Reduction of Bacterial Resistance with Inhaled Antibiotics in the Intensive Care Unit

Rationale: Multidrug-resistant organisms (MDRO) are the dominant airway pathogens in the intensive care unit (ICU) and present a major treatment challenge to intensivists. Aerosolized antibiotics (AA) result in airway concentrations of drug 100-fold greater than the minimal inhibitory concentration of most bacteria including MDRO. These levels, without systemic toxicity, may eradicate MDRO and reduce the pressure for selection of new resistant organisms. Objectives: To determine if AA effectively eradicate MDPO in the intubated patient without promoting new resistance. Methods: In a double-blind placebo-controlled study, critically ill intubated patients were randomized if they exhibited signs of respiratory infection (purulent secretions and Clinical Pulmonary Infection Score Using a well-characterized aerosol delivery system, AA or saline placebo was given for 14 days or until extubation. The responsible clinician determined administration of systemic antibiotics for ventilator-associated pneumonia and any other infection. Measurements and Main Results: AA eradicated 26 of 27 organisms present at randomization compared with 2 of 23 organisms with placebo (P < 0.0001). AA eradicated the original resistant organism on culture and Gram stain at end of treatment in 14 out of 16 patients compared with 1 of 11 for placebo (P < 0.001) New drug resistance to AA was not seen. Compared with AA, resistance to systemic antibiotics significantly increased in placebo patients (P = 0.03). Compared with placebo, AA significantly reduced Clinical Pulmonary Infection Score (mean SEM, +/- 9.3 +/- 2.7 to 5.3 +/- 2.6 vs. 8.0 +/- 23 to 8.6 +/- 2.10; P = 0.0008). Conclusions: In chronically intubated critically ill patients, AA successfully eradicated existing MDRO organisms and reduced the pressure from systemic agents for new respiratory resistance. Clinical trial registered with www.clinicaltrials.gov (NCT 01878643).