Dull W L, Alexander M R, Kasik J E
Antimicrob Agents Chemother. 1979 Dec;16(6):767-71. doi: 10.1128/AAC.16.6.767.
Amikacin was given to 14 noninfected men as three consecutive intramuscular injections (7.5 mg/kg) at 12-h intervals. Serum and bronchial secretion specimens were obtained at various times during flexible fiberoptic bronchoscopy after the final dose. Serum and bronchial secretion concentrations obtained between 1.5 and 2.0 h after the final dose ranged from 17 to 40 mug/ml and 2.3 to 8.4 mug/ml with a mean of 23.7 +/- 2.9 and 5.23 +/- 1.5 mug/ml, +/-1 standard error of the mean, respectively. The highest bronchial secretion concentration in each subject correlated with the highest serum concentration (r = 0.83, P < 0.001), and all concurrent serum and bronchial secretion concentrations demonstrated a significant correlation (r = 0.82, P < 0.001). Clearance occurred at the same rate (half-life serum = 2.84 h; half-life of bronchial secretion = 2.60 h, P > 0.5). The mean bronchial secretion concentration of the 15 specimens obtained more than 7 h after the final dose was less than 1.0 mug/ml, with a range from 0.3 to 1.6 mug/ml. It is concluded that amikacin may achieve minimal inhibitory concentrations for many gram-negative bacteria in the bronchial secretions of noninfected patients 1 to 2 h after the final dose. However, levels fall below the reported minimal inhibitory concentrations against negative bacteria 6 to 7 h after the final dose. Furthermore, bronchial secretion levels may never reach the minimal inhibitory concentration against Pseudomonas aeruginosa.
对14名未受感染的男性连续3次肌内注射阿米卡星(7.5毫克/千克),间隔12小时。在最后一剂后的不同时间,通过可弯曲纤维支气管镜检查获取血清和支气管分泌物标本。最后一剂后1.5至2.0小时测得的血清和支气管分泌物浓度范围分别为17至40微克/毫升和2.3至8.4微克/毫升,平均值分别为23.7±2.9和5.23±1.5微克/毫升(±1平均标准误差)。每个受试者的最高支气管分泌物浓度与最高血清浓度相关(r = 0.83,P < 0.001),所有同时测得的血清和支气管分泌物浓度均显示出显著相关性(r = 0.82,P < 0.001)。清除率相同(血清半衰期 = 2.84小时;支气管分泌物半衰期 = 2.60小时,P > 0.5)。最后一剂后7小时以上获取的15份标本的平均支气管分泌物浓度低于1.0微克/毫升,范围为0.3至1.6微克/毫升。结论是,在最后一剂后1至2小时,阿米卡星可能在未受感染患者的支气管分泌物中对许多革兰氏阴性菌达到最低抑菌浓度。然而,在最后一剂后6至7小时,其水平降至低于报道的对阴性菌的最低抑菌浓度。此外,支气管分泌物水平可能永远达不到对铜绿假单胞菌的最低抑菌浓度。