Multidrug-resistant pathogens and ventilator-associated pneumonia in critically ill COVID-19 and non-COVID-19 patients: a prospective observational monocentric comparative study.

BACKGROUND: The COVID-19 pandemic has increased the incidence of ventilator-associated pneumonia (VAP) among critically ill patients. However, a comparison of VAP incidence in COVID-19 and non-COVID-19 cohorts, particularly in a context with a high prevalence of multidrug-resistant (MDR) organisms, is lacking. MATERIAL AND METHODS: We conducted a single-center, mixed prospective and retrospective cohort study comparing COVID-19 patients admitted to the intensive care unit (ICU) of the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021 (COVID-19 group), with a historical cohort of ICU patients admitted between June 2016 and March 2018 (NON-COVID-19 group). The primary objective was to define the incidence of VAP in both cohorts. Secondary objectives were to evaluate the microbial cause, resistance patters, risk factors and impact on 28 days, ICU and in-hospital mortality, duration of ICU stay, and duration of hospitalization). RESULTS: We found a significantly higher incidence of VAP (51.9% - n = 125) among the 241 COVID-19 patients compared to that observed (31.2% - n = 78) among the 252 NON-COVID-19 patients. The median SOFA score was significantly lower in the COVID-19 group (9, Interquartile range, IQR: 7-11 vs. 10, IQR: 8-13, p < 0.001). The COVID-19 group had a higher prevalence of Gram-positive bacteria-related VAP (30% vs. 9%, p < 0.001), but no significant difference was observed in the prevalence of difficult-to-treat (DTR) or MDR bacteria. ICU and in-hospital mortality in the COVID-19 and NON-COVID-19 groups were 71% and 74%, vs. 33% and 43%, respectively. The presence of COVID-19 was significantly associated with an increased risk of 28-day all-cause hospital mortality (Hazard ratio, HR: 7.95, 95% Confidence Intervals, 95% CI: 3.10-20.36, p < 0.001). Tracheostomy and a shorter duration of mechanical ventilation were protective against 28-day mortality, while dialysis and a high SOFA score were associated with a higher risk of 28-day mortality. CONCLUSION: COVID-19 patients with VAP appear to have a significantly higher ICU and in-hospital mortality risk regardless of the presence of MDR and DTR pathogens. Tracheostomy and a shorter duration of mechanical ventilation appear to be associated with better outcomes.

Bacterial profiles detected in ventilator-associated pneumonia in Japan: A systematic review.

The primary objective of this study was to identify the predominant organisms associated with ventilator-associated pneumonia (VAP) in Japan. Studies on VAP conducted in Japan were systematically reviewed, and seven studies with a total of 374 cases were included. The detection rate of each bacterium and multidrug-resistant (MDR) pathogen was analyzed using the inverse variance method. Pseudomonas aeruginosa was identified as the predominant pathogen in 29.2 % of cases, followed by methicillin-resistant Staphylococcus aureus (MRSA) (12.0 %), and Klebsiella spp. (9.5 %). An integrated analysis revealed a detection rate of 57.8 % (95 % confidence interval: 48.7%-66.8 %) for MDR pathogens. This review highlights P. aeruginosa and MRSA as the predominant VAP-associated organisms in Japan, with a significant prevalence of MDR pathogens. This analysis provides valuable insights based on the regional distribution of bacteria detected in VAP, which is critical for selecting appropriate empirical therapy.

Role of soluble urokinase plasminogen activator receptor in critically ill children with hospital-acquired pneumonia: an observational study in hospital with controls.

BACKGROUND: Diagnosing hospital-acquired pneumonia (HAP) (ventilator-associated pneumonia (VAP) and non-ventilator associated pneumonia (Non-VAP)) is still a hot issue. Soluble urokinase plasminogen activator receptor (suPAR) is prognostic in critically ill children with sepsis regarding mortality prediction. Our aim was to evaluate suPAR levels in children with HAP. METHODS: An observational, prospective study was conducted on 45 children diagnosed HAP (VAP and Non-VAP) and 40 healthy controls. Paediatric Sequential Organ Failure assessment Score (pSOFA) was assessed for each patient. Plasma suPAR levels were measured with ELISA on the day of diagnosis. RESULTS: On comparison levels of plasma suPAR for the children with HAP with the healthy control group, no statistically significant difference was observed (148 pg/mL (22.4-1939.7) and 184.4 pg/mL (31.6-1311.7), respectively, (p=0.32). suPAR was significantly increased in children with elevated pSOFA score on the day of diagnosis of pneumonia (p=0.034). suPAR was significantly increased in children with shock (p=0.005). suPAR levels was negatively correlated with oxygen saturation (rs=0.31,p=0.048). suPAR was not significantly correlated with C reactive protein. CONCLUSIONS: suPAR can be used as a predictor for severity of illness in children with HAP. We firmly know that plasma suPAR, a novel marker, could indicate the disease if carried out on larger patient groups.

A quasi-experimental study of a bundled diagnostic stewardship intervention for ventilator-associated pneumonia.

OBJECTIVES: Diagnostic error in the use of respiratory cultures for ventilator-associated pneumonia (VAP) fuels misdiagnosis and antibiotic overuse within intensive care units. In this prospective quasi-experimental study (NCT05176353), we aimed to evaluate the safety, feasibility, and efficacy of a novel VAP-specific bundled diagnostic stewardship intervention (VAP-DSI) to mitigate VAP over-diagnosis/overtreatment. METHODS: We developed and implemented a VAP-DSI using an interruptive clinical decision support tool and modifications to clinical laboratory workflows. Interventions included gatekeeping access to respiratory culture ordering, preferential use of non-bronchoscopic bronchoalveolar lavage for culture collection, and suppression of culture results for samples with minimal alveolar neutrophilia. Rates of adverse safety outcomes, positive respiratory cultures, and antimicrobial utilization were compared between mechanically ventilated patients (MVPs) in the 1-year post-intervention study cohort (2022-2023) and 5-year pre-intervention MVP controls (2017-2022). RESULTS: VAP-DSI implementation did not associate with increases in adverse safety outcomes but did associate with a 20% rate reduction in positive respiratory cultures per 1000 MVP days (pre-intervention rate 127 [95% CI: 122-131], post-intervention rate 102 [95% CI: 92-112], p < 0.01). Significant reductions in broad-spectrum antibiotic days of therapy per 1000 MVP days were noted after VAP-DSI implementation (pre-intervention rate 1199 [95% CI: 1177-1205], post-intervention rate 1149 [95% CI: 1116-1184], p 0.03). DISCUSSION: Implementation of a VAP-DSI was safe and associated with significant reductions in rates of positive respiratory cultures and broad-spectrum antimicrobial use. This innovative trial of a VAP-DSI represents a novel avenue for intensive care unit antimicrobial stewardship. Multicentre trials of VAP-DSIs are warranted.

Pulmonary superinfection diagnosed with bronchoalveolar lavage at intubation in COVID patients: A Swedish single-centre study.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID) pneumonia and acute respiratory distress syndrome (C-ARDS) on invasive mechanical ventilation (IMV) have been found to be prone to having other microbial findings than severe acute respiratory syndrome coronavirus 2 (SARS-2)-CoV-19 in the bronchoalveolar lavage (BAL) fluid at intubation causing a superinfection. These BAL results could guide empirical antibiotic treatment in complex clinical situations. However, there are limited data on the relationship between microbial findings in the initial BAL at intubation and later ventilator-associated pneumonia (VAP) diagnoses. OBJECTIVE: To analyse the incidence of, and microorganisms responsible for, superinfections in C-ARDS patients at the time of first intubation through microbial findings in BAL fluid. To correlate these findings to markers of inflammation in plasma and later VAP development. DESIGN: Retrospective single-centre study. SETTING: One COVID-19 intensive care unit (ICU) at a County Hospital in Sweden during the first year of the pandemic. PATIENTS: All patients with C-ARDS who were intubated in the ICU. RESULTS: We analysed BAL fluid specimens from 112 patients at intubation, of whom 31 (28%) had superinfections. Blood levels of the C-reactive protein, procalcitonin, neutrophil granulocytes, and lymphocytes were indistinguishable between patients with and without a pulmonary superinfection. Ninety-eight (88%) of the patients were treated with IMV for more than 48 h and of these patients, 37% were diagnosed with VAP. The microorganisms identified in BAL at the time of intubation are normally found at the oral, pharyngeal, and airway sites. Only one patient had an indistinguishable bacterial strain responsible for both superinfection at intubation and in VAP. CONCLUSIONS: One fourth of the patients with C-ARDS had a pulmonary superinfection in the lungs that was caused by another microorganism identified at intubation. Routine serum inflammatory markers could not be used to identify this complication. Microorganisms located in BAL at intubation were rarely associated with later VAP development.

Qualitative and quantitative rapid detection of VOCs differentially released by VAP-associated bacteria using PTR-MS and FGC-PTR-MS.

Ventilator-associated pneumonia (VAP) is a prevalent disease caused by microbial infection, resulting in significant morbidity and mortality within the intensive care unit (ICU). The rapid and accurate identification of pathogenic bacteria causing VAP can assist clinicians in formulating timely treatment plans. In this study, we attempted to differentiate bacterial species in VAP by utilizing the volatile organic compounds (VOCs) released by pathogens. We cultured 6 common bacteria in VAP in vitro, including Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Staphylococcus aureus, which covered most cases of VAP infection in clinic. After the VOCs released by bacteria were collected in sampling bags, they were quantitatively detected by a proton transfer reaction-mass spectrometry (PTR-MS), and the characteristic ions were qualitatively analyzed through a fast gas chromatography-proton transfer reaction-mass spectrometry (FGC-PTR-MS). After conducting principal component analysis (PCA) and analysis of similarities (ANOSIM), we discovered that the VOCs released by 6 bacteria exhibited differentiation following 3 h of quantitative cultivation in vitro. Additionally, we further investigated the variations in the types and concentrations of bacterial VOCs. The results showed that by utilizing the differences in types of VOCs, 6 bacteria could be classified into 5 sets, except for A. baumannii and E. cloacae which were indistinguishable. Furthermore, we observed significant variations in the concentration ratio of acetaldehyde and methyl mercaptan released by A. baumannii and E. cloacae. In conclusion, the VOCs released by bacteria could effectively differentiate the 6 pathogens commonly associated with VAP, which was expected to assist doctors in formulating treatment plans in time and improve the survival rate of patients.

Early Predictors of Ventilator Associated Pneumonia in Preterm Neonates Admitted in a Special Newborn Care Unit.

OBJECTIVES: To determine the utility of microscopic examination and culture of endotracheal aspirate (ETA) in the early diagnosis of ventilator-associated pneumonia (VAP) in preterm neonates. METHODS: We enrolled 80 consecutive neonates (both inborn and out-born) with gestational age of < 37 weeks admitted in Special Newborn Care Unit (SNCU) and requiring mechanical ventilation (MV) for ≥ 48 hours. The diagnosis of VAP was made using the criteria laid down by the Centers for Disease Control (CDC). RESULTS: 47 preterm neonates (58.5%) developed VAP; the overall incidence was 74.7/1000 ventilator-days. The mean (SD) time (hours) to ETA culture was less as compared to diagnosis based on CDC criteria [108.9 (8.00 hrs) vs 132.4 (53.24); P = 0.004] with sensitivity and specificity of 80.8% and 72.7%, respectively. Outborn delivery was the single most important risk factor for VAP. Multidrug resistant (MDR) Klebsiella pneumoniae (63.9%) was the most prevalent organism. CONCLUSIONS: We noticed a very high incidence of VAP among preterm neonates in SNCU. ETA culture can aid in early diagnosis.

Ventilator-associated pneumonia by Weeksella virosa: case report.

BACKGROUND: Weeksella virosa pneumonia is an infection that has been described as a healthcare-associated infection. This is a rare gram-negative anaerobic bacterium associated with the use of mechanical ventilation for a long period of time and is more frequent in immunosuppressed patients. This is the first case reported in the state of Veracruz and the second in Mexico. CASE PRESENTATION: We present the case of a 64-year-old female from Veracruz, Mexico who developed an infectious process in the right pelvic limb after a transcatheter aortic valve replacement procedure and subsequently developed sudden cardiorespiratory arrest requiring mechanical ventilation, with subsequent imaging studies demonstrating a pneumonic process associated with a nosocomial infection. DISCUSSION AND CONCLUSIONS: We should take into consideration that this pathogen affects not only adults with multiple comorbidities but also children with renal, hepatic, or oncological pathologies, as well as immunocompromised patients, who should be considered high-risk populations for W. virosa infection.

The Role of Biomarkers in the Diagnosis and Management of Pneumonia.

Biomarkers are used in the diagnosis, severity determination, and prognosis for patients with community-acquired pneumonia (CAP). Selected biomarkers may indicate a bacterial infection and need for antibiotic therapy (C-reactive protein, procalcitonin, soluble triggering receptor expressed on myeloid cells). Biomarkers can differentiate CAP patients who require hospital admission and severe CAP requiring intensive care unit admission. Biomarker-guided antibiotic therapy may limit antibiotic exposure without compromising outcome and thus improve antibiotic stewardship. The authors discuss the role of biomarkers in diagnosing, determining severity, defining the prognosis, and limiting antibiotic exposure in CAP and ventilator-associated pneumonia patients.

Management of Ventilator-Associated Pneumonia: Guidelines.

Two recent major guidelines on diagnosis and treatment of ventilator-associated pneumonia (VAP) recommend consideration of local antibiotic resistance patterns and individual patient risks for resistant pathogens when formulating an initial empiric antibiotic regimen. One recommends against invasive diagnostic techniques with quantitative cultures to determine the cause of VAP; the other recommends either invasive or noninvasive techniques. Both guidelines recommend short-course therapy be used for most patients with VAP. Although neither guideline recommends use of procalcitonin as an adjunct to clinical judgment when diagnosing VAP, they differ with respect to use of serial procalcitonin to shorten the length of antibiotic treatment.

VAP risk index: Early prediction and hospital phenotyping of ventilator-associated pneumonia using machine learning.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality in intensive care units (ICUs). Early identification of patients at risk of VAP enables early intervention, which in turn improves patient outcomes. We developed a predictive model for individualized risk assessment utilizing machine learning to identify patients at risk of developing VAP. METHODS: The Philips eRI dataset, a multi-institution electronic medical record (EMR), was used for model development. For adult (≥18y) patients, we propose a set of criteria using indications of the start of a new antibiotic treatment temporally contiguous to a microbiological test to mark suspected infection events, of which those with a positive culture are labeled as presumed VAP if 1) the event occurs at least 48 h after intubation, and 2) there are no indications of community-acquired pneumonia (CAP) or other hospital-acquired infections (HAI) in the patient charts. The resulting VAP and no-VAP (control) cases were then used to build an ensemble of decision trees to predict the risk of VAP in the next 24 h using data on patients' demographics, vitals, labs, and ventilator settings. RESULTS: The resulting model predicts the development of VAP 24 h in advance with an AUC of 76 % and AUPRC of 75 %. Additionally, we group hospitals that are similar in healthcare processes into distinct clusters and characterize VAP prediction for the identified hospital clusters. We show inter-hospital (teaching status and healthcare processes) and cohort-specific (age groups, gender, early vs late VAP, ICU mortality status) differences in VAP prediction and associated symptomologies. CONCLUSIONS: Our proposed VAP criteria use clinical actions to mark incidences of presumed VAP infection, which enables the development of models for early detection of these events. We curated a patient cohort using these criteria and used it to build a model for predicting impending VAP events prior to clinical suspicions. We present a clustering approach for tailoring the VAP prediction model for different hospital types based on their EMR data characteristics. The model provides an instantaneous risk score that allows early interventions and confirmatory diagnostic actions.

Application of ventilator-associated events (VAE) in ventilator-associated pneumonia (VAP) notified in Brazil (IMPACTO MR-PAV): a protocol for a cohort study.

INTRODUCTION: Certain criteria for ventilator-associated events (VAE) definition might influence the type of an event, its detection rate and consequently the resource expenditure in intensive care unit. The Impact of Infections by Antimicrobial-Resistant Microorganisms - Ventilator-Associated Pneumonia (IMPACTO MR-PAV) aims to evaluate the incidence and diagnostic accuracy of ventilator-associated pneumonia (VAP) using the current criteria for VAP surveillance in Brazil versus the VAE criteria defined by the US National Healthcare Safety Network-Center for Diseases Control and Prevention (CDC) criteria. METHODS AND ANALYSIS: The study will be conducted in around 15 centres across Brazil from October 2022 to December 2023. Trained healthcare professionals will collect data and compare the incidence of VAP using both the current criteria for VAP surveillance in Brazil and the VAE criteria defined by the CDC. The accuracy of the two criteria for identifying VAP will also be analysed. It will also characterise other events associated with mechanical ventilation (ventilator-associated condition, infection-related ventilator-associated complication) and adjudicate VAP reported to the Brazilian Health Regulatory Agency (ANVISA) using current epidemiological diagnostic criteria. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board under the number 52354721.0.1001.0070. The study's primary outcome measure will be the incidence of VAP using the two different surveillance criteria, and the secondary outcome measures will be the accuracy of the two criteria for identifying VAP and the adjudication of VAP reported to ANVISA. The results will contribute to the improvement of VAP surveillance in Brazil and may have implications for other countries that use similar criteria. TRIAL REGISTRATION NUMBER: NCT05589727; Clinicaltrials.gov.

A metagenomics method for the quantitative detection of bacterial pathogens causing hospital-associated and ventilator-associated pneumonia.

IMPORTANCE: The management of ventilator-associated pneumonia and hospital-acquired pneumonia requires rapid and accurate quantitative detection of the infecting pathogen. To this end, we propose a metagenomic sequencing assay that includes the use of an internal sample processing control for the quantitative detection of 20 relevant bacterial species from bronchoalveolar lavage samples.

Systematic review of ceftaroline fosamil in the management of patients with methicillin-resistant Staphylococcus aureus pneumonia.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for an array of problematic community- and healthcare-acquired infections, including pneumonia, and is frequently associated with severe disease and high mortality rates. Standard recommended treatments for empiric and targeted coverage of suspected MRSA in patients with community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), are vancomycin and linezolid. However, adverse events such as acute kidney injury and Clostridium difficile infection have been associated with these antibiotics. Ceftaroline fosamil is a ß-lactam/extended-spectrum cephalosporin approved for the treatment of adults and children with CAP and complicated skin and soft tissue infections. Ceftaroline has in vitro activity against a range of common Gram-positive bacteria and is distinct among the ß-lactams in retaining activity against MRSA. Due to the design of the pivotal randomised controlled trials of ceftaroline fosamil, outcomes in patients with MRSA CAP were not evaluated. However, various reports of real-world outcomes with ceftaroline fosamil for pneumonia caused by MRSA, including CAP and HAP/VAP, been published since its approval. A systematic literature review and qualitative analysis of relevant publications was undertaken to collate and summarise relevant published data on the efficacy and safety of ceftaroline fosamil in patients with MRSA pneumonia. While relatively few real-world outcomes studies are available, the available data suggest that ceftaroline fosamil is a possible alternative to linezolid and vancomycin for MRSA pneumonia. Specific scenarios in which ceftaroline fosamil might be considered include bacteraemia and complicating factors such as empyema.

European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI.

PURPOSE: Lower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes. METHODS: A prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups. RESULTS: 1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates. CONCLUSION: VHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.

Incidence, microbiological and immunological characteristics of ventilator-associated pneumonia assessed by bronchoalveolar lavage and endotracheal aspirate in a prospective cohort of COVID-19 patients: CoV-AP study.

BACKGROUND: No univocal recommendation exists for microbiological diagnosis of ventilator-associated pneumonia (VAP). Sampling of either proximal or distal respiratory tract likely impacts on the broad range of VAP incidence between cohorts. Immune biomarkers to rule-in/rule-out VAP diagnosis, although promising, have not yet been validated. COVID-19-induced ARDS made VAP recognition even more challenging, often leading to overdiagnosis and overtreatment. We evaluated the impact of different respiratory samples and laboratory techniques on VAP incidence and microbiological findings in COVID-19 patients. METHODS: Prospective single-centre cohort study conducted among COVID-19 mechanically ventilated patients in Policlinico Hospital (Milan, Italy) from January 2021 to May 2022. Microbiological confirmation of suspected VAP (sVAP) was based on concomitant endotracheal aspirates (ETA) and bronchoalveolar lavage (BAL). Conventional and fast microbiology (FILMARRAY® Pneumonia Panel plus, BALFAPPP) as well as immunological markers (immune cells and inflammatory cytokines) was analysed. RESULTS: Seventy-nine patients were included. Exposure to antibiotics and steroid therapy before ICU admission occurred in 51/79 (64.6%) and 60/79 (65.9%) patients, respectively. Median duration of MV at VAP suspicion was 6 (5-9) days. Incidence rate of microbiologically confirmed VAP was 33.1 (95% CI 22.1-44.0) and 20.1 (95% CI 12.5-27.7) according to ETA and BAL, respectively. Concordance between ETA and BAL was observed in 35/49 (71.4%) cases, concordance between BALFAPPP and BAL in 39/49 (79.6%) cases. With BAL as reference standard, ETA showed 88.9% (95% CI 70.8-97.7) sensitivity and 50.0% (95% CI 28.2-71.8) specificity (Cohen's Kappa 0.40, 95% CI 0.16-0.65). BALFAPPP showed 95.0% (95% CI 75.1-99.9) sensitivity and 69% (95% CI 49.2-84.7) specificity (Cohen's Kappa 0.60, 95% CI 0.39-0.81). BAL IL-1ß differed significantly between VAP (135 (IQR 11-450) pg/ml) and no-VAP (10 (IQR 2.9-105) pg/ml) patients (P = 0.03). CONCLUSIONS: In COVID-19 ICU patients, differences in microbial sampling at VAP suspicion could lead to high variability in VAP incidence and microbiological findings. Concordance between ETA and BAL was mainly limited by over 20% of ETA positive and BAL negative samples, while BALFAPPP showed high sensitivity but limited specificity when evaluating in-panel targets only. These factors should be considered when comparing results of cohorts with different sampling. BAL IL-1ß showed potential in discriminating microbiologically confirmed VAP. CLINICAL TRIAL REGISTRATION: NCT04766983, registered on February 23, 2021.

Transcriptomics reveals shared immunosuppressive landscapes in ventilator-associated lower respiratory tract infections (VA-LRTI) patients.

BACKGROUND: Ventilator-associated pneumonia (VAP) represents a transitory status of immunoparalysis, and we hypothesized that ventilator-associated tracheobronchitis (VAT) could share also some degree of immune response to a respiratory infection. RESEARCH DESIGN AND METHODS: A prospective observational study in five medical ICUs to evaluate immunological alterations of patients with VA-LRTI. Immunological gene expression profiles in the blood using whole transcriptome microarrays in the first 24 hours following diagnosis. The area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of mRNA levels to differentiate VA-LRTI and lack of infection. A principal component analysis (PCA) was employed for analyzing the impact of each genetic expression footprint variable in explaining the variance of the cohort. RESULTS: There was overlapping between the three classes of patients encompassing gene expression levels of 8 genes (i.e. HLA, IL2RA, CD40LG, ICOS, CCR7, CD1C, CD3E). HLA-DRA was equally low among VAT and VAP patients characterizing immune depression, and significantly lower than the control group. CONCLUSIONS: Our findings suggest that VAP and VAT are not so different regarding gene expression levels suggesting a degree of immunosuppression. Our results indicate a state of immunoparalysis in respiratory infections in critically ill patients.