Aerosolized tobramycin for Pseudomonas aeruginosa ventilator-associated pneumonia in patients with acute respiratory distress syndrome

Abstract Background The data on incidence, clinical presentation, and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. We performed this retrospective cohort study to assess frequency, clinical characteristics, responsible pathogens, and outcomes of VAP in patients COVID-19 pneumonia requiring MV between March 12th and April 24th, 2020 (all had RT-PCR-confirmed SARS-CoV-2 infection). Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) requiring ECMO were compared with an historical cohort of 45 patients with severe influenza-associated ARDS requiring ECMO admitted to the same ICU during the preceding three winter seasons. Results Among 50 consecutive patients with Covid-19-associated ARDS requiring ECMO included [median (IQR) age 48 (42–56) years; 72% male], 43 (86%) developed VAP [median (IQR) MV duration before the first episode, 10 (8–16) days]. VAP-causative pathogens were predominantly Enterobacteriaceae (70%), particularly inducible AmpC-cephalosporinase producers (40%), followed by Pseudomonas aeruginosa (37%). VAP recurred in 34 (79%) patients and 17 (34%) died. Most recurrences were relapses (i.e., infection with the same pathogen), with a high percentage occurring on adequate antimicrobial treatment. Estimated cumulative incidence of VAP, taking into account death and extubation as competing events, was significantly higher in Covid-19 patients than in influenza patients (p = 0.002). Despite a high P. aeruginosa-VAP rate in patients with influenza-associated ARDS (54%), the pulmonary infection recurrence rate was significantly lower than in Covid-19 patients. Overall mortality was similar for the two groups. Conclusions Patients with severe Covid-19-associated ARDS requiring ECMO had a very high late-onset VAP rate. Inducible AmpC-cephalosporinase-producing Enterobacteriaceae and Pseudomonas aeruginosa frequently caused VAP, with multiple recurrences and difficulties eradicating the pathogen from the lung.

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A Ventilator-associated Pneumonia Prediction Model in Patients With Acute Respiratory Distress Syndrome

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1518 ◽

2020 ◽

Vol 71 (Supplement_4) ◽

pp. S400-S408

Author(s):

Zongsheng Wu ◽

Yao Liu ◽

Jingyuan Xu ◽

Jianfeng Xie ◽

Shi Zhang ◽

...

Keyword(s):

Mechanical Ventilation ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Neuromuscular Blocking ◽

Calibration Plot ◽

Binary Logistic Regression Analysis ◽

Ventilator Associated Pneumonia ◽

Mechanical Ventilation Duration

Abstract Background Mechanical ventilation is crucial for acute respiratory distress syndrome (ARDS) patients and diagnosis of ventilator-associated pneumonia (VAP) in ARDS patients is challenging. Hence, an effective model to predict VAP in ARDS is urgently needed. Methods We performed a secondary analysis of patient-level data from the Early versus Delayed Enteral Nutrition (EDEN) of ARDSNet randomized controlled trials. Multivariate binary logistic regression analysis established a predictive model, incorporating characteristics selected by systematic review and univariate analyses. The model’s discrimination, calibration, and clinical usefulness were assessed using the C-index, calibration plot, and decision curve analysis (DCA). Results Of the 1000 unique patients enrolled in the EDEN trials, 70 (7%) had ARDS complicated with VAP. Mechanical ventilation duration and intensive care unit (ICU) stay were significantly longer in the VAP group than non-VAP group (P < .001 for both) but the 60-day mortality was comparable. Use of neuromuscular blocking agents, severe ARDS, admission for unscheduled surgery, and trauma as primary ARDS causes were independent risk factors for VAP. The area under the curve of the model was .744, and model fit was acceptable (Hosmer-Lemeshow P = .185). The calibration curve indicated that the model had proper discrimination and good calibration. DCA showed that the VAP prediction nomogram was clinically useful when an intervention was decided at a VAP probability threshold between 1% and 61%. Conclusions The prediction nomogram for VAP development in ARDS patients can be applied after ICU admission, using available variables. Potential clinical benefits of using this model deserve further assessment.

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Risks Of Ventilator-Associated Pneumonia And Invasive Pulmonary Aspergillosis In Patients With Viral Acute Respiratory Distress Syndrome Related or Not To Coronavirus 19 Disease

10.21203/rs.3.rs-44275/v1 ◽

2020 ◽

Author(s):

Keyvan Razazi ◽

Romain ARRESTIER ◽

Anne-Fleur Haudebourg ◽

Brice Benelli ◽

Guillaume Carteaux ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Invasive Aspergillosis ◽

Distress Syndrome ◽

Invasive Pulmonary Aspergillosis ◽

Resistant Bacteria ◽

Ventilator Associated Pneumonia ◽

Retrospective Case ◽

Pulmonary Aspergillosis

Abstract Background The goal of this study was to assess risk factors of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with SARS-CoV-2 infection.Methods. We conducted a monocenter retrospective study comparing the prevalence of VAP and invasive aspergillosis between patients with COVID-19 related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS).Results. We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 hours. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p<0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS : 58 (64%) vs. 36 (44%), p=0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning [sub-hazard ratio = 1.72 (1.14-2.52), p<0.01].The prevalence of multi-drug resistant bacteria (MDR) related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p=0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p<0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS [2 (2%) vs. 12 (15%), p=0.003], but there was no difference in Aspergillus colonization.Conclusions. In this retrospective case-control study, we evidenced a higher prevalence of VAP and MDR-VAP in C-ARDS than in NC-ARDS, and a lower risk for invasive aspergillosis in the former group.

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Analysis of pulmonary vascular injury and repair during Pseudomonas aeruginosa infection-induced pneumonia and acute respiratory distress syndrome

Pulmonary Circulation ◽

10.1177/2045894019826941 ◽

2019 ◽

Vol 9 (1) ◽

pp. 204589401982694 ◽

Cited By ~ 3

Author(s):

Ashley S. Lindsey ◽

Lydia M. Sullivan ◽

Nicole A. Housley ◽

Anna Koloteva ◽

Judy A. King ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Vascular Injury ◽

Post Infection ◽

Vascular Function ◽

Distress Syndrome ◽

Proliferative Phase ◽

Injury And Repair

Herein we describe lung vascular injury and repair using a rodent model of Pseudomonas aeruginosa pneumonia-induced acute respiratory distress syndrome (ARDS) during: 1) the exudative phase (48-hour survivors) and 2) the reparative/fibro-proliferative phase (1-week survivors). Pneumonia was induced by intratracheal instillation of P. aeruginosa strain PA103, and lung morphology and pulmonary vascular function were determined subsequently. Pulmonary vascular function was assessed in mechanically ventilated animals in vivo (air dead space, PaO2, and lung mechanics) and lung permeability was determined in isolated perfused lungs ex vivo (vascular filtration coefficient and extravascular lung water). At 48 hours post infection, histological analyses demonstrated capillary endothelial disruption, diffuse alveolar damage, perivascular cuffs, and neutrophil influx into lung parenchyma. Infected animals displayed clinical hallmarks of ARDS, including increased vascular permeability, increased dead space, impaired gas exchange, and decreased lung compliance. Overall, the animal infection model recapitulated the morphological and functional changes typically observed in lungs from patients during the exudative phase of ARDS. At 1 week post infection, there was lung histological and pulmonary vascular functional evidence of repair when compared with 48 hours post infection; however, some parameters were still impaired when compared with uninfected controls. Importantly, lungs displayed increased fibrosis and cellular hyperplasia reminiscent of lungs from patients during the fibro-proliferative phase of ARDS. Control, sham inoculated animals showed normal lung histology and function. These data represent the first comprehensive assessment of lung pathophysiology during the exudative and reparative/fibro-proliferative phases of P. aeruginosa pneumonia-induced ARDS, and position this pre-clinical model for use in interventional studies aimed at advancing clinical care.

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Increased Plasminogen Activator Inhibitor-1 Concentrations in Bronchoalveolar Lavage Fluids Are Associated with Increased Mortality in a Cohort of Patients with Pseudomonas aeruginosa

Anesthesiology ◽

10.1097/00000542-200702000-00012 ◽

2007 ◽

Vol 106 (2) ◽

pp. 252-261 ◽

Cited By ~ 32

Author(s):

Yuanlin Song ◽

Susan V. Lynch ◽

Judith Flanagan ◽

Hanjing Zhuo ◽

Wynnson Tom ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Bronchoalveolar Lavage ◽

Distress Syndrome ◽

Plasminogen Activator Inhibitor ◽

Ventilator Associated Pneumonia ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

Background Increased plasminogen activator inhibitor-1 (PAI-1) concentrations are found in bronchoalveolar lavage (BAL) fluids from patients with ventilator-associated pneumonia or acute respiratory distress syndrome. The authors hypothesized that PAI-1 concentrations were associated with increased mortality in patients with either Pseudomonas aeruginosa-induced ventilator-associated pneumonia or tracheobronchial colonization. Methods In a prospective cohort study, daily aspirates from intubated patients were cultured for P. aeruginosa. Positive patients had blind BAL (bBAL) that was processed for biomarker concentrations. Secretion of type III secretion cytotoxins were also analyzed from the P. aeruginosa strains. Results Thirty-three patients were enrolled. Ten of the 33 patients died. bBAL PAI-1 concentrations were significantly increased in nonsurvivors compared with survivors (31.7 vs. 3.4 ng/ml, P = 0.001 for hospital mortality; 35.9 vs. 4.7 ng/ml, P = 0.02 for 28-day mortality). Even when acute respiratory distress syndrome patients were excluded, there was a significant difference between the survivors and nonsurvivors for bBAL PAI-1 concentrations (P = 0.005). Eighty-three percent of P. aeruginosa strains isolated from patients with high concentrations of bBAL PAI-1 also had strains that secreted cytotoxins. Conclusions PAI-1 concentrations in bBALs correlated with mortality in ventilated patients with positive cultures for P. aeruginosa. Elevated bBAL PAI-1 concentrations also correlated with the secretion of type III exotoxins by P. aeruginosa.

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Effects of dexamethasone on immune dysfunction and ventilator-associated pneumonia in COVID-19 acute respiratory distress syndrome: an observational study

Journal of Intensive Care ◽

10.1186/s40560-021-00580-6 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Martin Cour ◽

Marie Simon ◽

Laurent Argaud ◽

Guillaume Monneret ◽

Fabienne Venet

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Observational Study ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Invasive Mechanical Ventilation ◽

Human Leukocyte ◽

Immune Dysfunction ◽

Ventilator Associated Pneumonia ◽

Mechanically Ventilated

AbstractDexamethasone improves survival of patients with COVID-19 acute respiratory distress syndrome, but might shorten the delay between the start of invasive mechanical ventilation and the occurrence of ventilator-associated pneumonia, suggesting possible worsening of COVID-19-induced immune dysfunction with this treatment. In a prospective observational study, we found that mechanically ventilated patients with COVID-19 treated with dexamethasone presented earlier ventilator-associated pneumonia, had significantly lower monocyte Human Leukocyte Antigen-DR expression and number of circulating CD4 + cells after ICU admission, than those not treated with corticoids.

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Lung Microbiome in Critically Ill Patients

Life ◽

10.3390/life12010007 ◽

2021 ◽

Vol 12 (1) ◽

pp. 7

Author(s):

Mélanie Fromentin ◽

Jean-Damien Ricard ◽

Damien Roux

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Bacterial Pathogen ◽

Normal Lung ◽

Ventilator Associated Pneumonia ◽

Bacterial Populations ◽

Chronic Respiratory Diseases

The historical hypothesis of sterility of the lungs was invalidated over a decade ago when studies demonstrated the existence of sparse but very diverse bacterial populations in the normal lung and the association between pulmonary dysbiosis and chronic respiratory diseases. Under mechanical ventilation, dysbiosis occurs rapidly with a gradual decline in diversity over time and the progressive predominance of a bacterial pathogen (mainly Proteobacteria) when lung infection occurs. During acute respiratory distress syndrome, an enrichment in bacteria of intestinal origin, mainly Enterobacteriaceae, is observed. However, the role of this dysbiosis in the pathogenesis of ventilator-associated pneumonia and acute respiratory distress syndrome is not yet fully understood. The lack of exploration of other microbial populations, viruses (eukaryotes and prokaryotes) and fungi is a key issue. Further analysis of the interaction between these microbial kingdoms and a better understanding of the host-microbiome interaction are necessary to fully elucidate the role of the microbiome in the pathogenicity of acute diseases. The validation of a consensual and robust methodology in order to make the comparison of the different studies relevant is also required. Filling these different gaps should help develop preventive and therapeutic strategies for both acute respiratory distress syndrome and ventilator-associated pneumonia.

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Ventilator-associated pneumonia among SARS-CoV-2 acute respiratory distress syndrome patients

Current Opinion in Critical Care ◽

10.1097/mcc.0000000000000908 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Jacopo Fumagalli ◽

Mauro Panigada ◽

Michael Klompas ◽

Lorenzo Berra

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Ventilator Associated Pneumonia

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Pseudomonas Aeruginosa Induced Cell Death in Acute Lung Injury and Acute Respiratory Distress Syndrome

International Journal of Molecular Sciences ◽

10.3390/ijms21155356 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5356

Author(s):

Rushikesh Deshpande ◽

Chunbin Zou

Keyword(s):

Pseudomonas Aeruginosa ◽

Cell Death ◽

Acute Respiratory Distress Syndrome ◽

Acute Lung Injury ◽

Lung Injury ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Lung Epithelial ◽

Epithelial Cell Death

Pseudomonas aeruginosa is an important opportunistic pathogen responsible for the cause of acute lung injury and acute respiratory distress syndrome. P. aeruginosa isthe leading species isolated from patients with nosocomial infection and is detected in almost all the patients with long term ventilation in critical care units. P. aeruginosa infection is also the leading cause of deleterious chronic lung infections in patients suffering from cystic fibrosis as well as the major reason for morbidity in people with chronic obstructive pulmonary disease. P. aeruginosa infections are linked to diseases with high mortality rates and are challenging for treatment, for which no effective remedies have been developed. Massive lung epithelial cell death is a hallmark of severe acute lung injury and acute respiratory distress syndrome caused by P. aeruginosa infection. Lung epithelial cell death poses serious challenges to air barrier and structural integrity that may lead to edema, cytokine secretion, inflammatory infiltration, and hypoxia. Here we review different types of cell death caused by P. aeruginosa serving as a starting point for the diseases it is responsible for causing. We also review the different mechanisms of cell death and potential therapeutics in countering the serious challenges presented by this deadly bacterium.

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Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease

Critical Care ◽

10.1186/s13054-020-03417-0 ◽

2020 ◽

Vol 24 (1) ◽

Author(s):

Keyvan Razazi ◽

Romain Arrestier ◽

Anne Fleur Haudebourg ◽

Brice Benelli ◽

Guillaume Carteaux ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Invasive Aspergillosis ◽

Distress Syndrome ◽

Invasive Pulmonary Aspergillosis ◽

Ventilator Weaning ◽

Resistant Bacteria ◽

Ventilator Associated Pneumonia ◽

Pulmonary Aspergillosis

Abstract Background Data on incidence of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with severe SARS-CoV-2 infection are limited. Methods We conducted a monocenter retrospective study comparing the incidence of VAP and invasive aspergillosis between patients with COVID-19-related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS). Results We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 h. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p < 0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS: 58 (64%) vs. 36 (44%), p = 0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning [sub-hazard ratio = 1.72 (1.14–2.52), p < 0.01]. The incidence of multi-drug-resistant bacteria (MDR)-related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p = 0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p < 0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS [2 (2%) vs. 12 (15%), p = 0.003], but there was no difference in Aspergillus colonization. Conclusions In our experience, we evidenced a higher incidence of VAP and MDR-VAP in C-ARDS than in NC-ARDS and a lower risk for invasive aspergillosis in the former group.

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