Grimwood K, To M, Rabin H R, Woods D E
Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Alberta, Canada.
J Antimicrob Chemother. 1989 Dec;24(6):937-45. doi: 10.1093/jac/24.6.937.
Using the agar-bead rat lung model, we evaluated the effects of subinhibitory antibiotic treatment upon Pseudomonas aeruginosa exoenzyme expression and lung injury in vivo. One hundred and twenty-eight animals were separated into two groups of 64 animals. One group was inoculated with P. aeruginosa DG1, and the other with P. aeruginosa 3740. Each of these two groups was divided into four subgroups of 16 animals on the basis of ten-day antibiotic treatment with ciprofloxacin, tobramycin and ceftazidime or untreated controls. P. aeruginosa DG1 is non-mucoid and expresses significant yields of exoenzyme S and elastase. P. aeruginosa 3740 is a mucoid organism isolated from the sputum of a cystic fibrosis patient, and demonstrates modest elastase activity only (10% of DG1 levels). Lung bacterial counts were similar in treatment and control groups. Lungs from antibiotic-treated rats demonstrated fewer histological changes than those from untreated animals (P less than 0.001). DG1 lung isolates from antibiotic-treated animals yielded less elastase and exoenzyme S compared with isolates from untreated animals (P less than 0.001). No detectable decrease in elastase or mucoid phenotype was observed in 3740 lung isolates from antibiotic treated animals. Thus, antibiotic protection against lung injury by P. aeruginosa may involve modulation of virulence factors.
利用琼脂珠大鼠肺模型，我们在体内评估了亚抑菌浓度抗生素治疗对铜绿假单胞菌外毒素表达及肺损伤的影响。128只动物被分为两组，每组64只。一组接种铜绿假单胞菌DG1，另一组接种铜绿假单胞菌3740。基于用环丙沙星、妥布霉素和头孢他啶进行为期十天的抗生素治疗或未治疗的对照，这两组中的每组又被分为四个亚组，每组16只动物。铜绿假单胞菌DG1是非黏液型的，能产生大量的外毒素S和弹性蛋白酶。铜绿假单胞菌3740是从一名囊性纤维化患者痰液中分离出的黏液型菌株，仅表现出适度的弹性蛋白酶活性（为DG1水平的10%）。治疗组和对照组的肺细菌计数相似。与未治疗动物的肺相比，抗生素治疗大鼠的肺组织学变化更少（P<0.001）。与未治疗动物分离株相比，抗生素治疗动物的DG1肺分离株产生的弹性蛋白酶和外毒素S更少（P<0.001）。在抗生素治疗动物的3740肺分离株中未观察到弹性蛋白酶或黏液型表型有可检测到的降低。因此，抗生素对铜绿假单胞菌所致肺损伤的保护作用可能涉及毒力因子的调节。
