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The Role of Aerosolized Colistin in the Treatment of Ventilator-Associated Pneumonia: A Systematic Review and Metaanalysis*

Valachis, Antonis MD, PhD1; Samonis, George MD, PhD2; Kofteridis, Diamantis P. MD, PhD2

doi: 10.1097/CCM.0000000000000771
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Objectives: The present meta-analysis and systematic review evaluated the efficacy and safety of aerosolized colistin as adjunctive therapy to IV antimicrobials or as monotherapy in the treatment of ventilator-associated pneumonia.

Design: The databases of MEDLINE and Cochrane Library up to June 2013 and all reference lists of the included studies and relevant reviews were searched. Studies were eligible if the efficacy and safety of aerosolized colistin in the treatment of ventilator-associated pneumonia was evaluated. An overall effect estimate for all dichotomous data as an odds ratio with 95% CI was calculated by the Mantel-Haenszel or the DerSimonian and Laird method depending on the statistical heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to interpret the findings.

Interventions: None.

Measurements and Main Results: Sixteen studies fulfilled the inclusion criteria: eight were comparing adjunctive aerosolized versus IV colistin (seven observational cohort or case-control studies and one randomized trial) and were meta-analyzed, and eight were single arm and were only systematically reviewed. The Grading of Recommendations Assessment, Development, and Evaluation approach showed limitations of the study design and presence of inconsistency in most of the outcomes, but no obvious indirectness or imprecision of results reporting. Based on the above assessments, the quality of evidence presented for each outcome ranged from “very low” to “low.” A significant improvement in clinical response (odds ratio, 1.57; 95% CI, 1.14–2.15; p = 0.006; I2 = 37%), microbiological eradication (odds ratio, 1.61; 95% CI, 1.11–2.35; p = 0.01; I2 = 0%), and infection-related mortality (odds ratio, 0.58; 95% CI, 0.34–0.96; p = 0.04; I2 = 46%) was observed with the addition of aerosolized colistin to IV treatment, whereas the addition of aerosolized colistin did not affect overall mortality (odds ratio, 0.74; 95% CI, 0.54–1.01; p = 0.06; I2 = 25%) or nephrotoxicity (odds ratio, 1.18; 95% CI, 0.76–1.83; p = 0.45; I2 = 0%).

Conclusion: Based on the present results and awaiting further evidence from randomized trials, aerosolized colistin is associated with improved outcome in the treatment of ventilator-associated pneumonia although the level of evidence was low.

1Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.

2Department of Internal Medicine-Infectious Disease Unit, University Hospital of Heraklion, Crete, Greece.

* See also p. 697.

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Dr. Samonis’ research team has received grant support from Astellas, Pfizer, Novartis, Merck Sharp & Dohme, and Unipharma. Dr. Kofteridis has received grant support from Astellas and Unipharma. Dr. Valachis has disclosed that he does not have any potential conflicts of interest.

For information regarding this article, E-mail: kofterid@med.uoc.gr

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