DOI: 10.1097/CCM.0b013e3181959d2a

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Issn Print: 0090-3493

Publication Date: 2009/02/01


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Aerosolized antibiotics are not a good idea—Don’t go with the flow: Premum Non Nocere!

Saad Nseir

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I thank Cunha (1) for his comments. In fact, respiratory tract colonization is difficult to differentiate from lower respiratory tract infections. However, patients with high amounts of bacteria in the respiratory specimen without local and systemic signs of infection should not be treated with intravenous or aerosolized antibiotics. Antibiotic use is a recognized risk factor for multidrug-resistant bacteria emergence (2). Patients in the intensive care unit with infections related to these bacteria often receive inappropriate initial antibiotic treatment, resulting in higher morbidity and mortality rates.
Cunha stated that aerosolized antibiotics offer no advantage on parental antibiotic use. However, the better understanding of physiologic factors influencing lung deposition of aerosolized particles together with improvements in aerosol technology has markedly reduced extrapulmonary deposition and increased the delivery of nebulized antibiotics to the deep lung. Nebulization of antimicrobial agents, by achieving higher concentration in the respiratory secretions and in the infected lung, could increase the antibacterial activity of antibiotics in the case of concentration-dependent antibiotics, such as aminoglycosides, or restore the bactericidal activity of antibiotics in the case of infections caused by pathogens of impaired sensitivity. Furthermore, by limiting systemic exposure, it could also allow the administration of antibiotics characterized by a high systemic toxicity, such as polymixins (3). In mechanically ventilated piglets with bronchopneumonia related to Escherichia coli, the deposition of amikacin in infected lung parenchyma and the efficiency of bacterial killing were greater after nebulization than after intravenous administration (4). In addition, in mechanically ventilated piglets with Pseudomonas aeruginosa pneumonia, nebulization of ceftazidime induced a 5- to 30-fold increase in lung tissue concentration compared with intravenous administration (5). A recent randomized, double-blind, placebo-controlled study was conducted in patients with Gram-negative ventilator-associated pneumonia to determine the efficacy of aerosolized amikacin as an adjunctive treatment (6). The authors found a significantly reduced number of intravenous antibiotics at the end of the study in the aerosolized amikacin group compared with the placebo group. Mean trough levels were very low, tracheal aspirate levels were 6.9 mg/mL (daily aerosol) and 16.2 mg/mL (twice daily), and aerosol amikacin was well tolerated, with no difference in adverse effects. Furthermore, Palmer et al (7) performed a randomized, double-blind, placebo-controlled study to determine the impact of aerosolized antibiotics on systemic antibiotic use in patients with ventilator-associated tracheobronchitis. Aerosolized antibiotics decreased ventilator-associated pneumonia and other signs and symptoms of respiratory infection, facilitated weaning, and reduced bacterial resistance and use of systemic antibiotics.
All these data suggest that aerosolized antibiotics could be beneficial in patients with lower respiratory tract infections. However, use of aerosolized antibiotics should not be generalized to all mechanically ventilated patients with ventilator-associated tracheobronchitis or ventilator-associated pneumonia. A large multicenter randomized study is required to confirm these promising preliminary results.
The author has not disclosed any potential conflicts of interest.
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