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Randomized Controlled Trial
. 2014 May 15;189(10):1225-33.
doi: 10.1164/rccm.201312-2161OC.

Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit

Lucy B Palmer  1 , Gerald C Smaldone
Affiliations
Randomized Controlled Trial

Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit

Lucy B Palmer et al. Am J Respir Crit Care Med. .

Abstract

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 MDRO 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 ≥6). 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).

Trial registration: ClinicalTrials.gov NCT01878643.

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Comment in

  • Antibiotics might do more than cause resistance.
    Bonten MJ, Waterer GW. Bonten MJ, et al. Am J Respir Crit Care Med. 2014 May 15;189(10):1157-8. doi: 10.1164/rccm.201404-0672ED. Am J Respir Crit Care Med. 2014. PMID: 24832740 No abstract available.
  • Inhaled antibiotics or inhaled hazard?
    Hurley JC. Hurley JC. Am J Respir Crit Care Med. 2014 Aug 15;190(4):480. doi: 10.1164/rccm.201406-1033LE. Am J Respir Crit Care Med. 2014. PMID: 25127310 No abstract available.
  • Reply: inhaled antibiotics or inhaled hazard?
    Palmer LB, Smaldone GC. Palmer LB, et al. Am J Respir Crit Care Med. 2014 Aug 15;190(4):480-1. doi: 10.1164/rccm.201406-1091LE. Am J Respir Crit Care Med. 2014. PMID: 25127311 No abstract available.

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