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.

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.

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.

High-flow nasal cannula oxygen therapy for the treatment of acute respiratory failure secondary to SARS-CoV-2 pneumonia out of ICU.

INTRODUCTION AND OBJECTIVES: High-flow nasal cannula oxygen therapy (HFNC) has been successfully used for the treatment of acute hypoxaemic respiratory failure (AHRF) secondary to SARS-CoV-2 pneumonia and being effective in reducing progression to invasive mechanical ventilation. The objective of this study was to assess the usefulness of HFNC on a hospital ward for the treatment of AHRF secondary to SARS-CoV-2 pneumonia and its impact on the need for intensive care unit (ICU) admission and endotracheal intubation. Other objectives include identifying potential physiological parameters and/or biomarkers for predicting treatment failure and assessing the clinical course and survival. METHODS: Observational study based on data collected prospectively between March 2020 and February 2021 in a single hospital on patients diagnosed with AHRF secondary to SARS-CoV-2 pneumonia who received HFNC outside an ICU. RESULTS: One hundred and seventy-one patients out of 1090 patients hospitalised for SARS-CoV-2 infection. HFNC was set as the ceiling of treatment in 44 cases; 12 survived (27.3%). Among the other 127 patients, intubation was performed in 25.9% of cases with a mortality of 11.8%. Higher creatinine levels (OR 1.942, 95% CI 1.04; 3.732; p = 0.036) and Comorbidity-Age-Lymphocyte-LDH (CALL) score (OR 1.273, 95% CI 1.033; 1.617; p = 0.033) were associated with a higher risk of intubation. High platelet count at HFNC initiation was predictive of good treatment response (OR 0.935, 95% CI 0.884; 0.983; p = 0.012). CONCLUSIONS: HFNC outside an ICU is a treatment with high success rate in patients with AHRF secondary to SARS-CoV-2 pneumonia, including in patients in whom this therapy was deemed to be the ceiling of treatment.

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.

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.

Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review.

Community-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed.

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.

Estimating the risk of bacteraemia in hospitalised patients with pneumococcal pneumonia.

OBJECTIVE: To construct a prediction model for bacteraemia in patients with pneumococcal community-acquired pneumonia (P-CAP) based on variables easily obtained at hospital admission. METHODS: This prospective observational multicentre derivation-validation study was conducted in patients hospitalised with P-CAP between 2000 and 2020. All cases were diagnosed based on positive urinary antigen tests in the emergency department and had blood cultures taken on admission. A risk score to predict bacteraemia was developed. RESULTS: We included 1783 patients with P-CAP (1195 in the derivation and 588 in the validation cohort). A third (33.3%) of the patients had bacteraemia. In the multivariate analysis, the following were identified as independent factors associated with bacteraemia: no influenza vaccination the last year, no pneumococcal vaccination in the last 5 years, blood urea nitrogen (BUN) ≥30 mg/dL, sodium <130 mmol/L, lymphocyte count <800/µl, C-reactive protein ≥200 mg/L, respiratory failure, pleural effusion and no antibiotic treatment before admission. The score yielded good discrimination (AUC 0.732; 95% CI: 0.695-0.769) and calibration (Hosmer-Lemeshow p-value 0.801), with similar performance in the validation cohort (AUC 0.764; 95% CI:0.719-0.809). CONCLUSIONS: We found nine predictive factors easily obtained on hospital admission that could help achieve early identification of bacteraemia. The prediction model provides a useful tool to guide diagnostic decisions.

Early Recognition of Low-Risk SARS-CoV-2 Pneumonia: A Model Validated With Initial Data and Infectious Diseases Society of America/American Thoracic Society Minor Criteria.

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/Fio2 > 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.

WITHDRAWN: Validation of IDSA/ATS Guidelines for ICU Admission in Adults Over 80 Years Old With Community-acquired Pneumonia.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.arbres.2022.08.012. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal

New-onset atrial fibrillation in patients with pneumococcal pneumonia. Impact of timing and duration on short- and medium-term mortality.

OBJETIVES: To assess the incidence, related factors, timing and duration of new- onset atrial fibrillation in a cohort of consecutive patients diagnosed with pneumococcal pneumonia. METHODS: Observational study including all immunocompetent adults hospitalized for pneumococcal pneumonia. Patients were classified by time (atrial fibrillation recognized on emergency room arrival or developed during hospitalization) and duration (paroxysmal or persistent). Patients were followed-up for 6 months after discharge. RESULTS: We included 1092 patients, of whom 109 (9.9%) had new-onset atrial fibrillation. An early event was documented in 87 (79.8%) cases. Arrhythmia was classified as paroxysmal in 78 patients. Older age, heavy drinking, respiratory rate ≥ 30/minute, leukopenia, severe inflammation and bacteremia were independent risk factors for developing new-onset atrial fibrillation on admission. Overall, 48 (4.4%) patients died during hospitalization, the rate being higher in those patients who developed new-onset arrhythmia (17.9% vs 2.9% p<0.001). Among patients with events recognized at admission, in-hospital mortality was higher in those with persistent arrhythmia (34.8% vs 6.3%, p = 0.002) and 6-month survival was better among those who developed paroxysmal event. CONCLUSIONS: The development of new-onset atrial fibrillation was associated with pneumonia severity, and higher in-hospital mortality. Bacteremia and severe systemic inflammation were factors associated with its development.

Non-bacteremic pneumococcal pneumonia: general characteristics and early predictive factors for poor outcome.

Purpose: Nowadays, most cases of pneumococcal community-acquired pneumonia (PCAP) are diagnosed by positive urinary antigen. Our aims were to analyse process of care in patients hospitalised with non-bacteremic PCAP (NB-PCAP) and identify factors associated with poor outcome (PO) in this population.Methods: We conducted a prospective study, including patients hospitalised for NB-PCAP (positive urinary antigen and negative blood culture) over a 15 year period. We performed multivariate analysis of predisposing factors for PO, defined as need for mechanical ventilation and/or shock and/or in-hospital death.Results: Of the 638 patients included, 4.1% died in hospital and 12.8% had PO. Host-related factors were similar in patients with and without PO, but patients with PO had higher illness severity on admission. Adjusted analysis revealed the following independent factors associated with PO: being a nursing home resident (OR: 6.156; 95% CI: 1.827-20.750; p = .003), respiratory rate ≥30 breaths/min (OR: 3.030; 95% CI: 1.554-5.910; p = .001), systolic blood pressure <90 mmHg (OR: 4.789; 95% CI: 1.967-11.660; p = .001), diastolic blood pressure <60 mmHg (OR: 2.820; 95% CI: 1.329-5.986; p = .007), pulse rate ≥125 beats/min (OR: 3.476; 95% CI: 1.607-7.518; p = .002), pH <7.35 (OR: 9.323; 95% CI: 3.680-23.622; p < .001), leukocytes <4000/µL (OR: 10.007; 95% CI: 2.960-33.835; p < .001), and severe inflammation (OR: 2.364; 95% CI 1.234-4.526; p = .009). The area under the curve for predicting PO was 0.890 (95% CI: 0.851-0.929).Conclusions: Since patients with PO seem different and had worse in-hospital course, we identified eight independent risk factors for PO measurable on admission.

Evolution of serotypes in bacteremic pneumococcal adult pneumonia in the period 2001-2014, after introduction of the pneumococcal conjugate vaccine in bizkaia (spain).

The introduction of pneumococcal conjugate vaccines (PCV7 and PCV13) in children has led to a change in the pattern of pneumococcal serotypes causing pneumococcal disease in adults. The aim of this study is to analyze the distribution of pneumococcal serotypes in adults with bacteremic pneumococcal community-acquired pneumonia (BPP) after the introduction of PCVs in childhood, and the impact of age and comorbidity on this distribution. We conducted an observational study of all adults hospitalized with BPP between 2001 and 2014, in two tertiary hospitals. Overall, we identified 451 cases of BPP (2001-2005: 194, 2006-2010: 134, 2011-2014: 123). The rate of appearance of new cases decreased over the study period. In 70% of the cases, the serotypes found were among those included in PCV13. The most prevalent serotypes were 3 (23.1%), 7F (14.6%), 19A (8.4%) and 1 (7.5%). There was a significant trend to decrease in the percentage of BPP cases due to PCV7 from period 2001-2005 to 2011-2014 (p = 0.0166) and a significant trend to increase in the six serotypes added to form PCV 13 (p = 0.0003). Serotype 3 was the most frequent in patients who developed complications during hospitalization. We did not detect a significant increase in cases caused by non-PCV13 serotypes. The most frequent non-PCV13 serotype was 22F. In conclusion, a significant proportion of adults continue to develop BPP with vaccine serotypes despite infant pneumococcal vaccination. There is a need for further strategies to reduce the current burden of this disease on adults.

Factors influencing long-term survival after hospitalization with pneumococcal pneumonia.

OBJECTIVE: To assess survival and identify predictors of survival more than 30-days after discharge in a cohort of consecutive patients diagnosed with pneumococcal pneumonia. METHODS: Observational study including all consecutive immunocompetent adult patients surviving more than 30-days after hospitalization. The bacteriological diagnosis was based on the results of urinary antigen testing and/or blood culture. Life expectancy was calculated for each patient considering their sex, age and date of discharge. RESULTS: We included 1114 patients that survived more than 30- days after discharge. Of them, 431 (38.6%) died during follow-up (median follow-up of 6.7 years). Age, history of cancer, liver disease, chronic renal disease, chronic obstructive pulmonary disease, cerebrovascular disease, atrial arrhythmia and coronary disease, red cell distribution width (RDW) > 15%, positive blood culture, hematocrit < 30% and living in a nursing home were independent risk factors for reduced long-term survival after hospital discharge. Cumulative 1-, 3- and 5-year survival rates were 93.9%, 85.3% and 76%, respectively. Among non-survivors, 361 (83.8%) died earlier than expected given their life expectancy. CONCLUSIONS: Survival after hospital discharge is mainly associated with age and comorbidities. The findings of bacteremia and elevated RDW on admission could help identify patients at high risk of long-term mortality.

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)