Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults

Abstract

Background Nebulization of antiinfective agents is a common but unstandardized practice in critically ill patients. Methods A systematic review of 1,435 studies was performed in adults receiving invasive mechanical ventilation. Two different administration strategies (adjunctive and substitute) were considered clinically relevant. Inclusion was restricted to studies using jet, ultrasonic, and vibrating-mesh nebulizers. Studies involving children, colonized-but-not-infected adults, and cystic fibrosis patients were excluded. Results Five of the 11 studies included had a small sample size (fewer than 50 patients), and only 6 were randomized. Diversity of case-mix, dosage, and devices are sources of bias. Only a few patients had severe hypoxemia. Aminoglycosides and colistin were the most common antibiotics, being safe regarding nephrotoxicity and neurotoxicity, but increased respiratory complications in 9% (95% CI, 0.01 to 0.18; I2 = 52%), particularly when administered to hypoxemic patients. For tracheobronchitis, a significant decrease in emergence of resistance was evidenced (risk ratio, 0.18; 95% CI, 0.05 to 0.64; I2 = 0%). Similar findings were observed in pneumonia by susceptible pathogens, without improvement in mortality or ventilation duration. In pneumonia caused by resistant pathogens, higher clinical resolution (odds ratio, 1.96; 95% CI, 1.30 to 2.96; I2 = 0%) was evidenced. These findings were not consistently evidenced in the assessment of efficacy against pneumonia caused by susceptible pathogens. Conclusions Performance of randomized trials evaluating the impact of nebulized antibiotics with more homogeneous populations, standardized drug delivery, predetermined clinical efficacy, and safety outcomes is urgently required. Infections by resistant pathogens might potentially have higher benefit from nebulized antiinfective agents. Nebulization, without concomitant systemic administration of the drug, may reduce nephrotoxicity but may also be associated with higher risk of respiratory complications.

Resistance Trends and Treatment Options in Gram-Negative Ventilator-Associated Pneumonia

“…A meta-analysis of a randomized controlled trial and observational studies (437 total patients) examined the use of adjunctive nebulized antibiotics in MDR VAP and showed significantly higher clinical resolution among patients receiving nebulization (OR 1.96; 95% CI: 1.30–2.96) [91]. Nebulization has been used with the following Gram-negative antibiotics: gentamicin, tobramycin, amikacin, aztreonam, ceftazidime, and colistin [92].…”

Porous Silicon Nanoparticle Delivery of Tandem Peptide Anti‐Infectives for the Treatment of Pseudomonas aeruginosa Lung Infections

“…Antibiotic delivery via pSiNPs has yet to be established for treatment of lung infections. [1, 2] Together, these elements combined to form an anti-infective nanomaterial that we applied to a P. aeruginosa lung infection model (Figure 1A). We found the anti-infective nanomaterial significantly decreased bacterial numbers and improved survival in a mouse model of lung infection.…”

Study of the disposition of nebulized tobramycin

“…expiratory ratio was set at 1:2, positive end-expiratory pressure (PEEP) at 5 cm H2O and the flow set at 40 litres per minute in a square wave pattern. As per the recommendations for aerosolised antibiotics with MV, the humidifier was turned off [250]. The inspiratory limb of the ventilator was connected to the VMN before the Ypiece as per previous studies [259,260], in keeping with local and international practice [259] and the manufacturer's recommendations.…”

“…Ventilator associated pneumonia (VAP) occurs commonly in hospitals and is associated with significant mortality and morbidity worldwide [3][4][5][6]. Due to the emergence of multidrug resistant organisms causing VAP and scarcity of newer antibiotics, aerosolized antibiotics are increasingly being used to treat VAP either as monotherapy or as an adjuvant agent [250]. Recent guidelines have suggested using both inhaled and intravenous antibiotics for VAP due to resistant organisms [251,252].…”

“…For treatment of VAP, nebulized tobramycin is used frequently, either as monotherapy or as an adjuvant [257], [250]. However, aerosol delivery and lung deposition (and hence antibiotic concentrations in the lung) can be affected by mechanical ventilation parameters [13].…”