抗生素对肺、肝、肾和胰腺组织穿透能力及杀菌效力的实验研究

The penetration of antibiotics into the lung, liver, kidney and pancreas and their tissue bactericidal indexes

目的:测定头孢唑肟等7种抗生素对肺、肝、肾和胰腺组织的穿透能力,为临床选择用药提供参考。方法:小鼠灌服或静脉注射抗生素后不同时间点采集血清、肺、肝、肾和胰腺组织标本,按微生物琼脂扩散法测定抗生素浓度。测定抗生素对6种常见病原菌的最小抑菌浓度(MIC_(90))。计算出抗生素对组织的穿透率(组织浓度/血清浓度)及在组织中的杀菌指数(组织浓度/MIC_(90))。结果:抗生素对肺、肝、肾和胰腺组织的穿透率分别是:头孢唑肟为60%、99%、202.7%和44.6%,头孢曲松为121.9%、92.4%、199.3%和22%,头孢哌酮为77.8%、408.8%、229.2%和33.3%,头孢布烯为29.0%、17.2%、132.3%和0,氨曲南为94.3%、472.9%、161.7%和82.7%,奈替米星为38.6%、5.8%、72.4%和8.7%,万古霉素为95.4%、11.6%、148.5%和9%。结论:氨曲南、头孢唑肟、头孢曲松和头孢哌酮适用于肺、肝、肾和胰腺组织细菌感染。头孢布烯、奈替米星和万古霉素在肺、泌尿系感染中有较好抗菌效果,但在肝、胰组织中浓度低,难望有好的疗效。

Objective: To examine the penetration rates to lung, liver, kidney and pancreas and tissue bactericidal indexes of 7 antibiotics. Methods: Kunming mice received intravenous bolus of azotreonam, ceftizoxime, ceftriaxone, cefoperazone, neltimiein and vancomycin and oral bolus of ceftibuten, respectively, and serum, pulmonary, hepatic and pancreatic tissue concentrations of the antibiotics were measured by microbiological agar diffusion method in 15,30,60,120 min, respectively. The MIC_(90) of above—mentioned drugs for common causative pathogens were determined. Penetration rates(tissue concentration/serum concentration) and bactericidal indexes (tissue concentration/MIC, BI) were calculated. Results: Drug penetration rates into pulmonary, hepatic, renal and pancreatic tissues were: 94.3%, 472.9%, 161.7% and 82.7%, respectively, for aztreonam, 60%, 99%, 202.7% and 44.6% for ceftizoxime, 121.9%, 92.4%, 199.3% and 22% for ceftriaxone, 77.8%, 408.8%, 229.2% and 33.3%% for cefoperazone, 29.0%, 17.2%. 132.3% and 0 for ceftibuten, 38.6%, 5.8%, 72.4% and 8.7% for netilmicin, and 95.4%, 11.6%, 148.5% and 9% for vancomycin. Aztreonam, ceftizoxime, ceftriaxone and cefoperazone had high bactericidal indexes(>100) to enterobacteraceae in lung, liver and pancreas. Conclusion: Aztreonam, ceftizoxime, ceftriaxone and cefoperazone could be effective for treatment of bacterial in fections in lung, liver, kidney and pancreas; Ceftibuten, netilmicin and vancomycin were effective for infections in lung and kidney, but failed to give high concentration to liver and pancreas.