Ventilator-Associated Pneumonia and PaO(2)/F(I)O(2) Diagnostic Accuracy: Changing the Paradigm?

Background: Ventilator-associated pneumonia (VAP) is associated to longer stay and poor outcomes. Lacking definitive diagnostic criteria, worsening gas exchange assessed by PaO2/FIO2 ≤ 240 in mmHg has been proposed as one of the diagnostic criteria for VAP. We aim to assess the adequacy of PaO2/FIO2 ≤ 240 to diagnose VAP. Methods: Prospective observational study in 255 consecutive patients with suspected VAP, clustered according to PaO2/FIO2 ≤ 240 vs. > 240 at pneumonia onset. The primary analysis was the association between PaO2/FIO2 ≤ 240 and quantitative microbiologic confirmation of pneumonia, the most reliable diagnostic gold-standard. Results: Mean PaO2/FIO2 at VAP onset was 195 ± 82; 171 (67%) cases had PaO2/FIO2 ≤ 240. Patients with PaO2/FIO2 ≤ 240 had a lower APACHE-II score at ICU admission; however, at pneumonia onset they had higher CPIS, SOFA score, acute respiratory distress syndrome criteria and incidence of shock, and less microbiological confirmation of pneumonia (117, 69% vs. 71, 85%, p = 0.008), compared to patients with PaO2/FIO2 > 240. In multivariate logistic regression, PaO2/FIO2 ≤ 240 was independently associated with less microbiological confirmation (adjusted odds-ratio 0.37, 95% confidence interval 0.15-0.89, p = 0.027). The association between PaO2/FIO2 and microbiological confirmation of VAP was poor, with an area under the ROC curve 0.645. Initial non-response to treatment and length of stay were similar between both groups, while hospital mortality was higher in patients with PaO2/FIO2 ≤ 240. Conclusion: Adding PaO2/FIO2 ratio ≤ 240 to the clinical and radiographic criteria does not help in the diagnosis of VAP. PaO2/FIO2 ratio > 240 does not exclude this infection. Using this threshold may underestimate the incidence of VAP

Community-Acquired Pneumonia Due to Multidrug- and Non–Multidrug-Resistant Pseudomonas aeruginosa

Background: Pseudomonas aeruginosa is not a frequent pathogen in community-acquired pneumonia (CAP). However, in patients with severe CAP, P aeruginosa can be the etiology in 1.8% to 8.3% of patients, with a case-fatality rate of 50% to 100%. We describe the prevalence, clinical characteristics, outcomes, and risk factors associated with CAP resulting from multidrug-resistant (MDR) and non-MDR P aeruginosa. Methods: Prospective observational study of 2,023 consecutive adult patients with CAP with definitive etiology. Results: P aeruginosa was found in 77 (4%) of the 2,023 cases with microbial etiology. In 22 (32%) of the 68 cases of P aeruginosa with antibiogram data, the isolates were MDR. Inappropriate therapy was present in 49 (64%) cases of P aeruginosa CAP, including 17/22 (77%) cases of MDR P aeruginosa CAP. Male sex, chronic respiratory disease, C-reactive protein <12.35 mg/dL, and pneumonia severity index risk class IV to V were independently associated with P aeruginosa CAP. Prior antibiotic treatment was more frequent in MDR P aeruginosa CAP compared with non-MDR P aeruginosa (58% vs 29%, P = .029), and was the only risk factor associated with CAP resulting from MDR P aeruginosa. In the multivariate analysis, age ≥65 years, CAP resulting from P aeruginosa, chronic liver disease, neurologic disease, nursing home, criteria of ARDS, acute renal failure, ICU admission, and inappropriate empiric treatment were the factors associated with 30-day mortality. Conclusions: P aeruginosa is an individual risk factor associated with mortality in CAP. The risk factors described can help clinicians to suspect P aeruginosa and MDR P aeruginosa

Machine-Learning Model for Mortality Prediction in Patients With Community-Acquired Pneumonia Development and Validation Study

Background: Artificial intelligence tools and techniques such as machine learning (ML) are increasingly seen as a suitable manner in which to increase the prediction capacity of currently available clinical tools, including prognostic scores. However, studies evaluating the efficacy of ML methods in enhancing the predictive capacity of existing scores for community-acquired pneumonia (CAP) are limited. We aimed to apply and validate a causal probabilistic network (CPN) model to predict mortality in patients with CAP. Research question: Is a CPN model able to predict mortality in patients with CAP better than the commonly used severity scores? Study design and methods: This was a derivation-validation retrospective study conducted in two Spanish university hospitals. The ability of a CPN designed to predict mortality in sepsis (SepsisFinder [SeF]), and adapted for CAP (SeF-ML), to predict 30-day mortality was assessed and compared with other scoring systems (Pneumonia Severity Index [PSI], Sequential Organ Failure Assessment [SOFA], quick Sequential Organ Failure Assessment [qSOFA], and CURB-65 criteria [confusion, urea, respiratory rate, BP, age ≥ 65 years]). The SeF models are proprietary software. Differences between receiver operating characteristic curves were assessed by the DeLong method for correlated receiver operating characteristic curves. Results: The derivation cohort comprised 4,531 patients, and the validation cohort consisted of 1,034 patients. In the derivation cohort, the areas under the curve (AUCs) of SeF-ML, CURB-65, SOFA, PSI, and qSOFA were 0.801, 0.759, 0.671, 0.799, and 0.642, respectively, for 30-day mortality prediction. In the validation study, the AUC of SeF-ML was 0.826, concordant with the AUC (0.801) in the derivation data (P = .51). The AUC of SeF-ML was significantly higher than those of CURB-65 (0.764; P = .03) and qSOFA (0.729, P = .005). However, it did not differ significantly from those of PSI (0.830; P = .92) and SOFA (0.771; P = .14). Interpretation: SeF-ML shows potential for improving mortality prediction among patients with CAP, using structured health data. Additional external validation studies should be conducted to support generalizability

Risk and Prognostic Factors in Very Old Patients with Sepsis Secondary to Community-Acquired Pneumonia

Little is known about risk and prognostic factors in very old patients developing sepsis secondary to community-acquired pneumonia (CAP). Methods: We conducted a retrospective observational study of data prospectively collected at the Hospital Clinic of Barcelona over a 13-year period. Consecutive patients hospitalized with CAP were included if they were very old (≥80 years) and divided into those with and without sepsis for comparison. Sepsis was diagnosed based on the Sepsis-3 criteria. The main clinical outcome was 30-day mortality. Results: Among the 4219 patients hospitalized with CAP during the study period, 1238 (29%) were very old. The prevalence of sepsis in this age group was 71%. Male sex, chronic renal disease, and diabetes mellitus were independent risk factors for sepsis, while antibiotic therapy before admission was independently associated with a lower risk of sepsis. Thirty-day and intensive care unit (ICU) mortality did not differ between patients with and without sepsis. In CAP-sepsis group, chronic renal disease and neurological disease were independent risk factors for 30-day mortality. Conclusion: In very old patients hospitalized with CAP, in-hospital and 1-year mortality rates were increased if they developed sepsis. Antibiotic therapy before hospital admission was associated with a lower risk of sepsis

Assessment of in vivo versus in vitro biofilm formation of clinical methicillin-resistant Staphylococcus aureus isolates from endotracheal tubes

Our aim was to demonstrate that biofilm formation in a clinical strain of methicillin-resistant Staphylococcus aureus (MRSA) can be enhanced by environment exposure in an endotracheal tube (ETT) and to determine how it is affected by systemic treatment and atmospheric conditions. Second, we aimed to assess biofilm production dynamics after extubation. We prospectively analyzed 70 ETT samples obtained from pigs randomized to be untreated (controls, n = 20), or treated with vancomycin (n = 32) or linezolid (n = 18). A clinical MRSA strain (MRSA-in) was inoculated in pigs to create a pneumonia model, before treating with antibiotics. Tracheally intubated pigs with MRSA severe pneumonia, were mechanically ventilated for 69 ± 16 hours. All MRSA isolates retrieved from ETTs (ETT-MRSA) were tested for their in vitro biofilm production by microtiter plate assay. In vitro biofilm production of MRSA isolates was sequentially studied over the next 8 days post-extubation to assess biofilm capability dynamics over time. All experiments were performed under ambient air (O2) or ambient air supplemented with 5% CO2. We collected 52 ETT-MRSA isolates (placebo N = 19, linezolid N = 11, and vancomycin N = 22) that were clonally identical to the MRSA-in. Among the ETT-MRSA isolates, biofilm production more than doubled after extubation in 40% and 50% under 5% CO2 and O2, respectively. Systemic antibiotic treatment during intubation did not affect this outcome. Under both atmospheric conditions, biofilm production for MRSA-in was at least doubled for 9 ETT-MRSA isolates, and assessment of these showed that biofilm production decreased progressively over a 4-day period after extubation. In conclusion, a weak biofilm producer MRSA strain significantly enhances its biofilm production within an ETT, but it is influenced by the ETT environment rather than by the systemic treatment used during intubation or by the atmospheric conditions used for bacterial growth

Effect of combined β-Lactam/Macrolide therapy on mortality according to the microbial etiology and inflammatory status of patients with community-acquired pneumonia

Antibiotic combinations that include macrolides have shown lower mortality rates than β-lactams in monotherapy or combined with fluoroquinolones in patients with community-acquired pneumonia (CAP). However, this effect has not been studied according to the levels of C-reactive protein in CAP with identified microbial cause. In patients with CAP and known microbial cause we aimed to evaluate 30-day mortality of a β-lactam plus macrolide (BL + M) compared with a fluoroquinolone alone or with a β-lactam (FQ ± BL). METHODS: We analyzed a prospective observational cohort of patients with CAP admitted to the Hospital Clinic of Barcelona between 1996 and 2016. We included only patients with known microbial cause. RESULTS: Of 1,715 patients (29%) with known etiology, a total of 932 patients (54%) received BL + M. Despite lower crude mortality in the BL + M group in the overall population (BL + M, 5% vs FQ ± BL, 8%; P = .015), after adjustment by a propensity score and baseline characteristics, the combination of BL + M had a protective effect on mortality only in patients with high inflammatory response (C-reactive protein, > 15 mg/dL) and pneumococcal CAP (adjusted OR, 0.28; 95% CI, 0.09-0.93). No benefits on mortality were observed for the population without high inflammatory response and pneumococcal CAP or with other etiologies. CONCLUSIONS: The combination of a β-lactam with a macrolide was associated with decreased mortality in patients with pneumococcal CAP and in patients with high systemic inflammatory response. When both factors occurred together, BL + M was protective for mortality in the multivariate analysis

SARS-CoV-2-induced Acute Respiratory Distress Syndrome: Pulmonary Mechanics and Gas-Exchange Abnormalities

In January 2020, the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were reported in Europe. Multiple outbreaks have since then led to a global pandemic, as well as to massive medical, economic, and social repercussions. SARS-CoV-2 pneumonia can develop into acute respiratory distress syndrome (ARDS) when mechanical ventilation (MV) is needed (3, 4). ARDS produces abnormalities in gas exchange with a variable degree of shunt (5), high dead space ventilation (dead space volume [Vd]/tidal volume [Vt] ratio) (6), diminished pulmonary compliance (7), and alterations to the pulmonary circulation (8). The cornerstone of ARDS management is to provide adequate gas exchange without further lung injury as a result of MV. To date, information regarding the characteristics of SARS-CoV-2-induced ARDS is not completely known. However, this information is crucial to better apply MV and facilitate organ support strategies. We therefore present the characteristics of gas exchange, pulmonary mechanics, and ventilatory management of 50 patients with laboratory-confirmed SARS-CoV-2 infection, who developed ARDS and underwent invasive MV (IMV). Methods: Descriptive analysis included 50 consecutive patients with laboratory-confirmed SARS-CoV-2 infection who developed ARDS (9) and underwent IMV. These patients were admitted to the SARS-CoV-2-dedicated intensive care units (ICUs) at Hospital Clinic of Barcelona, Spain, between March 7 and March 25, 2020. Upon ICU admission, epidemiological characteristics, the severity of SARS-CoV-2 infection with the Acute Physiology and Chronic Health Evaluation II score, prognostic biomarkers of SARS-CoV-2 infection (described in Reference 4), time from hospital to ICU admission, time from ICU admission to intubation, oxygen therapy or noninvasive ventilation (NIV) use, and microbiology were investigated. On the day that criteria for ARDS diagnosis were met (9) and IMV was needed, the following assessments were performed: impairment in oxygenation was analyzed with the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, and abnormalities of CO2 metabolism were studied with the ventilatory ratio (VR), a surrogate parameter of Vd/Vt. In addition, adjunctive therapies and MV parameters related with ventilation-induced lung injury (VILI) described elsewhere (11-15) were investigated. Correlations of SARS-CoV-2 prognostic biomarkers (4), pulmonary mechanics, and gas-exchange data were performed. Twenty-eight-day and hospital mortality, ventilator- and ICU-free days at Day 28, hospital and ICU lengths of stay, and need for tracheostomy were also evaluated (16). Finally, a subanalysis assessing differences before and after prone positioning was performed. For additional detail on the method, see the online supplement. Results: By March 25th, 2020, 50 patients with laboratory-confirmed SARS-CoV-2 infection and ARDS had been admitted to our hospital. Table 1 shows the demographic and clinical characteristics of these patients. The median (interquartile range [IQR]) age was 66 (57-74) years. Thirty-six patients (72%) were men. Upon ARDS diagnosis, 44% of patients were initially classified as having moderate ARDS, whereas 24% were classified as having mild ARDS and 32% were classified as having severe ARDS. The outcomes of these patients are shown in Table 1. ICU and hospital lengths of stay were prolonged, and tracheostomy was performed in 30 (60%) patients. Hospital mortality was 34%

Clinical consensus recommendations regarding non-invasive respiratory support in the adult patient with acute respiratory failure secondary to SARS-CoV-2 infection

La enfermedad por coronavirus 2019 (COVID-19) es una infección del tracto respiratorio causada por un nuevo coronavirus emergente que se reconoció por primera vez en Wuhan, China, en diciembre de 2019. Actualmente la Organización Mundial de la Salud (OMS) ha definido la infección como pandemia y existe una situación de emergencia sanitaria y social para el manejo de esta nueva infección. Mientras que la mayoría de las personas con COVID-19 desarrollan solo una enfermedad leve o no complicada, aproximadamente el 14% desarrollan una enfermedad grave que requiere hospitalización y oxígeno, y el 5% pueden requerir ingreso en una unidad de cuidados intensivos. En casos severos, COVID-19 puede complicarse por el síndrome de dificultad respiratoria aguda (SDRA), sepsis y shock séptico y fracaso multiorgánico. Este documento de consenso se ha preparado sobre directrices basadas en evidencia desarrolladas por un panel multidisciplinario de profesionales médicos de cuatro sociedades científicas españolas (Sociedad Española de Medicina Intensiva y Unidades Coronarias [SEMICYUC], Sociedad Española de Neumología y Cirugía Torácica [SEPAR], Sociedad Española de Urgencias y Emergencias [SEMES], Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor [SEDAR]) con experiencia en el manejo clínico de pacientes con COVID-19 y otras infecciones virales, incluido el SARS, así como en sepsis y SDRA. El documento proporciona recomendaciones clínicas para el soporte respiratorio no invasivo (ventilación no invasiva, oxigenoterapia de alto flujo con cánula nasal) en cualquier paciente con presentación sospechada o confirmada de COVID-19 con insuficiencia respiratoria aguda. Esta guía de consenso debe servir como base para una atención optimizada y garantizar la mejor posibilidad de supervivencia, así como permitir una comparación fiable de las futuras intervenciones terapéuticas de investigación que formen parte de futuros estudios observacionales o de ensayos clínicos.Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials

Polymicrobial intensive care unit-acquired pneumonia: prevalence, microbiology and outcome

Background Microbial aetiology of intensive care unit (ICU)-acquired pneumonia (ICUAP) determines antibiotic treatment and outcomes. The impact of polymicrobial ICUAP is not extensively known. We therefore investigated the characteristics and outcomes of polymicrobial aetiology of ICUAP. Method Patients with ICUAP confirmed microbiologically were prospectively compared according to identification of 1 (monomicrobial) or more (polymicrobial) potentially-pathogenic microorganisms. Microbes usually considered as non-pathogenic were not considered for the etiologic diagnosis. We assessed clinical characteristics, microbiology, inflammatory biomarkers and outcome variables. Results Among 441 consecutive patients with ICUAP, 256 (58 %) had microbiologic confirmation, and 41 (16 %) of them polymicrobial pneumonia. Methicillin-sensitive Staphylococcus aureus, Haemophilus influenzae, and several Enterobacteriaceae were more frequent in polymicrobial pneumonia. Multi-drug and extensive-drug resistance was similarly frequent in both groups. Compared with monomicrobial, patients with polymicrobial pneumonia had less frequently chronic heart disease (6, 15 % vs. 71, 33 %, p = 0.019), and more frequently pleural effusion (18, 50 %, vs. 54, 25 %, p = 0.008), without any other significant difference. Appropriate empiric antimicrobial treatment was similarly frequent in the monomicrobial (185, 86 %) and the polymicrobial group (39, 95 %), as were the initial response to the empiric treatment, length of stay and mortality. Systemic inflammatory response was similar comparing monomicrobial with polymicrobial ICUAP. Conclusion The aetiology of ICUAP confirmed microbiologically was polymicrobial in 16 % cases. Pleural effusion and absence of chronic heart disease are associated with polymicrobial pneumonia. When empiric treatment is frequently appropriate, polymicrobial aetiology does not influence the outcome of ICUAP