Estimating the attributable mortality of ventilator-associated pneumonia from randomized prevention studies*

Melsen, Wilhelmina G.; Rovers, Maroeska M.; Koeman, Mirelle; Bonten, Marc J. M.

doi:10.1097/ccm.0b013e3182281f33

Cited by 174 publications

(115 citation statements)

References 65 publications

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“…Hospital-or ventilator acquired pneumonia (HAP, VAP) is associated with a high mortality (1). Therefore, reaching efficacious effect-site concentrations of antibiotics is essential for successful treatment (2) and to suppress the emergence of resistance (3,4).…”

Section: Introductionmentioning

confidence: 99%

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

et al. 2015

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Purpose Obtaining pharmacologically relevant exposure levels of antibiotics in the epithelial lining fluid (ELF) is of critical importance to ensure optimal treatment of lung infections. Our objectives were to develop a model for the prediction of the ELF-plasma concentration ratio (EPR) of antibiotics based on their chemical structure descriptors (CSDs). Methods EPR data was obtained by aggregating ELF and plasma concentrations from historical clinical studies investigating antibiotics and associated agents. An elastic net regularized regression model was used to predict EPRs based on a large number of CSDs. The model was tuned using leave-one-drug-out cross validation, and the predictions were further evaluated using a test dataset. Results EPR data of 56 unique compounds was included. A high degree of variability in EPRs both between-and within drugs was apparent. No trends related to study design or pharmacokinetic factors could be identified. The model predicted 80% of the within-drug variability (R 2 WDV ) and 78.6% of drugs were within 3-fold difference from the observations. Key CSDs were related to molecular size and lipophilicity. When predicting EPRs for a test dataset the R 2 WDV was 75%. Conclusions This model is of relevance to inform dose selection and optimization during antibiotic drug development of agents targeting lung infections.

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Section: Introductionmentioning

confidence: 99%

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

et al. 2015

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“…5 Both the incidence of VAP and attributable mortality are difficult to discern, but are estimated to occur in 9 -28% of mechanically ventilated patients, 6 with an attributable mortality of 3-17%. 7 VAP has been estimated to prolong the duration of mechanical ventilation by up to 11 d, increase hospitalization stay by 6 -25 d, and incur additional expenditures ranging from $12,000 to $40,000 per episode. 1,[8][9][10][11][12][13][14] Annual health-care costs in the United States are approximately $2-2.7 trillion (17% of the gross domestic product), but these expenditures do not improve patient outcomes relative to other advanced nations that spend substantially less on health care.…”

Section: Introductionmentioning

confidence: 99%

The Vexing Problem of Ventilator-Associated Pneumonia: Observations on Pathophysiology, Public Policy, and Clinical Science

Kallet

2015

Respir Care

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SummaryVentilator-associated pneumonia (VAP) is an acquired infection related primarily to the consequences of prolonged endotracheal intubation. It is considered the most important infectious challenge in the critical care setting. Preventable complications of hospital care are considered an important source of wasted health-care costs believed to consume up to 47% of annual expenditures in the United States. Whether VAP is preventable has become a highly contentious debate since public reporting commenced a decade ago. This selective review focuses on specific aspects of this debate, including the inherent vagaries in the diagnosis of VAP and the marked disparities between VAP rates based on clinical diagnosis versus surveillance data. Also discussed is how this debate has impacted public policy, leading to the new paradigm of ventilator-associated events. The limited ability of artificial airways to prevent microaspiration and biofilm build-up, as well as non-modifiable conditions increasing the risk of VAP, is described in detail. In addition, the origins of the mistaken but widely embraced notion that zero VAP is a realistic achievement are examined.

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“…Eighty-six percent of nosocomial pneumonias are associated with mechanical ventilation and are termed ventilator-associated pneumonia (VAP). Between 250,000 and 300,000 cases per year occur in the United States alone, which is an incidence rate of 5 to 10 cases per 1,000 hospital admissions (McEachern et al, 1998;Melsen et al, 2011). The mortality attributable to VAP has been reported to range between 0 and 50% (Baker et al, 1996;Craig et al, 1984;Cunnion et al, 1996;Kappstein et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Incidence, Risk Factors and Outcome of Ventilator Associated Pneumonia at SRM Medical College Hospital –A Study under HICC

Sangamithra¹,

Manonmoney²,

karasi³

2017

Int.J.Curr.Microbiol.App.Sci

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Estimating the attributable mortality of ventilator-associated pneumonia from randomized prevention studies*

Cited by 174 publications

References 65 publications

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

The Vexing Problem of Ventilator-Associated Pneumonia: Observations on Pathophysiology, Public Policy, and Clinical Science

Incidence, Risk Factors and Outcome of Ventilator Associated Pneumonia at SRM Medical College Hospital –A Study under HICC

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