伯菌属（0.5微克/毫升）和流感嗜血杆菌（0.06微克/毫升）的最低抑菌浓度。实验过程耐受性良好，未观察到并发症。总之，支气管镜微量采样是一种可行且有前景的方法，可直接且反复地测量呼吸道靶部位的抗菌药物浓度。
