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Adamantia Liapikou,1 Catia Cillóniz,2 Antonio Torres216th Respiratory Department, Sotiria Chest Diseases Hospital, Athens, Greece; 2Pulmonology Department, Clinic Institute of Thorax (ICT), Hospital Clinic of Barcelona, Spain Insitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, SpainAbstract: Ceftobiprole, a new broad spectrum, parenteral cephalosporin, exhibits potent in vitro activity against a number of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae, and Gram-negative pathogens associated with hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP). Ceftobiprole has demonstrated noninferiority in two large-scale pivotal studies comparing it to ceftriaxone with or without linezolid in CAP, with clinical cure rates 86.6% versus 87.4%, or ceftazidime in HAP, with clinical cure rates of 77% versus 76%, respectively. However, ceftobiprole was inferior in the subgroup of patients undergoing mechanical ventilation. Ceftobiprole has so far demonstrated a good safety profile in preliminary studies, with similar tolerability to comparators. The most commonly observed adverse events of ceftobiprole included headache and gastrointestinal upset. It is the first cephalosporin monotherapy approved in the EU for the treatment of both CAP and HAP (excluding ventilator-associated pneumonia).Keywords: antibiotic resistance, methicillin-resistant staphylococci, community-acquired pneumonia, hospital-acquired pneumonia, cephalosporins

Background: The inflammatory response in community-acquired pneumonia (CAP) depends on the host and on the challenge of the causal microorganism. Here, we analyze the patterns of inflammatory cytokines, procalcitonin (PCT), and C-reactive protein (CRP) in order to determine their diagnostic value.Methods: This was a prospective study of 658 patients admitted with CAP. PCT and CRP were analyzed by immunoluminometric and immunoturbidimetric assays. Cytokines (tumor necrosis factor-α [TNF-α], IL-1β, IL-6, IL-8, and IL-10) were measured using enzyme immunoassay.Results: The lowest medians of CRP, PCT, TNF-α, and IL-6 were found in CAP of unknown cause, and the highest were found in patients with positive blood cultures. Different cytokine profiles and biomarkers were found depending on cause: atypical bacteria (lower PCT and IL-6), viruses (lower PCT and higher IL-10), Enterobacteriaceae (higher IL-8), Streptococcus pneumoniae (high PCT), and Legionella pneumophila (higher CRP and TNF-α). PCT ≥ 0.36 mg/dL to predict positive blood cultures showed sensitivity of 85%, specificity of 42%, and negative predictive value (NPV) of 98%, whereas a cutoff of ≤ 0.5 mg/dL to predict viruses or atypicals vs bacteria showed sensitivity of 89%/81%, specificity of 68%/68%, positive predictive value of 12%/22%, and NPV of 99%/97%. In a multivariate Euclidean distance model, the lowest inflammatory expression was found in unknown cause and the highest was found in L pneumophila, S pneumoniae, and Enterobacteriaceae. Atypical bacteria exhibit an inflammatory pattern closer to that of viruses.Conclusions: Different inflammatory patterns elicited by different microorganisms may provide a useful tool for diagnosis. Recognizing these patterns provides additional information that may facilitate a broader understanding of host inflammatory response to microorganisms. [ABSTRACT FROM AUTHOR]

Introduction: The frequency and clinical significance of polymicrobial aetiology in community-acquired pneumonia (CAP) patients admitted to the ICU have been poorly studied. The aim of the present study was to describe the prevalence, clinical characteristics and outcomes of severe CAP of polymicrobial aetiology in patients admitted to the ICU.Methods: The prospective observational study included 362 consecutive adult patients with CAP admitted to the ICU within 24 hours of presentation; 196 (54%) patients had an established aetiology.Results: Polymicrobial infection was present in 39 (11%) cases (20% of those with defined aetiology): 33 cases with two pathogens, and six cases with three pathogens. The most frequently identified pathogens in polymicrobial infections were Streptococcus pneumoniae (n = 28, 72%), respiratory viruses (n = 15, 39%) and Pseudomonas aeruginosa (n = 8, 21%). Chronic respiratory disease and acute respiratory distress syndrome criteria were independent predictors of polymicrobial aetiology. Inappropriate initial antimicrobial treatment was more frequent in the polymicrobial aetiology group compared with the monomicrobial aetiology group (39% vs. 10%, P < 0.001), and was an independent predictor of hospital mortality (adjusted odds ratio = 10.79, 95% confidence interval = 3.97 to 29.30; P < 0.001). The trend for higher hospital mortality of the polymicrobial aetiology group compared with the monomicrobial aetiology group (n = 8, 21% versus n = 17, 11%), however, was not significantly different (P = 0.10).Conclusions: Polymicrobial pneumonia occurs frequently in patients admitted to the ICU. This is a risk factor for inappropriate initial antimicrobial treatment, which in turn independently predicts hospital mortality. [ABSTRACT FROM AUTHOR]

Improved phenotyping in pneumonia is necessary to strengthen risk assessment. Via a feasible and multidimensional approach with basic parameters, we aimed to evaluate the effect of host response at admission on severity stratification in COVID-19 and community-acquired pneumonia (CAP). Three COVID-19 and one CAP multicenter cohorts including hospitalized patients were recruited. Three easily available variables reflecting different pathophysiologic mechanisms-immune, inflammation, and respiratory-were selected (absolute lymphocyte count [ALC], C-reactive protein [CRP] and, SpO 2 /FiO 2 ). In-hospital mortality and intensive care unit (ICU) admission were analyzed as outcomes. A multivariable, penalized maximum likelihood logistic regression was performed with ALC (< 724 lymphocytes/mm 3 ), CRP (> 60 mg/L), and, SpO 2 /FiO 2 (< 450). A total of 1452, 1222 and 462 patients were included in the three COVID-19 and 1292 in the CAP cohort for the analysis. Mortality ranged between 4 and 32% (0 to 3 abnormal biomarkers) and 0-9% in SARS-CoV-2 pneumonia and CAP, respectively. In the first COVID-19 cohort, adjusted for age and sex, we observed an increased odds ratio for in-hospital mortality in COVID-19 with elevated biomarkers altered (OR 1.8, 3, and 6.3 with 1, 2, and 3 abnormal biomarkers, respectively). The model had an AUROC of 0.83. Comparable findings were found for ICU admission, with an AUROC of 0.76. These results were confirmed in the other COVID-19 cohorts Similar OR trends were reported in the CAP cohort; however, results were not statistically significant. Assessing the host response via accessible biomarkers is a simple and rapidly applicable approach for pneumonia., (© 2024. The Author(s).)

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 β-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 β-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., Competing Interests: Conflict of interest: A. Torres has no conflicts of interest related to the current article. A. Kuraieva is an employee of Pfizer. G.G. Stone is an employee of Pfizer. C. Cillóniz has no conflicts of interest related to the current article., (Copyright ©The authors 2023.)

Introduction: There are no data on the association of type of pneumonia and long-term mortality by the type of pneumonia (COVID-19 or community-acquired pneumonia [CAP]) on long-term mortality after an adjustment for potential confounding variables. We aimed to assess the type of pneumonia and risk factors for long-term mortality in patients who were hospitalized in conventional ward and later discharged., Methods: Retrospective analysis of two prospective and multicentre cohorts of hospitalized patients with COVID-19 and CAP. The main outcome under study was 1-year mortality in hospitalized patients in conventional ward and later discharged. We adjusted a Bayesian logistic regression model to assess associations between the type of pneumonia and 1-year mortality controlling for confounders., Results: The study included a total of 1,693 and 2,374 discharged patients in the COVID-19 and CAP cohorts, respectively. Of these, 1,525 (90.1%) and 2,249 (95%) patients underwent analysis. Until 1-year follow-up, 69 (4.5%) and 148 (6.6%) patients from the COVID-19 and CAP cohorts, respectively, died ( p  = 0.008). However, the Bayesian model showed a low probability of effect (PE) of finding relevant differences in long-term mortality between CAP and COVID-19 (odds ratio 1.127, 95% credibility interval 0.862-1.591; PE = 0.774)., Conclusion: COVID-19 and CAP have similar long-term mortality after adjusting for potential confounders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Méndez, González-Jiménez, Latorre, Mengot, Zalacain, Ruiz, Serrano, España, Uranga, Cillóniz, Hervás, Torres, Menéndez, NEUMONAC and RECOVID.)

Background: A shortage of beds in ICUs and conventional wards during the COVID-19 pandemic led to a collapse of health care resources., Research Question: Can admission data and minor criteria by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) help identify patients with low-risk SARS-CoV-2 pneumonia?, Study Design and Methods: This multicenter cohort study included 1,274 patients in a derivation cohort and 830 (first wave) and 754 (second wave) patients in two validation cohorts. A multinomial regression analysis was performed on the derivation cohort to compare the following patients: those admitted to the ward (assessed as low risk); those admitted to the ICU directly; those transferred to the ICU after general ward admission; and those who died. A regression analysis identified independent factors for low-risk pneumonia. The model was subsequently validated., Results: In the derivation cohort, similarities existed among those either directly admitted or transferred to the ICU and those who died. These patients could, therefore, be merged into one group. Five independently associated factors were identified as being predictors of low risk (not dying and/or requiring ICU admission) (ORs, with 95% CIs): peripheral blood oxygen saturation/Fio 2 > 450 (0.233; 0.149-0.364); < 3 IDSA/ATS minor criteria (0.231; 0.146-0.365); lymphocyte count > 723 cells/mL (0.539; 0.360-0.806); urea level < 40 mg/dL (0.651; 0.426-0.996); and C-reactive protein level < 60 mg/L (0.454; 0.285-0.724). The areas under the curve were 0.802 (0.769-0.835) in the derivation cohort, and 0.779 (0.742-0.816) and 0.801 (0.757-0.845) for the validation cohorts (first and second waves, respectively)., Interpretation: Initial biochemical findings and the application of < 3 IDSA/ATS minor criteria make early identification of low-risk SARS-CoV-2 pneumonia (approximately 80% of hospitalized patients) feasible. This scenario could facilitate and streamline health care resource allocation for patients with COVID-19., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: Although there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19., Methods: Multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs. The primary outcome was 90-day mortality. Subsequent analyses in clinically relevant subgroups by age, ICU baseline illness severity, organ damage, laboratory findings and mechanical ventilation were performed. High doses of corticosteroids (≥ 12 mg/day equivalent dexamethasone dose), early administration of corticosteroid treatment (< 7 days since symptom onset) and long term of corticosteroids (≥ 10 days) were also investigated., Results: Between February 2020 and October 2021, 4226 patients were included. Of these, 3592 (85%) patients had received systemic corticosteroids during hospitalisation. In the propensity-adjusted multivariable analysis, the use of corticosteroids was protective for 90-day mortality in the overall population (HR 0.77 [0.65-0.92], p = 0.003) and in-hospital mortality (SHR 0.70 [0.58-0.84], p < 0.001). Significant effect modification was found after adjustment for covariates using propensity score for age (p = 0.001 interaction term), Sequential Organ Failure Assessment (SOFA) score (p = 0.014 interaction term), and mechanical ventilation (p = 0.001 interaction term). We observed a beneficial effect of corticosteroids on 90-day mortality in various patient subgroups, including those patients aged ≥ 60 years; those with higher baseline severity; and those receiving invasive mechanical ventilation at ICU admission. Early administration was associated with a higher risk of 90-day mortality in the overall population (HR 1.32 [1.14-1.53], p < 0.001). Long-term use was associated with a lower risk of 90-day mortality in the overall population (HR 0.71 [0.61-0.82], p < 0.001). No effect was found regarding the dosage of corticosteroids. Moreover, the use of corticosteroids was associated with an increased risk of nosocomial bacterial pneumonia and hyperglycaemia., Conclusion: Corticosteroid in ICU-admitted patients with COVID-19 may be administered based on age, severity, baseline inflammation, and invasive mechanical ventilation. Early administration since symptom onset may prove harmful., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Ventilator-associated pneumonia (VAP) is a leading infectious cause of morbidity in critically ill patients, yet current guidelines offer no indications for follow-up cultures. We aimed to evaluate the role of follow-up cultures and microbiological response 3 days after diagnosing VAP as predictors of short- and long-term outcomes., Methods: We performed a retrospective analysis of a cohort prospectively collected from 2004 to 2017. VAP was diagnosed based on clinical, radiographical and microbiological criteria. For microbiological identification, a tracheobronchial aspirate was performed at diagnosis and repeated after 72 h. We defined three groups when comparing the two tracheobronchial aspirate results: persistence, superinfection and eradication of causative pathogens., Results: 157 patients were enrolled in the study, among whom microbiological persistence, superinfection or eradication was present in 67 (48%), 25 (16%) and 65 (41%), respectively, after 72 h. Those with superinfection had the highest mortalities in the intensive care unit (p=0.015) and at 90 days (p=0.036), while also having the fewest ventilator-free days (p=0.019). Multivariable analysis revealed shock at VAP diagnosis (OR 3.43, 95% CI 1.25-9.40), Staphylococcus aureus isolation at VAP diagnosis (OR 2.87, 95% CI 1.06-7.75) and hypothermia at VAP diagnosis (OR 0.67, 95% CI 0.48-0.95, per +1°C) to be associated with superinfection., Conclusions: Our retrospective analysis suggests that VAP short- and long-term outcomes may be associated with superinfection in follow-up cultures. Follow-up cultures may help guide antibiotic therapy and its duration. Further prospective studies are necessary to verify our findings., Competing Interests: Conflict of interest: A. Ceccato has nothing to disclose. Conflict of interest: C. Dominedò has nothing to disclose. Conflict of interest: M. Ferrer has nothing to disclose. Conflict of interest: I. Martin-Loeches has nothing to disclose. Conflict of interest: E. Barbeta has nothing to disclose. Conflict of interest: A Gabarrús has nothing to disclose. Conflict of interest: C. Cilloniz has nothing to disclose. Conflict of interest: O. Ranzani has nothing to disclose. Conflict of interest: G. De Pascale has nothing to disclose. Conflict of interest: S. Nogas has nothing to disclose. Conflict of interest: P. Di Giannatale has nothing to disclose. Conflict of interest: M. Antonelli has nothing to disclose. Conflict of interest: A. Torres has nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Severe viral infections may result in severe illnesses capable of causing acute respiratory failure that could progress rapidly to acute respiratory distress syndrome (ARDS), related to worse outcomes, especially in individuals with a higher risk of infection, including the elderly and those with comorbidities such as asthma, diabetes mellitus and chronic respiratory or cardiovascular disease. In addition, in cases of severe viral pneumonia, co-infection with bacteria such as Streptococcus pneumoniae and Staphylococcus aureus is related to worse outcomes. Respiratory viruses like influenza, rhinovirus, parainfluenza, adenovirus, metapneumovirus, respiratory syncytial virus, and coronavirus have increasingly been detected. This trend has become more prevalent, especially in critically ill patients, due to the availability and implementation of molecular assays in clinical practice. Respiratory viruses have been diagnosed as a frequent cause of severe pneumonia, including cases of community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia. In this review, we will discuss the epidemiology, diagnosis, clinical characteristics, management, and prognosis of patients with severe infections due to respiratory viruses, with a focus on influenza viruses, non-influenza viruses, and coronaviruses., Competing Interests: None declared., (Thieme. All rights reserved.)

Severe pneumonia is associated with high mortality (short and long term), as well as pulmonary and extrapulmonary complications. Appropriate diagnosis and early initiation of adequate antimicrobial treatment for severe pneumonia are crucial in improving survival among critically ill patients. Identifying the underlying causative pathogen is also critical for antimicrobial stewardship. However, establishing an etiological diagnosis is challenging in most patients, especially in those with chronic underlying disease; those who received previous antibiotic treatment; and those treated with mechanical ventilation. Furthermore, as antimicrobial therapy must be empiric, national and international guidelines recommend initial antimicrobial treatment according to the location's epidemiology; for patients admitted to the intensive care unit, specific recommendations on disease management are available. Adherence to pneumonia guidelines is associated with better outcomes in severe pneumonia. Yet, the continuing and necessary research on severe pneumonia is expansive, inviting different perspectives on host immunological responses, assessment of illness severity, microbial causes, risk factors for multidrug resistant pathogens, diagnostic tests, and therapeutic options., Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: AT has participated in advisory boards for Pfizer. MN has participated in advisory boards for Pfizer, Merck, Bayer, Gilead, and Abbvie., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Rationale: In 2017, the International European Respiratory Society/European Society of Intensive Care Medicine/European Society of Clinical Microbiology and Infectious Diseases/Latin American Thoracic Society (European) guidelines defined new risk factors for multidrug-resistant (MDR) pathogens in patients with nosocomial pneumonia. Objectives: To assess the predictive performance of these newly defined risk factors for MDR pathogens. Methods: We enrolled 507 adult patients with nosocomial pneumonia who were treated in six intensive care units at the Hospital Clinic of Barcelona in Spain. Of the 503 patients at high MDR pathogen and mortality risk, 275 (54%) had no septic shock and 228 (46%) had septic shock. Results: Admission to hospital settings with high rates of MDR pathogens ( n  = 421; 83%) and prior antibiotic use ( n  = 399; 79%) showed the highest prevalence in the overall population, with sensitivities of 92% and 85% and negative predictive values of 85% and 82%, respectively. However, low specificities and low positive predictive values were found. Previous respiratory MDR pathogen isolation was less common ( n  = 17; 3%) but presented a specificity and positive predictive value of 100%. The area under the receiver operating characteristic curve was less than 0.6 for all risk factors and combinations. Conclusions: The risk factors proposed by the European Respiratory Society/European Society of Intensive Care Medicine/European Society of Clinical Microbiology and Infectious Diseases/Latin American Thoracic Society showed low accuracy for predicting MDR pathogens in intensive care unit acquired pneumonia (ICU-AP). Admission to hospital settings with high rates of MDR pathogens and prior antibiotic use were the most prevalent risk factors, with a high sensitivity for predicting these microorganisms; prior positive cultures for MDR pathogens showed high specificity but very low sensitivity. Combinations of risk factors did not show any great accuracy for predicting these microorganisms. Further studies assessing combined strategies of risk stratification and complementary methods are now warranted.

The systemic inflammatory response (SIR) may help to predict clinical progression, treatment failure, and prognosis in community-acquired pneumonia (CAP). Exposure to tobacco smoke may affect the SIR; the role of smoking in CAP has not been consolidated. We evaluated the SIR and outcomes of hospitalized CAP patients stratified by smoking habits and the presence of COPD. This retrospective analysis was conducted at the Hospital Clinic of Barcelona. Baseline, clinical, microbiological, and laboratory variables were collected at admission, using C-reactive protein (CRP) levels as a marker of SIR. The study outcomes were pleural complications, hospital stay, non-invasive and invasive mechanical ventilation (IMV), and intensive care unit (ICU) admission. We also considered the in-hospital and 30-day mortality. Data were grouped by smoking habit (non-, former-, and current-smokers) and the presence of COPD. Current smokers were younger, had fewer comorbidities, and fewer previous pneumonia episodes. CRP levels were higher in current smokers than in other groups. Current smokers had a higher risk of pleural complications independent of CRP levels, the presence of pleuritic pain, and a higher platelet count. Current smokers more often required IMV and ICU admission. Current smokers have a greater inflammatory response and are at increased risk of pleural complications.

Q fever is a zoonotic infectious disease caused by the Coxiella burnetii bacterium. It is an obligate intracellular pathogen with a high infection capacity that proliferates exclusively in an acidified medium, forming a lysosome-like vacuole. It presents a peculiar phenomenon called "antigenic phase variation," produced by a modification in the complexity of the membrane lipopolysaccharides. Q fever can be found worldwide and presents variable clinical features and geographical distribution. It mostly affects people in rural areas who are in contact with animals. The most common type of transmission to humans is via the inhalation of aerosols containing the pathogen, especially those formed from placental derivatives. Wild animals, domestic animals, and ticks are the principal reservoirs.Diagnosis is mainly made by indirect methods such as serology or by direct methods such as microbiological cultures or tests that detect the specific DNA. Typically, there are two clinical presentations: the acute disease, which is more frequent and often asymptomatic, and a persistent focalized infection in 4 to 5% of patients, generally with a poor evolution. Treatment of the acute form in both children and adults consists of administering doxycycline, while persistent focalized infection should be treated with at least two antibiotics, such as doxycycline and hydroxychloroquine. Several measures should be undertaken to minimize exposure among people working with animals or handling birth products. Different vaccines have been developed to prevent infection, though few data are available., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Pneumonia is a serious health concern, but it does not attract the attention it warrants. Perhaps this is due to a lack of understanding of the real extent of this infectious disease in the general population., Methods: A literature review was performed to assess the role of social networks as a means to raise awareness over pneumonia worldwide and increase its visibility., Results: In 2017, approximately 800,000 children under 5 years and approximately one million older people died of pneumonia. The importance of this pathology remains underestimated, despite the publication of many articles, comments, and editorials dedicated to rectifying the imbalance and to reduce its impact and associated mortality. Current misperceptions about pneumonia are alarming. Education and awareness are essential in the fight against this major public health threat; in this endeavor, social networks can be used to distribute science-based information about the disease and thus raise awareness among the general public about the dangers it poses. Approximately 3.8 billion people were using social media at the beginning of 2020, representing more than half of the world's population., Conclusion: Social networks offer a valuable tool for disseminating scientific information about pneumonia, increasing its visibility, and in general raising awareness about this preventable disease., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Introduction: Community-acquired pneumonia (CAP) is the most common type of lower respiratory tract infection and a major cause of morbidity and mortality in adults worldwide. Sex and gender play an active role in the incidence and outcomes of major infectious diseases, including CAP., Evidence Acquisition: We searched the following electronic databases from January 2001 to December 2018: MEDLINE, EMBASE, CINHAIL, CENTRAL (Cochrane Central register of Controlled Trials), DARE (Database of Abstracts of Reviews of Effectiveness), Cochrane Database of Systematic Reviews and ACP Journal Club database., Evidence Synthesis: Several studies have reported higher male susceptibility to pulmonary infections and higher risk of death due to sepsis. Biological differences (e.g. hormonal cycles and cellular immune-mediated responses) together with cultural, behavioral and socio-economic differences are important determinants of the course and outcome of CAP. However, gender-related bias in the provision of care and use of hospital resources has been reported among women, resulting in delayed hospital admission and consequently necessary care., Conclusions: CAP is more severe in males than in females, leading to higher mortality in males, especially in older age. To identify gender differences in CAP can guide patient's prognostication and management.

Very old (aged ≥80 years) adults constitute an increasing proportion of the global population. Currently, this subgroup of patients represents an important percentage of patients admitted to the intensive care unit. Community-acquired pneumonia (CAP) frequently affects very old adults. However, there are no specific recommendations for the management of critically ill very old CAP patients. Multiple morbidities, polypharmacy, immunosenescence and frailty contribute to an increased risk of pneumonia in this population. CAP in critically ill very old patients is associated with higher short- and long-term mortality; however, because of its uncommon presentation, diagnosis can be very difficult. Management of critically ill very old CAP patients should be guided by their baseline characteristics, clinical presentation and risk factors for multidrug-resistant pathogens. Hospitalisation in intermediate care may be a good option for critical ill very old CAP patients who do not require invasive procedures and for whom intensive care is questionable in terms of benefit., Competing Interests: Conflict of interest: C. Cillóniz has nothing to disclose. Conflict of interest: C. Dominedò has nothing to disclose. Conflict of interest: J.M. Pericàs has nothing to disclose. Conflict of interest: D. Rodriguez-Hurtado has nothing to disclose. Conflict of interest: A. Torres has nothing to disclose., (Copyright ©ERS 2020.)

Despite advances in its prevention, pneumonia remains associated with high morbidity, mortality, and health costs worldwide. Studies carried out in the last decade have indicated that more patients with community-acquired pneumonia (CAP) now require hospitalization. In addition, pneumonia management poses many challenges, especially due to the increase in the number of elderly patients with multiple comorbidities, antibiotic-resistant pathogens, and the difficulty of rapid diagnosis. In this new call to action, we present a wide-ranging review of the information currently available on CAP and offer some reflections on ways to raise awareness of this disease among the general public. We discuss the burden of CAP and the importance of attaining better, faster microbiological diagnosis and initiating appropriate treatment. We also suggest that closer cooperation between health professionals and the population at large could improve the management of this largely preventable infectious disease that takes many lives each year., Competing Interests: The authors declare that they have no competing interests.

The use of artificial intelligence (AI) to support clinical medical decisions is a rather promising concept. There are two important factors that have driven these advances: the availability of data from electronic health records (EHR) and progress made in computational performance. These two concepts are interrelated with respect to complex mathematical functions such as machine learning (ML) or neural networks (NN). Indeed, some published articles have already demonstrated the potential of these approaches in medicine. When considering the diagnosis and management of pneumonia, the use of AI and chest X-ray (CXR) images primarily have been indicative of early diagnosis, prompt antimicrobial therapy, and ultimately, better prognosis. Coupled with this is the growing research involving empirical therapy and mortality prediction, too. Maximizing the power of NN, the majority of studies have reported high accuracy rates in their predictions. As AI can handle large amounts of data and execute mathematical functions such as machine learning and neural networks, AI can be revolutionary in supporting the clinical decision-making processes. In this review, we describe and discuss the most relevant studies of AI in pneumonia.

Purpose of Review: Multidrug-resistant (MDR) Gram-negative pathogens in hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are associated with poor clinical outcomes. These pathogens represent a global threat with few therapeutic options. In this review, we discuss current guidelines for the empiric management of HAP/VAP caused by MDR Gram-negative pathogens., Recent Findings: The incidence of MDR Gram-negative bacteria is rising among cases of nosocomial pneumonia, such that it is now becoming a significant challenge for clinicians. Adherence to international guidelines may ensure early and adequate antimicrobial therapy, guided by local microbiological data and awareness of the risk factors for MDR bacteria., Summary: Due to the increasing prevalence of HAP/VAP caused by MDR Gram-negative pathogens, management should be guided by the local ecology and the patient's risk factors for MDR pathogens. The main risk factors are prior hospitalization for at least 5 days, prior use of broad-spectrum antibiotics, prior colonization with resistant pathogens, admission to hospital settings with high rates of MDR pathogens, and septic shock at the time of diagnosis with nosocomial pneumonia.

Introduction : Pneumocystis pneumonia (PcP) has classically been described as a serious complication in patients infected with the human immunodeficiency virus (HIV). However, the emerging number of conditions associated with immunosuppression has led to its appearance in other patient populations. Areas covered : This article reviews the most recent publications on PcP in the HIV-infected and HIV-uninfected population, focusing on epidemiology, diagnostic, therapy and prevention. The data discussed here were mainly obtained from a non-systematic review using Medline and references from relevant articles including randomized clinical trials, meta-analyses, observational studies and clinical reviews. Expert opinion : The growing incidence of Pneumocystis infection in the HIV-uninfected population suggests the need for new global epidemiological studies in order to identify the true scale of the disease in this population. These data would allow us to improve diagnosis, therapeutic strategies, and clinical management. It is very important that both patients and physicians realize that HIV-uninfected patients are at risk of PcP and that rapid diagnosis and early initiation of treatment are associated with better prognosis. Currently, in-hospital mortality rates are very high: 15% for HIV-infected patients and 50% in some HIV-uninfected patients. Therefore, adequate preventive measures should be implemented to avoid the high mortality rates seen in recent decades.

Ceftobiprole is a fifth-generation cephalosporin with potent antimicrobial activity against Gram positive and Gram-negative bacteria. It has been approved in major European countries for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), excluding ventilator-associated pneumonia (VAP). Ceftobiprole is currently in a phase 3 clinical program for registration in the U.S. In 2015, it was designated as an infectious disease product qualified for the treatment of lung and skin infections by the FDA. The efficacy of ceftobiprole in pneumonia has been demonstrated in two-phase III clinical trials conducted in patients with CAP and HAP. The recommended dose in the adult with pneumonia is 500 mg every 8 h infused in 2 h; in case of renal failure, the regimen of administration must be adjusted according to the patient's renal function. It is not necessary to adjust the dose according to gender, age, body weight or liver failure. In case of hyperfiltration, an extension to 4 h infusion of the 500mg TID is required.

We investigated the risk and prognostic factors of pure viral sepsis in adult patients with community-acquired pneumonia (CAP), using the Sepsis-3 definition. Pure viral sepsis was found in 3% of all patients (138 of 4028) admitted to the emergency department with a diagnosis of CAP, 19% of those with CAP (138 of 722) admitted to the intensive care unit, and 61% of those (138 of 225) with a diagnosis of viral CAP. Our data indicate that males and patients aged ≥65 years are at increased risk of viral sepsis., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: We aimed to analyze the impact of cefotaxime non-susceptibility on the 30-day mortality rate in patients receiving a third-generation cephalosporin for pneumococcal bacteremic pneumonia., Methods: We conducted a retrospective observational study of prospectively collected data from the Hospital Clinic of Barcelona. All adult patients with monomicrobial bacteremic pneumonia due to Streptococcus pneumoniae and treated with a third-generation cephalosporin from January 1991 to December 2016 were included. Risk factors associated with 30-day mortality were evaluated by univariate and multivariate analyses., Results: During the study period, 721 eligible episodes were identified, and data on the susceptibility to cefotaxime was obtainable for 690 episodes. Sixty six (10%) cases were due to a cefotaxime non-susceptible strain with a 30-day mortality rate of 8%. Variables associated with 30-day mortality were age, chronic liver disease, septic shock, and the McCabe score. Infection by a cefotaxime non-susceptible S. pneumoniae did not increase the mortality rate., Conclusion: Despite the prevalence of cefotaxime, non-susceptible S. pneumoniae has increased in recent years. We found no evidence to suggest that patients hospitalized with bacteremic pneumonia due to these strains had worse clinical outcomes than patients with susceptible strains.

Background: 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.

Introduction : Hospital-acquired pneumonia is a common and therapeutically challenging diagnosis that can lead to severe sepsis, critical illness, and respiratory failure. In this review, we focus on efforts to enhance microbiological diagnosis of hospital-acquired pneumonia, including ventilator-associated pneumonia. Areas covered : A systematic literature review was conducted by searching Medline from inception to December 2018, including hand-searching of the reference lists for additional studies. The search strategy comprised the following common search terms: hospital pneumonia OR nosocomial pneumonia OR noninvasive OR molecular diagnostic tests (OR point-of-care systems OR VOC [i.e. volatile organic compounds]) OR rapid (or simple or quick test), including brand names for the most common commercial tests. Expert opinion : In recent years, the microbiological diagnosis of respiratory pathogens has improved significantly by the development and implementation of molecular diagnostic tests for pneumonia. Real-time polymerase chain reaction, hybridization, and mass spectrometry-based platforms dominate the scene, with microarray-based assays, multiplex polymerase chain reaction, and MALDI-TOF mass spectrometry capable of detecting the determinants of antimicrobial resistance (mainly β-lactamase genes). Introducing these assays into routine clinical practice for rapid identification of the causative microbes and their resistance patterns could transform the care of pneumonia, improving antimicrobial selection, de-escalation, and stewardship.

Sepsis is a serious health condition worldwide, affecting more than 30 million people globally each year. Blood culture (BC) is generally used to diagnose sepsis because of the low quantity of microbes occurring in the blood during such infections. However, ~50% of bloodstream infections (BSI) give negative BC, this figure being higher for sepsis, which delays the start of appropriate antimicrobial therapy. This prospective study evaluated a multiplex real-time polymerase chain reaction, the Magicplex TM Sepsis test (MP), for the detection of pathogens from whole blood, comparing it to routine BC. We analyzed 809 blood samples from 636 adult patients, with 132/809 (16.3%) of the samples positive for one or more relevant microorganism according to BC and/or MP. The sensitivity and specificity of MP were 29 and 95%, respectively, while the level of agreement between BC and MP was 87%. The rate of contaminated samples was higher for BC (10%) than MP (4.8%) ( P < 0.001). Patients with only MP-positive samples were more likely to be on antimicrobial treatment (47%) than those with only BC-positive samples (18%) ( P = 0.002). In summary, the MP test could be useful in some clinical setting, such as among patients on antibiotic therapy. Nevertheless, a low sensitivity demonstrated impairs its use as a part of a routine diagnostic algorithm.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Worldwide, there is growing concern about the burden of pneumonia. Severe community-acquired pneumonia (CAP) is frequently complicated by pulmonary and extra-pulmonary complications, including sepsis, septic shock, acute respiratory distress syndrome, and acute cardiac events, resulting in significantly increased intensive care admission rates and mortality rates. Streptococcus pneumoniae (Pneumococcus) remains the most common causative pathogen in CAP. However, several bacteria and respiratory viruses are responsible, and approximately 6% of cases are due to the so-called PES ( Pseudomonas aeruginosa , extended-spectrum β-lactamase Enterobacteriaceae , and methicillin-resistant Staphylococcus aureus ) pathogens. Of these, P. aeruginosa and methicillin-resistant Staphylococcus aureus are the most frequently reported and require different antibiotic therapy to that for typical CAP. It is therefore important to recognize the risk factors for these pathogens to improve the outcomes in patients with CAP.

Purpose of Review: Despite the improvements in its management, community-acquired pneumonia (CAP) still exhibits high global morbidity and mortality rates, especially in elderly patients. This review focuses on the most recent findings on the epidemiology, cause, diagnosis and management of CAP., Recent Findings: There is consistent evidence that the trend in CAP mortality has declined over time. However, the mortality of pneumococcal CAP has not changed in the last two decades, with an increase in the rate of hospitalization and more severe forms of CAP. Streptococcus pneumoniae remains the most frequent cause of CAP in all settings, age groups and regardless of comorbidities. However, the implementation of molecular diagnostic tests in the last years has identified respiratory viruses as a common cause of CAP too. The emergency of multidrug-resistance pathogens is a worldwide concern. An improvement in our ability to promptly identify the causative cause of CAP is required in order to provide pathogen-directed antibiotic therapy, improve antibiotic stewardship programs and implement appropriate vaccine strategies., Summary: It is time to apply all the knowledge generated in the last decade in order to optimize the management of CAP.

Viruses utilize a number of host factors in order to carry out their replication cycles. Influenza A virus (IAV) and human respiratory syncytial virus (RSV) both infect the tissues of the respiratory tract, and as such we hypothesize that they might require similar host factors. Several published genome-wide screens have identified putative IAV host factors; however, there is significant discordance between their hits. In order to build on this work, we integrated a variety of "OMICS" data sources using two complementary network analyses, yielding 51 genes enriched for both IAV and RSV replication. We designed a targeted small interfering RNA (siRNA)-based assay to screen these genes against IAV under robust conditions and identified 13 genes supported by two IAV subtypes in both primary and transformed human lung cells. One of these hits, RNA binding motif 14 (RBM14), was validated as a required host factor and furthermore was shown to relocalize to the nucleolus upon IAV infection but not with other viruses. Additionally, the IAV NS1 protein is both necessary and sufficient for RBM14 relocalization, and relocalization also requires the double-stranded RNA (dsRNA) binding capacity of NS1. This work reports the discovery of a new host requirement for IAV replication and exposes a novel example of interplay between IAV NS1 and the host protein, RBM14. IMPORTANCE Influenza A virus (IAV) and respiratory syncytial virus (RSV) present major global disease burdens. There are high economic costs associated with morbidity as well as significant mortality rates, especially in developing countries, in children, and in the elderly. There are currently limited therapeutic options for these viruses, which underscores the need for novel research into virus biology that may lead to the discovery of new therapeutic approaches. This work extends existing research into host factors involved in virus replication and explores the interaction between IAV and one such host factor, RBM14. Further study to fully characterize this interaction may elucidate novel mechanisms used by the virus during its replication cycle and open new avenues for understanding virus biology., (Copyright © 2018 Beyleveld et al.)

Purpose of Review: This article reviews the most recent publications on community-acquired pneumonia (CAP) in the HIV-infected population on antiretroviral therapy (ART), focusing on epidemiology, prognostic factors, etiology, and antimicrobial therapy. The data discussed here were mainly obtained from a non-systematic review using Medline and references from relevant articles., Recent Findings: CAP remains a major cause of morbidity and mortality among HIV-infected patients and incurs high health costs despite the introduction of ART. HIV-infected patients are generally known to be more susceptible to bacterial pneumonia. Streptococcus pneumoniae is the most frequently reported pathogen in HIV-infected patients on ART, who present a higher rate of bacteremia than non-HIV-infected patients. Several studies have also examined microbial etiology and prognostic factors of CAP in HIV-infected patients on ART. Despite the high rate of bacterial pneumonia in these patients, mortality rates are not higher than in patients without HIV infection.

Community-acquired pneumonia (CAP) remains a major health problem worldwide. The incidence of pneumonia increases with both age and the presence of specific risk factors, which lead to increased health care costs. However, although there is some controversy over the observed trend in CAP mortality over recent decades, it is clear that mortality in CAP patients who require intensive care unit care remains high. The increase in antibiotic resistance is an important global health problem that needs to be addressed, especially for pneumococcus the most frequent pathogen of CAP. The prudent use of current antibiotics will help to limit the spread of antibiotic resistant clones of pneumococcus. Pneumococcal and influenza vaccinations remain the primary strategy for the prevention of CAP, especially in an at-risk population. This article reviews CAP, with a focus on epidemiology, diagnosis, prognostic factors, microbial etiology, therapy, complications, and prevention.

We investigate whether the clinical presentations and outcomes of Legionella pneumonia in human immunodeficiency virus (HIV)-infected patients were comparable to those seen in non-HIV-infected patients (case-control design). HIV-infected individuals presented neither a more severe disease nor a worse clinical outcome than matched HIV-negative control patients.

Rationale: Assessment of the inflammatory response can help the decision-making process when diagnosing community-acquired pneumonia (CAP), but there is a lack of information about the influence of time since onset of symptoms., Objectives: We studied the impact of the number of days since onset of symptoms on inflammatory cytokines and biomarker concentrations at CAP diagnosis in hospitalized patients., Methods: We performed a secondary analysis in two prospective cohorts including 541 patients in the derivation cohort and 422 in the validation cohort. The time since onset of symptoms was self-reported, and patients were classified as early presenters (<3 d) and nonearly presenters. Biomarkers (C-reactive protein [CRP] and procalcitonin [PCT] in both cohorts) and cytokines in the derivation cohort (IL-1, - 6, -8, -10, and tumor necrosis factor-α) were measured within 24 hours of hospital admission., Measurements and Main Results: In early presenters, CRP was significantly lower, whereas PCT, IL-6, and IL-8 were higher. Nonearly presenters showed significantly lower PCT, IL-6, and IL-8 levels. In the validation cohort, CRP and PCT exhibited identical patterns: CRP levels were 36.4% greater in patients with 3 or more days since onset of symptoms than in those with less than 3 days since symptom onset in the derivation cohort and 38.2% in the validation cohort. PCT levels were 40% lower in patients with 3 or more days since onset of symptoms in the derivation cohort and 56% in the validation cohort., Conclusions: Time since symptom onset modifies the systemic inflammatory profile at CAP diagnosis. This information has relevant clinical implications for management, and it should be taken into account in the design of future clinical trials.