CONTEXT: In critically ill intubated patients, signs of
respiratory infection often persist despite treatment with potent
systemic antibiotics. OBJECTIVE: The purpose of this study was to determine whether
aerosolized antibiotics, which achieve high
drug concentrations in the target
organ, would more effectively treat
respiratory infection and decrease the need for
systemic antibiotics. DESIGN:
Double-blind,
randomized, placebo-controlled study performed from 2003 through 2004. SETTING: The medical and
surgical intensive care units of a university hospital. PATIENTS: Critically ill intubated patients were
randomized if: 1) > or = 18 yrs of age, intubated for a minimum of 3 days, and expected to survive at least 14 days; and 2) had ventilator-associated
tracheobronchitis defined as the production of
purulent secretions (> or = 2 mL during 4 hrs) with organism(s) on
Gram stain. Of 104 patients monitored, 43 consented for treatment and completed the study. No patients were withdrawn from the study for
adverse events. INTERVENTION:
Aerosol antibiotic (AA) or
aerosol saline
placebo was given for 14 days or until extubation. The responsible clinician determined the administration of
systemic antibiotics (SA). Patients were followed for 28 days. MAIN OUTCOME MEASURES: Primary: Centers for Disease Control National
Nosocomial Infection Survey diagnostic criteria for
ventilator-associated pneumonia (VAP) and clinical
pulmonary infection score. Secondary:
white blood cell count, SA use,
acquired antibiotic resistance, and
weaning from
mechanical ventilation. RESULTS: Most patients had VAP at
randomization. With treatment, the AA group had reduced signs of
respiratory infection: reduced Centers for Disease Control National
Nosocomial Infection Survey VAP (14/19; 73.6%) to (5/14; 35.7%) vs.
placebo (18/24; 75%) to (11/14; 78.6%), reduction in clinical
pulmonary infection score, lower
white blood cell count at day 14, reduced
bacterial resistance, reduced use of SA, and increased
weaning (all p < or = .05). CONCLUSIONS: In critically ill patients with ventilator-associated
tracheobronchitis, AA decrease VAP and other signs and
symptoms of
respiratory infection, facilitate
weaning, and reduce
bacterial resistance and use of
systemic antibiotics.
