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Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults: A Systematic Review and Meta-Analysis
Solé-Lleonart C, Rouby JJ, Blot S, et al. Anesthesiology. 2017; 126: 890-908.
Study Question: Is there literature to support the safe and effective administration of nebulized antibiotics in mechanically ventilated adult patients?
Study Description: This was a systematic review and meta-analysis of studies that evaluated mechanically ventilated, critically ill, adult patients with a diagnosis of ventilator-associated tracheobronchitis (VAT), ventilator-associated pneumonia (VAP), or hospital-acquired pneumonia (HAP) who received nebulized antiinfective agents as adjunctive or substitutive treatment. Safety and efficacy outcomes were evaluated.
Results: Eleven studies evaluating nebulized antibiotics (aminoglycosides, colistin, or both) were included in the meta-analysis; six were randomized controlled trials and five were observational (n = 826).
Two studies evaluated VAT. Patients who received nebulized antibiotics had a reduction in their Clinical Pulmonary Infection Score (mean difference: -3.11 points; 95% CI 0.05-0.64; I2 = 0%) and less emergence of resistant organisms (risk ratio = 0.18; 95% CI 0.05-0.64; I2 = 0%). Six studies evaluated VAP caused by resistant organisms. Patients who received nebulized antibiotics experienced a higher rate of clinical resolution in the adjunctive (OR 0.53; 95% CI 0.36-0.8; I2 = 0%) and substitutive (OR 9.53; 95% CI 1.85-49.2) strategies. One study evaluating VAP caused by susceptible organisms found no difference in clinical resolution.
When used as a substitution for systemic therapy, there was a decrease in nephrotoxicity (risk difference -0.33; 95% CI -0.54 - 0.12; I2 = 0%). Nebulized antibiotics increased the risk of respiratory complications (risk difference, 0.04; 95% CI -0.02 - 0.11; I2 = 75%).
Conclusion(s): Nebulized antibiotics may be of benefit in patients with resistant organisms and may decrease nephrotoxicity when used as an alternative to systemic therapy, but may have a higher risk of respiratory complications.
Perspective: There were few well-designed trials that could be included in this analysis. Most trials had a small sample size, a heterogeneous population, utilized different nebulizing devices, evaluated different types of infections, and had different administration strategies. Based on this information, it is still questionable whether nebulized antibiotics have a place in therapy for treatment of VAT or VAP.