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

Abstract

IntroductionNebulized antibiotics are a promising new treatment option for ventilator-associated pneumonia. However, more evidence of the benefit of this therapy is required.MethodsThe 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.ResultsTwelve 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; I2 = 34%; D2 = 45%). Nebulized antibiotics were not associated with microbiological cure (RR = 1.24; 95% CI, 0.95 to 1.62; I2 = 62.5), mortality (RR = 0.90; CI 95%, 0.76 to 1.08; I2 = 0%), duration of mechanical ventilation (standardized mean difference = −0.10 days; 95% CI, −1.22 to 1.00; I2 = 96.5%), ICU length of stay (standardized mean difference = 0.14 days; 95% CI, −0.46 to 0.73; I2 = 89.2%) or renal toxicity (RR = 1.05; 95% CI, 0.70 to 1.57; I2 = 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.ConclusionsNebulized 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 numberCRD42014009116. Registered 29 March 2014Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0868-y) contains supplementary material, which is available to authorized users.

Aerosolized Antibiotics

“…24 We discuss the most relevant literature regarding the clinical application of aerosolized antibiotics for patients with CF, NCFB, and VAP infected with difficult-to-treat pathogens. 4,10,[25][26][27][28][29] …”

Efficacy of nebulized colistin-based therapy without concurrent intravenous colistin for ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii

“…Colistin is usually recommended as a first-line agent based on proven efficacy and safety (6,7,25,26). Recent meta-analyses showed the benefits of nebulized colistin for VAP caused by multidrug-resistant pathogens; however, the role of this form of colistin might be adjunctive to intravenous colistin (27)(28)(29). We posit that the use of nebulized colistin can be supported by pharmacokineticpharmacodynamic (PK-PD) data regarding antimicrobial efficacy and delivery to the lungs (10,11,30), and that our present study has important implications which suggests that nebulized colistin may be used for VAP caused by CRAB, even without concurrent intravenous administration.…”

Inhaled Antibiotics for Gram-Negative Respiratory Infections

“…VAP is defined as pneumonia occurring Ͼ48 h after endotracheal intubation and initiation of mechanical ventilation (24). Ventilator-associated pneumonia develops in upwards of 30% of patients who undergo mechanical ventilation for Ͼ48 h and increases the risk of all-cause mortality up to 2.5 times, with an attributable mortality rate of up to 1.5% (260)(261)(262). The actual attributable mortality rate for VAP is difficult to determine due to the challenges of firmly establishing a diagnosis and variances in diagnostic criteria, and thus, a wide range of estimates have been reported (263)(264)(265).…”