Reduction of SputumPseudomonas aeruginosaDensity by Antibiotics Improves Lung Function in Cystic Fibrosis More than Do Bronchodilators and Chest Physiotherapy Alone

Abstract

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 (FEF25-75). 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 the density of P. aeruginosa and was assigned to the antibiotic group. During the next 14 days of therapy, the antibiotic group showed significantly (p less than 0.01) greater reductions in log10 colony-forming units (cfu) of P. aeruginosa per gram of sputum and greater increases in FVC, FEV1, and FEF25-75 than did the placebo group. The degree of decrease in log10 cfu P. aeruginosa/g sputum correlated significantly (p less than 0.001) with the degree of improvement in FVC, FEV1, and FEF25-75.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinically Feasible Biofilm Susceptibility Assay for Isolates of Pseudomonas aeruginosa from Patients with Cystic Fibrosis

“…Studies of young patients with CF who have recent acquisition of P. aeruginosa and of older patients with non-CF bronchiectasis have shown evidence of eradication (4,13,14,24,37). In contrast, although antibiotic therapy may improve clinical status and reduce bacterial burden by up to 2 log 10 in older CF patients (23,25,33), efforts to eradicate P. aeruginosa in the setting of more established CF airway infections have generally failed. Among a group of CF patients with chronic persistent P. aeruginosa infection, 28 days of tobramycin inhalation decreased the geometric mean bacterial density by only 1.9 log 10 CFU/g (23).…”

Single and Combination Antibiotic Susceptibilities of Planktonic, Adherent, and Biofilm-Grown Pseudomonas aeruginosa Isolates Cultured from Sputa of Adults with Cystic Fibrosis

“…However, many CF-associated P. aeruginosa strains are multiresistant to single antibiotics (11,17) and acute CF exacerbations caused by P. aeruginosa infection are almost always treated clinically with combination antibiotic therapy (24,27). Thus, traditional antibiotic susceptibility testing using single antibiotics has limited relevance in this clinical context.…”

Aerosolized rhDNase in cystic fibrosis: effect on leucocyte proteases in sputum

“…We considered this result as a sign of stability rather than a real improvement of infection, because a change of bacterial density by 1 or 2 log cfu·mL -1 appears to be of questionable significance: when CF patients received i.v. antibiotics for pulmonary exacerbation, a mean decrease by 6 log cfu·mL -1 was reported [25]. Furthermore, in a controlled study, SMITH et al [26] were unable to demonstrate that treatment with rhDNase significantly decreased bacterial density in sputum, as a consequence of facilitated clearance of respiratory secretions.…”