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


METHODS
Prospective, randomized, double-blind, placebo-controlled clinical trial.


METHODS
University teaching hospital.


METHODS
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-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were determined at baseline and the end of therapy (days 4-7).


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-alpha, IL-beta, 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-alpha and IL-beta (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.
Wood
G Christopher
GC
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis 38163, USA.
Boucher
Bradley A
BA
Croce
Martin A
MA
Hanes
Scott D
SD
Herring
Vanessa L
VL
Fabian
Timothy C
TC
D000328:Adult; D000336:Aerosols; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002442:Ceftazidime / Q000494:pharmacology / Q000627:therapeutic use*; D016638:Critical Illness; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D011446:Prospective Studies; D012121:Respiration, Artificial / Q000009:adverse effects; D014193:Trauma Centers; D014947:Wounds and Injuries / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
D000336:Aerosols; D000900:Anti-Bacterial Agents; D016207:Cytokines; D002442:Ceftazidime