Chest
Clinical InvestigationsCYSTIC FIBROSISSusceptibility Testing of Pseudomonas aeruginosa Isolates and Clinical Response to Parenteral Antibiotic Administration: Lack of Association in Cystic Fibrosis
Section snippets
Materials and Methods
Five hundred twenty CF patients with chronic P aeruginosa infection were enrolled in two identical, double-blind, simultaneously conducted, phase 3 clinical trials.14 Patients were randomized to treatment with aerosol administration of either a tobramycin solution for inhalation (n = 258) or a taste-masked placebo (n = 262). The study drug was administered in a series of cycles consisting of 28 days of drug administration followed by 28 days off drug administration. The selection criteria, the
Results
The response of 77 CF subjects receiving combination IV tobramycin and ceftazidime therapy for pulmonary exacerbations were analyzed. Treatment responses among the 77 subjects ranged from a relative decrease of 40.3% in FEV1 percent predicted to an increase of 139.9%. The mean relative change was an increase of 17.7%. This improvement, which was expressed as an average change in FEV1, is of the same order of magnitude as that seen with antibiotic treatment of a pulmonary exacerbation seen in
Discussion
At one time, antibiotic resistance was defined as the persistence of the bacterium in the infectious focus despite standard, nontoxic doses of the antibiotic.1718 Subsequently, quantitative antibiotic susceptibility testing revealed that bacteria persisting in infectious foci during antibiotic therapy had the ability to grow in vitro in antibiotic concentrations that were toxic to mammalian cells.19 In these early studies with Gram-negative bacilli, including P aeruginosa, the definition of a
ACKNOWLEDGMENT
The authors acknowledge the assistance of Xin Yu, Jill Van Dalfsen, and Dutch VanDevanter of Chiron Corporation for providing access to clinical trial data.
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Chiron Corporation provided some statistical support for the analysis of the data under the supervision of the authors. The authors of this manuscript received no financial support for its preparation, although they have received grant support and/or honoraria from Chiron for other projects. Dr. Smith is a consultant to the Chiron Corporation. This work was supported in part by a grant from the Cystic Fibrosis Foundation.