Reduction of sputum Pseudomonas aeruginosa density by antibiotics improves lung function in cystic fibrosis more than do bronchodilators and chest physiotherapy alone

We evaluated patients with cystic fibrosis (CF) and moderate obstructive lung disease in pulmonary exacerbation in a double-blind placebo-controlled trial to determine the contribution of antibiotic-mediated reduction in sputum bacterial density to clinical improvement. For the first 4 days of study, all patients received bronchodilating aerosols and chest physiotherapy but no antibiotics. During this time, the patients showed significant improvement in mean FVC, FEV₁, and maximal midexpiratory flow rate (FEF_25-75). In 12 of 13 trials, the patients showed no significant increases in the density of Pseudomonas aeruginosa during these first 4 days. In these 12 trials, the patients were stratified by their initial FVC and randomized to receive either parenteral tobramycin and ticarcillin (n = 7) or placebo (n = 5), in addition to continued aerosol and chest physiotherapy. In the remaining trial, the patient had a significant rise in density of P. aeruginosa and was assigned to the antibiotic group. During the next 14 days of therapy, the antibiotic group showed significantly (p < 0.01) greater reductions in log₁₀ colony-forming units (cfu) of P. aeruginosa per gram of sputum and greater increases in FVC, FEV₁, and FEV_25-75 than did the placebo group. The degree of decrease in log₁₀ cfu P. aeruginosa/g sputum correlated significantly (p < 0.001) with the degree of improvement in FVC, FEV₁, and FEF_25-75. Moreover, significantly (p < 0.01) more patients in the antibiotic group achieved better than a 2 log₁₀ reduction in cfu P. aeruginosa/g of sputum, a 10% increase in FVC, a 20% increase in FEV₁, and a 30% increase in FEF_25-75 than did those in the placebo group. These results show that appropriate antibiotic therapy provides significant additional benefit to bronchodilators and chest physiotherapy in patients with CF, pulmonary exacerbation, and P. aeruginosa in their sputums. Moreover, the degree of improvement correlates with the degree of reduction of P. aeruginosa and total bacterial density in the sputum.