Aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients

G Christopher Wood, Bradley Boucher, Martin Croce, Scott D. Hanes, Vanessa L. Herring, Timothy Fabian

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Study Objectives. To evaluate the safety and efficacy of aerosolized ceftazidime for prevention of ventilator-associated pneumonia (VAP) and to evaluate the effects of the drug on the proinflammatory response. Design. Prospective, randomized, double-blind, placebo-controlled clinical trial. Setting. University teaching hospital. Patients. Forty critically ill trauma patients at high risk for VAP. Intervention. Within 48 hours of admission to the intensive care unit (ICU), patients were randomly assigned to receive aerosolized ceftazidime 250 mg every 12 hours or placebo (normal saline) for up to 7 days. Bronchoalveolar concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 were determined at baseline and the end of therapy (days 4-7). Measurements and Main Results. The frequency of VAP in patients receiving aerosolized ceftazidime was 73% lower than that in patients receiving placebo at ICU day 14 (15% vs 55%, p=0.021), and 54% lower for the entire ICU stay (30% vs 65%, p=0.022). No clinically significant changes in bacterial culture and sensitivity patterns were observed. No adverse events from aerosolized ceftazidime were reported. Pulmonary TNF-α, IL-1β, and IL-8 concentrations were attenuated in the ceftazidime group compared with those in the placebo group (p<0.001, p=0.02, and p=0.003). The frequency of VAP was related directly to changes in TNF-α and IL-1β (p<0.001, p=0.02). Conclusions. Aerosolized ceftazidime decreased the frequency of VAP in critically ill trauma patients, without adversely affecting ICU flora. Aerosolized ceftazidime also may attenuate the proinflammatory response in the lung.

Original languageEnglish (US)
Pages (from-to)972-982
Number of pages11
JournalPharmacotherapy
Volume22
Issue number8
DOIs
StatePublished - Jan 1 2002

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Ventilator-Associated Pneumonia
Ceftazidime
Critical Illness
Wounds and Injuries
Intensive Care Units
Pharmaceutical Preparations
Interleukin-1
Placebos
Tumor Necrosis Factor-alpha
Interleukin-8
Lung
Controlled Clinical Trials
Teaching Hospitals
Interleukin-6
Safety

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

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Aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients. / Wood, G Christopher; Boucher, Bradley; Croce, Martin; Hanes, Scott D.; Herring, Vanessa L.; Fabian, Timothy.

In: Pharmacotherapy, Vol. 22, No. 8, 01.01.2002, p. 972-982.

Research output: Contribution to journalArticle

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abstract = "Study Objectives. To evaluate the safety and efficacy of aerosolized ceftazidime for prevention of ventilator-associated pneumonia (VAP) and to evaluate the effects of the drug on the proinflammatory response. Design. Prospective, randomized, double-blind, placebo-controlled clinical trial. Setting. University teaching hospital. Patients. Forty critically ill trauma patients at high risk for VAP. Intervention. Within 48 hours of admission to the intensive care unit (ICU), patients were randomly assigned to receive aerosolized ceftazidime 250 mg every 12 hours or placebo (normal saline) for up to 7 days. Bronchoalveolar concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 were determined at baseline and the end of therapy (days 4-7). Measurements and Main Results. The frequency of VAP in patients receiving aerosolized ceftazidime was 73{\%} lower than that in patients receiving placebo at ICU day 14 (15{\%} vs 55{\%}, p=0.021), and 54{\%} lower for the entire ICU stay (30{\%} vs 65{\%}, p=0.022). No clinically significant changes in bacterial culture and sensitivity patterns were observed. No adverse events from aerosolized ceftazidime were reported. Pulmonary TNF-α, IL-1β, and IL-8 concentrations were attenuated in the ceftazidime group compared with those in the placebo group (p<0.001, p=0.02, and p=0.003). The frequency of VAP was related directly to changes in TNF-α and IL-1β (p<0.001, p=0.02). Conclusions. Aerosolized ceftazidime decreased the frequency of VAP in critically ill trauma patients, without adversely affecting ICU flora. Aerosolized ceftazidime also may attenuate the proinflammatory response in the lung.",
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N2 - Study Objectives. To evaluate the safety and efficacy of aerosolized ceftazidime for prevention of ventilator-associated pneumonia (VAP) and to evaluate the effects of the drug on the proinflammatory response. Design. Prospective, randomized, double-blind, placebo-controlled clinical trial. Setting. University teaching hospital. Patients. Forty critically ill trauma patients at high risk for VAP. Intervention. Within 48 hours of admission to the intensive care unit (ICU), patients were randomly assigned to receive aerosolized ceftazidime 250 mg every 12 hours or placebo (normal saline) for up to 7 days. Bronchoalveolar concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 were determined at baseline and the end of therapy (days 4-7). Measurements and Main Results. The frequency of VAP in patients receiving aerosolized ceftazidime was 73% lower than that in patients receiving placebo at ICU day 14 (15% vs 55%, p=0.021), and 54% lower for the entire ICU stay (30% vs 65%, p=0.022). No clinically significant changes in bacterial culture and sensitivity patterns were observed. No adverse events from aerosolized ceftazidime were reported. Pulmonary TNF-α, IL-1β, and IL-8 concentrations were attenuated in the ceftazidime group compared with those in the placebo group (p<0.001, p=0.02, and p=0.003). The frequency of VAP was related directly to changes in TNF-α and IL-1β (p<0.001, p=0.02). Conclusions. Aerosolized ceftazidime decreased the frequency of VAP in critically ill trauma patients, without adversely affecting ICU flora. Aerosolized ceftazidime also may attenuate the proinflammatory response in the lung.

AB - Study Objectives. To evaluate the safety and efficacy of aerosolized ceftazidime for prevention of ventilator-associated pneumonia (VAP) and to evaluate the effects of the drug on the proinflammatory response. Design. Prospective, randomized, double-blind, placebo-controlled clinical trial. Setting. University teaching hospital. Patients. Forty critically ill trauma patients at high risk for VAP. Intervention. Within 48 hours of admission to the intensive care unit (ICU), patients were randomly assigned to receive aerosolized ceftazidime 250 mg every 12 hours or placebo (normal saline) for up to 7 days. Bronchoalveolar concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 were determined at baseline and the end of therapy (days 4-7). Measurements and Main Results. The frequency of VAP in patients receiving aerosolized ceftazidime was 73% lower than that in patients receiving placebo at ICU day 14 (15% vs 55%, p=0.021), and 54% lower for the entire ICU stay (30% vs 65%, p=0.022). No clinically significant changes in bacterial culture and sensitivity patterns were observed. No adverse events from aerosolized ceftazidime were reported. Pulmonary TNF-α, IL-1β, and IL-8 concentrations were attenuated in the ceftazidime group compared with those in the placebo group (p<0.001, p=0.02, and p=0.003). The frequency of VAP was related directly to changes in TNF-α and IL-1β (p<0.001, p=0.02). Conclusions. Aerosolized ceftazidime decreased the frequency of VAP in critically ill trauma patients, without adversely affecting ICU flora. Aerosolized ceftazidime also may attenuate the proinflammatory response in the lung.

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