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.

Pneumonia presenting with organ dysfunctions: Causative microorganisms, host factors and outcome.

Community-acquired pneumonia (CAP) is a serious infection that may occasionally rapidly evolve provoking organ dysfunctions. We aimed to characterize CAP presenting with organ dysfunctions at the emergency room, with regard to host factors and causative microorganisms, and its impact on 30-day mortality. 460 of 4070 (11.3%) CAP patients had ≥2 dysfunctions at diagnosis, with a 30-day mortality of 12.4% vs. 3.4% in those with one or no dysfunctions. Among them, the most frequent causative microorganisms were Streptococcus pneumoniae, gram-negatives and polymicrobial etiology. Independent host risk factors for presenting with ≥2 dysfunctions were: liver (OR 2.97) and renal diseases (OR 3.91), neurological disorders (OR 1.86), and COPD (OR 1.30). Methicillin-resistant Staphylococcus aureus (OR 6.41) and bacteraemic episodes (OR 1.68) had the higher independent risk among microorganisms. The number of organ dysfunctions vs. none increased at 30-day mortality: three organs (OR 11.73), two organs (OR 4.29), and one organ (OR 2.42) whereas Enterobacteria (OR 3.73) were also independently related to mortality. The number of organ dysfunctions was the strongest 30-day mortality risk factor while Enterobacteriaceae was also associated with poorer outcome. The assessment of organ dysfunctions in CAP should be implemented for management, allocation and treatment decisions on initial evaluation.

Age-related risk factors for bacterial aetiology in community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate the effect of age and comorbidities, smoking and alcohol use on microorganisms in patients with community-acquired pneumonia (CAP). METHODS: A prospective multicentre study was performed with 4304 patients. We compared microbiological results, bacterial aetiology, smoking, alcohol abuse and comorbidities in three age groups: young adults (<45 years), adults (45-64 years) and seniors (>65 years). RESULTS: Bacterial aetiology was identified in 1522 (35.4%) patients. In seniors, liver disease was independently associated with Gram-negative bacteria (Haemophilus influenzae and Enterobacteriaceae), COPD with Pseudomonas aeruginosa (OR = 2.69 (1.46-4.97)) and Staphylococcus aureus (OR = 2.8 (1.24-6.3)) and neurological diseases with S. aureus. In adults, diabetes mellitus (DM) was a risk factor for Streptococcus pneumoniae and S. aureus, and COPD for H. influenzae (OR = 3.39 (1.06-10.83)). In young adults, DM was associated with S. aureus. Smoking was a risk factor for Legionella pneumophila regardless of age. Alcohol intake was associated with mixed aetiology and Coxiella burnetii in seniors, and with S. pneumoniae in young adults. CONCLUSION: It should be considered that the bacterial aetiology may differ according to the patient's age, comorbidities, smoking and alcohol abuse. More extensive microbiological testing is warranted in those with risk factors for infrequent microorganisms.

Predictors of Severe Sepsis among Patients Hospitalized for Community-Acquired Pneumonia.

BACKGROUND: Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP). OBJECTIVE: To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP. RESULTS: We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospitalized CAP patients, 1529 of whom (37.6%) presented with severe sepsis. Severe sepsis CAP was independently associated with older age (>65 years), alcohol abuse (OR, 1.31; 95% CI, 1.07-1.61), chronic obstructive pulmonary disease (COPD) (OR, 1.75; 95% CI, 1.50-2.04) and renal disease (OR, 1.57; 95% CI, 1.21-2.03), whereas prior antibiotic treatment was a protective factor (OR, 0.62; 95% CI, 0.52-0.73). Bacteremia (OR, 1.37; 95% CI, 1.05-1.79), S pneumoniae (OR, 1.59; 95% CI, 1.31-1.95) and mixed microbial etiology (OR, 1.65; 95% CI, 1.10-2.49) were associated with severe sepsis CAP. CONCLUSIONS: CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis.

Sensitivity, Specificity, and Positivity Predictors of the Pneumococcal Urinary Antigen Test in Community-Acquired Pneumonia.

RATIONALE: Detection of the C-polysaccharide of Streptococcus pneumoniae in urine by an immune-chromatographic test is increasingly used to evaluate patients with community-acquired pneumonia. OBJECTIVES: We assessed the sensitivity and specificity of this test in the largest series of cases to date and used logistic regression models to determine predictors of positivity in patients hospitalized with community-acquired pneumonia. METHODS: We performed a multicenter, prospective, observational study of 4,374 patients hospitalized with community-acquired pneumonia. MEASUREMENTS AND MAIN RESULTS: The urinary antigen test was done in 3,874 cases. Pneumococcal infection was diagnosed in 916 cases (21%); 653 (71%) of these cases were diagnosed exclusively by the urinary antigen test. Sensitivity and specificity were 60 and 99.7%, respectively. Predictors of urinary antigen positivity were female sex; heart rate≥125 bpm, systolic blood pressure<90 mm Hg, and SaO2<90%; absence of antibiotic treatment; pleuritic chest pain; chills; pleural effusion; and blood urea nitrogen≥30 mg/dl. With at least six of all these predictors present, the probability of positivity was 52%. With only one factor present, the probability was only 12%. CONCLUSIONS: The urinary antigen test is a method with good sensitivity and excellent specificity in diagnosing pneumococcal pneumonia, and its use greatly increased the recognition of community-acquired pneumonia due to S. pneumoniae. With a specificity of 99.7%, this test could be used to direct simplified antibiotic therapy, thereby avoiding excess costs and risk for bacterial resistance that result from broad-spectrum antibiotics. We also identified predictors of positivity that could increase suspicion for pneumococcal infection or avoid the unnecessary use of this test.

T-cell profiling and the immunodiagnosis of latent tuberculosis infection in patients with inflammatory bowel disease.

BACKGROUND: Factors associated with performance of interferon-γ release assays (IGRA) and the tuberculin skin test (TST) in screening for latent tuberculosis infection in patients with inflammatory bowel diseases (IBD) are still poorly understood. The influence of peripheral T-cell subset counts on the results also remain unclear. METHODS: Prospective single-center study in 205 patients with IBD. Latent tuberculosis infection screening included a chest radiograph, TST (retest if negative), and 2 IGRAs: QuantiFERON-TB Gold In-Tube (QFT-GIT) and TSPOT-TB (TSPOT). T-cell subpopulations were determined by flow cytometry. RESULTS: Twenty-one (10.2%) patients had an abnormal chest radiograph, 55 (26.8%) had a positive TST, 16 (7.8%) had a positive QFT-GIT, and 25 (12.6%) had a positive TSPOT. TST positivity was lower in patients on ≥2 immunosuppressants compared with the controls (5-aminosalicylic acid treatment) (10.4% versus 38.2%, respectively) (P = 0.0057). No other drugs influenced TST or IGRA positivity. In patients on corticosteroid treatment, anti-TNF treatment, or ≥2 immunosuppressants, IGRAs detected 10 cases of latent tuberculosis infection not identified by TST. TSPOT and QFT-GIT increased yield by 56% and 22%, respectively. No significant differences in T-cell subpopulations were found between patients with positive or negative TST or TSPOT results. However, patients with positive QFT-GIT findings had more CD8 T cells (mean, 883 ± 576 versus 484 ± 385 cells per microliter in patients with negative results) (P = 0.022). CONCLUSIONS: IGRAs can improve TST-based screening in patients with IBD on immunosuppressive therapy. A low CD8 count can affect QFT-GIT results. We suggest combining TSPOT and TST screening in patients with IBD on immunosuppressants.

Pleural effusion Due to Streptococcus milleri: Case descriptions.

In this study we analyzed the characteristics of patients with pleural effusion secondary to Streptococcus milleri studied retrospectively between January and March 2013 and found seven patients with a mean age of 60 years, 43% of which were smokers and 57% with a drinking habit. The most common associated factors were alcoholism, previous pneumonia and diabetes. Other bacteria were identified as Enterobacter aerogenes, Bacteroides and Prevotella intermedia capillosus in two patients. The mean duration of antibiotic therapy was 28 days; six patients underwent pleural drainage by chest tube and one patient needed surgery due to poor clinical progress. The mean duration of hospitalization was 30 days with satisfactory outcome in all cases, despite some changes in residual function.

Microbial aetiology of healthcare associated pneumonia in Spain: a prospective, multicentre, case-control study.

INTRODUCTION: Healthcare-associated pneumonia (HCAP) is actually considered a subgroup of hospital-acquired pneumonia due to the reported high risk of multidrug-resistant pathogens in the USA. Therefore, current American Thoracic Society/Infectious Diseases Society of America guidelines suggest a nosocomial antibiotic treatment for HCAP. Unfortunately, the scientific evidence supporting this is contradictory. METHODS: We conducted a prospective multicentre case-control study in Spain, comparing clinical presentation, outcomes and microbial aetiology of HCAP and community-acquired pneumonia (CAP) patients matched by age (±10 years), gender and period of admission (±10 weeks). RESULTS: 476 patients (238 cases, 238 controls) were recruited for 2 years from June 2008. HCAP cases showed significantly more comorbidities (including dysphagia), higher frequency of previous antibiotic use in the preceding month, higher pneumonia severity score and worse clinical status (Charslon and Barthel scores). While microbial aetiology did not differ between the two groups (HCAP and CAP: Streptococcus pneumoniae: 51% vs 55%; viruses: 22% vs 12%; Legionella: 4% vs 9%; Gram-negative bacilli: 5% vs 4%; Pseudomonas aeruginosa: 4% vs 1%), HCAP patients showed worse mortality rates (1-month: HCAP, 12%; CAP 5%; 1-year: HCAP, 24%; CAP, 9%), length of hospital stay (9 vs 7 days), 1-month treatment failure (5.5% vs 1.5%) and readmission rate (18% vs 11%) (p<0.05, each). CONCLUSIONS: Despite a similar clinical presentation, HCAP was more severe due to patients' conditions (comorbidities) and showed worse clinical outcomes. Microbial aetiology of HCAP did not differ from CAP indicating that it is not related to increased mortality and in Spain most HCAP patients do not need nosocomial antibiotic coverage.

Compliance with guidelines-recommended processes in pneumonia: impact of health status and initial signs.

Initial care has been associated with improved survival of community-acquired pneumonia (CAP). We aimed to investigate patient comorbidities and health status measured by the Charlson index and clinical signs at diagnosis associated with adherence to recommended processes of care in CAP. We studied 3844 patients hospitalized with CAP. The evaluated recommendations were antibiotic adherence to Spanish guidelines, first antibiotic dose <6 hours and oxygen assessment. Antibiotic adherence was 72.6%, first dose <6 h was 73.4% and oxygen assessment was 90.2%. Antibiotic adherence was negatively associated with a high Charlson score (Odds ratio [OR], 0.91), confusion (OR, 0.66) and tachycardia ≥100 bpm (OR, 0.77). Delayed first dose was significantly lower in those with tachycardia (OR, 0.75). Initial oxygen assessment was negatively associated with fever (OR, 0.61), whereas tachypnea ≥30 (OR, 1.58), tachycardia (OR, 1.39), age >65 (OR, 1.51) and COPD (OR, 1.80) were protective factors. The combination of antibiotic adherence and timing <6 hours was negatively associated with confusion (OR, 0.69) and a high Charlson score (OR, 0.92) adjusting for severity and hospital effect, whereas age was not an independent factor. Deficient health status and confusion, rather than age, are associated with lower compliance with antibiotic therapy recommendations and timing, thus identifying a subpopulation more prone to receiving lower quality care.

Guidelines for the treatment of community-acquired pneumonia: predictors of adherence and outcome.

RATIONALE: Some studies highlight the association of better clinical responses with adherence to guidelines for empiric treatment of community-acquired pneumonia (CAP), but little is known about factors that influence this adherence. OBJECTIVES: Our objectives were to identify factors influencing adherence to the guidelines for empiric treatment of CAP, and to evaluate the impact of adherence on outcome. METHODS: We studied 1,288 patients with CAP admitted to 13 Spanish hospitals. Collected variables included the patients' clinical and demographic data, initial severity of the disease, antibiotic treatment, and specialty and training status of the prescribing physician. MEASUREMENTS AND MAIN RESULTS: Adherence to guidelines was high (79.7%), with significant differences between hospitals (range, 47-97%) and physicians (pneumologists, 81%; pneumology residents, 84%; nonpneumology residents, 82%; other specialists, 67%). The independent factors related to higher adherence were hospital, physician characteristics, and initial high-risk class of Fine, whereas admission to intensive care unit decreased adherence. Seventy-four patients died (6.1%), and treatment failure was found in 175 patients (14.2%). After adjusting for Fine risk class, adherence to the guidelines was found protective for mortality (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.3-0.9) and for treatment failure (OR, 0.65; 95% CI, 0.5-0.9). Treatment prescribed by pneumologists and residents was associated with lower treatment failure (OR, 0.6; 95% CI, 0.4-0.9). CONCLUSIONS: Adherence to guidelines mainly depends on the hospital and the specialty and training status of prescribing physicians. Nonadherence was higher in nonpneumology specialists, and is an independent risk factor for treatment failure and mortality.

Reaching stability in community-acquired pneumonia: the effects of the severity of disease, treatment, and the characteristics of patients.

BACKGROUND: The natural history of the resolution of infectious parameters in patients with community-acquired pneumonia (CAP) is not completely known. The aim of our study was to identify those factors related to host characteristics, the severity of pneumonia, and treatment that influence clinical stability. METHODS: In a prospective, multicenter, observational study, we observed 1424 patients with CAP who were admitted to 15 Spanish hospitals. The main outcome variable was the number of days needed to reach clinical stability (defined as a temperature of or=90 mm Hg, and oxygen saturation >or=90% or arterial oxygen partial pressure of >or=60 mm Hg). RESULTS: The median time to stability was 4 days. A Cox proportional hazard model identified 6 independent variables recorded during the first 24 h after hospital admission related to the time needed to reach stability: dyspnea (hazard ratio [HR], 0.76), confusion (HR, 0.66), pleural effusion (HR, 0.67), multilobed CAP (HR, 0.72), high pneumonia severity index (HR, 0.73), and adherence to the Spanish guidelines for treatment of CAP (HR, 1.22). A second Cox model was performed that included complications and response to treatment. This model identified the following 10 independent variables: chronic bronchitis (HR, 0.81), dyspnea (HR, 0.79), confusion (HR, 0.61), multilobed CAP (HR, 0.84), initial severity of disease (HR, 0.73), treatment failure (HR, 0.31), cardiac complications (HR, 0.66), respiratory complications (HR, 0.77), empyema (HR, 0.57), and admission to the intensive care unit (HR, 0.57). CONCLUSIONS: Some characteristics of CAP are useful at the time of hospital admission to identify patients who will need a longer hospital stay to reach clinical stability. Empirical treatment that follows guidelines is associated with earlier clinical stability. Complications and treatment failure delay clinical stability.

Immunodetection of pneumolysin in human urine by ELISA.

An ELISA test has been employed for the detection of pneumolysin (PLY) in urine from 14 pneumococcal pneumonia patients and from 11 healthy adult volunteers. The urines of all the 11 healthy adult volunteers developed signals around the mean of the blanks, whereas all the pneumococcal pneumonia patient urines rendered signals at least five times this mean. Chemiluminescent Western blot analyses of these urines, carried out with the PLY-specific rabbit polyclonal IgG preparation used in ELISA, were negative. The 30-kDa filtrates of three high-signal urines were ELISA negative, suggesting that this ELISA test mainly detected high molecular weight forms in urine rather than free PLY-derived antigenic fragments. The urine sample, which rendered the highest ELISA signal, was then concentrated by filtration through a 10-kDa filter. When this concentrate was subjected to Western blot with the ELISA-capture monoclonal antibody, a major band was developed. Its relative molecular mass was similar to that of recombinant PLY and its peptide mass fingerprinting showed peptides corresponding to amino acid stretches from the four domains of the PLY molecule. When the pool of PLY-negative urines was sham-contaminated with purified recombinant pneumolysin, a conspicuous matrix effect was observed; nevertheless, this ELISA test was still reproducible and highly sensitive, detecting pneumolysin in the order of picograms per milliliter. A comparison was also made between this PLY-ELISA and the Binax NOW Streptococcus pneumoniae Urinary Antigen Test in analysing bacterial isolates. On the basis of the minimum number of pneumococci examined, both tests were shown to have similar potency, but strain-dependent discrepancies were observed. This ELISA could provide an alternative to the Binax NOW Streptococcus pneumoniae Urinary Antigen Test in the diagnosis of pneumococcal pneumonia.