PulmonaryEffect of antibiotics administered via the respiratory tract in the prevention of ventilator-associated pneumonia: A systematic review and meta-analysis
Introduction
VAP is defined as pneumonia that occurs 48–72 h or thereafter following endotracheal intubation [1]. Despite the adoption of preventive measures, pneumonia continues to be a frequent complication in mechanically ventilated patients, and it is associated with a prolonged stay in the ICU and hospital, as well as dramatically increasing hospital costs [2].
VAP results from the invasion of the lung parenchyma by pathogenic bacteria, overwhelming the host's defense [3], The main sources of these bacteria are oropharyngeal colonization, secretions around the endotracheal tube cuff, and biofilm in the internal face of the endotracheal tube [3], [4]. Most VAP prevention strategies have been focused on controlling the bacterial inoculum which reaches the lower respiratory tract (e.g. oral care, selective oral decontamination, use of endotracheal tube with subglottic suction or with improved tracheal sealing) [5], [6], [7], [8]. Regarding the biofilm, studies have shown that a silver-coated endotracheal tube and antibiotics administered via the respiratory tract are effective in reducing its formation and may decrease the occurrence of VAP [9], [10], [11]. Antibiotics administered via the respiratory tract have several advantages over the intravenous therapy. They reach the target organ quickly and in high concentrations leading to decreased bacterial lung burden and potential damage of lungs. High pulmonary to plasma concentration is result of low systemic absorption that is reflected in lower risks of adverse events including C. difficile infections [12], [13]. In spite of these potential benefits, the American Thoracic Society guidelines for the management of adults with hospital-acquired and ventilator-associated pneumonia do not recommend the administration of antibiotics via the respiratory tract for the prevention of VAP [14], and the Centers for Disease Control and Prevention discourage this strategy as well [15].
A meta-analysis focused on antibiotics administrated via the respiratory tract was published in 2006, and provided positive results [16]. However, the fact that it included studies with non-ventilated subjects may have compromised its extrapolation to mechanically ventilated patients. Therefore, the aim of this systematic review and meta-analysis is to evaluate the effect of antibiotics administered via respiratory tract to prevent the VAP in mechanically ventilated patients.
Section snippets
Eligibility criteria
Studies (randomized clinical trials, and observational studies with matched groups) that have assessed the effect of antibiotics given via the respiratory tract, compared to placebo, on the prevention of VAP were considered eligible. The antibiotics could have been administered either by nebulization or intratracheal instillation. We included studies reporting the occurrence of VAP. There was no restriction regarding the date of publication, but the language was limited to English, Spanish and
Results
Our literature search and review of reference lists initially identified 27,261 articles: 7313 were repeated and 19,932 were excluded because they were not related to the topic of the meta-analysis. Ten of the remaining 16 articles were not considered due to language constraints (n = 3), because antibiotics were not given for prophylaxis but for treatment of VAP (n = 2), because of the inclusion of patients without mechanical ventilation (n = 2) or due to the use of other methodology (n = 3) (see
Discussion
This meta-analysis, which is the first one to include solely mechanically ventilated patients, demonstrates that prophylactic antibiotics administered via the respiratory tract reduce the occurrence of VAP without increasing the risk of VAP due to MDR pathogens.
The observed protective effect of antibiotics administered through the respiratory tract may be explained by the reduction of the biofilm formation on the inner surface of the endotracheal tube and subsenquently by decreased colonization
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflicts of interest
None.
References (34)
- et al.
Epidemiology and outcomes of ventilator-associated pneumonia in a large US database
Chest
(2002) - et al.
A randomized clinical trial of continuous aspiration of subglottic secretions in cardiac surgery patients
Chest
(1999) - et al.
Endotracheally administered gentamicin for the prevention of infections of the respiratory tract in patients with tracheostomy: a double-blind study
Chest
(1974) - et al.
Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies
Lancet Infect Dis
(2013) - et al.
Ventilator-associated pneumonia in the ICU
Crit Care
(2014) The prevention of ventilator-associated pneumonia
N Engl J Med
(1999)- et al.
Ventilator-associated pneumonia
Am J Respir Crit Care Med
(2002) - et al.
Recognition and prevention of nosocomial pneumonia in the intensive care unit and infection control in mechanical ventilation
Crit Care Med
(2010) - et al.
Decontamination of the digestive tract and oropharynx in ICU patients
N Engl J Med
(2009) - et al.
Influence of an endotracheal tube with polyurethane cuff and subglottic secretion drainage on pneumonia
Am J Respir Crit Care Med
(2007)
Reduced burden of bacterial airway colonization with a novel silver-coated endotracheal tube in a randomized multiple-center feasibility study
Crit Care Med
Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial
JAMA
Aerosolized antibiotics in critically ill ventilated patients
Curr Opin Crit Care
A randomized double-blind placebo-controlled dose-escalation phase 1 study of aerosolized amikacin and fosfomycin delivered via the PARI investigational eFlow® inline nebulizer system in mechanically ventilated patients
J Aerosol Med Pulm Drug Deliv
Aerosolized antibiotics: do they add to the treatment of pneumonia?
Curr Opin Infect Dis
Executive summary: management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society
Clin Infect Dis
Guidelines for preventing health-care-associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee MMWR Recomm Rep
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