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; I-2 =
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; I-2 = 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; I-2 = 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
