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Nebulization of antiinfective agents in invasively mechanically ventilated adults : a systematic review and meta-analysis

Candela Solé-Lleonart, Jean-Jacques Rouby, Stijn Blot UGent, Garyfallia Poulakou, Jean Chastre, Lucy B Palmer, Matteo Bassetti, Charles-Edouard Luyt, Jose M Pereira, Jordi Riera, et al. (2017) ANESTHESIOLOGY. 126(5). p.890-908
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; 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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
GRAM-NEGATIVE BACTERIA, SERIOUSLY ILL PATIENTS, INTENSIVE-CARE-UNIT, RENAL REPLACEMENT THERAPY, AEROSOL DRUG-DELIVERY, NOSOCOMIAL PNEUMONIA, RESPIRATORY-TRACT, PSEUDOMONAS-AERUGINOSA, ANTIMICROBIAL AGENTS, ADJUNCTIVE TREATMENT
journal title
ANESTHESIOLOGY
Anesthesiology
volume
126
issue
5
pages
890 - 908
Web of Science type
Article
Web of Science id
000402746000017
ISSN
0003-3022
DOI
10.1097/aln.0000000000001570
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
8529903
handle
http://hdl.handle.net/1854/LU-8529903
date created
2017-08-30 12:56:53
date last changed
2017-10-25 11:53:21
@article{8529903,
  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; 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.},
  author       = {Sol{\'e}-Lleonart, Candela and Rouby, Jean-Jacques and Blot, Stijn and Poulakou, Garyfallia and Chastre, Jean and Palmer, Lucy B and Bassetti, Matteo and Luyt, Charles-Edouard and Pereira, Jose M and Riera, Jordi and Felton, Tim and Dhanani, Jayesh and Welte, Tobias and Garcia-Alamino, Jose M and Roberts, Jason A and Rello, Jordi},
  issn         = {0003-3022},
  journal      = {ANESTHESIOLOGY},
  keyword      = {GRAM-NEGATIVE BACTERIA,SERIOUSLY ILL PATIENTS,INTENSIVE-CARE-UNIT,RENAL REPLACEMENT THERAPY,AEROSOL DRUG-DELIVERY,NOSOCOMIAL PNEUMONIA,RESPIRATORY-TRACT,PSEUDOMONAS-AERUGINOSA,ANTIMICROBIAL AGENTS,ADJUNCTIVE TREATMENT},
  language     = {eng},
  number       = {5},
  pages        = {890--908},
  title        = {Nebulization of antiinfective agents in invasively mechanically ventilated adults : a systematic review and meta-analysis},
  url          = {http://dx.doi.org/10.1097/aln.0000000000001570},
  volume       = {126},
  year         = {2017},
}

Chicago
Solé-Lleonart, Candela, Jean-Jacques Rouby, Stijn Blot, Garyfallia Poulakou, Jean Chastre, Lucy B Palmer, Matteo Bassetti, et al. 2017. “Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults : a Systematic Review and Meta-analysis.” Anesthesiology 126 (5): 890–908.
APA
Solé-Lleonart, C., Rouby, J.-J., Blot, S., Poulakou, G., Chastre, J., Palmer, L. B., Bassetti, M., et al. (2017). Nebulization of antiinfective agents in invasively mechanically ventilated adults : a systematic review and meta-analysis. ANESTHESIOLOGY, 126(5), 890–908.
Vancouver
1.
Solé-Lleonart C, Rouby J-J, Blot S, Poulakou G, Chastre J, Palmer LB, et al. Nebulization of antiinfective agents in invasively mechanically ventilated adults : a systematic review and meta-analysis. ANESTHESIOLOGY. 2017;126(5):890–908.
MLA
Solé-Lleonart, Candela, Jean-Jacques Rouby, Stijn Blot, et al. “Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults : a Systematic Review and Meta-analysis.” ANESTHESIOLOGY 126.5 (2017): 890–908. Print.