Project description:BackgroundPandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP).ObjectivesTo study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients.MethodsIn this retrospective observational study, we compared the incidence of VAP and secondary infections using a combination of microbial culture and a TaqMan multi-pathogen array. In addition, we determined the lung microbiome composition using 16S RNA analysis in a subset of samples. The study involved 81 COVID-19 and 144 non-COVID-19 patients receiving invasive ventilation in a single University teaching hospital between March 15th 2020 and August 30th 2020.ResultsCOVID-19 patients were significantly more likely to develop VAP than patients without COVID (Cox proportional hazard ratio 2.01 95% CI 1.14-3.54, p = 0.0015) with an incidence density of 28/1000 ventilator days versus 13/1000 for patients without COVID (p = 0.009). Although the distribution of organisms causing VAP was similar between the two groups, and the pulmonary microbiome was similar, we identified 3 cases of invasive aspergillosis amongst the patients with COVID-19 but none in the non-COVID-19 cohort. Herpesvirade activation was also numerically more frequent amongst patients with COVID-19.ConclusionCOVID-19 is associated with an increased risk of VAP, which is not fully explained by the prolonged duration of ventilation. The pulmonary dysbiosis caused by COVID-19, and the causative organisms of secondary pneumonia observed are similar to that seen in critically ill patients ventilated for other reasons.
Project description:Among hospital-acquired infections (HAIs) in children, ventilator-associated pneumonia (VAP) is the most common after blood stream infection (BSI). VAP can prolong length of ventilation and hospitalization, increase mortality rate, and directly change a patient's outcome in Pediatric Intensive Care Units (PICU).The research on VAP in children is limited, especially in Iran; therefore, the identification of VAP incidence and mortality rate will be important for both clinical and epidemiological implications.Mechanically ventilated pediatric patients were assessed for development of VAP during hospital course on the basis of clinical, laboratory and imaging criteria. We matched VAP group with control group for assessment of VAP related mortality in the critically ill ventilated children.VAP developed in 22.9% of critically ill children undergoing mechanical ventilation. Early VAP and late VAP were found in 19.3% and 8.4% of VAP cases, respectively. Among the known VAP risk factors that were investigated, immunodeficiency was significantly greater in the VAP group (p = 0.014). No significant differences were found between the two groups regarding use of corticosteroids, antibiotics, PH (potential of hydrogen) modifying agents (such as ranitidine or pantoprazole), presence of nasogastric tube and total or partial parenteral nutrition administration. A substantial number of patients in the VAP group had more than four risk factors for development of VAP, compared to those without VAP (p = 0.087). Mortality rate was not statistically different between the VAP and control groups (p = 0.477).VAP is still one of the major causes of mortality in PICUs. It is found that altered immune status is a significant risk factor for acquiring VAP. Also, occurrence of VAP was high in the first week after admission in PICU.
Project description:RationaleVentilator-associated pneumonia (VAP) is a common complication in patients with acute lung injury (ALI) and can lead to increased morbidity and mortality. Identifying protein profiles specific to VAP in bronchoalveolar lavage fluid (BALF) may aid in earlier diagnosis, elucidate mechanisms of disease, and identify putative targets for therapeutic intervention.MethodsBALF was obtained from 5 normal subjects and 30 ALI patients: 14 with VAP (VAP(+)) and 16 without VAP (VAP(-)). Each sample underwent shotgun proteomic analysis based on tandem mass spectrometry. Differentially expressed proteins between the groups were identified using statistical methods based on spectral counting. Mechanisms of disease were explored using functional annotation and protein interaction network analysis. Supervised classification algorithms were implemented to discover a proteomic classifier for identifying critically ill patients with VAP.ResultsALI patients had distinct BALF proteomic profiles compared to normal controls. Within the ALI group, we identified 76 differentially expressed proteins between VAP(+) and VAP(-). Functional analysis of these proteins suggested activation of pro-inflammatory pathways during VAP. We identified and validated a limited proteomic signature that discriminated VAP(+) from VAP(-) patients comprised of three proteins: S100A8, lactotransferrin (LTF), and actinin 1 (ACTN1).ConclusionsCombining proteomic with computational analyses is a powerful approach to study the BALF proteome during lung injury and development of VAP. This integrative methodology is a promising strategy to differentiate clinically relevant subsets of ALI patients, including those suffering from VAP.
Project description:COVID pneumonitis can cause patients to become critically ill. They may require intensive care and mechanical ventilation. Ventilator-associated pneumonia (VAP) is a concern. This review discusses VAP in this group. Several reasons have been proposed to explain the elevated rates of VAP in critically ill COVID patients compared to non-COVID patients. Extrinsic factors include understaffing, lack of personal protective equipment and use of immunomodulating agents. Intrinsic factors include severe parenchymal damage and immune dysregulation, along with pulmonary vascular endothelial inflammation and thrombosis. The rate of VAP has been reported at 45.4%, with an intensive care unit mortality rate of 42.7%. Multiple challenges to diagnosis exist. Other conditions such as acute respiratory distress syndrome, pulmonary oedema and atelectasis can present with similar features. Frequent growth of gram-negative bacteria has been shown in multiple studies, with particularly high rates of Pseudomonas aeruginosa. The rate of invasive pulmonary aspergillosis has been reported at 4-30%. We would recommend the use of invasive techniques when possible. This will enable de-escalation of antibiotics as soon as possible, decreasing overuse. It is also important to keep other possible causes of VAP in mind, e.g. COVID-19-associated pulmonary aspergillosis or cytomegalovirus. Diagnostic tests such as galactomannan and β-D-glucan should be considered. These patients may face a long treatment course, with risk of re-infection, along with prolonged weaning, which carries its own long-term consequences.
Project description:Ventilator-associated pneumonia (VAP) is the most frequent intensive care unit (ICU)-acquired infection that is independently associated with mortality. Accurate diagnosis and timely treatment have been shown to improve the prognosis of VAP. Chest X-ray or computed tomography imaging are used for conventional assessment of VAP, but these methods are impractical for real-time measurement in critical patients. Therefore, lung ultrasound (LUS) has been increasingly used for the assessment of VAP in the ICU. Traditionally, LUS has seemed unsuitable for the detection of lung parenchyma owing to the high acoustic impedance of air; however, the fact that the reflection and reverberation in the detection region of the ultrasound reflect the underlying pathology of lung diseases has led to the increased use of ultrasound imaging as a standard of care supported by evidence-based and expert consensus in the ICU. Considering that any type of pneumonia causes air volume changes in the lungs, accumulating evidence has shown that LUS effectively measures the presence of VAP as well as dynamic changes in VAP. This review offers evidence for ultrasound as a noninvasive, easily repeatable, and bedside means to assess VAP; in addition, it establishes a protocol for qualitative and quantitative monitoring of VAP.
Project description:Objective: Identify genes that are differentially expressed between critically ill trauma patients who go on to develop ventilator-associated pneumonia (VAP) compared to similar patients who do not develop VAP Using gene expression differences, develop a model that predicts which patients are at greater risk of developing VAP. Prospective observational study, analysis of gene expression in 20 patient samples, 10 that developed ventilator-associated pneumonia, 10 that did not
Project description:The accuracy of the signs and tests that clinicians use to diagnose ventilator-associated pneumonia (VAP) and initiate antibiotic treatment has not been well characterized. We sought to characterize and compare the accuracy of physical examination, chest radiography, endotracheal aspirate (ETA), bronchoscopic sampling cultures (protected specimen brush [PSB] and bronchoalveolar lavage [BAL]), and CPIS?>?6 to diagnose VAP. We searched six databases from inception through September 2019 and selected English-language studies investigating accuracy of any of the above tests for VAP diagnosis. Reference standard was histopathological analysis. Two reviewers independently extracted data and assessed study quality. We included 25 studies (1639 patients). The pooled sensitivity and specificity of physical examination findings for VAP were poor: fever (66.4% [95% confidence interval [CI]: 40.7-85.0], 53.9% [95% CI 34.5-72.2]) and purulent secretions (77.0% [95% CI 64.7-85.9], 39.0% [95% CI 25.8-54.0]). Any infiltrate on chest radiography had a sensitivity of 88.9% (95% CI 73.9-95.8) and specificity of 26.1% (95% CI 15.1-41.4). ETA had a sensitivity of 75.7% (95% CI 51.5-90.1) and specificity of 67.9% (95% CI 40.5-86.8). Among bronchoscopic sampling methods, PSB had a sensitivity of 61.4% [95% CI 43.7-76.5] and specificity of 76.5% [95% CI 64.2-85.6]; while BAL had a sensitivity of 71.1% [95% CI 49.9-85.9] and specificity of 79.6% [95% CI 66.2-85.9]. CPIS?>?6 had a sensitivity of 73.8% (95% CI 50.6-88.5) and specificity of 66.4% (95% CI 43.9-83.3). Classic clinical indicators had poor accuracy for diagnosis of VAP. Reliance upon these indicators in isolation may result in misdiagnosis and potentially unnecessary antimicrobial use.
Project description:ImportanceGrowing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported.ObjectiveTo evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU).Design, setting, and participantsRandomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020).InterventionsEnteral L rhamnosus GG (1 × 1010 colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU.Main outcomes and measuresThe primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality.ResultsAmong 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, -2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P < .001).Conclusions and relevanceAmong critically ill patients requiring mechanical ventilation, administration of the probiotic L rhamnosus GG compared with placebo, resulted in no significant difference in the development of ventilator-associated pneumonia. These findings do not support the use of L rhamnosus GG in critically ill patients.Trial registrationClinicalTrials.gov Identifier: NCT02462590.
Project description:The primary objective of this multicenter, observational, retrospective study was to assess the incidence rate of ventilator-associated pneumonia (VAP) in coronavirus disease 2019 (COVID-19) patients in intensive care units (ICU). The secondary objective was to assess predictors of 30-day case-fatality of VAP. From 15 February to 15 May 2020, 586 COVID-19 patients were admitted to the participating ICU. Of them, 171 developed VAP (29%) and were included in the study. The incidence rate of VAP was of 18 events per 1000 ventilator days (95% confidence intervals [CI] 16-21). Deep respiratory cultures were available and positive in 77/171 patients (45%). The most frequent organisms were Pseudomonas aeruginosa (27/77, 35%) and Staphylococcus aureus (18/77, 23%). The 30-day case-fatality of VAP was 46% (78/171). In multivariable analysis, septic shock at VAP onset (odds ratio [OR] 3.30, 95% CI 1.43-7.61, p = 0.005) and acute respiratory distress syndrome at VAP onset (OR 13.21, 95% CI 3.05-57.26, p < 0.001) were associated with fatality. In conclusion, VAP is frequent in critically ill COVID-19 patients. The related high fatality is likely the sum of the unfavorable prognostic impacts of the underlying viral and the superimposed bacterial diseases.