Nebulization of Anti-infective Agents in Invasively Mechanically Ventilated Adult Patients:  a systematic review and meta-analysis.
CCCF ePoster library. Solé-Lleonart C. Oct 26, 2015; 117367; P31 Disclosure(s): Project supported in part by ESGCIP - ESCMID and CIBERES
Candela Solé-Lleonart
Candela Solé-Lleonart
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Abstract
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P31


Topic: Systematic Review/Meta-analysis


Nebulization of Anti-infective Agents in Invasively Mechanically Ventilated Adult Patients:  a systematic review and meta-analysis.



Candela Solé-Lleonart, J. Rouby, J. Chastre, T. Welte, G. Poulakou, S. Blot, L. Palmer, C. Luyt, J. Riera, J. Garcia-Alamino, J. Dhanani, T. Felton, J. Pereira, M. Bassetti, J. Roberts, J. Rello

Critical Care Department, UHN & Mount Sinai Hospital. University of Toronto. Universitat Autònoma de Barcelona., Barcelona, Spain | Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care, La Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, University Pierre et Marie Curie (UPMC) of Paris., Paris, France | Service de Réanimation Médicale., Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie of Paris., Paris, France | Department of Pulmonary Medicine, Hannover Medical School, Hannover, Germany | 4th Department of Internal Medicine, Athens University School of Medicine, Attikon University General Hospital., Athens, Greece | Department of Internal Medicine., Faculty of Medicine & Health Science, Ghent University., Ghent, Belgium | Pulmonary, Critical Care and Sleep Division, Department of Medicine., State University of New York at Stony Brook, Stony Brook., New York, United States of America | Service de Réanimation Médicale, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre

Introduction: Nebulization of anti-infective agents, particularly antibiotics, is an extended but not yet standardized practice. The lack of evidence-based recommendations for both their delivery and indications may increase the possibility of suboptimal therapy.


Objectives: The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of nebulized antibiotics for the treatment of ventilator-associated pneumonia (VAP) in critically ill invasively mechanically ventilated adult patients.

Methods:

Random effects meta-analysis using the Mantel-Haenszel model approach was chosen to obtain pooled study results. The Higgins I2 test was predefined to quantify heterogeneity. Trial sequential analysis was performed, combining an estimation of information size and an adjusted threshold for statistical significance, adjusted for heterogeneity.




Results:

Nine studies (four randomized controlled trials) were included for meta-analysis regarding both efficacy and safety. Nebulization of antibiotics for the treatment of VAP caused by resistant pathogens was associated with higher rates of clinical resolution (OR=1.96; 95% CI, 1.30-2.96; I2=0%) and significant decrease in the length of mechanical ventilation support (3.72 days less; 95% CI from -5.86 to -1.59 days; I2=0%) when a combination of both nebulized and intravenous colistin or aminoglycosides was used. Even though the number of patients included was below the information size required for a definitive conclusion by trial sequencial analysis, boundaries of benefit were crossed for important efficacy outcomes such as duration of mechanical ventilation. No significant increase was found in the occurrence of systemic toxicities, including nephrotoxicity and neurotoxicity, or in respiratory complications. However, there were reports of severe adverse events when inadequate administration techniques were used (e.g. cardiac arrest secondary to occlusion of the expiratory filter).



Conclusion:

Antibiotic nebulization for the treatment of VAP seems to be an effective and safe therapy. These benefits appear to be enhanced when the agent is both nebulized and administered intravenously. Evidence-based recommendations should be provided to diminish the risk of inadequate practices that could potentially lead to an increased risk of adverse events.



References:

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2. Kofteridis DP, Alexopoulou C, Valachis A, Maraki S, Dimopoulou D, Georgopoulos D, Samonis G. Aerosolized plus Intravenous Colistin versus Intravenous Colistin Alone for the Treatment of Ventilator-Associated Pneumonia: A Matched Case-Control Study. Clinical Infectious Diseases 2010; 51(11): 1238-1244.

3. Doshi NM, Cook CH, Mount KL, Stawicki SP, Frazee EN, Personett HA, Schramm GE, Arnold HM, Murphy CV. Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a retrospective study. Anesthesiology 2013, 13:45.

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6. Hallal A, Cohn S, Namias N, Habib F, Baracco G, Manning R, et al. Aerosolized Tobramycin in the treatment of Ventilator-associated pneumonia: a pilot study. Surgical Infections, 2007; 8 (1):73-81.

7. Rattanaumpawan P, Lorsutthitham J, Ungprasert P, Angkasekwinai N, Thamlikitkul V. Randomized controlled trial of nebulized colistimethate sodium as adjunctive therapy of ventilator-associated pneumonia caused by Gram-negative bacteria. J Antimicrob Chemother, 2010; 65:2645-2649.

8.

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