Reduction of Bacterial Resistance with Inhaled Antibiotics in the ICU.
Am J Respir Crit Care Med. 2014 Mar 19;
Authors: Palmer LB, Smaldone GC
Background Multi-drug resistant organisms (MDRO) are the dominant airway pathogens in the ICU and present a major treatment challenge to intensivists. Aerosolized antibiotics (AA) result in airway concentrations of drug 100 fold greater than the MIC of most bacteria including MDRO. These levels, without systemic toxicity, may eradicate MDRO and reduce the pressure for selection of new resistant organisms. Our objective was 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 (CPIS) ≥ 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 (SA) for VAP and any other infection. Results AA eradicated 26 of 27 organisms present at randomization compared to 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 to 1 of 11 for placebo (P<0.001). New drug resistance to AA was not seen. Compared to AA, resistance to systemic antibiotics significantly increased in placebo patients (P=0.03). Compared to placebo, AA significantly reduced CPIS, (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 registration information available at www.clinicaltrials.gov, i.d. NCT01878643.
PMID: 24646034 [PubMed - as supplied by publisher]