Elixhauser comorbidity method in predicting death of Spanish inpatients with asplenia and pneumococcal pneumonia.

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.

[Mortality in bacterial pneumonia due to pneumococcus]. / Mortalidad en neumonía bacteriémica por neumococo.

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.

Introducción: A pesar de las mejoras en los cuidados de la salud, la mortalidad asociada a neumonía continúa siendo alta. El objetivo de este estudio fue analizar los factores asociados a mortalidad en neumonía bacteriémica por neumococo. Métodos: Estudio de cohorte retrospectiva en pacientes adultos con diagnóstico de neumonía y neumococo aislado en hemocultivos, entre enero 2012 y mayo 2021. Se analizaron: variables clínicas y de laboratorio, compromiso radiológico, evolución y mortalidad durante la internación. Se comparó el grupo de pacientes fallecidos con el de sobrevivientes. Resultados: Se incluyeron 152 pacientes. La mediana de edad fue de 58 años y el 58.9% fueron hombres. El 33% presentó un CURB-65 mayor a 2 al momento de internación. La mortalidad global fue 34% (n=52). Los pacientes fallecidos se encontraban más frecuentemente taquipneicos al ingreso (frecuencia respiratoria 26 vs. 22; p=0.003), presentaban más frecuentemente alteración del sensorio (58% vs. 14%; p< 0.001), PaO2/fracción inspirada de oxígeno (PAFI) < 250 (58% vs. 22%; p<0.001), compromiso radiológico bilateral (50% vs. 32%; p=0.03), necesidad de asistencia respiratoria mecánica (ARM) (50% vs. 12%; p< 0.001), mayor valor de creatinina en sangre (1.6 vs. 1.15; p=0.01), menor recuento de glóbulos blancos (10 900 vs. 17 400; p=0.002), menor valor de glucemia (111 vs. 120; p=0.01) y menos días de estancia hospitalaria (6 vs. 9; p=0.015). En el análisis de regresión logística multivariable se mantuvieron diferencias significativas en los siguientes factores asociados a mortalidad: ventilación mecánica (OR=3.54), confusión (OR=5.95), radiografía con compromiso bilateral (OR= 3.20) y PAFI < 250 (OR=3.62). Conclusión: Los factores relacionados con mortalidad, a pesar de la presencia de bacteriemia, no difieren de los publicados en la literatura y forman parte de los scores pronósticos de práctica habitual.

CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice.

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.

Effect of the PCV 10 vaccination on community-acquired pneumonia hospitalisations after four years of its introduction into the Polish National Immunisation Programme: Follow-up study.

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.

Unveiling the role of preceding seasonal influenza in the development of bacteremic pneumococcal pneumonia in older adults before the COVID-19 pandemic in Japan.

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.

Clinical and economic burden of invasive pneumococcal disease and noninvasive all-cause pneumonia in hospitalized US adults: A multicenter analysis from 2015 to 2020.

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.

Isolation and Characterization of Human Monoclonal Antibodies to Pneumococcal Capsular Polysaccharide 3.

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 (VH) and light (VL) chain domains (VH3-9*01/VL2-14*03) both altered ST3 gene expression in vitro; however, C10 had fewer VL 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 VL swaps, C10VH/C27VL exhibited reduced ST3 binding and agglutination, but C27VH/C10VL 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 VL 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.

European data sources for computing burden of (potential) vaccine-preventable diseases in ageing adults.

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.

Predictors of mortality in invasive pneumococcal disease: a meta-analysis.

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.

Non-bacteremic pneumococcal pneumonia: general characteristics and early predictive factors for poor outcome.

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.

Omega-3 fatty acids in contrast to omega-6 protect against pneumococcal pneumonia.

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.

Pneumococcal conjugate vaccine modulates macrophage-mediated innate immunity in pneumonia caused by Streptococcus pneumoniae following influenza.

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.

Monitoring of community-acquired pneumonia hospitalisations before the introduction of pneumococcal conjugate vaccine into Polish National Immunisation Programme (2009-2016): A nationwide retrospective database analysis.

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.

Factors influencing long-term survival after hospitalization with pneumococcal pneumonia.

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.

Mortality and costs of pneumococcal pneumonia in adults: a cross-sectional study. / Mortalidade e custos da pneumonia pneumocócica em adultos: um estudo transversal.

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.

OBJETIVO: A pneumonia pneumocócica é uma causa significativa de morbimortalidade entre adultos. Desta maneira, o objetivo principal deste estudo foi avaliar a mortalidade intra-hospitalar e os custos relacionados à doença adquirida em adultos. MÉTODOS: Este estudo transversal utilizou prontuários de pacientes adultos com pneumonia pneumocócica internados em um hospital universitário no Brasil, de outubro de 2009 a abril de 2017. Todos os pacientes com idade ≥ 18 anos e diagnosticados com pneumonia pneumocócica foram incluídos. Dados como os fatores de risco, a internação em unidade de terapia intensiva, o tempo de internação, a mortalidade hospitalar e os custos diretos e indiretos foram analisados. RESULTADOS: No total, 186 pacientes foram selecionados. A taxa média de mortalidade intra-hospitalar foi de 18% para adultos com idade < 65 anos e 23% para os idosos (≥ 65 anos). A pneumonia pneumocócica bacterêmica acometeu 20% dos pacientes em ambos os grupos, principalmente por doença respiratória crônica (OR ajustada: 3,07; IC95%: 1,23­7,65; p < 0,01). Após levantamento das internações ocorridas no período de sete anos de tratamento, verificou-se que os custos diretos e indiretos totais anuais foram de US$ 28.188 para adultos < 65 anos (US$ 1.746 per capita) e US$ 16.350 para os idosos (US$ 2.119 per capita). CONCLUSÃO: A pneumonia pneumocócica continua sendo uma importante causa de morbimortalidade entre adultos, afetando significativamente os custos diretos e indiretos. Esses resultados sugerem a necessidade de estratégias de prevenção para todos os adultos, especialmente para pacientes com doenças respiratórias crônicas.

Risk factor profiles and clinical outcomes for children and adults with pneumococcal infections in Singapore: A need to expand vaccination policy?

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.

23-valent pneumococcal polysaccharide vaccine improves survival in dialysis patients by preventing cardiac events.

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.

Rethinking results from the Japanese 23-valent pneumococcal polysaccharide vaccine randomized clinical trial.

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.

Risk modelling the mortality impact of antimicrobial resistance in secondary pneumococcal pneumonia infections during the 2009 influenza pandemic.

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.