Elsevier

Journal of Critical Care

Volume 43, February 2018, Pages 240-245
Journal of Critical Care

Pulmonary
Effect of antibiotics administered via the respiratory tract in the prevention of ventilator-associated pneumonia: A systematic review and meta-analysis

https://doi.org/10.1016/j.jcrc.2017.09.019Get rights and content

Highlights

  • Prophylactic antibiotics administered via the respiratory tract reduce the occurrence of ventilator-associated pneumonia.

  • This prophylactic strategy didn’t have significant effect on ICU mortality.

Abstract

Purpose

We evaluated the effect of antibiotics administered via the respiratory tract to prevent the ventilator-associated pneumonia (VAP) in mechanically ventilated (MV) patients.

Methods

We searched relevant articles for trials that evaluated the impact of prophylactic antibiotics administered through the respiratory tract on the occurrence of VAP. The end-point was the occurrence of VAP in MV patients.

Results

We included 6 comparative trials involving 1158 patients (632 received prophylactic antibiotic). Our meta-analysis revealed that prophylactic antibiotics administered through the respiratory tract reduced the occurrence of VAP when compared to placebo or no treatment (OR 0.53; 95% CI 0.34–0.84). This effect was seen when the antibiotics were given by nebulization (OR 0.46; 95% CI 0.22–0.97), but not when they were administered by intratracheal instillation (OR 0.57; 95% CI 0.28–1.15). We did not find a significant difference between the compared groups in the intensive care unit (ICU) mortality (OR 0.89; 95% CI 0.64–1.25). Antibiotic prophylaxis did not impact occurrence of VAP due to multidrug resistant (MDR) pathogens (OR 0.67; 95% CI 0.17–2.62).

Conclusions

Prophylactic antibiotics administered through the respiratory tract by nebulization reduce the occurrence of VAP, without a significant effect on either the ICU mortality or occurrence of VAP due to MDR pathogens.

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.

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