Iwasaki Y, Yamashita N, Jozaki K, Tojo M, Sato Y, Iwata S, Akita H, Sunakawa K, Oikawa T, Osano M
Jpn J Antibiot. 1983 Mar;36(3):547-51.
We compared the efficacy of intravenously, intramuscularly administered or intravenously infused over 45 minutes gentamicin (GM) by the experimental system in rabbits using diffusion chambers. Serum concentrations of GM obtained with 3 administration methods were different, while the peak values after intramuscular injection and intravenous drip infusion were similar. Similar concentration time curves of GM in the chambers were revealed after intramuscular injection and intravenous infusion. No marked difference in 3 administration methods was showed in the effects on the growth of P. aeruginosa in the chamber. Viable bacterial number in the chambers decreased when the GM concentration in the chamber was 4--5 times of MIC, and thereafter regrowth was observed after the decrease of GM concentration in the chambers to 2--3 times of MIC. About 8 hours were required for growth to the base line value. In the leucocyte containing chambers, viable bacterial number similarly decreased, but the rate of regrowth was slow. About 12 hours were required for growth to the base line value. The regrowth rate in the GM containing chamber was similar to that in the antibiotic free chamber. From this result, it is suggested that, when the antibiotic concentration in the chamber is 1--2 times of MIC, antibiotic does not show the growth suppressive effect and the activating effect on phagocytosis of leucocytes in the environment closed to the practical pathological condition such as this model. For the patients with qualitative or quantitative abnormal changes of phagocyte, short interval of drug administration might be needed. For this purpose, intravenous drip infusion under monitoring of serum concentration is more suitable than intramuscular injection, which might be accompanied with severe pain and contracture of injected muscle.
我们采用扩散小室实验系统，比较了静脉注射、肌肉注射及静脉输注45分钟庆大霉素（GM）在兔体内的疗效。三种给药方式所获得的GM血清浓度各不相同，而肌肉注射和静脉滴注后的峰值相似。肌肉注射和静脉输注后，小室内GM的浓度-时间曲线相似。三种给药方式对小室内铜绿假单胞菌生长的影响无明显差异。当小室内GM浓度为最低抑菌浓度（MIC）的4至5倍时，小室内活菌数减少，随后小室内GM浓度降至MIC的2至3倍时，观察到细菌再度生长。细菌生长至基线值约需8小时。在含有白细胞的小室内，活菌数同样减少，但再度生长的速率较慢。细菌生长至基线值约需12小时。含GM小室内的细菌再度生长速率与不含抗生素小室内相似。据此结果表明，当小室内抗生素浓度为MIC的1至2倍时，在这种接近实际病理状况的封闭环境中，抗生素对白细胞吞噬作用既无抑制生长的作用，也无激活作用。对于吞噬细胞有定性或定量异常变化的患者，可能需要缩短给药间隔时间。为此，在血清浓度监测下静脉滴注比肌肉注射更合适，因为肌肉注射可能伴有严重疼痛和注射部位肌肉挛缩。
