Real-world corticosteroid use in severe pneumonia: a propensity-score-matched study.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide despite correct antibiotic use. Corticosteroids have long been evaluated as a treatment option, but heterogeneous effects on survival have precluded their widespread implementation. We aimed to evaluate whether corticosteroids might improve clinical outcomes in patients with severe CAP and high inflammatory responses. STUDY DESIGN AND METHODS: We analyzed two prospective observational cohorts of patients with CAP in Barcelona and Rome who were admitted to intensive care with a high inflammatory response. Propensity score (PS) matching was used to obtain balance among the baseline variables in both groups, and we excluded patients with viral pneumonia or who received hydrocortisone. RESULTS: Of the 610 patients admitted with severe CAP, 198 (32%) received corticosteroids and 387 had major criteria for severe CAP. All patients had a baseline serum C-reactive protein above 15 mg/dL. Patients who received corticosteroids were more commonly male, had more comorbidities (e.g., cancer or chronic obstructive pulmonary disease), and presented with significantly higher sequential organ failure assessment scores. Eighty-nine patients met major severity criteria (invasive mechanical ventilation and/or septic shock) and were matched per group. Twenty-eight-day mortality was lower among patients receiving corticosteroids (16 patients, 18%) than among those not receiving them (28 patients, 31%; p = 0.037). After PS matching, corticosteroid therapy reduced the 28-day mortality risk in patients who met major severity criteria (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.29-0.98) (p = 0.043). In patients who did not meet major severity criteria, no benefits were observed with corticosteroid use (HR 0.88 (95%CI 0.32-2.36). CONCLUSIONS: Corticosteroid treatment may be of benefit for patients with CAP who have septic shock and/or a high inflammatory response and requirement for invasive mechanical ventilation. Corticosteroids appear to have no impact on mortality when these features are not present.

Risk factors associated with mortality among elderly patients with COVID-19: Data from 55 intensive care units in Spain.

INTRODUCTION AND OBJECTIVES: Critically-ill elderly ICU patients with COVID-19 have poor outcomes. We aimed to compare the rates of in-hospital mortality between non-elderly and elderly critically-ill COVID-19 ventilated patients, as well as to analyze the characteristics, secondary outcomes and independent risk factors associated with in-hospital mortality of elderly ventilated patients. PATIENTS AND METHODS: We conducted a multicentre, observational cohort study including consecutive critically-ill patients admitted to 55 Spanish ICUs due to severe COVID-19 requiring mechanical ventilation (non-invasive respiratory support [NIRS; include non-invasive mechanical ventilation and high-flow nasal cannula] and invasive mechanical ventilation [IMV]) between February 2020 and October 2021. RESULTS: Out of 5,090 critically-ill ventilated patients, 1,525 (27%) were aged ≥70 years (554 [36%] received NIRS and 971 [64%] received IMV. In the elderly group, median age was 74 years (interquartile range 72-77) and 68% were male. Overall in-hospital mortality was 31% (23% in patients <70 years and 50% in those ≥70 years; p<0.001). In-hospital mortality in the group ≥70 years significantly varied according to the modality of ventilation (40% in NIRS vs. 55% in IMV group; p<0.001). Factors independently associated with in-hospital mortality in elderly ventilated patients were age (sHR 1.07 [95%CI 1.05-1.10], p<0.001); previous admission within the last 30 days (sHR 1.40 [95%CI 1.04-1.89], p = 0.027); chronic heart disease (sHR 1.21 [95%CI 1.01-1.44], p = 0.041); chronic renal failure (sHR 1.43 [95%CI 1.12- 1.82], p = 0.005); platelet count (sHR 0.98 [95% CI 0.98-0.99], p<0.001); IMV at ICU admission (sHR 1.41 [95% CI 1.16- 1.73], p<0.001); and systemic steroids (sHR 0.61 [95%CI 0.48- 0.77], p<0.001). CONCLUSIONS: Amongst critically-ill COVID-19 ventilated patients, those aged ≥70 years presented significantly higher rates of in-hospital mortality than younger patients. Increasing age, previous admission within the last 30 days, chronic heart disease, chronic renal failure, platelet count, IMV at ICU admission and systemic steroids (protective) all comprised independent factors for in-hospital mortality in elderly patients.

Impact of outdoor air pollution on severity and mortality in COVID-19 pneumonia.

The relationship between exposure to air pollution and the severity of coronavirus disease 2019 (COVID-19) pneumonia and other outcomes is poorly understood. Beyond age and comorbidity, risk factors for adverse outcomes including death have been poorly studied. The main objective of our study was to examine the relationship between exposure to outdoor air pollution and the risk of death in patients with COVID-19 pneumonia using individual-level data. The secondary objective was to investigate the impact of air pollutants on gas exchange and systemic inflammation in this disease. This cohort study included 1548 patients hospitalised for COVID-19 pneumonia between February and May 2020 in one of four hospitals. Local agencies supplied daily data on environmental air pollutants (PM10, PM2.5, O3, NO2, NO and NOX) and meteorological conditions (temperature and humidity) in the year before hospital admission (from January 2019 to December 2019). Daily exposure to pollution and meteorological conditions by individual postcode of residence was estimated using geospatial Bayesian generalised additive models. The influence of air pollution on pneumonia severity was studied using generalised additive models which included: age, sex, Charlson comorbidity index, hospital, average income, air temperature and humidity, and exposure to each pollutant. Additionally, generalised additive models were generated for exploring the effect of air pollution on C-reactive protein (CRP) level and SpO2/FiO2 at admission. According to our results, both risk of COVID-19 death and CRP level increased significantly with median exposure to PM10, NO2, NO and NOX, while higher exposure to NO2, NO and NOX was associated with lower SpO2/FiO2 ratios. In conclusion, after controlling for socioeconomic, demographic and health-related variables, we found evidence of a significant positive relationship between air pollution and mortality in patients hospitalised for COVID-19 pneumonia. Additionally, inflammation (CRP) and gas exchange (SpO2/FiO2) in these patients were significantly related to exposure to air pollution.

Severity and outcomes of hospitalised community-acquired pneumonia in COPD patients.

Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with community-acquired pneumonia (CAP). We investigated the impact of COPD on outcomes of CAP patients. We prospectively studied the clinical presentation of 1,379 patients admitted with CAP during a 4-yr period. A comparative analysis of disease severity and course was performed between 212 patients with COPD, as confirmed by spirometry, and 1,167 non-COPD patients. COPD patients (mean forced expiratory volume in 1 s 47.7 ± 16.3% predicted) were older and more likely to have previously received antibiotics (37.1% versus 28.3%; p<0.01) than those without COPD. They presented with more severe respiratory failure (arterial oxygen tension/inspiratory oxygen fraction 270.4 versus 287.8; p<0.01) and more severe pneumonia (pneumonia severity index 118.3 versus 108.5; p<0.001) compared with non-COPD patients. However, COPD patients had less multilobar infiltration (44 (21%) versus 349 (30%); p<0.01) and fewer pulmonary complications (24 (14%) versus 241 (24%); p<0.01). A total of 89 (6.5%) patients died within 30 days. COPD patients had no significant difference in their 30-day mortality rate compared with non-COPD patients (nine (4.2%) patients versus 81 (7%); p = 0.14). Despite worse clinical presentation, COPD patients had a similar mortality rate compared to non-COPD patients. Previous antibiotic treatment and the decreased incidence of pulmonary complications in COPD may account for these findings.

Steroid therapy and antiviral treatment in SARS-CoV-2 pneumonia: clinical contexts and indications.

Critically ill patients with COVID-19 face a higher risk of disease progression and complications. The current standard of care includes supportive care measures and fluid management. The Recovery trial observed a reduction in all-cause, 28-day mortality (p<0.001) when patients with COVID-19 requiring oxygen therapy received 6 mg of dexamethasone per day for 10 days. In contrast, in patients not requiring oxygen, no benefit was observed: 28-day mortality rates for the dexamethasone and routine care groups were 17.8% and 14%, respectively. To corroborate these results, the World Health Organization (WHO) performed a meta-analysis. The study showed that the use of systemic corticosteroids compared with routine care placebo was associated with a decrease in all-cause, 28-day mortality. With respect to the effectiveness of remdesivir, the ACTT-1 trial found that the drug conferred a benefit on time to clinical improvement. The subgroup analysis in the clinical trial also showed a benefit per mortality in patients requiring supplemental oxygen, albeit not those in need of mechanical ventilation.

Aspiration pneumonia.

The growing population of older people worldwide represents a great challenge for health systems. The elderly are at increased risk of infectious diseases such as pneumonia, which is associated with increased morbidity and mortality related mainly to age-related physiological changes in the immune system (immunosenescence), the presence of multiple chronic comorbidities, and frailty. In pneumonia, microaspiration is recognized as the main pathogenic mechanism; while macroaspiration which refers to the aspiration of a large amount of oropharyngeal or upper gastrointestinal content passing through the vocal cords and trachea into the lungs is identified as "aspiration pneumonia". Although there are strategies for the prevention and management of patients with pneumonia that have been shown to be effective in older people with pneumonia, more research is needed on aspiration pneumonia, its risk factors and outcomes, especially since there are no specific criteria for its diagnosis and consequently, the studies on aspiration pneumonia include heterogeneous populations.

Ceftaroline in severe community-acquired pneumonia.

Severe community-acquired pneumonia (SCAP) is associated with high mortality. Factor such as early adequate antibiotic therapy, delay in intensive care unit (ICU) care and pneumonia caused by resistant pathogens are associated with worse outcomes in SCAP patients. Ceftaroline is a fifth-generation cephalosporin with bactericidal activity against Gram-positive pathogens (including methicillin-resistant Staphylococcus aureus [MRSA] and multidrug-resistant Streptococcus pneumoniae) and common Gram-negative organisms. The efficacy and safety for the treatment of pneumonia was evaluated in three randomized control trials were ceftaroline demonstrated superiority against ceftriaxone for the treatment of pneumonia in hospitalized patients with Pneumonia Severity Index (PSI) III - IV.

Factors associated with inflammatory cytokine patterns in community-acquired pneumonia.

Raised systemic levels of interleukin (IL)-6 and IL-10 cytokines have been associated with poorer outcome in community-acquired pneumonia. The aim of our study was to identify potential associated factors with increased levels of IL-6, IL-10, or both cytokines. We performed a prospective study of 685 patients admitted to hospital with community-acquired pneumonia. IL-6 and IL-10 were measured in blood in the first 24 h. 30-day mortality increased from 4.8% to 11.4% (p = 0.003) when both cytokines were higher than the median. Independent associated factors with an excess of IL-6 were neurologic disease, confusion, serum sodium < 130 mEq·L⁻¹, pleural effusion, and bacteraemia. The associated factors for an excess of IL-10 were respiratory rate ≥ 30 breaths·min⁻¹, systolic blood pressure < 90 mmHg and glycaemia ≥ 250 mg·dL⁻¹. The independent associated factors for an excess of both cytokines were confusion, systolic blood pressure < 90 mmHg, pleural effusion and bacteraemia. Protective factors were prior antibiotic treatment and pneumococcal vaccination. Different independent factors are related to an excess of IL-6 and IL-10. Confusion, hypotension, pleural effusion and bacteraemia were associated with the inflammatory profile with the highest mortality rate, whereas anti-pneumococcal vaccination and previous antibiotic treatment appeared to be protective factors.

Influenza pneumonia: a comparison between seasonal influenza virus and the H1N1 pandemic.

We compared clinical presentation, complications and outcome in patients with influenza A (H1N1) and seasonal influenza pneumonia. The group of patients with influenza A (H1N1) pneumonia consisted of 75 patients. 52 patients with pneumonia associated with seasonal influenza were included for comparison. Patients with pneumonia associated with novel H1N1 influenza were younger (mean age 39.7 yrs versus 69.6 yrs) and had fewer chronic comorbidities and less alcoholism. Infiltrates were more extensive and frequently interstitial. Respiratory failure was more frequent (those with an arterial oxygen tension/inspiratory oxygen fraction ratio <200 28% versus 12%, p = 0.042), leading to a higher rate of intensive care unit (ICU) admission and mechanical ventilation (29.3% versus 7.7% (p<0.0030) and 18.7% versus 2% (p<0.0045)). Mortality was twice as high in patients with novel H1N1 (12% versus 5.8%; p = 0.238), although this was not significant, and was attributable to pneumonia in most instances (77.8% versus 0%; p = 0.046). Younger age, fewer comorbidities, more extensive radiographic extension and more severe respiratory compromise, and ICU admissions are key features of the clinical presentation of patients with novel H1N1-associated pneumonia compared with seasonal influenza pneumonia.

Nursing home-acquired pneumonia: a 10 year single-centre experience.

BACKGROUND: Pneumonia among nursing home (NH) residents has increased considerably in recent years, but it remains unclear whether it should be considered as community-acquired pneumonia (CAP) or a new category of infection. METHODS: 150 consecutive cases of NH-acquired pneumonia (NHAP) (from 1 February 1997 to 1 July 2007) were analysed. RESULTS: Patients (median age, 82 years; range, 77-87 years) showed numerous co-morbidities, (neurological, 55%; pulmonary, 38%; cardiac, 35%) and severe disability for daily activities (partial, 32%; total, 31%). Cases of NHAP were mainly classified as mild to moderate according to the CRB-65 score (CRB-65 classes 0-1 and 2, 41% each). In-hospital and 30-day mortality were 8.7% and 20%, respectively. Aetiology was defined in 57 cases (38%). The most common isolates were Streptococcus pneumoniae (58%), Enterobacteriaceae (Gram-negative bacteria (GNB)) (9%), atypical bacteria (7%), respiratory viruses (5%), methicillin-resistant Staphylococcus aureus (MRSA) (5%) and Legionella pneumophila (5%). The most frequent causes of treatment inadequacy were use of beta-lactams alone (25%) and lack of aspiration assessment (15%). Prognostic factors of 1-month mortality were neurological comorbidities (OR 4.5; 95% CI 1.3 to 15.7; p=0.020), septic shock (OR 6.6; 95% CI 1.3 to 34.0; p=0.025), pleural effusion (OR 3.6; 95% CI 1.1 to 11.7; p=0.036) and isolation of GNB or MRSA (OR 16.4; 95% CI 2.1 to 128.9; p=0.008). CONCLUSIONS: The patients show clinical characteristics (eg, age and co-morbidities) comparable with those with hospital-acquired pneumonia. However, microbiological and mortality data of patients with NHAP are more similar to the data of those with CAP. Isolation of GNB or MRSA was associated with increased mortality risk. CAP empirical antibiotic coverage is still indicated in NHAP, although specific risk factors for multidrug-resistant infections should be assessed on an individual basis.

Ceftobiprole for the treatment of pneumonia.

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.

Effectiveness of combination therapy versus monotherapy with a third-generation cephalosporin in bacteraemic pneumococcal pneumonia: A propensity score analysis.

OBJECTIVE: Combining a macrolide or a fluoroquinolone to beta-lactam regimens in the treatment of patients with moderate to severe community-acquired pneumonia is recommended by the international guidelines. However, the information in patients with bacteraemic pneumococcal pneumonia is limited. METHODS: A propensity score technique was used to analyze prospectively collected data from all patients with bacteraemic pneumococcal pneumonia admitted from 2000 to 2015 in our institution, who had received empirical treatment with third-generation cephalosporin in monotherapy or plus macrolide or fluoroquinolone. RESULTS: We included 69 patients in the monotherapy group and 314 in the combination group. After adjustment by PS for receiving monotherapy, 30-day mortality (OR 2.89; 95% CI 1.07-7.84) was significantly higher in monotherapy group. A higher 30-day mortality was observed in monotherapy group in both 1:1 and 1:2 matched samples although it was statistically significant only in 1:2 sample (OR: 3.50 (95% CI 1.03-11.96), P = 0.046). CONCLUSIONS: Our study suggests that in bacteraemic pneumococcal pneumonia, empirical therapy with a third-generation cephalosporin plus a macrolide or a fluoroquinolone is associated with a lower mortality rate than beta-lactams in monotherapy. These results support the recommendation of combination therapy in patients requiring admission with moderate to severe disease.

Empirical treatment of adults with hospital-acquired pneumonia: lights and shadows of the 2016 Clinical Practice ATS/IDSA Guidelines.

Hospital-acquired pneumonia (HAP) is a common cause of nosocomial infection associated with significant morbidity and mortality. New clinical practice guidelines for the management of adults with hospital-acquired pneumonia have been published in 2016 by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS). This review focuses on the recent recommendations and their limitations. We also focus on new therapeutic options that might improve the treatment and outcomes of these patients.

Pulmonary complications of pneumococcal community-acquired pneumonia: incidence, predictors, and outcomes.

The aim of this study was to evaluate the clinical characteristics, predictors and outcomes of pneumococcal pneumonia developing pulmonary complications and the distribution of pneumococcal serotypes. It was a prospective study including all adult patients admitted to the Hospital Clinic of Barcelona, Spain (2001-2009) with the diagnosis of pneumococcal pneumonia. Microbiological investigation was systematically performed, including antimicrobial susceptibility and serotype distribution (only invasive strains isolated during 2006-2009). Complicated pneumonia was defined as the presence of one or more pulmonary complications: pleural effusion, empyema, or multilobar infiltrates. We included 626 patients, and 235 (38%) had the following pulmonary complications: pleural effusion, 122 (52%); empyema, 18 (8%); and multilobar infiltration, 151 (64%). Forty-six (20%) patients had more than one complication. Patients with pulmonary complications showed a higher rate of intensive-care unit admission (34% vs. 13%, p <0.001), a higher rate of shock (16% vs. 7%, p <0.001), a longer length of stay (9 days vs. 6 days, p <0.001), and a lower rate of penicillin resistance (14% vs. 25%, p 0.013), but similar mortality (9% vs. 8%). No significant differences were observed in the serotype distribution between complicated and uncomplicated pneumonia. Chronic obstructive pulmonary disease (COPD) (OR 0.38, 95% CI 0.23-0.63; p <0.001) was a protective factor against pulmonary complications, whereas chronic liver disease (OR 3.60, 95% CI 1.71-7.60; p 0.001), admission C-reactive protein level ≥18 mg/dL (OR 2.77, 95% CI 1.91-4.00; p <0.001) and admission creatinine level >1.5 mg/dL (OR 2.01, 95% CI 1.31-3.08; p 0.001) were risk factors for pulmonary complications. Complicated pneumonia was characterized by a more severe clinical presentation, but was not associated with increased mortality. Resistance to antibiotics was lower in complicated cases. No significant differences were observed in the serotype distribution between complicated and uncomplicated pneumonia. In the multivariate analysis, COPD was a protective factor against pulmonary complications.