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Background: Vaccination against 5 prominent meningococcal serogroups (A/B/C/W/Y) is necessary for broad disease protection. We report immunopersistence through 4 years after a 2-dose (6-month interval) pentavalent MenABCWY primary vaccine series and safety and immunogenicity of a booster administered 4 years after primary vaccination., Methods: This randomized, active-controlled, observer-blinded study was conducted in the United States and Europe. In stage 1, healthy MenACWY vaccine-naive or -experienced 10- to 25-year-olds were randomized 1:2 to receive MenABCWY and placebo or MenB-fHbp and MenACWY-CRM. Eligible participants were randomly selected to participate in stage 2, which was an open-label immunopersistence and booster extension. Immunogenicity was assessed through serum bactericidal antibody using human complement (hSBA) assays with serogroups A/C/W/Y (MenA/C/W/Y) and 4 primary serogroup B (MenB) test strains. Immunogenicity endpoints included hSBA seroprotection rates through 48 months after primary vaccination and 1 month after the booster. Safety endpoints included booster reactogenicity events and adverse events (AEs)., Results: Of 1379 eligible participants, 353 entered stage 2; 242 completed the 48-month blood draw after primary vaccination and 240 completed the booster vaccination phase. MenA/C/W/Y seroprotection rates remained high for 4 years following a 2-dose MenABCWY primary series (MenACWY-naive, 62.0 %-100.0 %; MenACWY-experienced, 98.7 %-100.0 %) and trended higher than those after a single MenACWY-CRM dose (MenACWY-naive, 38.1 %-95.2 %; MenACWY-experienced, 89.7 %-100.0 %). Corresponding seroprotection rates against MenB remained stable and generally higher than baseline (MenABCWY, 18.2 %-36.6 %; MenB-fHbp, 16.2 %-31.9 % across strains). Following a booster, seroprotection rates against all 5 serogroups were ≥ 93.8 % across groups. Most booster dose reactogenicity events were mild or moderate in severity, and AEs were infrequent., Conclusions: Immune responses remained high for MenA/C/W/Y and above baseline for MenB through 4 years after the MenABCWY primary series, with robust responses for all 5 serogroups observed following a booster. The MenABCWY booster had an acceptable safety and tolerability profile consistent with the primary series. NCT03135834., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. James Peterson reports a relationship with Pfizer Inc. that includes: funding grants. Dr. Daniel Drazab reports a relationship with Pfizer Inc. that includes: funding grants. Dr. Beth Moughan reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. Dr. Jason D. Maguire reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. Dr. Lefteris Zolotas reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. Roger Maansson reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. Dr. Robert O'Neill reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. Dr. Paula Payrani reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. Dr. Luis Jodar reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. Dr. William C. Gruber reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. Dr. Annaliesa S. Anderson reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. Dr. Johannes Beeslaar reports a relationship with Pfizer Inc. that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Pfizer Inc. Published by Elsevier Ltd.. All rights reserved.)

Background: Assessing the likelihood for Legionella sp. in community-acquired pneumonia is important because of differences in treatment regimens. Currently used antigen tests and culture have limited sensitivity with important time delays, making empirical broad-spectrum coverage necessary. Therefore, a score with 6 variables recently has been proposed. We sought to validate these parameters in an independent cohort., Methods: We analyzed adult patients with community-acquired pneumonia from a large multinational database (Community Acquired Pneumonia Organization) who were treated between 2001 and 2012 with more than 4 of the 6 prespecified clinical variables available. Association and discrimination were assessed using logistic regression analysis and area under the curve (AUC)., Results: Of 1939 included patients, the infectious cause was known in 594 (28.9%), including Streptococcus pneumoniae in 264 (13.6%) and Legionella sp. in 37 (1.9%). The proposed clinical predictors fever, cough, hyponatremia, lactate dehydrogenase, C-reactive protein, and platelet count were all associated or tended to be associated with Legionella cause. A logistic regression analysis including all these predictors showed excellent discrimination with an AUC of 0.91 (95% confidence interval, 0.87-0.94). The original dichotomized score showed good discrimination (AUC, 0.73; 95% confidence interval, 0.65-0.81) and a high negative predictive value of 99% for patients with less than 2 parameters present., Conclusions: With the use of a large independent patient sample from an international database, this analysis validates previously proposed clinical variables to accurately rule out Legionella sp., which may help to optimize initial empiric therapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Nursing home-acquired pneumonia (NHAP) is the leading cause of death among long-term care patients and the second most common cause of transfers to acute care facilities. The aim of this study was to characterize the incidence, microbiology, and outcomes for hospitalized patients with community-acquired pneumonia (CAP) and NHAP., Methods: A secondary analysis of 5,160 patients from the Community-Acquired Pneumonia Organization database was performed. World regions were defined as the United States and Canada (I), Latin America (II), and Europe (III)., Results: From a total of 5,160 hospitalized patients with CAP, NHAP was identified in 287 (5.6%) patients. Mean age was 80 y. NHAP distribution by region was 6% in region I, 3% in region II, and 7% in region III. Subjects with NHAP had higher frequencies of neurological disease, diabetes mellitus, congestive heart failure, and renal failure than did subjects with CAP (P < .001). ICU admission was required in 32 (12%) subjects. Etiology was defined in 68 (23%) subjects with NHAP and 1,300 (27%) with CAP. The most common pathogens identified in NHAP included Streptococcus pneumoniae (31%), Staphylococcus species (31%), and Pseudomonas aeruginosa (7%). Presentation of NHAP more frequently included pleural effusions (34% vs 21%, P < .001) and multilobar involvement (31% vs 24%, P < .001). Thirty-day hospital mortality was statistically greater among subjects with NHAP than among those with CAP (42% vs 18%, P < .001)., Conclusions: Worldwide, only a very small proportion of hospitalized patients with CAP present with NHAP; the poor outcomes for these patients may be due primarily to a higher number of comorbidities compared with patients without NHAP., (Copyright © 2014 by Daedalus Enterprises.)

Background: Community-acquired pneumonia (CAP) causes considerable worldwide mortality, but limited data compare the mortality in different regions of the world. Our objective was to determine if there was a difference in mortality among hospitalized patients with CAP in three continental regions of the world., Methods: This was a cohort study of patients hospitalized for CAP between November 2001 and December 2011 from 70 institutions in 16 countries in US/Canada, Europe and Latin America; the Community-Acquired Pneumonia Organization (CAPO) international database. The primary outcome was mortality, and factors of interest included world region, processes of care, severity of disease, associated pathogen, specific comorbidities, and antimicrobial therapy. Multivariable logistic regression was performed to adjust for confounding effects on differences in mortality between regions. Patients were analyzed separately based on their intensive care unit admission status., Results: A total of 6371 patients were reviewed. Latin America had the highest mortality (13.3%) followed by Europe (9.1%) and the USA/Canada (7.3%) (P < 0.001 for differences between regions). Important confounding variables included comorbidities (i.e., congestive heart failure, cerebrovascular disease), elevated blood urea nitrogen level, antimicrobial therapy (macrolide or fluoroquinolone use), and whether the patient had prior vaccinations (influenza, pneumococcal). After adjustment for confounding variables, estimated differences in mortality between the three regions were significantly reduced for both patients in the ICU and the ward., Conclusions: There was an observed discrepancy in CAP mortality between three world regions. Identified factors that contributed to these differences included incidence of H1N1 infection, elevated BUN, cerebrovascular disease, macrolide use, fluoroquinolone use, and vaccinations. Treatment regimen (fluoroquinolone and macrolide use) and preventive measures (vaccinations) were variables that may be modified to help alleviate the differences., (Copyright © 2013 Elsevier Ltd. All rights reserved.)