Pseudomonas Article

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Chest. 2003;123:1495-1502.)

© 2003 American College of Chest Physicians

Susceptibility Testing of Pseudomonas aeruginosa Isolates and Clinical

Response to Parenteral Antibiotic Administration

Lack of Association in Cystic Fibrosis

Arnold L. , MD; Stanley B. Fiel, MD, FCCP; Mayer-Hamblett,

PhD; Bonnie Ramsey, MD and Jane L. Burns, MD * From the Seattle

Biomedical Research Institute (Dr. ), Seattle, WA; the Division of

Pulmonary/Critical Care Medicine (Dr. Fiel), MCP Hahnemann University

School of Medicine, Philadelphia, PA; the CF Therapeutics Development

Network (Dr. Mayer-Hamblett), the Division of Pulmonary Medicine (Dr.

Ramsey), and the Division of Infectious Disease (Dr. Burns), Department

of Pediatrics, Children’s Hospital and Regional Medical Center, Seattle,

WA. Correspondence to: Arnold L. , MD, Seattle Biomedical Research

Institute, 4 Nickerson St, Suite 200, Seattle, WA 98109;

e-mail:

arnold.smith@...

Study objective:

To determine the relationship between the antibiotic susceptibility of

Pseudomonas aeruginosa isolatedfrom the sputum of patients with cystic

fibrosis (CF) and the patient’s response to parenteral antibiotic

administration, we performed a

retrospective analysis using data from patients in the placebo arm of a

phase 3 trial of tobramycin solution for inhalation. All patients were

chronically infected with P aeruginosa. Seventy-seven of the 262 patients

receiving placebo experienced a pulmonary exacerbation during the trial

for which they received therapy with IV tobramycin and ceftazidime. The

susceptibility of the P aeruginosa isolates to ceftazidime and tobramycin

was determined at trial enrollment by broth microdilution.

Design:

The clinical response to combination antibiotic therapy was assessed by

analyzing differences in spirometry before and after antibiotic

administration. The FEV1 percent predicted at the first visit after the

conclusion of antibiotic administration was compared to the FEV1 percent

predicted prior to antibiotic therapy. The results were analyzed both

descriptively and by regression analyses.

Results:

The conditions of 54 patients improved, and those of 9 patients worsened, and

in 14 patients there was no change in FEV1 with antibiotic administration. No

correlation was observed between the susceptibility of P aeruginosa to

tobramycin or ceftazidime and clinical response. Only the three following

variables were observed to significantly correlate with FEV1 after

antibiotic treatment on regression analysis: FEV1 prior to treatment (p <

0.0001); number of days elapsed between the previous FEV1 measurement and

the initiation of IV antibiotic therapy (p < 0.002); and the number of

days elapsed between the determination of the minimum inhibitory

concentration and the initiation of IV therapy (p < 0.03). No significant

trends were observed between the antibiotic susceptibility of P

aeruginosa isolates and treatment outcomes. Conclusion: While lack of

statistical significance for a trend between bacterial susceptibilities

and the response to parenteral antibiotic administration does not mean

that no such trend exists, the precision of the confidence intervals

allows us to conclude that even if isolate antibiotic susceptibilities

affect outcome, the impact would be small and not clinically relevant.

Key Words: antibiotic administration • cystic fibrosis • Pseudomonas

aeruginosa • pulmonary exacerbation

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