Clinical and Bacteriological Responses to Three Antibiotic Regimens for Acute Exacerbations of Cystic Fibrosis: Tlcarcillln-Tobramycin, Azlocillin-Tobramycin, and Azlocillin-Placebo

Abstract

In a randomized, double-blind study, cystic fibrosis patients 11-30 years of age with an acute exacerbation of their pulmonary disease were treated with either ticarcillin-tobramycin, azlocillin-tobramycin, or azlocillin-placebo for 10 days. There was significant improvement in Shwachman scores and pulmonary function tests. Concentrations of sputum bacteria were significantly reduced, but after therapy patients had a mean of 10(7) bacteria/ml of sputum. Pseudomonas was transiently eliminated in only one patient. The three regimens had similar impacts on pulmonary function and sputum bacterial concentration. Antibiotic resistance was noted more frequently in the azlocillin-placebo group, but this trend was not statistically significant. Improvement in pulmonary function did not correlate with bacteriological response. Four weeks after discharge, 62% of the improvement in forced expiratory volume in one second and 75% of the improvement in vital capacity remained, but concentrations of sputum bacteria had returned to pretreatment levels, and antibiotic-resistant bacteria persisted.

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

“…Neither antimicrobial therapy was associated with infection by B. cepacia or other inherently resistant pathogens (320). The author of this study concludes that in agreement with previous studies on the use of aerosolized combination therapy of tobramycin and azlocillin as well as the triple combination of tobramycin plus azlocillin and ticarcillin-clavulanic acid (Timentin), conventional measures of antimicrobial resistance may underestimate the clinical efficacy of tobramycin and colistin when delivered at the high concentrations achieved with the TSI formulation (320)(321)(322). These findings are in agreement with the poor predictability of clinical success by conventional susceptibility testing (31,79,80,(118)(119)(120)(121)(122)(123).…”

Lung Infections Associated with Cystic Fibrosis

“…As treatment standards for CF patients improved over the years, the average mean survival of CF patients increased dramatically. Most notable among such advances was the refinement of nutritional regimens (4,19,290) and the advent of antibiotic chemotherapy (122,193,197,228). While essentially all patients prior to the 1950s died by the age of 10 years, reports published in the 1950s (192) and 1960s (297) described a considerable proportion of CF patients surviving well beyond this age.…”

Clinical Significance of Microbial Infection and Adaptation in Cystic Fibrosis

“…Thus, it is difficult to attribute improved outcomes to the eradication of any one microbial species. Conversely, clinical or functional improvement may occur in the apparent absence of a microbiological response (216,389,554,555). These and other complexities may account for the often apparently contradictory results of CF outcome studies.…”