Limits...
Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis.

Zampieri FG, Nassar AP, Gusmao-Flores D, Taniguchi LU, Torres A, Ranzani OT - Crit Care (2015)

Bottom Line: However, more evidence of the benefit of this therapy is required.Secondary outcomes were microbiological cure, ICU and hospital mortality, duration of mechanical ventilation, ICU length of stay and adverse events.A mixed-effect model meta-analysis was performed.

View Article: PubMed Central - PubMed

Affiliation: Cooperative Network for Research - AMIB-Net, Associação de Medicina Intensiva Brasileira, São Paulo, Brazil. fgzampieri@gmail.com.

ABSTRACT

Introduction: Nebulized antibiotics are a promising new treatment option for ventilator-associated pneumonia. However, more evidence of the benefit of this therapy is required.

Methods: The Medline, Scopus, EMBASE, Biological Abstracts, CAB Abstracts, Food Science and Technology Abstracts, CENTRAL, Scielo and Lilacs databases were searched to identify randomized controlled trials or matched observational studies that compared nebulized antibiotics with or without intravenous antibiotics to intravenous antibiotics alone for ventilator-associated pneumonia treatment. Two reviewers independently collected data and assessed outcomes and risk of bias. The primary outcome was clinical cure. Secondary outcomes were microbiological cure, ICU and hospital mortality, duration of mechanical ventilation, ICU length of stay and adverse events. A mixed-effect model meta-analysis was performed. Trial sequential analysis was used for the main outcome of interest.

Results: Twelve studies were analyzed, including six randomized controlled trials. For the main outcome analysis, 812 patients were included. Nebulized antibiotics were associated with higher rates of clinical cure (risk ratio (RR) = 1.23; 95% confidence interval (CI), 1.05 to 1.43; I(2) = 34%; D(2) = 45%). Nebulized antibiotics were not associated with microbiological cure (RR = 1.24; 95% CI, 0.95 to 1.62; I(2) = 62.5), mortality (RR = 0.90; CI 95%, 0.76 to 1.08; I(2) = 0%), duration of mechanical ventilation (standardized mean difference = -0.10 days; 95% CI, -1.22 to 1.00; I(2) = 96.5%), ICU length of stay (standardized mean difference = 0.14 days; 95% CI, -0.46 to 0.73; I(2) = 89.2%) or renal toxicity (RR = 1.05; 95% CI, 0.70 to 1.57; I(2) = 15.6%). Regarding the primary outcome, the number of patients included was below the information size required for a definitive conclusion by trial sequential analysis; therefore, our results regarding this parameter are inconclusive.

Conclusions: Nebulized antibiotics seem to be associated with higher rates of clinical cure in the treatment of ventilator-associated pneumonia. However, the apparent benefit in the clinical cure rate observed by traditional meta-analysis does not persist after trial sequential analysis. Additional high-quality studies on this subject are highly warranted.

Trial registration number: CRD42014009116 . Registered 29 March 2014.

Show MeSH

Related in: MedlinePlus

Trial sequential analysis results. RR, relative risk.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4403838&req=5

Fig4: Trial sequential analysis results. RR, relative risk.

Mentions: Clinical cure was assessed in 11 studies totaling 812 patients. Nebulized antibiotics were associated with higher rates of clinical cure (RR = 1.23; 95% CI, 1.05 to 1.43; I2 = 34%; D2 = 45%) (Figure 3). The Biggertaff-Tweedie model produced similar results (RR = 1.21; 95% CI, 1.19 to 1.22; I2 = 34%; D2 = 35%). Within the subgroup analysis according to study design (randomized controlled trial versus observational) there was a presence of heterogeneity (Figure 3); however, the difference in the effect of nebulized antibiotics by study design was not significant in the meta-regression (P = 0.517). A bubble plot for the meta-regression is shown in Additional file 1 (Figure S1). A funnel plot for the clinical cure analysis is shown in Additional file 1 (Figure S2). The TSA results are shown in Figure 4. Considering the boundaries defined in the methods section, our meta-analysis was insufficiently powered to detect an increase in treatment success with a 5% alpha error limit (information size required 1,895 patients).Figure 3


Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis.

Zampieri FG, Nassar AP, Gusmao-Flores D, Taniguchi LU, Torres A, Ranzani OT - Crit Care (2015)

Trial sequential analysis results. RR, relative risk.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4403838&req=5

Fig4: Trial sequential analysis results. RR, relative risk.
Mentions: Clinical cure was assessed in 11 studies totaling 812 patients. Nebulized antibiotics were associated with higher rates of clinical cure (RR = 1.23; 95% CI, 1.05 to 1.43; I2 = 34%; D2 = 45%) (Figure 3). The Biggertaff-Tweedie model produced similar results (RR = 1.21; 95% CI, 1.19 to 1.22; I2 = 34%; D2 = 35%). Within the subgroup analysis according to study design (randomized controlled trial versus observational) there was a presence of heterogeneity (Figure 3); however, the difference in the effect of nebulized antibiotics by study design was not significant in the meta-regression (P = 0.517). A bubble plot for the meta-regression is shown in Additional file 1 (Figure S1). A funnel plot for the clinical cure analysis is shown in Additional file 1 (Figure S2). The TSA results are shown in Figure 4. Considering the boundaries defined in the methods section, our meta-analysis was insufficiently powered to detect an increase in treatment success with a 5% alpha error limit (information size required 1,895 patients).Figure 3

Bottom Line: However, more evidence of the benefit of this therapy is required.Secondary outcomes were microbiological cure, ICU and hospital mortality, duration of mechanical ventilation, ICU length of stay and adverse events.A mixed-effect model meta-analysis was performed.

View Article: PubMed Central - PubMed

Affiliation: Cooperative Network for Research - AMIB-Net, Associação de Medicina Intensiva Brasileira, São Paulo, Brazil. fgzampieri@gmail.com.

ABSTRACT

Introduction: Nebulized antibiotics are a promising new treatment option for ventilator-associated pneumonia. However, more evidence of the benefit of this therapy is required.

Methods: The Medline, Scopus, EMBASE, Biological Abstracts, CAB Abstracts, Food Science and Technology Abstracts, CENTRAL, Scielo and Lilacs databases were searched to identify randomized controlled trials or matched observational studies that compared nebulized antibiotics with or without intravenous antibiotics to intravenous antibiotics alone for ventilator-associated pneumonia treatment. Two reviewers independently collected data and assessed outcomes and risk of bias. The primary outcome was clinical cure. Secondary outcomes were microbiological cure, ICU and hospital mortality, duration of mechanical ventilation, ICU length of stay and adverse events. A mixed-effect model meta-analysis was performed. Trial sequential analysis was used for the main outcome of interest.

Results: Twelve studies were analyzed, including six randomized controlled trials. For the main outcome analysis, 812 patients were included. Nebulized antibiotics were associated with higher rates of clinical cure (risk ratio (RR) = 1.23; 95% confidence interval (CI), 1.05 to 1.43; I(2) = 34%; D(2) = 45%). Nebulized antibiotics were not associated with microbiological cure (RR = 1.24; 95% CI, 0.95 to 1.62; I(2) = 62.5), mortality (RR = 0.90; CI 95%, 0.76 to 1.08; I(2) = 0%), duration of mechanical ventilation (standardized mean difference = -0.10 days; 95% CI, -1.22 to 1.00; I(2) = 96.5%), ICU length of stay (standardized mean difference = 0.14 days; 95% CI, -0.46 to 0.73; I(2) = 89.2%) or renal toxicity (RR = 1.05; 95% CI, 0.70 to 1.57; I(2) = 15.6%). Regarding the primary outcome, the number of patients included was below the information size required for a definitive conclusion by trial sequential analysis; therefore, our results regarding this parameter are inconclusive.

Conclusions: Nebulized antibiotics seem to be associated with higher rates of clinical cure in the treatment of ventilator-associated pneumonia. However, the apparent benefit in the clinical cure rate observed by traditional meta-analysis does not persist after trial sequential analysis. Additional high-quality studies on this subject are highly warranted.

Trial registration number: CRD42014009116 . Registered 29 March 2014.

Show MeSH
Related in: MedlinePlus