Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Center for Infectious Diseases and Infection Control, Keio University, School of Medicine, Tokyo, Japan.
J Infect Chemother. 2014 Oct;20(10):607-11. doi: 10.1016/j.jiac.2014.05.007. Epub 2014 Jun 25.
Arbekacin is a unique aminoglycoside antibiotic with anti-methicillin-resistant Staphylococcus aureus activity. The efficacy of aminoglycosides is related to their serum maximum concentration. Local concentration of antibiotics in pulmonary epithelial lining fluid, rather than its serum concentration, can help determine its clinical efficacy more precisely for treatment of respiratory infectious disease. The objective of this study was to sequentially measure arbekacin concentration in epithelial lining fluid after infusion of a single clinically available dose.
After the initial blood sampling, arbekacin was intravenously infused into 6 healthy volunteers over 1 h. Epithelial lining fluid and serum samples were collected by bronchoscopic microsampling 1, 1.5, 2, 2.5, 3, 4, 5, and 6 h after the start of 200 mg arbekacin infusion.
Each probe sampled 10.1 ± 5.2 μl bronchial epithelial lining fluid. The sample dilution factor was 266.7 ± 157.1. Drug concentration was successfully measured in all but 2 of the epithelial lining fluid samples. The maximum concentration of arbekacin in epithelial lining fluid and serum was 10.4 ± 1.9 μg/ml and 26.0 ± 12.2 μg/ml, respectively. The ratio of the maximum drug concentration in the epithelial lining fluid to that in the serum was 0.47 ± 0.19.
The maximum concentration of epithelial lining fluid reached levels that would effectively treat most clinical strains of methicillin-resistant S. aureus.
阿贝卡星是一种具有抗耐甲氧西林金黄色葡萄球菌活性的独特氨基糖苷类抗生素。氨基糖苷类药物的疗效与其血清最大浓度有关。抗生素在肺上皮衬液中的局部浓度，而不是其血清浓度，可以更准确地帮助确定其治疗呼吸道感染性疾病的临床疗效。本研究的目的是在单次临床可用剂量输注后，连续测量上皮衬液中的阿贝卡星浓度。
初始采血后，6 名健康志愿者静脉输注 200mg 阿贝卡星 1 小时。在开始输注 200mg 阿贝卡星后 1、1.5、2、2.5、3、4、5 和 6 小时，通过支气管镜微采样收集上皮衬液和血清样本。
每个探头采集了 10.1±5.2μl 支气管上皮衬液。样品稀释因子为 266.7±157.1。除 2 个上皮衬液样本外，所有样本均成功测量了药物浓度。上皮衬液和血清中阿贝卡星的最大浓度分别为 10.4±1.9μg/ml 和 26.0±12.2μg/ml。上皮衬液中药物最大浓度与血清中药物最大浓度的比值为 0.47±0.19。
上皮衬液中的最大浓度达到了有效治疗大多数临床耐甲氧西林金黄色葡萄球菌株的水平。
