Impact of severe lymphopenia on the early prediction of clinical outcome in hospitalized patients with pneumococcal community-acquired pneumonia.

PURPOSE: To evaluate the impact of an optimal and reproducible cutoff value set according to a predefined lymphopenia scale as an early predictor of in-hospital mortality and other outcomes in patients hospitalized with pneumococcal pneumonia and positive urinary antigen at admission to the emergency department. METHODS: An observational cohort study was conducted based on analysis of a prospective registry of consecutive immunocompetent adults hospitalized for pneumococcal pneumonia in two tertiary hospitals. Generalized additive models were constructed to assess the smooth relationship between in-hospital mortality and lymphopenia. RESULTS: We included 1173 patients. Lymphopenia on admission was documented in 686 (58.4%). No significant differences were observed between groups regarding the presence of comorbidities. Overall, 299 (25.5%) patients were admitted to intensive care and 90 (7.6%) required invasive mechanical ventilation. Fifty-nine (5%) patients died, among them 23 (38.9%) in the first 72 h after admission. A lymphocyte count < 500/µL, documented in 282 (24%) patients, was the predefined cutoff point that best predicted in-hospital mortality. After adjustment, these patients had higher rates of intensive care admission (OR 2.9; 95% CI 1.9-4.3), invasive mechanical ventilation (OR 2.2; 95% CI 1.2-3.9), septic shock (OR 1.8; 95% CI 1.1-2.9), treatment failure (OR 2.1; 95% CI 1.2-3.5), and in-hospital mortality (OR 2.2; 95% 1.1-4.9). Severe lymphopenia outperformed PSI score in predicting early and 30-day mortality in patients classified in the higher-risk classes. CONCLUSION: Lymphocyte count < 500/µL could be used as a reproducible predictor of complicated clinical course in patients with an early diagnosis of pneumococcal pneumonia.

Impact of prior SARS-COV-2 infection and vaccination on COVID-19 hospital admission and mortality amongst nursing home residents.

BACKGROUND: Nursing home residents (NHRs) have experienced disproportionately high risk of severe outcomes due to COVID-19 infection. AIM: We investigated the impact of COVID-19 vaccinations and previous SARS-CoV-2 episodes in preventing hospitalization and mortality in NHRs. METHODS: Retrospective study of a cohort of all NHRs in our area who were alive at the start of the vaccination campaign. The first three doses of SARS-CoV-2 vaccine and prior COVID-19 infections were registered. The main outcomes were hospital admission and mortality during each follow up. Random effects time-varying Cox models adjusted for age, sex, and comorbidities were fitted to estimate hazard ratios (HRs) according to vaccination status. RESULTS: COVID-19 hospitalization and death rates for unvaccinated NHRs were respectively 2.39 and 1.42 per 10,000 person-days, falling after administration of the second dose (0.37 and 0.34) and rising with the third dose (1.08 and 0.8). Rates were much lower amongst people who had previously had COVID-19. Adjusted HRs indicated a significant decrease in hospital admission amongst those with a two- and three-dose status; those who had had a previous COVID-19 infection had even lower hospital admission rates. Death rates decreased as NHRs received two and three doses, and the probability of death was much lower among those who had previously had the infection. CONCLUSIONS: The effectiveness of current vaccines against severe COVID-19 disease in NHRs remains high and SARS-CoV-2 episodes prior to vaccination entail a major reduction in hospitalization and mortality rates. The protection conferred by vaccines appears to decline in the following months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04463706.

COVID-19 in young and middle-aged adults: predictors of poor outcome and clinical differences.

INTRODUCTION: Young and middle-aged adults are the largest group of patients infected with SARS-CoV-2 and some of them develop severe disease. OBJECTIVE: To investigate clinical manifestations in adults aged 18-65 years hospitalized for COVID-19 and identify predictors of poor outcome. Secondary objectives: to explore differences compared to the disease in elderly patients and the suitability of the commonly used community-acquired pneumonia prognostic scales in younger populations. METHODS: Multicenter prospective registry of consecutive patients hospitalized for COVID-19 pneumonia aged 18-65 years between March and May 2020. We considered a composite outcome of "poor outcome" including intensive care unit admission and/or use of noninvasive ventilation, continuous positive airway pressure or high flow nasal cannula oxygen and/or death. RESULTS: We identified 513 patients < 65 years of age, from a cohort of 993 patients. 102 had poor outcomes (19.8%) and 3.9% died. 78% and 55% of patients with poor outcomes were classified as low risk based on CURB and PSI scores, respectively. A multivariate Cox regression model identified six independent factors associated with poor outcome: heart disease, absence of chest pain or anosmia, low oxygen saturation, high LDH and lymphocyte count < 800/mL. CONCLUSIONS: COVID-19 in younger patients carries significant morbidity and differs in some respects from this disease in the elderly. Baseline heart disease is a relevant risk factor, while anosmia and pleuritic pain are associated to better prognosis. Hypoxemia, LDH and lymphocyte count are predictors of poor outcome. We consider that CURB and PSI scores are not suitable criteria for deciding admission in this population.

Q Fever (Coxiella Burnetii).

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.

Impact of reducing the duration of antibiotic treatment on the long-term prognosis of community acquired pneumonia.

BACKGROUND: The optimal duration of antibiotic treatment for community-acquired pneumonia (CAP) is not well established. The aim of this study was to assess the impact of reducing the duration of antibiotic treatment on long-term prognosis in patients hospitalized with CAP. METHODS: This was a multicenter study assessing complications developed during 1 year of patients previously hospitalized with CAP who had been included in a randomized clinical trial concerning the duration of antibiotic treatment. Mortality at 90 days, at 180 days and at 1 year was analyzed, as well as new admissions and cardiovascular complications. A subanalysis was carried out in one of the hospitals by measuring C-reactive protein (CRP), procalcitonin (PCT) and proadrenomedullin (proADM) at admission, at day 5 and at day 30. RESULTS: A total of 312 patients were included, 150 in the control group and 162 in the intervention group. Ninety day, 180 day and 1-year mortality in the per-protocol analysis were 8 (2.57%), 10 (3.22%) and 14 (4.50%), respectively. There were no significant differences between both groups in terms of 1-year mortality (p = 0.94), new admissions (p = 0.84) or cardiovascular events (p = 0.33). No differences were observed between biomarker level differences from day 5 to day 30 (CRP p = 0.29; PCT p = 0.44; proADM p = 0.52). CONCLUSIONS: Reducing antibiotic treatment in hospitalized patients with CAP based on clinical stability criteria is safe, without leading to a greater number of long-term complications.

Streptococcus pneumoniae antigen in urine: diagnostic usefulness and impact on outcome of bacteraemic pneumococcal pneumonia in a large series of adult patients.

BACKGROUND AND OBJECTIVE: Urinary pneumococcal antigen detection provides good results in the diagnosis of pneumococcal pneumonia but has rarely been used in bacteraemic pneumococcal pneumonia and it is not known whether it is associated with outcome in this type of pneumonia. Our objectives were to assess the usefulness of an immunochromatographic technique for detecting the pneumococcal antigen in urine in a large prospective study of patients with bacteraemic pneumococcal pneumonia and explore any potential association with outcomes. METHODS: This study, carried out over 8 years, included all adult immunocompetent patients admitted for bacteraemic pneumococcal pneumonia. An immunochromatographic test for the Streptococcus pneumoniae antigen in urine was performed in the first 24 h. The sensitivity of test was assessed and patients were divided into two groups according to test results to explore differences on admission and during the course of the illness using logistic regression models. RESULTS: Of the 350 patients with bacteraemic pneumococcal pneumonia included, 261 (74.6%) were positive for the antigen. Patient characteristics were very similar on admission and differences in severity (Pneumonia Severity Index) were not statistically significant. In the adjusted analysis, antigen-positive patients had a higher risk of intensive care unit admission, treatment failure and adverse outcome. CONCLUSIONS: The sensitivity of the immunochromatographic urinary antigen test was 74.6% and positive results were associated with poorer clinical outcome. We therefore recommend systematic use of this test when pneumonia is diagnosed in the emergency department.

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.

Short- and long-term prognosis of patients with community-acquired Legionella or pneumococcal pneumonia diagnosed by urinary antigen testing.

OBJECTIVES: To analyze the differences in short- and long-term prognosis and the predictors of survival between patients with community-acquired Legionella and Streptococcus pneumoniae pneumonia, diagnosed early by urinary antigen testing (UAT). METHODS: Prospective multicenter study conducted in immunocompetent patients hospitalized with community-acquired Legionella or pneumococcal pneumonia (L-CAP or P-CAP) between 2002-2020. All cases were diagnosed based on positive UAT. RESULTS: We included 1452 patients, 260 with community-acquired Legionella pneumonia (L-CAP) and 1192 with community-acquired pneumococcal pneumonia (P-CAP). The 30-day mortality was higher for L-CAP (6.2%) than for P-CAP (5%). After discharge and during the median follow-up durations of 11.4 and 8.43 years, 32.4% and 47.9% of patients with L-CAP and P-CAP died, and 82.3% and 97.4% died earlier than expected, respectively. The independent risk factors for shorter long-term survival were age >65 years, chronic obstructive pulmonary disease, cardiac arrhythmia, and congestive heart failure in L-CAP and the same first three factors plus nursing home residence, cancer, diabetes mellitus, cerebrovascular disease, altered mental status, blood urea nitrogen ≥30 mg/dl, and congestive heart failure as a cardiac complication during hospitalization in P-CAP. CONCLUSION: In patients diagnosed early by UAT, the long-term survival after L-CAP or P-CAP was shorter (particularly after P-CAP) than expected, and this shorter survival was mainly associated with age and comorbidities.

Bacterial Patterns and Empiric Antibiotic Use in COPD Patients With Community-Acquired Pneumonia.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is strongly associated with the development of community-acquired pneumonia (CAP). Limited data are available on risk factors for difficult to manage bacteria such as Pseudomonas aeruginosa in COPD patients with CAP. Our objective was to assess the microbiological patterns associated with risk factors that determine empiric antibiotic therapy in hospitalized COPD patients with CAP. METHODS: We performed a secondary data analysis of an international, multicenter, observational, point-prevalence study involving hospitalized COPD patients with CAP from March to June 2015. After identifying the risk factors associated with different microorganisms, we developed a scoring system to guide decision-making about empiric anti-pseudomonal antibiotic therapy in this population. RESULTS: We enrolled 689 hospitalized COPD patients with CAP with documented microbiological testing. The most frequent microorganisms isolated were Streptococcus pneumoniae (8%) and Gram-negative bacteria (8%), P. aeruginosa (7%) and Haemophilus influenzae (3%). We developed a scoring system incorporating the variables independently associated with P. aeruginosa that include a previous P. aeruginosa isolation or infection (OR 14.2 [95%CI 5.7-35.2]), hospitalization in the past 12 months (OR 3.7 [1.5-9.2]), and bronchiectasis (OR 3.2 [1.4-7.2]). Empiric anti-pseudomonal antibiotics were overutilized in COPD patients with CAP. The new scoring system has the potential to reduce empiric anti-pseudomonal antibiotic use from 54.1% to 6.2%. CONCLUSIONS: COPD patients with CAP present different microbiological profiles associated with unique risk factors. Anti-pseudomonal treatment is a critical decision when selecting empiric antibiotic therapy. We developed a COPD scoring system to guide decision-making about empiric anti-pseudomonal antibiotic therapy.