Basic host response parameters to classify mortality risk in COVID-19 and community-acquired pneumonia.

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, SpO2/FiO2). 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/mm3), CRP (> 60 mg/L), and, SpO2/FiO2 (< 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.

Diabetes Mellitus and Pneumococcal Pneumonia.

Currently, there are more than 500 million people suffering from diabetes around the world. People aged 65 years or older are the most affected by this disease, and it is estimated that approximately 96% of diabetes cases worldwide are type 2 diabetes. People with diabetes mellitus are at an increased risk of infections such as pneumonia, due to a series of factors that may contribute to immune dysfunction, including hyperglycemia, inhibition of neutrophil chemotaxis, impaired cytokine production, phagocytic cell dysfunction, altered T cell-mediated immune responses and the co-existence of chronic comorbidities. Rates of infection, hospitalization and mortality in diabetic patients are reported to be higher than in the general population. Research into the risk of infectious diseases such as pneumonia in these patients is very important because it will help improve their management and treatment.

Viral Pneumonia: From Influenza to COVID-19.

Respiratory viruses are increasingly recognized as a cause of community-acquired pneumonia (CAP). The implementation of new diagnostic technologies has facilitated their identification, especially in vulnerable population such as immunocompromised and elderly patients and those with severe cases of pneumonia. In terms of severity and outcomes, viral pneumonia caused by influenza viruses appears similar to that caused by non-influenza viruses. Although several respiratory viruses may cause CAP, antiviral therapy is available only in cases of CAP caused by influenza virus or respiratory syncytial virus. Currently, evidence-based supportive care is key to managing severe viral pneumonia. We discuss the evidence surrounding epidemiology, diagnosis, management, treatment, and prevention of viral pneumonia.

Pneumococcal Serotypes Associated with Community-Acquired Pneumonia Hospitalizations in Adults in Spain, 2016-2020: The CAPA Study.

Newer higher valency pneumococcal conjugate vaccines (PCVs) have the potential to reduce the adult community-acquired pneumonia (CAP) burden. We describe the evolution and distribution of adult community-acquired pneumonia (CAP) serotypes in Spain, focusing on serotypes contained in the 20-valent PCV (PCV20). This was a prospective, observational study of chest X-ray (CXR)-confirmed CAP in immunocompetent adults hospitalized in one of four Spanish hospitals between November 2016 and November 2020. Pneumococci were isolated from cultures and detected in urine using BinaxNow® and Pfizer serotype-specific urinary antigen tests UAD1 and UAD2. We included 1948 adults hospitalized with CXR-CAP. The median age was 69.0 years (IQR: 24 years). At least one comorbidity was present in 84.8% (n = 1653) of patients. At admission, 76.1% of patients had complicated pneumonia. Pneumococcus was identified in 34.9% (n = 680) of study participants. The PCV20 vaccine-type CAP occurred in 23.9% (n = 465) of all patients, 68.4% (n = 465) of patients with pneumococcal CAP, and 82.2% (83/101) of patients who had pneumococcus identified by culture. Serotypes 8 (n = 153; 7.9% of all CAP) and 3 (n = 152; 7.8% of all CAP) were the most frequently identified. Pneumococcus is a common cause of hospitalized CAP among Spanish adults and serotypes contained in PCV20 caused the majority of pneumococcal CAP.

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.

Is the long-term mortality similar in COVID-19 and community-acquired pneumonia?

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.

The pharmacokinetic evaluation of omadacycline (Oral Only Dosing Regimen) for the treatment of Community-Acquired Bacterial Pneumonia (CABP).

INTRODUCTION: Omadacycline is a new analog of the tetracycline class active against atypical bacteria, as well as against staphylococci, including methicillin-resistant strains, and Streptococcus pneumoniae. AREAS COVERED: This review has summarized the available clinical evidence on the use of oral omadacycline in the treatment of community-acquired pneumonia (CAP) and described the mechanism of action, pharmacokinetic/pharmacodynamic (PK/PD) parameters in healthy and special populations and the latest research on omadacycline. EXPERT OPINION: The available clinical evidence on oral omadacycline for the treatment of CAP shows that its properties provide reliable empirical coverage for pathogens such as Haemophilus influenzae, Moraxella catarrhalis, and species of Legionella, Chlamydia, and Mycoplasma. Omadacycline is also active against methicillin-resistant Staphylococcus aureus (MRSA); penicillin-resistant and multidrug-resistant Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus agalactiae; and vancomycin-resistant Enterococcus spp. A dose of 450 mg orally once daily is recommended, followed by a maintenance dose of 300 mg orally once daily. Importantly, omadacycline does not require dose adjustment for patients based on BMI, age, gender, or renal or hepatic impairment.

Interventions to improve outcomes in community-acquired pneumonia.

INTRODUCTION: Community-acquired pneumonia (CAP) is a common infection associated with high morbimortality and a highly deleterious impact on patients' quality of life and functionality. We comprehensively review the factors related to the host, the causative microorganism, the therapeutic approach and the organization of health systems (e.g. setting for care and systems for allocation) that might have an impact on CAP-associated outcomes. Our main aims are to discuss the most controversial points and to provide some recommendations that may guide further research and the management of patients with CAP, in order to improve their outcomes, beyond mortality. AREA COVERED: In this review, we aim to provide a critical account of potential measures to improve outcomes of CAP and the supporting evidence from observational studies and clinical trials. EXPERT OPINION: CAP is associated with high mortality and a highly deleterious impact on patients' quality of life. To improve CAP-associated outcomes, it is important to understand the factors related to the patient, etiology, therapeutics, and the organization of health systems.

Clinical-epidemiological characteristics of deaths due to dengue during an outbreak in northern Peru. / Características clínicas y epidemiológicas de las muertes por dengue durante un brote en el norte del Perú.

Motivation for the study. To describe the characteristics of patients who died from severe dengue fever during the 2017 El Niño in Piura. Main findings. Mortality from severe dengue was higher in adult women. First contact with healthcare took place mostly in higher level hospitals. Admission to a specialized unit was late for severe dengue cases. Implications. Control of dengue fever involves several aspects, such as, access to health, prevention, water availability, vector control and education; therefore, it is important to strengthen public health policies in this regard. In order to achieve this goal, local and central government sectors must be involved.

Motivación para realizar el estudio. Describir las características de los pacientes fallecidos por dengue grave durante el fenómeno de El Niño del 2017 en Piura. Principales hallazgos. La mortalidad del dengue grave fue mayoritaria en las mujeres adultas, la primera atención se realizó en hospitales de mayor nivel y la atención para casos graves de dengue en una unidad especializada fue tardía. Implicancias. La mortalidad del dengue grave fue mayoritaria en las mujeres adultas, la primera atención se realizó en hospitales de mayor nivel y la atención para casos graves de dengue en una unidad especializada fue tardía.

Immunocompromised Host Pneumonia: Definitions and Diagnostic Criteria: An Official American Thoracic Society Workshop Report.

Pneumonia imposes a significant clinical burden on people with immunocompromising conditions. Millions of individuals live with compromised immunity because of cytotoxic cancer treatments, biological therapies, organ transplants, inherited and acquired immunodeficiencies, and other immune disorders. Despite broad awareness among clinicians that these patients are at increased risk for developing infectious pneumonia, immunocompromised people are often excluded from pneumonia clinical guidelines and treatment trials. The absence of a widely accepted definition for immunocompromised host pneumonia is a significant knowledge gap that hampers consistent clinical care and research for infectious pneumonia in these vulnerable populations. To address this gap, the American Thoracic Society convened a workshop whose participants had expertise in pulmonary disease, infectious diseases, immunology, genetics, and laboratory medicine, with the goal of defining the entity of immunocompromised host pneumonia and its diagnostic criteria.

Pneumococcal Vaccination in Adults: What Can We Learn From Observational Studies That Evaluated PCV13 and PPV23 Effectiveness in the Same Population?

Introduction: Fifteen and 20-valent pneumococcal conjugate vaccines (PCV15; PCV20) were recently licensed to prevent pneumococcal disease in adults. In the absence of efficacy or effectiveness data for these new vaccines, studies comparing 23-valent pneumococcal polysaccharide vaccine (PPV23) and PCV13 might help inform decision-making on how to best implement expanded-valency PCVs. Comparing PPV23 and PCV13 is problematic, as no head-to-head clinical trials evaluated efficacy. Comparing effectiveness results across observational studies that vary by population, design, and outcomes is difficult. To address these limitations, we undertook a narrative review of studies that assessed PPV23 and PCV13 vaccine effectiveness (VE) in the same adult populations. Methods: We conducted a literature search in PubMed and Google Scholar and screened 525 studies using a standardized evaluation framework. Results: Nine studies met inclusion criteria, all from high-income countries. None evaluated invasive pneumococcal disease (IPD) alone. VE against vaccine-type pneumococcal pneumonia ranged from 2 to 6% for PPV23 and 41 to 71% for PCV13. VE against pneumococcal pneumonia or severe pneumococcal disease (IPD or pneumococcal pneumonia) ranged from −10 to 11% for PPV23, 40 to 79% for PCV13, and 39 to 83% for sequential PCV13/PPV23. VE against all-cause pneumonia or lower respiratory tract infection ranged from −8 to 3% for PPV23 and 9 to 12% for PCV13. Conclusions: Overall, PCV13 demonstrated better protection than PPV23 against pneumococcal disease and all-cause respiratory outcomes in the included studies. Where evaluated, sequential PCV13/PPV23 vaccination showed little benefit over PCV13 alone. Results support the use of PCVs to protect against pneumococcal disease and respiratory infections in adults. (AU)

Pneumococcal Vaccination in Adults: What Can We Learn From Observational Studies That Evaluated PCV13 and PPV23 Effectiveness in the Same Population?

INTRODUCTION: Fifteen and 20-valent pneumococcal conjugate vaccines (PCV15; PCV20) were recently licensed to prevent pneumococcal disease in adults. In the absence of efficacy or effectiveness data for these new vaccines, studies comparing 23-valent pneumococcal polysaccharide vaccine (PPV23) and PCV13 might help inform decision-making on how to best implement expanded-valency PCVs. Comparing PPV23 and PCV13 is problematic, as no head-to-head clinical trials evaluated efficacy. Comparing effectiveness results across observational studies that vary by population, design, and outcomes is difficult. To address these limitations, we undertook a narrative review of studies that assessed PPV23 and PCV13 vaccine effectiveness (VE) in the same adult populations. METHODS: We conducted a literature search in PubMed and Google Scholar and screened 525 studies using a standardized evaluation framework. RESULTS: Nine studies met inclusion criteria, all from high-income countries. None evaluated invasive pneumococcal disease (IPD) alone. VE against vaccine-type pneumococcal pneumonia ranged from 2 to 6% for PPV23 and 41 to 71% for PCV13. VE against pneumococcal pneumonia or severe pneumococcal disease (IPD or pneumococcal pneumonia) ranged from -10 to 11% for PPV23, 40 to 79% for PCV13, and 39 to 83% for sequential PCV13/PPV23. VE against all-cause pneumonia or lower respiratory tract infection ranged from -8 to 3% for PPV23 and 9 to 12% for PCV13. CONCLUSIONS: Overall, PCV13 demonstrated better protection than PPV23 against pneumococcal disease and all-cause respiratory outcomes in the included studies. Where evaluated, sequential PCV13/PPV23 vaccination showed little benefit over PCV13 alone. Results support the use of PCVs to protect against pneumococcal disease and respiratory infections in adults.

Validation of IDSA/ATS Guidelines for ICU Admission in Adults Over 80 Years Old With Community-Acquired Pneumonia

Introduction: The 2007 IDSA/ATS guidelines for community-acquired pneumonia (CAP) recommended intensive care unit (ICU) admission for adults meeting severe CAP criteria. We aimed to validate the accuracy of IDSA/ATS criteria in patients≥80 years old (very elderly patients, VEP) with CAP. Methods: Prospective cohort study of VEP with CAP admitted to three Spanish hospitals between 1996 and 2019. We compared patients who did and did not require ICU admission. We also assessed factors independently associated with ICU admission, as well as the accuracy of severe CAP criteria for ICU admission and mortality. Major criteria include septic shock and invasive mechanical ventilation while minor criteria encompass other variables related to hemodynamics and respiratory insufficiency as well as level of consciousness, renal function, blood parameters indicative of sepsis and body temperature. Results: Of the 2006 VEP with CAP, 519 (26%) met severe CAP criteria, while 204 (10%) required ICU admission. Concordance between severe CAP criteria and the decision to admit the patient to the ICU occurred in 1591 (79%) cases (k coefficient, 0.33), with a sensitivity of 75% and specificity of 80% in predicting ICU admission. All patients with invasive mechanical ventilation received care in ICUs, while 45 (44%) patients with septic shock—previously stabilized in the emergency room—did not. Thirty-day mortality of ICU-admitted patients with septic shock was lower than that of patients in wards (30% vs. 60%, p=0.013). In contrast, patients with severe CAP and only minor criteria had similar mortality. Conclusions: IDSA/ATS criteria for severe CAP predict ICU admission in VEP moderately well. While patients with septic shock and invasive mechanical ventilation warrant ICU admission, severe CAP without major severity criteria in VEP may be acceptably manageable in wards. (AU)

Características clínicas y epidemiológicas de las muertes por dengue durante un brote en el norte del Perú / Clinical-epidemiological characteristics of dengue deaths during an outbreak in northern Peru

Con el objetivo de describir las características clínicas y epidemiológicas de los pacientes fallecidos por dengue durante el 2017 en Piura, se realizó un estudio retrospectivo de revisión de 24 historias clínicas. El 67% de los casos fueron mujeres y tres (12,5%) estaban embarazadas. La diabetes (12,5%) y la hipertensión (16,7%) fueron las comorbilidades más frecuentes. Sólo en el 12,5% se reportó dengue previo. El tiempo transcurrido desde asistencia sanitaria hasta la muerte fue de 4,10 (DE: 5,34) días. Se hicieron transfusiones de glóbulos rojos en el 45,8% de los casos, plasma en el 25%, plaquetas en el 16,8% y crioprecipitado en el 16,8%. También fueron frecuentes la terapia con cristaloides (91,7%) y el tratamiento con fármacos vasoactivos (70,8%). En conclusión, la mortalidad del dengue grave fue mayoritaria en las mujeres adultas y el tiempo de atención desde el primer establecimiento de salud hasta una unidad especializada fue prolongada.

Objective: To describe the clinical-epidemiological characteristics of patients who died from dengue during 2017. Methods: We conducted a retrospective study of the information related to cases of dengue deaths in the department of Piura. Results: We reviewed 24 medical records. Sixty-seven percent were women and 3 (12.5%) were pregnant. Diabetes (12.5%) and hypertension (16.7%) were the most frequent comorbidities. Previous dengue fever was reported in only 12.5%. The time from health care and death was 4.10 ± 5.34 days. Red blood cell transfusions were performed in 45.8%, plasma in 25%, platelets in 16.8% and cryoprecipitate in 16.8% of cases. Crystalloid therapy (91.7%) and treatment with vasoactive drugs (70.8%) were also frequent. In conclusion, mortality from severe dengue fever was predominantly in adult women, and the time of care from the first health facility to a specialized unit was prolonged.