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Background: Pneumococcal conjugate vaccines (PCVs) provide strong direct protection in children, while limited data are available on their indirect effect on mortality among older age groups. This multicountry study aimed to assess the population-level impact of pediatric PCVs on all-cause pneumonia mortality among children ≥5 years of age, and invasive pneumococcal disease (IPD) cases in Chile., Methods: Demographic and mortality data from Argentina, Brazil, Chile, Colombia, and Mexico were collected considering the ≥ 5-year-old population, from 2000 to 2019, with 1 795 789 deaths due to all-cause pneumonia. IPD cases in Chile were also evaluated. Time series models were employed to evaluate changes in all-cause pneumonia deaths during the postvaccination period, with other causes of death used as synthetic controls for unrelated temporal trends., Results: No significant change in death rates due to all-cause pneumonia was detected following PCV introduction among most age groups and countries. The proportion of IPD cases caused by vaccine serotypes decreased from 29% (2012) to 6% (2022) among people aged ≥65 years in Chile., Discussion: While an effect of PCV against pneumonia deaths (a broad clinical definition that may not be specific enough to measure indirect effects) was not detected, evidence of indirect PCV impact was observed among vaccine-type-specific IPD cases., Competing Interests: Potential conflicts of interest . D. M. W. has received consulting fees from Pfizer, Merck, Affinivax, and Matrivax for work unrelated to this article; and is Principal Investigator on grants from Pfizer and Merck to Yale University for work unrelated to this article. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: People with immune-mediated inflammatory disease are at increased risk of pneumococcal pneumonia. The effectiveness of pneumococcal vaccination in people with immune-mediated inflammatory diseases has not been evaluated. We investigated the effectiveness of pneumococcal vaccination in preventing morbidity and mortality associated with pneumonia in patients with immune-mediated inflammatory diseases., Methods: In this matched case-control study, we used primary-care electronic health record data from the Clinical Practice Research Datalink Gold database in the UK, with linked hospitalisation and mortality data. Adults with incident common immune-mediated inflammatory diseases diagnosed between April 1, 1997, and Dec 31, 2019, were followed up from the first diagnosis date to the occurrence of an outcome or date of last follow-up. Cases (ie, those with an outcome of interest) were age-matched and sex-matched to up to ten contemporaneous controls by use of incidence density sampling. Outcomes were hospitalisation due to pneumonia, death due to pneumonia, or primary-care consultation for lower respiratory tract infection requiring antibiotics. We defined hospital admission for pneumonia using hospital discharge diagnoses, death due to pneumonia using death certification data, and lower respiratory tract infection as present when primary-care consultation and antibiotic prescription occurred on the same date. We used multivariable, unconditional, logistical regression and constructed three models to examine the association between pneumococcal vaccination as an exposure and each of the three outcomes., Findings: The first nested case-control analysis included 12 360 patients (7326 [59·3%] women and 5034 [40·7%] men): 1884 (15·2%) who were hospitalised due to pneumonia and 10 476 (84·8%) who were not admitted to hospital due to pneumonia. The second analysis included 5321 patients (3112 [58·5%] women and 2209 [41·5%] men): 781 (14·7%) who died due to pneumonia and 4540 (85·3%) who were alive on the index date. The third analysis included 54 530 patients (33 605 [61·6%] women and 20 925 [38·4%] men): 10 549 (19·3%) with lower respiratory tract infection treated with antibiotics and 43 981 (80·7%) without infection. In the multivariable analysis, pneumococcal vaccination was negatively associated with hospitalisation due to pneumonia (adjusted odds ratio 0·70 [95% CI 0·60-0·81]), death due to pneumonia (0·60 [0·48-0·76]), and lower respiratory tract infection treated with antibiotics (0·76 [0·72-0·80])., Interpretation: Pneumococcal vaccination is associated with protection against hospitalisation and death due to pneumonia in patients with immune-mediated inflammatory diseases, without apparent residual confounding. However, residual unmeasured confounding cannot be fully excluded in observational research, which includes nested case-control studies. These findings should also be corroborated with data from other countries, given that this study used UK-based data., Funding: National Institute for Health and Care Research., Competing Interests: Declaration of interests AA reports personal fees from UpToDate (royalty), Cadilla Pharmaceuticals (lecture fees), and Limbic (consulting), unrelated to this work. CDM is Director of the National Institute for Health and Care Research (NIHR) School for Primary Care Research. Keele University has received research funding for CDM from the NIHR and the Medical Research Council. JSNV-T was seconded to the UK Department of Health and Social Care from October, 2017, to March, 2022. He performed a one-off consultancy for MSD, which manufactures PPV23, in May, 2023. All other authors declare no competing interests. The views expressed in this manuscript are those of its authors and not necessarily those of the NIHR, the Department of Health and Social Care, or any other entity mentioned above., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aim: Animal models of fatal pneumonia caused by Streptococcus pneumoniae ( Spn ) have not been reliably generated using many strains of less virulent serotypes. Materials & methods: Pulmonary infection of a less virulent Spn serotype1 strain in the immunocompetent mice was established via the intratracheal aerosolization (ITA) route. The survival, local and systemic bacterial spread, pathological changes and inflammatory responses of this model were compared with those of mice challenged via the intratracheal instillation, intranasal instillation and intraperitoneal injection routes. Results: ITA and intratracheal instillation both induced fatal pneumonia; however, ITA resulted in better lung bacterial deposition and distribution, pathological homogeneity and delivery efficiency. Conclusion: ITA is an optimal route for developing animal models of severe pulmonary infections.

Background: Pneumococcal pneumonia (PP) is a serious infection caused by Streptococcus pneumoniae (pneumococcus), with a wide spectrum of clinical manifestations. The aim of this study was to analyze the comorbidity factors that influenced the mortality in patients with asplenia according to PP., Methods: Discharge reports from the Spanish Minimum Basic Data Set (MBDS) was used to retrospectively analyze patients with asplenia and PP, from 1997 to 2021. Elixhauser Comorbidity Index (ECI) was calculated to predict in-hospital mortality (IHM)., Results: 97,922 patients with asplenia were included and 381 cases of PP were identified. The average age for men was 63.87 years and for women 65.99 years. In all years, ECI was larger for splenectomized than for non-splenectomized patients, with men having a higher mean ECI than women. An association was found between risk factors ECI, splenectomy, age group, sex, pneumococcal pneumonia, and increased mortality (OR = 0.98; 95% CI: 0.97-0.99; p < 0.001). The IHM increased steadily with the number of comorbidities and index scores in 1997-2021., Conclusions: Asplenia remain a relevant cause of hospitalization in Spain. Comorbidities reflected a great impact in patients with asplenia and PP, which would mean higher risk of mortality., (© 2024. The Author(s).)

Objective: We aimed to investigate the impact of preceding seasonal influenza on the clinical characteristics of adult patients with invasive pneumococcal disease (IPD) in Japan., Methods: Data for 1722 adult patients with IPD were analyzed before (2017-2019) and during the COVID-19 pandemic (2020-2022)., Results: The seasonal influenza epidemic disappeared soon after the emergence of the pandemic. Compared with that before the pandemic (66.7%), we observed a lower bacteremic pneumonia proportion in patients with IPD during the pandemic (55.6%). The clinical presentations of IPD cases significantly differed between those with and without preceding influenza. The proportion of bacteremic pneumonia was higher in IPD patients with preceding influenza than in those without in both younger (44.9% vs 84.2%) and older adults (65.5% vs 87.0%) before the pandemic. The case fatality rate was significantly higher in IPD patients with preceding influenza (28.3%) than in those without (15.3%) in older adults before the pandemic (P = 0.020). Male and aging are high risk factors for death in older patients with IPD who had preceding influenza., Conclusion: Our study reveals that preceding seasonal influenza plays a role in the development of bacteremic pneumococcal pneumonia, increasing the risk of death in older adults., Competing Interests: Declaration of competing interest The authors have no competing interests relevant to this article to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: To evaluate the clinical and economic outcomes in adults hospitalized with invasive pneumococcal disease (IPD) and noninvasive all-cause pneumonia (ACP) overall and by antimicrobial resistance (AMR) status., Methods: Hospitalized adults from the BD Insights Research Database with an ICD10 code for IPD, noninvasive ACP or a positive Streptococcus pneumoniae culture/urine antigen test were included. Descriptive statistics and multivariable analyses were used to evaluate outcomes (in-hospital mortality, length of stay [LOS], cost per admission, and hospital margin [costs - payments])., Results: The study included 88,182 adult patients at 90 US hospitals (October 2015-February 2020). Most (98.6%) had noninvasive ACP and 40.2% were <65 years old. Of 1450 culture-positive patients, 37.7% had an isolate resistant to ≥1 antibiotic class. Observed mortality, median LOS, cost per admission, and hospital margins were 8.3%, 6 days, $9791, and $11, respectively. Risk factors for mortality included ≥50 years of age, higher risk of pneumococcal disease (based on chronic or immunocompromising conditions), and intensive care unit admission. Patients with IPD had similar mortality rates and hospital margins compared with noninvasive ACP, but greater costs per admission and LOS., Conclusion: IPD and noninvasive ACP are associated with substantial clinical and economic burden across all adult age groups. Expanded pneumococcal vaccination programs may help reduce disease burden and decrease hospital costs., (Copyright © 2024 Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Vaccination against pneumococci is currently the most effective method of protection against pneumococcal infections. The aim of the study was to analyse changes in hospitalisations and in-hospital deaths due to pneumonia before (2009-2016) and after (2017-2020) the introduction of PCV 10 vaccinations in the National Immunisation Programme in Poland., Methods: Data on hospitalisations related to community acquired pneumonia (CAP) in the years 2009-2020 were obtained from the Nationwide General Hospital Morbidity Study. Analyses were made in the age groups: <2, 2-3, 4-5, 6-19, 20-59, 60+ years in 2009-2016 and 2017-2020., Results: Overall, there were 1,503,105 CAP-related hospitalisations in 2009-2020, 0.7% of which were caused by Streptococcus pneumoniae infections. Children <2 years of age were the most frequently hospitalised for CAP per 100,000 population, followed by patients aged 2-3, 4-5 and 60+ years. In the years 2009-2016, the percentage of CAP hospital admissions increased significantly, and after the year 2017, it decreased significantly in each of the age groups (p<0.001). In the years 2009-2016, a significant increase in hospitalisations for Streptococcus pneumoniae infections was observed in the age groups <2, 2-3 and 4-5 years (p<0.05). A significant reduction in hospitalisations was observed in the age groups <2, 20-59 and 60+ in 2017-2020 (p<0.05). In the years 2009-2020, there were 84,367 in-hospital deaths due to CAP, 423 (0.5%) of which due to Streptococcus pneumoniae, with patients mainly aged 60+., Conclusions: Implementation of the PCV vaccination programme has effectively decreased the incidence of CAP hospitalisations, including children <2 years of age. The group that is most at risk of death are persons aged 60+. The results of our study can be useful in evaluating the vaccine efficacy and benefits, and they can be an essential part of public health policy. Effective prevention strategies for CAP should be implemented in different age groups., Competing Interests: Declaration of competing interest The authors 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 The Author(s). Published by Elsevier India Pvt Ltd. All rights reserved.)

Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing levels of HDL-C by inhibition of cholesteryl ester transfer protein (CETP) decreases mortality from intraabdominal polymicrobial sepsis in APOE*3-Leiden.CETP mice. Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden.CETP and APOA1.CETP mice. Mechanistically, CETP inhibition reduced the host proinflammatory response via attenuation of proinflammatory cytokine transcription and release. This effect was dependent on the presence of HDL, leading to attenuation of immune-mediated organ damage. In addition, CETP inhibition promoted monocyte activation in the blood prior to the onset of sepsis, resulting in accelerated macrophage recruitment to the lung and liver. In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.

Introduction: Despite improvements in health care, pneumonia-associated mortality remains high. The objective of this study was to analyze the factors associated with mortality in bacteremic pneumonia caused by pneumococcus., Methods: Retrospective cohort study in adult patients with pneumonia diagnosis and isolation of pneumococcus in blood cultures, between January 2012 and May 2021, was carried out. Clinical and laboratory variables, radiological involvement, evolution and mortality during hospitalization were analyzed. The group of deceased patients was compared with that of survivors., Results: 152 patients were included. Median age: 58 years; men: 58.9%; 33% presented a CURB-65 > than 2 at admission. Overall mortality: 34% (n=52). Deceased patients were more tachypneic on admission (respiratory rate 26 vs. 22; p=0.003), presented sensory alteration more frequently (58% vs. 14%; p< 0.001), PaO2/fraction of inspired oxygen ratio < 250 (58% vs. 22%; p<0.001), bilateral radiological compromise (50% vs. 32%; p=0.03), needed mechanical ventilation (50% vs 12%; p< 0.001), higher blood creatinine values (1.6 vs. 1.15; p=0.01), lower white blood cell count (10 900 vs 17 400; p=0.002), a lower glucose dosage (111 vs. 120; p=0.01), and fewer days of hospital stay (6 vs. 9; p=0.015). In logistic regression model, significant differences were maintained in the following factors associated with mortality: mechanical ventilation (OR=3.54), altered mental status (OR=5.95), chest X-ray with bilateral compromise (OR 3.20) and PAFI less than 250 (OR=3.62)., Conclusion: In our series, the factors related to mortality, despite the presence of bacteremia, do not differ from those published in the literature and which are part of the different prognostic scores used in routine practice.

The current pneumococcal capsular polysaccharide (PPS) conjugate vaccine (PCV13) is less effective against Streptococcus pneumoniae serotype 3 (ST3), which remains a major cause of pneumococcal disease and mortality. Therefore, dissecting structure-function relationships of human ST3 pneumococcal capsular polysaccharide (PPS3) antibodies may reveal characteristics of protective antibodies. Using flow cytometry, we isolated PPS3-binding memory B cells from pneumococcal vaccine recipients and generated seven PPS3-specific human monoclonal antibodies (humAbs). Five humAbs displayed ST3 opsonophagocytic activity, four induced ST3 agglutination in vitro , and four mediated both activities. Two humAbs, namely, C10 and C27, that used the same variable heavy (V H ) and light (V L ) chain domains (V H 3-9*01/V L 2-14*03) both altered ST3 gene expression in vitro ; however, C10 had fewer V L somatic mutations, higher PPS3 affinity, and promoted in vitro ST3 opsonophagocytic and agglutinating activity, whereas C27 did not. In C57BL/6 mice, both humAbs reduced nasopharyngeal colonization with ST3 A66 and a clinical strain, B2, and prolonged survival following lethal A66 intraperitoneal infection, but only C10 protected against lethal intranasal infection with the clinical strain. After performing V L swaps, C10V H /C27V L exhibited reduced ST3 binding and agglutination, but C27V H /C10V L binding was unchanged. However, both humAbs lost the ability to reduce colonization in vivo when their light chains were replaced. Our findings associate the ability of PPS3-specific humAbs to reduce colonization with ST3 agglutination and opsonophagocytic activity, and reveal an unexpected role for the V L in their functional activity in vitro and in vivo . These findings also provide insights that may inform antibody-based therapy and identification of surrogates of vaccine efficacy against ST3. IMPORTANCE Despite the global success of vaccination with pneumococcal conjugate vaccines, serotype 3 (ST3) pneumococcus remains a leading cause of morbidity and mortality. In comparison to other vaccine-included serotypes, the ST3 pneumococcal capsular polysaccharide (PPS3) induces a weaker opsonophagocytic response, which is considered a correlate of vaccine efficacy. Previous studies of mouse PPS3 monoclonal antibodies identified ST3 agglutination as a correlate of reduced ST3 nasopharyngeal colonization in mice; however, neither the agglutinating ability of human vaccine-elicited PPS3 antibodies nor their ability to prevent experimental murine nasopharyngeal colonization has been studied. We generated and analyzed the functional and in vivo efficacy of human vaccine-elicited PPS3 monoclonal antibodies and found that ST3 agglutination associated with antibody affinity, protection in vivo , and limited somatic mutations in the light chain variable region. These findings provide new insights that may inform the development of antibody-based therapies and next-generation vaccines for ST3.

Objectives: To assess risk factors for mortality in invasive pneumococcal disease (IPD)., Methods: We conducted a systemic literature search in January 2019. The main outcome measure included death within 30 days after diagnosis of IPD. The study protocol was registered in PROSPERO (CRD42019120189)., Results: After reviewing 2514 potentially relevant records, remaining 190 articles were included in the analysis. A total of 228,782 IPD patients were identified and the mortality rate was 17.2% in the included articles. No significant evidence of publication bias was found according to the funnel plot and Egger's test ( t = 1.464, p = 0.145). Male sex, older age, alcohol abuse, previous tuberculosis, meningitis, hospital acquired infections, multilobar infiltrate or effusion, Pitt bacteremia score≥4, Pneumonia Severity Index≥4, clinical conditions requiring intensive care, underlying clinical conditions, disease caused by serotypes 3, 6B, 9 N, 10A, 11A, 16 F, 17 F, 19, 19 F, 22 F, 23A, 23 F, 31 and 35 F, previous antibiotic use, inappropriate initial antibiotic therapy, penicillin resistance, and vancomycin use during the course of treatment were predicators of 30-day mortality., Conclusions: This meta-analysis highlights important risk factors for IPD-related mortality, many of which may be targeted through preventive measures.

Background: To guide decision-making on immunisation programmes for ageing adults in Europe, one of the aims of the Vaccines and InfecTious diseases in the Ageing popuLation (IMI2-VITAL) project is to assess the burden of disease (BoD) of (potentially) vaccine-preventable diseases ((P)VPD). We aimed to identify the available data sources to calculate the BoD of (P)VPD in participating VITAL countries and to pinpoint data gaps. Based on epidemiological criteria and vaccine availability, we prioritized (P) VPD caused by Extra-intestinal pathogenic Escherichia coli (ExPEC), norovirus, respiratory syncytial virus, Staphylococcus aureus, and pneumococcal pneumonia., Methods: We conducted a survey on available data (e.g. incidence, mortality, disability-adjusted life years (DALY), quality-adjusted life years (QALY), sequelae, antimicrobial resistance (AMR), etc.) among national experts from European countries, and carried out five pathogen-specific literature reviews by searching MEDLINE for peer-reviewed publications published between 2009 and 2019., Results: Morbidity and mortality data were generally available for all five diseases, while summary BoD estimates were mostly lacking. Available data were not always stratified by age and risk group, which is especially important when calculating BoD for ageing adults. AMR data were available in several countries for S. aureus and ExPEC., Conclusion: This study provides an exhaustive overview of the available data sources and data gaps for the estimation of BoD of five (P) VPD in ageing adults in the EU/EAA, which is useful to guide pathogen-specific BoD studies and contribute to calculation of (P)VPDs BoD.

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.

Pneumococcal conjugate vaccination (PCV) may prevent influenza-related pneumonia, including Streptococcus pneumoniae pneumonia. To investigate PCV efficacy against secondary pneumococcal pneumonia following influenza, PCV was administered intramuscularly 2 and 5 weeks before S. pneumoniae serotype-3 colonization of murine nasopharynges followed by intranasal challenge with a sublethal dose of influenza A virus. Bacterial and viral loads, including innate immune responses were compared across conditions. PCV vaccination improved the survival of mice with secondary pneumococcal pneumonia and significantly reduced the pulmonary bacterial burden. Increased monocyte/macrophage influx into the lungs, alleviated loss of alveolar macrophages and decreased neutrophil influx into the lungs occurred in PCV-treated mice irrespective of pneumococcal colonization. Higher monocyte chemoattractant protein 1 levels and lower levels of CXCL1, interferon-γ, interleukin-17A, and IL-10, were detected in PCV-treated mice. Additionally, PCV treatment activated the macrophage intracellular killing of S. pneumoniae. Collectively, PCV potentially modulates the host's innate immunity and specific antibodies induction. Macrophage-related innate immunity should be further explored to elucidate the efficacy and mechanisms of PCV versus influenza-related life-threatening diseases., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2020 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The aim of this study was to assess if long-term supplementation of omega-3 fatty acids or a diet rich in omega-6 fatty acids ameliorates disease severity in a murine model of pneumococcal pneumonia. We hypothesize that long-term dietary supplementation of omega-3 fatty acids will reduce inflammation, disease severity and improve survival compared to omega-6 fatty acids., Methods: Mice receiving diets supplemented with Omega-3 or Omega-6 for two months were intranasally infected with Streptococcus pneumoniae. We analyzed survival, bacterial burden, histopathology and inflammatory biomarkers., Results: Our results showed that Omega-3 supplementation had increased survival (p = 0.005), less bacteremia (p = 0.0001) and lower bacterial burden in the lungs (p = 0.0002) when compared to the Omega-6 supplementation. Overall, Omega-3 reduced lung pathology, in particular peribronchial inflammation and cell death. Analyses of lung homogenates showed the Omega-3 cohort had decreased levels of the inflammatory cytokine interleukin-6 and an increase in anti-inflammatory cytokine interleukin-10., Conclusions: Supplementation of mouse diets with Omega-3 fatty acids improved survival, bacterial invasion in the blood and lungs as well as decreased overall lung tissue inflammation and cell death when compared to the Omega-6 supplemented diets. Translation of these findings in humans may improve outcomes of patients at risk for pneumonia., Competing Interests: Declaration of competing interest No reported conflicts of interest from any authors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Community-acquired pneumonia (CAP) is a common infection with significant morbidity and mortality. In January 2017, Poland introduced pneumococcal conjugate vaccine (PCV) into their national immunisation programme to protect children against invasive pneumococcal disease. This study was designed to investigate pneumonia-related hospitalisation rates and trends from 2009 to 2016 prior to the introduction of nationally funded PCV vaccination., Methods: Using national public statistic data available from the National Institute of Public Health - National Institute of Hygiene, annual hospitalisation rates for pneumonia were analysed, categorised by aetiology and age (<2, 2-3, 4-5, 6-19, 20-59, 60+ years). Trends over time were assessed, as well as in-hospital mortality., Results: The overall hospitalisation rate due to pneumonia varied between 325.9 and 372.2/100,000 population. Higher rates of hospitalisation were seen in older adults and children ≤5 years. Trends were observed when analysing hospitalisations by pneumonia aetiology within age groups: between 2009 and 2016, Streptococcus pneumoniae hospitalisations significantly increased for children aged <2, 2-3, and 4-5 years, from 5.3 to 12.4, 5.2 to 8.2, and 1.9 to 4.6/100,000 population respectively. Whereas hospitalisations due to Haemophilus influenzae pneumonia decreased significantly from 7.8 to 1.8 and 4.8 to 1.9/100,000 children aged <2 and 2-3 years respectively. The numbers of in-hospital deaths increased from 5578 in 2009 to 8149 in 2016, with >85% of deaths in the 60+ age group., Conclusions: This is the first national study of pneumonia hospitalisations in Poland, providing the baseline data from which to investigate the impact of the change in vaccination policy on pneumonia hospitalisations in Poland., (Copyright © 2019 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: Pneumococcal pneumonia is a significant cause of morbidity and mortality among adults. The study's main aim was to evaluate the in-hospital mortality and related costs of community-acquired pneumococcal pneumonia in adults., Methods: This cross-sectional study used medical records of adult patients with pneumococcal pneumonia hospitalized in a university hospital in Brazil from October 2009 to April 2017. All patients aged ≥ 18 years diagnosed with pneumococcal pneumonia were included. Risk factors, intensive care unit admission, length of hospital stay, in-hospital mortality, and direct and indirect costs were analyzed., Results: In total, 186 patients were selected. The mean in-hospital mortality rate was 18% for adults aged < 65 years and 23% for the elderly (≥ 65 years). Bacteremic pneumococcal pneumonia affected 20% of patients in both groups, mainly through chronic respiratory disease (adjusted OR: 3.07, 95% CI: 1.23-7.65, p < 0.01). Over 7 years, annual total direct and indirect costs were USD 28,188 for adults < 65 years (USD 1,746 per capita) and USD 16,350 for the elderly (USD 2,119 per capita)., Conclusion: Pneumococcal pneumonia remains an important cause of morbidity and mortality among adults, significantly affecting direct and indirect costs. These results suggest the need for prevention strategies for all adults, especially for patients with chronic respiratory diseases.

Invasive pneumococcal infection is a major cause of morbidity and mortality worldwide despite the availability of pneumococcal vaccines. The aim of this study was to re-evaluate the clinical syndromes, prognostic factors and outcomes for pneumococcal disease in adults and children in Singapore during the period before and after the introduction of the pneumococcal vaccine. We retrospectively analyzed a large cohort of patients admitted to the four main public hospitals in Singapore with S. pneumoniae infection between 1997 and 2013. A total of 889 (64% of all isolates identified in the clinical laboratories) cases were included in the analysis; 561 (63.1%) were adult (≥16 years) cases with a median age of 62 years and 328 (36.9%) were paediatric cases with a median age of 3 years. Bacteraemic pneumonia was the most common syndrome in both groups (69.3% vs. 44.2%), followed by primary bacteraemia without pneumonia (14.3% vs. 13.4%), meningitis (6.4% vs. 7.6%) and non-bacteraemic pneumonia (5.2% vs. 21%). The major serotypes in adults were 3, 4, 6B, 14, 19F and 23F whereas in children they were 14, 6B and 19F, accounting both for nearly half of pneumococcal disease cases. No particular serotype was associated with mortality or severity of the pneumococcal disease. Overall mortality rate was 18.5% in adults and 3% in children. Risk factors for mortality included acute cardiac events in adults, meningitis in children and critical illness and bilateral pulmonary infiltrates in both adults and children. Penicillin resistance was not associated with increased mortality. Our results agree with global reports that the course of pneumococcal disease and its clinical outcome were more severe in adults than in children. The main serotypes causing invasive disease were mostly covered by the vaccines in use. The high mortality rates reflect an urgent need to increase vaccination coverage in both adults and children to tackle this vaccine-preventable infection., Competing Interests: OTN has received a grant from the Healthcare cluster and government research funding. PAT has received research grants from Sanofi Pasteur, GSK, Novartis and Janssen, and payment for lectures from 3M and meeting expenses from Biomerrieux. SCC has received research grants from Pfizer and GSK. BHT has received research funding from Pfizer (IIR portal). All grants and honoraria are paid into accounts within the respective institutions. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors have nothing to declare. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Background: Immunodeficient patients are recommended to receive pneumococcal vaccination. However, there is limited evidence showing effectiveness of the polysaccharide vaccine. Polysaccharide vaccination has shown an association with cardiovascular event risk reduction. We assessed the efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in relation to the risk of hospitalization and death due to pneumonia and acute cardiac events., Methods: The medical records of all dialysis patients attending our 8 study centers in 2010 were studied, and we selected 1038 consecutive patients. One-to-one propensity score matching was used to correct for potential selection bias in a PPSV23-vaccinated group versus a non-vaccinated group, and a total of 510 patients were identified for outcome analysis. Time to first admission, or deaths due to all-cause pneumonia or cardiac events until 2015 were compared between both groups., Results: The all-cause death rate was significantly decreased in the PPSV23-vaccinated group, (hazard ratio [HR] 0.62, 95% confidence interval [CI]; 0.46-0.83, P = 0.002). All-cause death was considered to be a competing risk for the other outcomes. Further outcomes were evaluated by competing risk analysis adjusting for mortality. There was no statistically significant difference in the hospitalization rate for pneumonia; however, the hospitalization rate due to cardiac events was significantly lower in the PPSV23-vaccinated group than in the non-vaccinated group (HR 0.44, 95% CI; 0.20-0.96, P = 0.040). There was no statistically significant difference in the death rate due to pneumonia; however, the rate of cardiac death was significantly lower in the PPSV23-vaccinated group than in the non-vaccinated group (HR 0.36, 95% CI; 0.18-0.71, P = 0.003)., Conclusions: The PPSV23 vaccination is associated with a good prognosis and a low-risk of cardiac events in dialysis patients; however, there was no evidence indicating enhanced protective efficacy against pneumonia, suggesting the PPSV23 vaccination might improve the prognosis by directly preventing cardiovascular events., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We review a previously published randomized clinical trial of 23-valent pneumococcal polysaccharide vaccine (PPSV23) that has been used extensively globally to support PPSV23 use among adults. We argue that serious issues with internal and external validity exist that affect the usefulness of these data when evaluating pneumococcal vaccines for the general adult population. As one example of internal data inconsistency, the values reported for the percent of all pneumonia cases due to pneumococcus and the vaccine efficacy (VE) for all cause pneumonia are mutually inconsistent, even based on unrealistically high values for PPSV23 VE against vaccine serotypes and the proportion of pneumococcal pneumonias due to vaccine serotypes., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of this study was to estimate the impact of antimicrobial resistance (AMR) in secondary pneumococcal pneumonia infections on global mortality during the 2009 influenza pandemic, to estimate future pandemic mortality risk and to inform pandemic preparedness., Methods: Risk analysis modelling was conducted using a multivariate risk formula. Literature reviews were conducted to generate global central estimates for each of the parameters of the risk formula in relation to the 2009 influenza pandemic, secondary pneumococcal pneumonia, rates of AMR, and pneumococcal vaccine efficacy as a component of pandemic preparedness., Results: Global Streptococcus pneumoniae AMR was estimated at 21.8% to 27.6%, and contributed to 1.8% to 2.3% of deaths during the 2009 influenza pandemic. When directly applied to mortality due to multidrug resistance, pneumococcal vaccination could potentially prevent 1277 to 3754 deaths and could have reduced mortality from multidrug-resistant S. pneumoniae to 1% to 1.2%., Conclusions: AMR in secondary pneumococcal infections contributed towards a small percentage of the global mortality during the 2009 influenza pandemic. Increased S. pneumoniae AMR could result in a three- to four-fold rise in mortality due to secondary pneumococcal infections in future influenza pandemics. Pneumococcal vaccination has an important role in preventing pneumococcal co-infections and combating AMR in all populations, and should be considered a key component of influenza pandemic preparedness or early action plans., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Antibiotic combinations that include macrolides have shown lower mortality rates than β-lactams in monotherapy or combined with fluoroquinolones in patients with community-acquired pneumonia (CAP). However, this effect has not been studied according to the levels of C-reactive protein in CAP with identified microbial cause. In patients with CAP and known microbial cause we aimed to evaluate 30-day mortality of a β-lactam plus macrolide (BL + M) compared with a fluoroquinolone alone or with a β-lactam (FQ ± BL)., Methods: We analyzed a prospective observational cohort of patients with CAP admitted to the Hospital Clinic of Barcelona between 1996 and 2016. We included only patients with known microbial cause., Results: Of 1,715 patients (29%) with known etiology, a total of 932 patients (54%) received BL + M. Despite lower crude mortality in the BL + M group in the overall population (BL + M, 5% vs FQ ± BL, 8%; P = .015), after adjustment by a propensity score and baseline characteristics, the combination of BL + M had a protective effect on mortality only in patients with high inflammatory response (C-reactive protein, > 15 mg/dL) and pneumococcal CAP (adjusted OR, 0.28; 95% CI, 0.09-0.93). No benefits on mortality were observed for the population without high inflammatory response and pneumococcal CAP or with other etiologies., Conclusions: The combination of a β-lactam with a macrolide was associated with decreased mortality in patients with pneumococcal CAP and in patients with high systemic inflammatory response. When both factors occurred together, BL + M was protective for mortality in the multivariate analysis., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Understanding the real-world effect of pneumococcal conjugate vaccines (PCVs) on pneumonia mortality is crucial because of the expectation that increased PCV use will substantially reduce the burden of pneumonia deaths in children younger than 5 years. However, few post-vaccine introduction studies have estimated the benefits of PCV use on childhood mortality and results have been inconsistent. Therefore, we set out to assess the effect of introduction of ten-valent pneumococcal conjugate vaccine (PCV10) on pneumonia mortality in children in Brazil., Methods: In this retrospective observational study, we used publicly available mortality data of children aged 3-59 months in Brazil. We separated data by age group (3-11 months, 3-23 months, and 3-59 months) and stratified data by three different socioeconomic factors of Brazilian municipalities (in 2010): Human Development Index, proportion of children living in extreme poverty, and proportion of mothers with no primary education. We first examined long-term trends in childhood pneumonia mortality in Brazil (from 1980 to 2014). We then assessed the effect of PCV10-introduced in Brazil in 2010-both nationally and in municipalities stratified by socioeconomic status, with a synthetic control approach as our primary analytical method., Findings: Between 1980 and 2010, a period during which Brazil's Human Development Index rose substantially, national pneumonia mortality in children younger than 5 years decreased from about 150 to 15 deaths per 100 000 children younger than 5 years. Despite rapid uptake of PCV10 after its introduction in 2010, we observed a further vaccine-associated decline of about 10% in national childhood pneumonia mortality with our primary analytical method, with a high degree of uncertainty in the estimates. We observed larger reductions in municipal childhood pneumonia mortality in all three age groups (3-11 months, 3-23 months, and 3-59 months) in municipalities with a high percentage of extreme childhood poverty and mothers with no primary education, with the largest decrease observed in children aged 3-23 months in municipalities with low maternal education (24%, 95% credible interval 7-35)., Interpretation: The large reduction observed from 1980 to 2010 in national pneumonia mortality in children younger than 5 years underscores that improvements in nutrition, hygiene, education, and health care have an important role in reducing pneumonia mortality. Although the PCV-associated reduction in childhood pneumonia mortality at the national level was modest, we found that PCV led to larger reductions in low-income municipalities. Similarly, large benefits might occur when PCVs are introduced in other low-income settings., Funding: Bill & Melinda Gates Foundation and National Institute of Allergy and Infectious Diseases., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Procalcitonin (PCT) is a useful marker for pneumonia. However, its clinical usefulness in elderly patients has not been studied extensively. This study aimed to assess the relationship between PCT and prognosis and pneumonia severity in elderly patients with pneumonia acquired outside the hospital., Methods: Data considered relevant to pneumonia severity and prognosis were retrospectively obtained from clinical charts of all patients with pneumonia who were admitted to our hospital from 2010 to 2017. The primary outcome was 30-day mortality in elderly patients (aged ≥75 years), and the relationship between PCT levels and pneumonia severity, as determined by the pneumonia severity index (PSI) was also examined., Results: Data were collected from 667 patients, of which 436 were elderly patients. Multivariate and receiver operating characteristic curve analysis revealed that albumin, body mass index, and PSI class rather than PCT are important factors related to 30-day mortality in elderly patients. PCT was also not an independent prognostic factor in younger patients. PCT levels significantly differed by pneumonia severity (mild, moderate, and severe) in both younger (p < 0.001) and elderly (p < 0.0001) patients, with levels increasing as severity increased. In contrast, C-reactive protein (CRP) levels and white blood cell counts did not significantly differ by pneumonia severity in younger and elderly patients. A subgroup analysis focused on Streptococcus pneumoniae pneumonia revealed that PCT levels differed by severity in elderly patients (p = 0.03), with levels increasing as severity increased., Conclusion: PCT was not an independent predictor of 30-day mortality in both of elderly and younger patients. PCT levels, but not CRP levels, significantly increased with increasing pneumonia severity in younger and elderly patients, although the degree of increase tended to be lower in elderly patients compared to younger patients for the same severity. PCT levels also significantly increased with increasing pneumonia severity in elderly patients with Streptococcus pneumoniae pneumonia.

Community-acquired pneumonia (CAP) results in substantial numbers of hospitalisations and deaths in older adults. There are known lifestyle and medical risk factors for pneumococcal disease but the magnitude of the additional risk is not well quantified in Australia. We used a large population-based prospective cohort study of older adults in the state of New South Wales (45 and Up Study) linked to cause-specific hospitalisations, disease notifications and death registrations from 2006 to 2015. We estimated the age-specific incidence of CAP hospitalisation (ICD-10 J12-18), invasive pneumococcal disease (IPD) notification and presumptive non-invasive pneumococcal CAP hospitalisation (J13 + J18.1, excluding IPD), comparing those with at least one risk factor to those with no risk factors. The hospitalised case-fatality rate (CFR) included deaths in a 30-day window after hospitalisation. Among 266 951 participants followed for 1 850 000 person-years there were 8747 first hospitalisations for CAP, 157 IPD notifications and 305 non-invasive pneumococcal CAP hospitalisations. In persons 65-84 years, 54.7% had at least one identified risk factor, increasing to 57.0% in those ⩾85 years. The incidence of CAP hospitalisation in those ⩾65 years with at least one risk factor was twofold higher than in those without risk factors, 1091/100 000 (95% confidence interval (CI) 1060-1122) compared with 522/100 000 (95% CI 501-545) and IPD in equivalent groups was almost threefold higher (18.40/100 000 (95% CI 14.61-22.87) vs. 6.82/100 000 (95% CI 4.56-9.79)). The CFR increased with age but there were limited difference by risk status, except in those aged 45 to 64 years. Adults ⩾65 years with at least one risk factor have much higher rates of CAP and IPD suggesting that additional risk factor-based vaccination strategies may be cost-effective.

Purpose: To assess the relative importance of host and bacterial factors associated with hospital mortality in patients admitted to the intensive care unit (ICU) for pneumococcal community-acquired pneumonia (PCAP)., Methods: Immunocompetent Caucasian ICU patients with PCAP documented by cultures and/or pneumococcal urinary antigen (UAg Sp) test were included in this multicenter prospective study between 2008 and 2012. All pneumococcal strains were serotyped. Logistic regression analyses were performed to identify risk factors for hospital mortality., Results: Of the 614 patients, 278 (45%) had septic shock, 270 (44%) had bacteremia, 307 (50%) required mechanical ventilation at admission, and 161 (26%) had a diagnosis based only on the UAg Sp test. No strains were penicillin-resistant, but 23% had decreased susceptibility. Of the 36 serotypes identified, 7 accounted for 72% of the isolates, with different distributions according to age. Although antibiotics were consistently appropriate and were started within 6 h after admission in 454 (74%) patients, 116 (18.9%) patients died. Independent predictors of hospital mortality in the adjusted analysis were platelets ≤ 100 × 10 9 /L (OR, 7.7; 95% CI, 2.8-21.1), McCabe score ≥ 2 (4.58; 1.61-13), age > 65 years (2.92; 1.49-5.74), lactates > 4 mmol/L (2.41; 1.27-4.56), male gender and septic shock (2.23; 1.30-3.83 for each), invasive mechanical ventilation (1.78; 1-3.19), and bilateral pneumonia (1.59; 1.02-2.47). Women with platelets ≤ 100 × 10 9 /L had the highest mortality risk (adjusted OR, 7.7; 2.8-21)., Conclusions: In critically ill patients with PCAP, age, gender, and organ failures at ICU admission were more strongly associated with hospital mortality than were comorbidities. Neither pneumococcal serotype nor antibiotic regimen was associated with hospital mortality.

Purpose of Review: Despite the improvements in its management, community-acquired pneumonia (CAP) still exhibits high global morbidity and mortality rates, especially in elderly patients. This review focuses on the most recent findings on the epidemiology, cause, diagnosis and management of CAP., Recent Findings: There is consistent evidence that the trend in CAP mortality has declined over time. However, the mortality of pneumococcal CAP has not changed in the last two decades, with an increase in the rate of hospitalization and more severe forms of CAP. Streptococcus pneumoniae remains the most frequent cause of CAP in all settings, age groups and regardless of comorbidities. However, the implementation of molecular diagnostic tests in the last years has identified respiratory viruses as a common cause of CAP too. The emergency of multidrug-resistance pathogens is a worldwide concern. An improvement in our ability to promptly identify the causative cause of CAP is required in order to provide pathogen-directed antibiotic therapy, improve antibiotic stewardship programs and implement appropriate vaccine strategies., Summary: It is time to apply all the knowledge generated in the last decade in order to optimize the management of CAP.

Background: Community-acquired pneumonia (CAP) remains a major cause of death worldwide. Mechanisms underlying the detrimental outcome despite adequate antibiotic therapy and comorbidity management are still not fully understood., Methods: To model timely versus delayed antibiotic therapy in patients, mice with pneumococcal pneumonia received ampicillin twice a day starting early (24 h) or late (48 h) after infection. Clinical readouts and local and systemic inflammatory mediators after early and late antibiotic intervention were examined., Results: Early antibiotic intervention rescued mice, limited clinical symptoms and restored fitness, whereas delayed therapy resulted in high mortality rates. Recruitment of innate immune cells remained unaffected by antibiotic therapy. However, both early and late antibiotic intervention dampened local levels of inflammatory mediators in the alveolar spaces. Early treatment protected from barrier breakdown, and reduced levels of vascular endothelial growth factor (VEGF) and perivascular and alveolar edema formation. In contrast, at 48 h post infection, increased pulmonary leakage was apparent and not reversed by late antibiotic treatment. Concurrently, levels of VEGF remained high and no beneficial effect on edema formation was evident despite therapy. Moreover, early but not late treatment protected mice from a vast systemic inflammatory response., Conclusions: Our data show that only early antibiotic therapy, administered prior to breakdown of the alveolar-capillary barrier and systemic inflammation, led to restored fitness and rescued mice from fatal streptococcal pneumonia. The findings highlight the importance of identifying CAP patients prior to lung barrier failure and systemic inflammation and of handling CAP as a medical emergency.

Background: This study investigated changes in plasma level of soluble endothelial protein C receptor (sEPCR) in association with outcome in patients with septic shock. We explored sEPCR for early sepsis prognosis assessment and constructed a scoring system based on clinical and biological data, in order to discriminate between surviving at hospital discharge and non-surviving patients., Methods: Clinical data and samples were extracted from the prospective "STREPTOGENE" cohort. We enrolled 278 patients, from 50 intensive care units (ICUs), with septic shock caused by pneumococcal pneumonia. Patients were divided into survivors (n = 194) and non-survivors (n = 84) based on in-hospital mortality. Soluble EPCR plasma levels were quantified at day 1 (D1) and day 2 (D2) by ELISA. The EPCR gene A3 haplotype was determined. Patients were followed up until hospital discharge. Univariate and multivariate analyses were performed. A scoring system was constructed using least absolute shrinkage and selection operator (lasso) logistic regression for selecting predictive variables., Results: In-hospital mortality was 30.2% (n = 84). Plasma sEPCR level was significantly higher at D1 and D2 in non-surviving patients compared to patients surviving to hospital discharge (p = 0.0447 and 0.0047, respectively). Early increase in sEPCR at D2 was found in non-survivors while a decrease was observed in the survival group (p = 0.0268). EPCR A3 polymorphism was not associated with mortality. Baseline sEPCR level and its variation from D1 to D2 were independent predictors of in-hospital mortality. The scoring system including sEPCR predicted mortality with an AUC of 0.75., Conclusions: Our findings confirm that high plasma sEPCR and its increase at D2 are associated with poor outcome in sepsis and thus we propose sEPCR as a key player in the pathogenesis of sepsis and as a potential biomarker of sepsis outcome.

Background: Children immunization with pneumococcal conjugate vaccine (PCV) had profound public health effects across the globe. Colombian adopted PCV10 universal vaccination, but PCV incremental impact need to be revalued. The objective of this analysis was to estimate the cost-effectiveness of switch to PCV13 versus continue PCV10 in Colombian children., Methods: A complete economic analysis was carried-out assessing potential epidemiological and economic impact of switching from PCV10 to PCV13. Epidemiological information on PCV10 impact was obtained from lab-based epidemiological surveillance on pneumococcal isolates at the Colombian National Institute of Health. Economic inputs were extracted from the literature. Incremental PCV13 effectiveness was based in additional serotypes included. Comparisons among alternatives were evaluated with the Incremental Cost-Effectiveness Ratio (ICER) at a willingness to pay of one GDP per capita (USD$ 6631) per Year of Live Saved (YLS). All costs were reported in 2014USD. Deterministic and probabilistic sensitivity analyses were performed, and 95% confidence interval reported., Results: After four years using PCV10 for universal vaccination on children the Colombian health surveillance system showed a relative increment on non PCV10 isolates. To change from PCV10 to PCV13 would avoid 587 (CI95% -49-1008) ambulatory Rx community-acquired pneumoniae (CAP), 1622 (CI95% 591-2343) Inpatient RxCAP, 10 (CI 95% 6-11) pneumococcal meningitis, and 79 (CI95% 76-98) deaths. ICER per YLS was USD$ 2319 (CI95% Dominated - USD$ 4225) for Keep-PCV10 and USD$ 1771 (CI95% USD$ 1285-9884) for Switch-to PCV13. In spite of its cost-effectiveness Keep-PCV10 is an extended dominated alternative and Switch-to PCV13 would be preferred. Results are robust to parameters changes in the sensitivity analyses., Conclusion: A national immunization strategy based in Switch-to PCV13 was found to be good value for money and prevent additional burden of pneumococcal disease saving additional treatment costs, when compared with to Keep-PCV10 in Colombia, however additional criteria to decision making must be taken into account., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The pneumococcal urinary antigen test (UAT) has been known to improve sensitivity and specificity for the diagnosis of pneumococcal pneumonia. Associations of UAT results with prognosis in community acquired pneumonia (CAP) are not known. We hypothesized that positive UAT is associated with a good prognosis, and incorporation of UAT into CRB65 would improve its prognostic performance., Methods: In this registry-based retrospective study, we analyzed CAP patients over a 10-year period beginning in April 2008. Patients who had UAT results were included in multivariable extended Cox-regression analyses to determine the association between UAT positivity and 30-day mortality. UAT results were incorporated for patients with a CRB65 score of 1 by subtracting 1 from the scoring system if the test was positive. The performance of the modified scoring systems was assessed with area under the receiver operating characteristic (AUROC) curves., Results: Among 5145 CAP patients, total 2280 patients had UAT results and were included in analyses. A positive UAT result was associated with a good prognosis after a week of hospitalization (aHR, 0.14; p = 0.007). After modification of CRB65 using UAT results, positive and negative predictive values for 30-day mortality were increased from 7.7 to 8.3 (p<0.001) and 98.9 to 99.1 (p = 0.010). The AUROC increased from 0.73 to 0.75 (p<0.001)., Conclusions: Positive results on UAT could be considered as a good prognostic factor in CAP. UAT could be used as a useful tool in deciding whether to refer patients to the hospital, especially in moderate CAP with a CRB score of 1., Competing Interests: The authors have declared that no competing interests exist.

Background: There is only limited information on mortality over extended periods in hospitalized patients with pneumococcal community-acquired pneumonia (CAP). We aimed to evaluate the 30-day mortality and whether is changed over a 20-year period among immunocompetent adults hospitalized with pneumococcal CAP., Methods: We conducted a retrospective observational study of data that were prospectively collected at the Hospital Clinic of Barcelona of all adult patients hospitalized with diagnosis of pneumococcal CAP over a 20-year period. To aid analysis, results were divided into four periods of 5 years each (1997-2001, 2002-2006, 2007-2011, 2012-2016). The primary outcome was 30-day mortality, but secondary outcomes included intensive care unit (ICU) admission, lengths of hospital and ICU-stays, ICU-mortality, and need of mechanical ventilation., Results: From a cohort of 6,403 patients with CAP, we analyzed the data for 1,120 (17%) adults with a diagnosis of pneumococcal CAP. Over time, we observed decreases in the rates of alcohol consumption, smoking, influenza vaccination, and older patients (age ≥65 years), but increases in admissions to ICU and the need for non-invasive mechanical ventilation. The overall 30-day mortality rate was 8% (95% confidence interval, 6%-9%; 84 of 1,120 patients) and did not change significantly between periods (p = 0.33). Although, we observed a decrease in ICU-mortality comparing the first period (26%) to the second one (10%), statistical differences disappeared with adjustment (p0.38)., Conclusion: Over time, 30-day mortality of hospitalized pneumococcal CAP did not change significantly. Nor did it change in the propensity-adjusted multivariable analysis. Since mortality in pneumococcal pneumonia has remained unaltered for many years despite the availability of antimicrobial agents with proven in vitro activity, other non-antibiotic strategies should be investigated., Competing Interests: The authors have declared that no competing interests exist.

Background: Bacteremic pneumococcal pneumonia (BPP) is a preventable disease with high morbimortality., Aim: To evaluate clinical aspects and mortality on BPP patients admitted to a Chilean regional hospital., Patients and Methods: We looked for adult patients with Streptococcus pneumoniae isolated from blood cultures between 2010 and 2014 years and reviewed clinical records of those who were admitted with pneumonia., Results: We identified 70 BPP patients: 58% were men, mean age was 56 years, 30% were > 65 years, 70% with basic public health insurance, 26% were alcoholics, 86% had comorbidities. Only two patients were vaccinated against S. pneumoniae. CURB-65 severity index for community acquired pneumonia was > 3 in 37% of patients. Twenty-four patients were admitted to ICU, twenty required mechanical ventilation and twenty-four died (34%). Mortality was associated with an age over 65 years, presence of comorbidities and complications of pneumonia. A total of 22 serotypes of S. pneumoniae were identified, five of them (1,3,7F,14 y 9V) were present in 57% of cases., Conclusions: Elevated mortality of our BNN patients was associated with comorbidities and possibly with socio economic factors, which conditioned a late access to medical care.

Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The 23-valent pneumococcal polysaccharide vaccine (PPV) is recommended for prevention of pneumococcal diseases in adults at risk. Few data exist on time-, age- and sex-dependent vaccine effectiveness on outcomes in pneumonia., Methods: We performed a population-based cohort study including adults ≥60 years of age (n = 738 927) based on statutory health insurance data from 2005 to 2011. Primary outcomes were all-cause pneumonia incidence and 30-day all-cause mortality. Pneumonia was identified by International Classification of Diseases, 10th Revision, German Modification (ICD-10-GM) codes, with ambulatory cases validated by antibiotic prescription within 7 days. The effect of PPV within 5 years was analysed after propensity score-based matching (three controls per case with PPV vaccination) including comorbidities, care status, age, sex and influenza vaccination. Evaluations were stratified by age group, sex and time of PPV., Results: Two-year incidence of all-cause pneumonia in 213 431 vaccinated individuals was 7501 (3.51%) of 213 431 vs. 23 243 (3.63%) of 640 293 in matched controls (difference -0.11, 95% confidence interval (CI) -0.22 to -0.002, p 0.046). After sex-dependent analysis, PPV effectiveness on pneumonia incidence was observed only in women (difference -0.15, 95% CI -0.28 to -0.02, p 0.02). Thirty-day mortality in vaccinated individuals with pneumonia was 1302 (17.36%) of 7501 vs. 4267 (18.96%) of 22 503 in matched controls (difference -1.60%, 95% CI -2.83 to -0.38, p 0.011). After analysis according to age group, significant mortality reduction was present only in adults aged 60 to 79 years (difference -2.31, 95% CI -3.79 to -0.83, p 0.002). Year of PPV vaccination showed no effect on outcomes., Conclusions: The findings support consideration of sex and age dependence of PPV effectiveness in future studies., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Benefits using the 13-valent pneumococcal conjugate vaccine (PCV13) in adults are controversial. This study investigated clinical effectiveness of PCV13 vaccination in preventing hospitalisation from pneumonia among middle-aged and older adults., Methods: Population-based cohort study involving 2,025,730 individuals ≥50 years in Catalonia, Spain, who were prospectively followed from 01/01/2015 to 31/12/2015. Primary outcomes were hospitalisation for pneumococcal or all-cause pneumonia and death from any cause. Cox regression models were used to evaluate the association between PCV13 vaccination and the risk of each outcome, adjusting for age, sex and major comorbidities/underlying risk conditions., Results: Cohort members were observed for a total of 1,990,701 person-years, of which 6912 person-years were PCV13 vaccinated. Overall, crude incidence rates (per 100,000 person-years) were 82.8 (95% confidence interval [CI]: 77.7-88.1) for pneumococcal pneumonia, 637.9 (95% CI: 599.0-678.7) for all-cause pneumonia and 2367.2 (95% CI: 2222.8-2518.7) for all-cause death. After multivariable adjustments we found that the PCV13 vaccination did not alter significantly the risk of pneumococcal pneumonia (multivariable-adjusted hazard ratio [mHR]: 1.17; 95% CI: 0.75-1.83; p = 0.493) and all-cause death (mHR: 1.07; 95% CI: 0.97-1.18; p = 0.190), although it remained significantly associated with an increased risk of all-cause pneumonia (mHR: 1.69; 95% CI: 1.48-1.94; p < 0.001). In stratified analyses focused on middle-aged or elderly persons and immunocompromised or immunocompetent subjects, PCV13 vaccination did not appear effective either., Conclusion: Our data does not support clinical benefits of PCV13 vaccination against pneumonia among adults in Catalonia. It must be closely monitored in future studies involving more vaccinated person-time at-observation.

Background: The burden of community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae (pneumococcus) among adults in Europe is poorly defined., Methods: Structured searches of PubMed were conducted to identify the incidence of pneumococcal CAP among adults across Europe., Results: The overall incidence rates for CAP was 68-7000 per 100,000 and the incidence in hospitalised CAP cases of all causes was 16-3581 per 100,000. In general the incidence of CAP increased consistently with age. Available data indicated higher burdens of pneumococcal CAP caused in groups with more comorbidities. Most cases of pneumococcal CAP (30%-78%) were caused by serotypes covered by PCV13 vaccine; the incidence of PCV13-related pneumonia decreased after the introduction of childhood vaccination., Conclusions: We observed a high burden adult pneumococcal CAP in Europe despite use of the 23-valent pneumococcal polysaccharide vaccine, particularly in elderly patients with comorbidities. CAP surveillance presented wide variations across Europe. Pneumococcal CAP has to be monitored very carefully due to the possible effect of current vaccination strategies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Pneumonia is a leading infectious cause of morbidity and mortality among adults. Pneumococcal pneumonia (PP) is the most common vaccine-preventable bacterial etiology of pneumonia. In this study, we estimated the incidence of community-acquired pneumonia (CAP) and pneumococcal diseases among Korean adults., Methods: Clinical and microbiological databases from three hospitals were retrospectively reviewed to determine the incidence and case fatality rates of CAP and pneumococcal diseases in Korean adults aged ≥19 years from 2011 to 2014. Incidence and case fatality rates of CAP, PP and invasive pneumococcal diseases (IPD) were evaluated based on the catchment population. Catchment population was calculated using national health insurance data, estimating the proportion of patients with pneumonia that were medically attended at each hospital., Results: Among 5,783 patients with medically attended CAP, 833 (14.4%) had PP. For IPD, a total of 91 culture-confirmed cases were identified. The overall incidence of CAP was 307.7 cases per 100,000 persons per year with an in-hospital mortality rate of 6.2%. The estimated annual incidence of pneumococcal pneumonia was 42.2-49.4 cases per 100,000 persons per year, increasing with age to >280 per 100,000 persons per year in older patients over 70 years. The annual incidence of IPD had a range of 4.1-6.5 cases per 100,000 persons per year. The overall case fatality rate for invasive pneumococcal diseases was 30.8% with the highest rate of 66.7% in patients over 80 years., Conclusion: Over the study period, incidences of CAP, PP and IPD were consistently high, particularly in older people. These results provide baseline data to establish healthcare strategies and estimate their impact among Korean adults.

Background: Pneumococcal pneumonia (PP) causes almost one in five deaths in children younger than 5 years worldwide. In Latin America and the Caribbean (LAC), pneumonia causes 14% of all deaths. Although pneumococcal disease is a vaccine-preventable disease that accounts for a significant proportion of this burden, the decision-making process to introduce pneumococcal conjugate vaccines in official schedules is still complex in LAC. Confirmed PP cases and epidemiology are the basis for broader projections., Objective: To gather all the information available in the LAC region to assist decision makers., Methods: We performed a systematic review of studies of consolidating and culture-confirmed pediatric PP in LAC (2000-2016) using a generic academic Internet search and search engines without language restrictions. Pairs of reviewers independently selected and assessed the studies' methodological quality. We analyzed meta-information on pneumococcal serotypes available from the SIREVA laboratory-based surveillance system., Results: A total of 35 out of 750 initially identified studies were included. In the age group between 0 and 59 years, the incidence of culture-confirmed PP ranged from 10.2 to 43.0/100,000 children, with a pooled incidence of 20.4/100,000 children (95% confidence interval 0.0-123.2). Mortality ranged from 0.4 to 5.7/100,000 children, and the pooled mortality was 2.9/100,000 children (95% confidence interval 0.3-8.2). The pooled serotype distribution from surveillance data showed that serotypes 14, 1, and 6B were the most frequent serotypes in LAC, all included in licensed vaccines., Conclusions: Studies on confirmed pediatric PP were scarce in LAC in 2000 to 2016. Epidemiology indicators and health resource use are still poorly defined., (Copyright © 2017. Published by Elsevier Inc.)

Background: Previous reports have shown that vaccination rates of adult at-risk populations are low in Turkey. There are differing reports with regards to the effectiveness of the influenza and the pneumococcal polysaccharide vaccine (PPSV23) on the clinical outcomes of community acquired pneumonia (CAP). The purpose of this study was to analyze the influenza (FV) and pneumococcal vaccination (PV) status, the factors that influence the receipt of influenza/pneumococcal vaccine and the effects of prior vaccination on the clinical outcomes in adults hospitalized with CAP., Patients and Methods: Patients hospitalized with CAP between March 2009 and October 2013 and registered at the web-based Turkish Thoracic Society Pneumonia Database (TURCAP) were included in this multicentric, observational study. Of a total of 787 cases, data were analyzed for 466 patients for whom self-reported information on PV and FV was available., Results: In this adult population with CAP, the vaccination rate with both the pneumococcal and influenza vaccines was found to be 6%. Prior FV was found to be the sole variable that was associated with the receipt of PV [OR 17.8, 95% CI (25-75:8.56-37.01), p < 0.001]. Conversely, being vaccinated with PPSV23 was the only predictor of receipt of FV [OR 18.1, 95% CI (25 - 75:8.75 - 37.83), p < 0.001]. Compared to the unvaccinated cases, the chest radiograms of the vaccinated patients revealed less consolidation. The latter also reported fatigue, muscle pain and gastrointestinal symptoms less frequently. Although there was a trend for lower 30-day mortality and for lower rates of intensive care unit (ICU) admission, these did not reach statistical significance. A pneumonia severity index (PSI) score ≥ 90, CURB-65 score ≥3 and multilobar involvement, but not the vaccination status, were identified as independent determinants of ICU admission., Conclusions: This study showed that, among patients hospitalized with CAP, the FV and/or PV rates are low. Prior vaccination does not appear to significantly affect the clinical outcomes.

Objectives: We aimed to investigate the association between the time to positivity of blood culture (TTP) with clinical outcome and severity of pneumococcal bacteremic pneumonia., Methods: Prospective observational study carried out in 278 hospitalized adult CAP patients with positive blood culture for Streptococcus pneumonia (2003-2015)., Results: A total of 278 cases of bacteremic pneumococcal pneumonia were analyzed, median age 62 (46; 79) years. Fifty-one percent of the cases had PSI IV-V. Twenty-one (8%) died within 30-days after admission. The analysis of the TTP showed that the first quartile of the TTP (9.2h) was the best cut-off for differentiating 2 groups of patients at risk, early (TTP <9.2 h) and late (TTP ≥9.2 h) detection groups (AUC 0.66 [95% CI 0.53 to 0.79]). Early TTP was associated with a statistically significant risk of invasive mechanical ventilation (18% vs. 6%, p = 0.007), longer length of hospital stay (12 days vs. 8 days, p<0.001), higher in-hospital mortality (15% vs. 4%, p = 0.010), and 30-day mortality (15% vs. 5%, p = 0.018). After adjustment for potential confounders, regression analyses revealed early TTP as independently associated with high risk of invasive mechanical ventilation (OR 4.60, 95% CI 1.63 to 13.03), longer length of hospital stay (β 5.20, 95% CI 1.81 to 8.52), higher in-hospital mortality (OR 5.35, 95% CI 1.55 to 18.53), and a trend to higher 30-day mortality (OR 2.47, 95% CI 0.85 to 7.21) to be a contributing factor., Conclusion: Our results demonstrate that TTP is an easy to obtain surrogate marker of the severity of pneumococcal pneumonia and a good predictor of its outcome.

Background: The study aimed to investigate whether the clinical presentations and outcomes (length of stay, ICU admission, and 30-day mortality) of pneumococcal pneumonia in virologically suppressed patients who were HIV-infected on ART with a CD4+ T-cell count > 350 cells/mm 3 are comparable to those seen in patients with HIV, using a case-control design., Methods: A case-control study was carried out in Hospital Clinic, Barcelona, Spain (2001-2016). Control patients were matched by age (±10 years), sex, comorbidities, and pneumonia diagnosis in the same calendar period. Clinical presentation and outcomes of pneumococcal pneumonia in patients who were and were not infected with HIV were compared., Results: Pneumococcal pneumonia was studied in 50 cases (HIV infection) and 100 control patients (non-HIV infection). Compared with the control patients, case patients had higher rates of influenza (14% vs 2%, P = .007) and pneumococcal vaccination (10% vs 1%, P = .016). The group of cases also presented a higher rate of coinfection with hepatitis B virus (6% vs 0%, P = .036). Both groups presented similar ICU admission (18% vs 27%, P = .22), need for mechanical ventilation (12% vs 8%; P = .43), length of stay (7 days vs 7 days, P = .76), and 0% of 30-day mortality. No evidence was found of a more severe presentation or a worse clinical outcome in cases than in control patients., Conclusions: Pneumococcal pneumonia episodes requiring hospitalization in virologically suppressed patients with HIV with > 350 CD4+ T-cell count/mm 3 were neither more severe nor had worse prognosis compared with uninfected patients. These results support the fact that such patients do not need treatment, admission, or care sites different to the general population., Trial Registry: ClinicalTrials.gov; No. 2009/5451; URL: www.clinicaltrials.gov., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: To describe trends in the incidence and outcomes of community-acquired pneumonia (CAP) hospitalizations among Spanish children from 2001 to 2014 and to assess the effect of the pneumococcal vaccination (PCV) coverage in this period., Methods: This study was conducted using the Spanish National Hospital Database from 2001 to 2014 including subjects <18years. We selected discharges with a primary diagnosis of CAP. Study variable included age, sex, comorbid conditions, procedures, isolated pathogens and hospital outcome variables. In order to estimate the effect of coverage of pneumococcal vaccination in hospitalizations for CAP, we used the number of commercialized doses of PCV (PCV7 PCV10, and PCV13) for each year. Incidence rates of admissions for CAP were calculated by dividing the number of admissions per year, sex, and age group by the corresponding number of people in that population group according to the census data., Results: We identified 194,419 admissions for CAP. Incidence rate was highest among children younger than 2years and decreased significantly by 3.67% per year over the study period in this age group. Among children aged 2-4years incidence of CAP seem to decrease after year 2009. S. pneumoniae isolations decreased significantly over time but virus isolations increased. In children aged <2years and 2-4years increase in PVC was associated to a decrease in the incidence of CAP hospitalizations. Overall crude in hospital mortality following CAP fell significantly from 4.1‰ in 2001-2003 to 2.8‰ in 2012-2014., Conclusions: CAP incidence rates decreased significantly among children <2years of age from 2001 to 2014. S. pneumoniae isolations decreased significantly over time but virus isolations increased. In hospital mortality paralleling CAP fell significantly in children and adolescents from 2001 to 2014. Improvement in vaccination coverage seems to have a mitigating effect on hospitalizations and outcomes for CAP in children., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Limited data are available regarding fit and healthy patients with pneumonia at different ages. We evaluated the association of age with clinical presentation, serotype and outcomes among healthy and well-functioning patients hospitalized for bacteremic pneumococcal community-acquired pneumonia., Methods: We performed a prospective cohort study of consecutive healthy and well-functioning patients hospitalized for this type of pneumonia. Patients were stratified into younger (18 to 64 years) and older (≥65 years) groups., Results: During the study period, 399 consecutive patients were hospitalized with bacteremic pneumococcal pneumonia. We included 203 (50.8%) patients who were healthy and well-functioning patients, of whom 71 (35%) were classified as older. No differences were found in antibiotic treatment, treatment failure rate, antibiotic resistance, or serotype, except for serotype 7F that was less common in older patients. In the adjusted multivariate analysis, the older patients had higher 30-day mortality (OR 6.83; 95% CI 1.22-38.22; P = 0.028), but were less likely to be admitted to the ICU (OR 0.14; 95% CI 0.05-0.39; P < 0.001) and had shorter hospital stays (OR 0.71; 95% CI 0.54-0.94; P = 0.017)., Conclusions: Healthy and well-functioning older patients have higher mortality than younger patients, but nevertheless, ICU admission was less likely and hospital stays were shorter. These results suggest that the aging process is a determinant of mortality, beyond the functional status of patients with bacteremic pneumococcal pneumonia.

Background: The burden of pneumococcal disease is measured only through patients with invasive pneumococcal disease. The urinary antigen test (UAT) for pneumococcus has exhibited high sensitivity and specificity. We aimed to compare the pneumococcal pneumonias diagnosed as invasive disease with pneumococcal pneumonias defined by UAT results., Methods: A prospective observational study of consecutive nonimmunosuppressed patients with community-acquired pneumonia was performed from January 2000 to December 2014. Patients were stratified into two groups: invasive pneumococcal pneumonia (IPP) defined as a positive blood culture or pleural fluid culture result and noninvasive pneumococcal pneumonia (NIPP) defined as a positive UAT result with negative blood or pleural fluid culture result., Results: We analyzed 779 patients (15%) of 5,132, where 361 (46%) had IPP and 418 (54%) had NIPP. Compared with the patients with IPP, those with NIPP presented more frequent chronic pulmonary disease and received previous antibiotics more frequently. Patients with IPP presented more severe community-acquired pneumonia, higher levels of inflammatory markers, and worse oxygenation at admission; more pulmonary complications; greater extrapulmonary complications; longer time to clinical stability; and longer length of hospital stay compared with the NIPP group. Age, chronic liver disease, mechanical ventilation, and acute renal failure were independent risk factors for 30-day crude mortality. Neither IPP nor NIPP was an independent risk factor for 30-day mortality., Conclusions: A high percentage of confirmed pneumococcal pneumonia is diagnosed by UAT. Despite differences in clinical characteristics and outcomes, IPP is not an independent risk factor for 30-day mortality compared with NIPP, reinforcing the importance of NIPP for pneumococcal pneumonia., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Streptococcus pneumoniae infection is the most common cause of community-acquired pneumonia in adults. Invasive pneumococcal disease (IPD) carries a high case fatality rate. We investigated the lifespan of adults who recovered from IPD during a 32-year follow-up., Materials and Methods: We determined whether adults discharged after an episode of IPD from hospitals affiliated with the Marshall University Joan C. Edwards School of Medicine in Huntington, West Virginia from 1983-2003 were alive on June 30, 2014. Lifespan was assessed by Kaplan-Meier methodology, Cox proportional hazards multivariate analysis, life expectancy using life tables for West Virginia, years of potential life lost and serotype occurrence., Results: The study group comprised 155 adults who survived IPD. They had a mean age at discharge of 64.6 years, mean lifespan after IPD of 7.1 years, mean expected lifespan after IPD of 17.0 years, mean age at death of 71.6 years and a mean life expectancy of 81.6 years. Only 14 (9.0%) patients lived longer than their life expectancy. Of the 13 comorbid diseases analyzed, cancer and neurologic diseases and the number of comorbid diseases suffered by each patient were the significant variables associated with survival. The mean years of potential life lost was 9.936 years. Only serotype 12 of 31 serotypes recovered occurred more often in patients who survived for 11 or more years after discharge (relative risk = 3.44, 95% CI: 1.19-9.95)., Conclusions: The fact that most adult patients who recovered from IPD died before their documented life expectancy argues for the pernicious severity of IPD and the importance of immunization of adults with pneumococcal vaccines., (Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)