Subinhibitory antibiotics reduce Pseudomonas aeruginosa tissue injury in the rat lung model

Abstract

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.