Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration: Lack of association in cystic fibrosis

Arnold L. Smith, Stanley B. Fiel, Nicole Mayer-Hamblett, Bonnie Ramsey, Jane L. Burns

Research output: Contribution to journalArticle

204 Citations (Scopus)

Abstract

Study objective: To determine the relationship between the antibiotic susceptibility of Pseudomonas aeruginosa isolated from 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.

Original languageEnglish (US)
Pages (from-to)1495-1502
Number of pages8
JournalChest
Volume123
Issue number5
DOIs
StatePublished - May 1 2003

Fingerprint

Cystic Fibrosis
Pseudomonas aeruginosa
Anti-Bacterial Agents
Tobramycin
Ceftazidime
Therapeutics
Placebos
Regression Analysis
Spirometry
Microbial Sensitivity Tests
Sputum
Inhalation
Confidence Intervals
Lung

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Smith, Arnold L. ; Fiel, Stanley B. ; Mayer-Hamblett, Nicole ; Ramsey, Bonnie ; Burns, Jane L. / Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration : Lack of association in cystic fibrosis. In: Chest. 2003 ; Vol. 123, No. 5. pp. 1495-1502.
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abstract = "Study objective: To determine the relationship between the antibiotic susceptibility of Pseudomonas aeruginosa isolated from 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.",
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Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration : Lack of association in cystic fibrosis. / Smith, Arnold L.; Fiel, Stanley B.; Mayer-Hamblett, Nicole; Ramsey, Bonnie; Burns, Jane L.

In: Chest, Vol. 123, No. 5, 01.05.2003, p. 1495-1502.

Research output: Contribution to journalArticle

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T1 - Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration

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AU - Smith, Arnold L.

AU - Fiel, Stanley B.

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N2 - Study objective: To determine the relationship between the antibiotic susceptibility of Pseudomonas aeruginosa isolated from 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.

AB - Study objective: To determine the relationship between the antibiotic susceptibility of Pseudomonas aeruginosa isolated from 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.

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