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Background: Community-acquired pneumonia (CAP) has a potential complication of bacteremia. The objective of this study was to define the clinical outcomes of patients with CAP and bacteremia treated with and without a macrolide. Materials and methods: Secondary analysis of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP. Patients with a positive blood culture were categorized based on the presence or absence of a macrolide in their initial antimicrobial regimen, and severity of their CAP. Outcomes included in-hospital all-cause mortality, 30-day mortality, length of stay, and time to clinical stability. Results: Among 549 patients with CAP and bacteremia, 247 (45%) were treated with a macrolide and 302 (55%) were not. The primary pathogen was Streptococcus pneumoniae (74%). Poisson regression with robust error variance models were used to compare the adjusted effects of each study group on the outcomes. The unadjusted 30-day mortality was 18.4% in the macrolide group, and 29.6% in the non-macrolide group (adjusted relative risk (aRR)0.81; 95% confidence interval (CI)0.50–1.33; P = 0.41). Unadjusted in-hospital all-cause mortality was 7.3% in the macrolide group, and 18.9% in the non-macrolide group (aRR 0.54, 95% CI 0.30–0.98; P = 0.043). Length of stay and time to clinical stability were not significantly different. Conclusions: In-hospital mortality, but not 30-day mortality, was significantly better in the macrolide group. Our data support the use of a macrolide in hospitalized patients with CAP and bacteraemia

© 2018 Background: Community-acquired pneumonia (CAP) has a potential complication of bacteremia. The objective of this study was to define the clinical outcomes of patients with CAP and bacteremia treated with and without a macrolide. Materials and methods: Secondary analysis of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP. Patients with a positive blood culture were categorized based on the presence or absence of a macrolide in their initial antimicrobial regimen, and severity of their CAP. Outcomes included in-hospital all-cause mortality, 30-day mortality, length of stay, and time to clinical stability. Results: Among 549 patients with CAP and bacteremia, 247 (45%) were treated with a macrolide and 302 (55%) were not. The primary pathogen was Streptococcus pneumoniae (74%). Poisson regression with robust error variance models were used to compare the adjusted effects of each study group on the outcomes. The unadjusted 30-day mortality was 18.4% in the macrolide group, and 29.6% in the non-macrolide group (adjusted relative risk (aRR)0.81; 95% confidence interval (CI)0.50–1.33; P = 0.41). Unadjusted in-hospital all-cause mortality was 7.3% in the macrolide group, and 18.9% in the non-macrolide group (aRR 0.54, 95% CI 0.30–0.98; P = 0.043). Length of stay and time to clinical stability were not significantly different. Conclusions: In-hospital mortality, but not 30-day mortality, was significantly better in the macrolide group. Our data support the use of a macrolide in hospitalized patients with CAP and bacteraemia.

The role and relationship between pro- and anti-inflammatory cytokines represents one of the least studied aspects of the pathogenesis of community-acquired pneumonia (CAP). The aim of the present study was to evaluate pro- and anti-inflammatory cytokines at both local (lung) and systemic (blood) levels and their relationship with the severity of the disease on admission and time for a patient to reach clinical stability during hospitalisation.

The aim of the present study was to define the prevalence, characteristics, risk factors and impact on clinical outcomes of acute myocardial infarction (AMI) versus other cardiovascular events (CVEs) in patients with community-acquired pneumonia (CAP). This was an international, multicentre, observational, prospective study of CAP patients hospitalised in eight hospitals in Italy and Switzerland. Three groups were identified: those without CVEs, those with AMI and those with other CVEs. Among 905 patients, 21 (2.3%) patients experienced at least one AMI, while 107 (11.7%) patients experienced at least one other CVE. Patients with CAP and either AMI or other CVEs showed a higher severity of the disease than patients with CAP alone. Female sex, liver disease and the presence of severe sepsis were independent predictors for the occurrence of AMI, while female sex, age >65 years, neurological disease and the presence of pleural effusion predicted other CVEs. In-hospital mortality was significantly higher among those who experienced AMI in comparison to those experiencing other CVEs (43% versus 21%, p=0.039). The presence of AMI showed an adjusted odds ratio for in-hospital mortality of 3.57 (p=0.012) and for other CVEs of 2.63 (p=0.002). These findings on AMI versus other CVEs as complications of CAP may be important when planning interventional studies on cardioprotective medications.

The objective of this study was to compare systemic and local cytokine profiles and neutrophil responses in patients with severe versus non-severe community-acquired pneumonia (CAP). Hospitalized patients with CAP were grouped according to the pneumonia severity index (PSI), as non-severe (PSI < 91 points) or severe (PSI ≥ 91 points). Blood and sputum samples were collected upon admission. Compared to non-severe CAP patients, the severe CAP group showed higher plasma levels of pro- and anti-inflammatory cytokines but in contrast, lower sputum concentrations of pro-inflammatory cytokines. Blood neutrophil functional responses were elevated in CAP patients compared to healthy controls. However, neutrophils from severe CAP patients showed reduced respiratory burst activity compared to the non-severe group. Results indicate that patients with severe CAP fail to mount a robust local pro-inflammatory response but exhibit instead a more substantial systemic inflammatory response, suggesting that a key driver of CAP severity may be the ability of the patient to generate an optimal local inflammatory response.

Background: The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) to prevent hospitalizations due to Streptococcus pneumoniae community-acquired pneumonia (SpCAP) is controversial. Recent literature suggests that vaccine effectiveness may be influenced by sex. In this study, we define the effectiveness of prior PPV23 vaccination for the prevention of hospitalizations due to SpCAP, and evaluate the impact of sex on this effectiveness. Methods: This was a nested case-control study from the CAPO international cohort study database. SpCAP was defined as CAP plus S. pneumoniae identified in blood, bronchoalveolar lavage, sputum, or urinary antigen. Vaccination with PPV23 prior to hospitalization was defined as documented in the medical record. A propensity score-weighted logistic regression model was used to calculate odds ratios. The adjusted vaccine effectiveness (aVE) was calculated as 1-adjusted odds ratio. Results: From a total of 2688 elderly adult hospitalized patients with CAP, SpCAP was identified in 279 (10%). The overall aVE was 37% (95% CI: 10.1-55.4%, P= 0.01). For males, the aVE was 34% (95% CI:-1.0% to 57.3%, P= 0.06). For females the aVE was 68% (95% CI: 40.3-83.0%, P= 0.001). Conclusions: PPV23 protects elderly patients from hospitalization due to SpCAP, but female sex drives the effectiveness. Future analysis of vaccine trials should consider the importance of sex as a stratification factor.

The 22 risk factors suggested by the Centers for Disease Control and Prevention (CDC) to suspect patents at risk for Mycobacterium tuberculosis (MTB) have not been evaluated in hospitalized patients with community-acquired pneumonia (CAP). Here, we evaluate which of the CDC risk factors best predict MTB in these patients. To our knowledge, this is the first time a score is developed assessing these risk factors.This was a secondary analysis of 6,976 patients hospitalized with CAP enrolled in the CAPO International Cohort Study. Using Poisson regression, we selected the subset of risk factors that best predicted the presence of CAP due to MTB. This subset was compared to the CDC risk factors using ROC curve analysis.Six risk factors were found to best predict CAP due to MTB: age <65, night sweats, hemoptysis, weight loss, MTB exposure, and upper lobe infiltrate. The area under the ROC curve for all CDC risk factors was 71%, and 89% for the subset of 6 risk factors.The CDC-suggested risk factors are poor at predicting the presence of MTB in hospitalized patients with CAP. With a subset of 6 risk factors identified in this study, we developed a new score, which will improve our capacity to isolate patients at risk of CAP due to MTB at the time of hospitalization.

Inflammation is a double-edged sword in the outcome of pneumonia. On the one hand, an effective and timely inflammatory response is required to eliminate the invading respiratory pathogen. On the other, a toxic and prolonged inflammatory response may result in lung injury and poor outcomes, even in those receiving advanced medical care. This review focuses on recent understanding of the dynamics of the cytokine response, neutrophil activity, and responsiveness to cytokines and neutrophil lifespan as major elements of lung inflammation resulting in favorable or poor outcomes in lung infection primarily due to pneumococcus and influenza virus. Although some progress has been made in our understanding of the molecular mechanisms of the pneumonia inflammation axis composed of cytokines modulating neutrophil activation and neutrophil apoptosis, important questions remain to be answered. The degree of neutrophil activation, generation of reactive oxygen species, and the release of granule antimicrobial peptides play a key role in microbial pathogen clearance; however, prolonged neutrophil activation may contribute to lung injury and poor outcomes in pneumonia. Molecular markers of the mechanisms regulating neutrophil survival and apoptosis may help in the identification of novel therapeutic targets to modulate inflammation by inducing timely neutrophil apoptosis. A major task is to identify the mechanisms of dysregulation in inflammation leading to toxic responses, thereby targeting a biomarker and enabling timely therapies to modulate inflammation.

Background: The effect of time of the first antimicrobial dose (TFAD) on the outcomes of community-acquired pneumonia (CAP) remains a controversy. Methods: This was an observational, retrospective study of consecutive adult patients hospitalized with CAP. TFAD was defined as the time in hours from arrival at the emergency department to the intravenous infusion of antimicrobial. All patients received appropriate antibiotic therapy according to available Infectious Diseases Society of America/American Thoracic Society guidelines during the time of our study. Multivariable analysis and a propensity score adjusted methodology were used to measure the association of TFAD with mortality, time to clinical stability (TCS), and length of stay in the hospital (LOS). Results: Data of 372 patients with CAP were studied. A total 29 (8.4%) patients died within 30 days of hospitalization. Our propensity-adjusted logistic regression model did not show a significant association between TFAD and mortality (p= 0.148). Patients who died received antimicrobials significantly earlier than survivors: 5.7. h vs. 7.5. h, respectively (p= 0.04). The LOS and TCS were not significantly affected by the TFAD; the LOS hazard ratio was 0.996 (95% confidence interval 0.97-1.02; p= 0.774) and the TCS hazard ratio was 1.01 (95% confidence interval 0.98-1.03; p= 0.604). Conclusions: TFAD does not seem to be associated with the clinical outcome of patients with CAP. Early TFAD should be considered as an important marker of optimal care of patients with CAP rather than as a factor predicting outcomes.

The American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) suggested two sets of criteria in 2001 and 2007 to define clinical stability (CS) in community-acquired pneumonia (CAP). We aim to evaluate the level of agreement between these two sets of criteria and how well they can predict clinical outcomes.A retrospective cohort study of 487 consecutive patients hospitalised with CAP. Level of agreement was tested using a survival curve analysis, while prediction of outcomes at 30-day follow-up was evaluated through receiver-operator curves (ROC).A discrepancy between ATS 2001 and ATS/IDSA 2007 criteria in identifying CS was detected in 62% of the patients. The median (IQR) time to CS was 2 (1-4) days based on ATS 2001 and 3 (2-5) days based on ATS/IDSA 2007 criteria (p=0.012). The daily distribution of patients who reached CS evaluated with both sets was different (p=0.002). The ROC analysis showed an area under the curve of 0.705 for the ATS 2001 criteria and 0.714 for ATS/IDSA 2007 criteria, p=0.645.ATS 2001 and ATS/IDSA 2007 criteria for CS in hospitalised patients with CAP are clinically equivalent and both can be used in clinical practice as well as in clinical research

BACKGROUND: Community-acquired pneumonia (CAP) severity scores can identify patients at low risk for mortality who may be suitable for ambulatory care. Here, we follow the clinical course of hospitalized patients with CAP due to 2009 H1N1 influenza. OBJECTIVE: To evaluate the role of CAP severity scores as predictors of mortality. METHODS: This was a secondary data analysis of patients hospitalized with CAP due to 2009 H1N1 influenza confirmed by reverse transcriptase polymerase chain reaction enrolled in the CAPO (Community-Acquired Pneumonia Organization) international cohort study. CAP severity scores PSI (Pneumonia Severity Index), CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥ 65 years) and CRB-65 (confusion, respiratory rate, blood pressure, age ≥ 65 years) were calculated. Actual and predicted mortality rates were compared. A total of 37 predictor variables were evaluated to define those associated with mortality. RESULTS: Data from 250 patients with CAP due to 2009 H1N1 influenza were analyzed. Patients with low predicted mortality rates (0-1.5%) had actual mortality rates ranging from 2.6% to 17.5%. Obesity and wheezing were the only novel variables associated with mortality. CONCLUSIONS: The decision to hospitalize a patient with CAP due to 2009 H1N1 influenza should not be based on current CAP severity scores, as they underestimate mortality rates in a significant number of patients. Patients with obesity or wheezing should be considered at an increased risk for mortality. © 2011 The Union.

BACKGROUND: The relationship between clinical judgment and indications of the CURB-65 score in deciding the site-of-care for patients with community-acquired pneumonia (CAP) has not been fully investigated. The aim of this study was to evaluate reasons for hospitalization of CAP patients with CURB-65 score of 0 and 1. METHODS: An observational, retrospective study of consecutive CAP patients was performed at the Fondazione Cà Granda, Milan, Italy, between January 2005 and December 2006. The medical records of hospitalized patients with CAP having a CURB-65 score of 0 and 1 were identified and reviewed to determine whether there existed a clinical basis to justify hospitalization. RESULTS: Among the 580 patients included in the study, 218 were classified with a CURB-65 score of 0 or 1. Among those, 127 were hospitalized, and reasons that justified hospitalization were found in 104 (83%) patients. Main reasons for hospitalization included the presence of hypoxemia on admission (35%), failure of outpatient therapy (14%) and the presence of cardiovascular events on admission (9.7%). Used as the sole indicator for inappropriate hospitalization, the CURB-65 score had a poor positive predictive value of 52%. CONCLUSIONS: Although the CURB-65 has been proposed as a tool to guide the site of care decision by international guidelines, this score is not ideal by itself, and should not be regarded as providing decision support information if a score of 0 and 1 is present. In CAP patients with CURB-65 scores of 0 or 1, further evaluations should be performed and completed by clinical judgment

Background: Adverse outcomes after discharge in patients hospitalized for community-acquired pneumonia (CAP) might be associated with the inflammatory response during hospitalization, recognized by the length of time needed for the patient to reach clinical stability (time to clinical stability [TCS]). The objective of this study was to assess the association between TCS and outcomes after discharge in hospitalized patients with CAP. Methods: A retrospective cohort study of consecutive patients discharged alive after an episode of CAP was conducted at the Veterans Hospital of Louisville, Kentucky, between 2001 and 2006. Results: Among the 464 patients enrolled in the study, 82 (18%) experienced an adverse outcome within 30 days after discharge, leading to either readmission or death. Patients with a TCS > 3 days showed a significantly higher rate of adverse outcomes after discharge compared with those with a TCS ≤ 3 days (26% vs 15%, respectively; OR, 1.98; 95% CI, 1.19-3.3; P = .008) as well as adverse outcomes after discharge related to pneumonia (16% vs 4.6%, respectively; OR, 4.07; 95% CI, 2-8.2; P < .001). The propensity-adjusted analysis showed that delay in reaching TCS during hospitalization was associated with a significant increased risk of adverse outcomes. Adjusted ORs comparing patients who reached TCS at days 2, 3, 4, and 5 to those who reached TCS at day 1 were 1.06, 1.54, 2.40, and 10.53, respectively. Conclusions: Patients with CAP who experienced a delay in reaching clinical stability during hospitalization are at high risk of adverse outcomes after discharge and should receive close observation and an early follow-up.