Massive sequencing of the V3-V4 hypervariable region of bronchoalveolar lavage from patients with COVID-19 and VAP reveals the collapse of the pulmonary microbiota.

Background. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a predisposing factor for the development of healthcare-associated infections, of which ventilator-associated pneumonia (VAP) is one.Hypothesis. VAP is caused by ESKAPE bacteria and other pathogens not detected by microbiological culture.Aim. To elucidate the bacterial pathogens of severe coronavirus disease 2019 (COVID-19) and VAP patients by massive sequencing and to predict their degree of relationship with the age and sex of the patients.Methods. Analysis of ribosomal libraries of the V3-V4 hypervariable region obtained by Illumina sequencing of bronchoalveolar lavages from COVID-19 and VAP (first wave) patients from Hospital Juárez de México.Results. Acinetobacter and Pseudomonas were the main bacterial genera in the bronchoalveolar lavages (BALs) analysed. Other members of the ESKAPE group, such as Enterococcus and Klebsiella, were also identified. Taxonomic composition per patient showed that non-ESKAPE genera were present with significant relative abundances, such as Prevotella, Stenotrophomas, Enterococcus, Mycoplasma, Serratia and Corynebacterium. Kruskal-Wallis analysis proved that VAP acquisition is an adverse event that is not influenced by the sex and age of COVID-19 patients.Discussion. Metagenomic findings in COVID-19/VAP patients highlight the importance of implementing comprehensive microbiological diagnostics by including alternative tools for the detection of the causal agents of healthcare-associated infections (HAIs).Conclusions. Timely identification of bacteria 'not sought' in diagnostic bacteriology laboratories will allow specific and targeted treatments. Implications for the restricted diagnosis of VAP causative agents in COVID-19 patients and the presence of pathogens not detected by classical microbiology are analysed and discussed.

How common is ventilator-associated pneumonia after coronavirus disease 2019?

PURPOSE OF REVIEW: The first studies on COVID-19 patients with acute respiratory distress syndrome (ARDS) described a high rate of secondary bacterial ventilator-associated pneumonia (VAP). The specificity of VAP diagnoses in these patients are reviewed, including their actual rate. RECENT FINDINGS: Published studies described high rates of bacterial VAP among COVID-19 patients with ARDS, and these VAP episodes are usually severe and of specifically poor prognosis with high mortality. Indeed, Severe acute respiratory syndrome - coronavirus disease 19 (SARS-CoV2) infection elicits alterations that may explain a high risk of VAP. In addition, breaches in the aseptic management of patients might have occurred when the burden of care was heavy. In addition, VAP in these patients is more frequently suspected, and more often investigated with diagnostic tools based on molecular techniques. SUMMARY: VAP is frequented and of particularly poor prognosis in COVID-19 patients with ARDS. It can be explained by SARS-CoV-2 pathophysiology, and also breaches in the aseptic procedures. In addition, tools based on molecular techniques allow an early diagnosis and unmask VAP usually underdiagnosed by traditional culture-based methods. The impact of molecular technique-based diagnostics in improving antibacterial therapy and COVID-19 prognosis remain to be evaluated.

Procalcitonin as a biomarker for ventilator associated pneumonia in COVID-19 patients: Is it an useful stewardship tool?

Ventilator associated pneumonia(VAP) is a severe complication that can lead to high mortality when not early identified or when therapy is delayed. The aim of this study was to evaluate procalcitonin(PCT) as a biomarker for VAP development. In total, 73 hospitalized patients with COVID-19 were analyzed. PCT levels greater than 0.975ng/mL were more related to VAP. No association was found for C-reactive protein (CRP). The results show that procalcitonin may be a pertinent biomarker for VAP diagnosis and can be a helpful tool for antibiotic withdrawal.

Lung ultrasound score as a tool to monitor disease progression and detect ventilator-associated pneumonia during COVID-19-associated ARDS.

BACKGROUND: Lung ultrasound can accurately detect pandemic coronavirus disease (COVID-19) pulmonary lesions. A lung ultrasound score (LUS) was developed to improve reproducibility of the technique. OBJECTIVES: To evaluate the clinical value of LUS monitoring to guide COVID-19-associated acute respiratory distress syndrome (ARDS) management. METHODS: We conducted a single center, prospective observational study, including all patients admitted with COVID-19-associated ARDS between March and April 2020. A systematic daily LUS evaluation was performed. RESULTS: Thirty-three consecutive patients were included. LUS was significantly and negatively correlated to PaO2/FIO2. LUS increased significantly over time in non-survivors compared to survivors. LUS increased in 83% of ventilatory associated pneumonia (VAP) episodes, when compared to the previous LUS evaluation. LUS was not significantly higher in patients presenting post-extubation respiratory failure. CONCLUSIONS: In conclusion, our study demonstrates that LUS variations are correlated to disease severity and progression, and LUS monitoring could contribute to the early diagnosis of VAPs.

COVID-19 influences lung microbiota dynamics and favors the emergence of rare infectious diseases: A case report of Hafnia Alvei pneumonia.

The coronavirus disease 2019 causes a wide degree of organ dysfunction and is associated with bacterial secondary infections. We reported lung microbiota dynamics in a critically ill patient with coronavirus disease 2019, who developed severe Hafnia alvei ventilator-associated pneumonia and required extracorporeal membrane oxygenation support.

Safe and Efficient Practice of Bronchoscopic Sampling from Mechanically Ventilated Patients: A Structured Evaluation of the Ambu Bronchosampler-Ascope 4 Integrated System.

BACKGROUND: Bronchoscopic sampling of bronchoalveolar fluid (BAL) should be safe and effective. Current sampling practice risks loss of sample to the attached negative flow, aerosolisation, or spillage, due to repeated circuit breaks, when replacing sample containers. Such concerns were highlighted during the recent coronavirus pandemic. OBJECTIVES: Evaluation of an alternative integrated sampling solution, with the Ambu Bronchosampler with aScope 4, by an experienced bronchoscopist in ICU. METHODS: An observational study of 20 sequential bronchoscopic diagnostic sampling procedures was performed on mechanically ventilated patients with suspected ventilator-associated pneumonia. Mixed methods assessment was done. The predefined outcome measures were (1) ease of set up, (2) ease of specimen collection, (3) ease of protecting specimen from loss or spillage, and (4) overall workflow. The duration of the procedure and the % volume of sample retrieved were recorded. RESULTS: The mean (±standard deviation [SD]) time for collecting 1 sample was 2.5 ± 0.8 min. The mean (±SD) specimen yield for instilled miniBAL was 54.2 ± 17.9%. Compared with standard sampling, the set-up was much easier in 18 (90%), or easier in 2 (10%) of procedures, reducing the connection steps. It was much more intuitive to use in 14 (70%), more intuitive in 4 (20%), and no more intuitive to use in 2 (10%). The overall set-up and workflow was much easier in 69% of the 13 intraprocedural connections and easier or as easy in the remaining 31% procedures. All procedures where pre connection was established were much easier (7, 100%). The Ambu Bronchosampler remained upright in all procedures with no loss or spillage of sample. Obtaining a sample was much easier in 60%, easier in 10%, no different in 20%, and worse in 10%. The ability to protect a sample from start to finish compared to standard procedures was much easier in 80%, easier in 15%, and no different in 5% of procedures. Overall workflow was much easier in 14 (70%), easier in 4 (20%), and no different in 2 (10%) of procedures. CONCLUSIONS: The Ambu Bronchosampler unit was a reliable, effective, and possibly safer technique for diagnostic sampling in ICU. It may improve safety standards during the coronavirus pandemic. A randomized control trial against the standard sampling technique is warranted.

Ventilator-associated pneumonia in critically ill patients with COVID-19.

BACKGROUND: Pandemic 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). OBJECTIVES: To study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients. METHODS: In 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. RESULTS: COVID-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. CONCLUSION: COVID-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.

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

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.