Immunogenicity of a seasonal influenza and a pneumococcal polysaccharide vaccine in multiple sclerosis patients under disease modifying therapies: A single-center prospective study.

BACKGROUND: Immunogenicity of influenza and pneumococcal vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs). METHODS: Adult MS patients who consented with vaccination after standard-of-care consultation by their treating physicians were enrolled. All received a single dose of an inactivated quadrivalent influenza vaccine and of the 23-valent pneumococcal vaccine. A blood sample was collected before and after four weeks of vaccination for measurement of antibodies against Influenza A, B and S. pneumoniae. Patients were followed-up for adverse events and MS relapse for 12 months. RESULTS: One hundred and seventy-two patients (65.7 % female, mean age 42 ± 13 years old, mean MS duration 7.6 ± 7.2 years, 81.4 % under DMTs) were enrolled from November 2019 to March 2020. Antibody measurements were available for 151 patients. Seropositivity for anti-PPSV23 did not differ between baseline and at 4 weeks of follow-up (n = 56, 37.1 %). There was a significant increase of absolute antibody titers post-vaccination for both influenza A and B (p < 0.001). For Influenza A, seropositivity was evident for 57 (37.7 %) patients at 4 weeks compared to 19 (12.6 %) patients at baseline (pMcNemar < 0.001). For Influenza Β, 110 (72.8 %) seroconverted 4 weeks after vaccination compared to 12 (7.9 %) at baseline (pMcNemar < 0.001). Interferon and fumarate did not affect influenza seroconversion while rituximab was associated with lower titers. Mild local AEs (pain, edema) were observed in 23.8 %; no severe AE was reported. Thirty-four patients (19.8 %) had a relapse during the 12-month follow-up; none was attributed to the vaccination. CONCLUSIONS: Seroconversion in MS patients on treatment was more frequent following influenza compared to PPSV23 vaccination. Rituximab had an effect on the height of the immune response. Better immunization coverage as well as future evaluation of the breadth of immune response elicited by immunization is necessary for these patients.

Diabetes Mellitus and Pneumococcal Pneumonia.

Currently, there are more than 500 million people suffering from diabetes around the world. People aged 65 years or older are the most affected by this disease, and it is estimated that approximately 96% of diabetes cases worldwide are type 2 diabetes. People with diabetes mellitus are at an increased risk of infections such as pneumonia, due to a series of factors that may contribute to immune dysfunction, including hyperglycemia, inhibition of neutrophil chemotaxis, impaired cytokine production, phagocytic cell dysfunction, altered T cell-mediated immune responses and the co-existence of chronic comorbidities. Rates of infection, hospitalization and mortality in diabetic patients are reported to be higher than in the general population. Research into the risk of infectious diseases such as pneumonia in these patients is very important because it will help improve their management and treatment.

Strategies for pneumococcal vaccination in older adults in the coming era.

Pneumonia, predominantly caused by Streptococcus pneumoniae, remains a leading cause of global mortality. The 23-valent Pneumococcal polysaccharide vaccine (PPSV23) and conjugate vaccines (PCVs) are vital measures to fight against it. This paper discussed the changes in pneumococcal vaccination strategies, particularly for older adults, as vaccine effectiveness and epidemiological patterns shift. While PPSV23 maintains effectiveness against invasive pneumococcal disease (IPD), its effectiveness against pneumococcal pneumonia is declining. Conversely, PCV13 consistently demonstrates effectiveness against both IPD and pneumonia. Consequently, the US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends using PCVs, notably PCV20 and PCV15, over PPSV23. Japanese studies indicate a change in the efficacy/effectiveness of PPSV23 following PCV introduction in children, likely owing to serotype replacement and herd immunity. Additionally, recent data reveals a plateau in the reduction of PCV13 and PPSV23-covered serotypes, posing a challenge to current strategies. This paper indicates a paradigm shift in pneumonia management, acknowledging its chronic nature and potential to exacerbate other diseases. The future of pneumococcal vaccination lies in broader serotype coverage through PCVs, adapting to serotype changes driven by childhood vaccination programs. Furthermore, continuous research and vaccine development are crucial in this evolving field.

Invasive pneumococcal disease caused by non-vaccine Streptococcus pneumoniae serotype 24B in an immunocompetent child.

Invasive pneumococcal disease typically occurs in immunocompromised patients, although some vaccine strains of Streptococcus pneumoniae have been reported to cause invasive pneumococcal disease in immunocompetent vaccine recipients. In this study, we presented a case of a 16-month-old immunocompetent patient with lung abscess and empyema caused by nonvaccine S. pneumoniae serotype 24B. A consolidation occupying the right upper lobe in the chest computed tomography results, as observed at presentation, changed to thick-walled cavitary lesions at the end of a month of intravenous antibiotics, and antibiotics were continued for a total of two months. To the best of our knowledge this is the first report that focuses on the risk of invasive pneumococcal disease caused by S. pneumoniae serotype 24B in an immunocompetent child.

Clinical features relating to pneumococcal colony phase variation in hospitalized adults with pneumonia.

Background. Streptococcus pneumoniae is a major causative bacteria of pneumonia and invasive pneumococcal disease (IPD); however, the mechanisms underlying its severity and invasion remain to be defined. Pneumococcal colonies exhibit opaque and transparent opacity phase variations, which have been associated with invasive infections and nasal colonization, respectively, in animal studies. This study evaluated the relationship between the opacity of pneumococcal colonies and the clinical presentation of pneumococcal pneumonia.Methods. This retrospective study included adult patients hospitalized with pneumococcal pneumonia between 2012 and 2019 at four tertiary medical institutions. Pneumococcal strains from lower respiratory tract specimens were determined for their serotypes and microscopic colony opacity, and the association between the opacity phase and the severity of pneumonia was evaluated. Serotypes 3 and 37 with mucoid colony phenotypes were excluded from the study because their colony morphologies were clearly different.Results. A total of 92 patients were included. Most patients were older adults (median age: 72 years) and males (67 %), and 59 % had community-acquired pneumonia. Of the 92 patients, 41 (45 %), 12 (13 %), and 39 (42 %) patients had opaque, transparent, and mixed variants in their pneumococcal colony, respectively. The opaque and non-opaque pneumococcal variants had no statistically significant difference in patient backgrounds. Although the pneumonia severity index score did not differ between the opaque and non-opaque groups, the rate of bacteremia was significantly higher in the opaque group than in the non-opaque group. Serotype distribution was similar between the groups.Conclusions. Opaque pneumococcal variants may cause pneumonia and invasive diseases in humans. This study could help elucidate IPD, and opacity assessment may serve as a predictor for IPD.

Immunomodulation of susceptibility to pneumococcal pneumonia infection in mouse lungs exposed to carbon nanoparticles via dysregulation of innate and adaptive immune responses.

Carbon nanotubes (CNTs) are emerging pollutants of occupational and environmental health concern. While toxicological mechanisms of CNTs are emerging, there is paucity of information on their modulatory effects on susceptibility to infections. Here, we investigated cellular and molecular events underlying the effect of multi-walled CNT (MWCNT) exposure on susceptibility to Streptococcus pneumoniae infection in our 28-day sub-chronic exposure mouse model. Data indicated reduced phagocytic function in alveolar macrophages (AMs) from MWCNT-exposed lungs evidenced by lower pathogen uptake in 1-h infection assay. At 24-h post-infection, intracellular pathogen count in exposed AMs showed 2.5 times higher net increase (2-fold in vehicle- versus 5-fold in MWCNT-treated), indicating a greater rate of intracellular multiplication and/or survival due to MWCNT exposure. AMs from MWCNT-exposed lungs exhibited downregulation of pathogen-uptake receptors CD163, Phosphatidyl-serine receptor (Ptdsr), and Macrophage scavenger receptors class A type 1 (Msr1) and type 2 (MSr2). In whole lung, MWCNT exposure shifted the macrophage polarization state towards the immunosuppressive phenotype M2b and increased the CD11c+ dendritic cell population required to activate the adaptive immune response. Notably, the MWCNT pre-exposure dysregulated T-cell immunity, evidenced by diminished CD4 and Th17 response, and exacerbated Th1 and Treg responses (skewed Th17/Treg ratio), thereby favoring the pneumococcal infection. Overall, these findings indicated that MWCNT exposure compromises both innate and adaptive immunity leading to diminished host lung defense against pneumonia infection. To our knowledge, this is the first report on an immunomodulatory role of CNT pre-exposure on pneumococcal infection susceptibility due to dysregulation of both innate and adaptive immunity targets.

Pneumococcal Serotypes Associated with Community-Acquired Pneumonia Hospitalizations in Adults in Spain, 2016-2020: The CAPA Study.

Newer higher valency pneumococcal conjugate vaccines (PCVs) have the potential to reduce the adult community-acquired pneumonia (CAP) burden. We describe the evolution and distribution of adult community-acquired pneumonia (CAP) serotypes in Spain, focusing on serotypes contained in the 20-valent PCV (PCV20). This was a prospective, observational study of chest X-ray (CXR)-confirmed CAP in immunocompetent adults hospitalized in one of four Spanish hospitals between November 2016 and November 2020. Pneumococci were isolated from cultures and detected in urine using BinaxNow® and Pfizer serotype-specific urinary antigen tests UAD1 and UAD2. We included 1948 adults hospitalized with CXR-CAP. The median age was 69.0 years (IQR: 24 years). At least one comorbidity was present in 84.8% (n = 1653) of patients. At admission, 76.1% of patients had complicated pneumonia. Pneumococcus was identified in 34.9% (n = 680) of study participants. The PCV20 vaccine-type CAP occurred in 23.9% (n = 465) of all patients, 68.4% (n = 465) of patients with pneumococcal CAP, and 82.2% (83/101) of patients who had pneumococcus identified by culture. Serotypes 8 (n = 153; 7.9% of all CAP) and 3 (n = 152; 7.8% of all CAP) were the most frequently identified. Pneumococcus is a common cause of hospitalized CAP among Spanish adults and serotypes contained in PCV20 caused the majority of pneumococcal CAP.

Community-Acquired Pneumococcal Pneumonia in Highly Vaccinated Population: Analysis by Serotypes, Vaccination Status, and Underlying Medical Conditions.

BACKGROUND: Targeted risk population has been highly vaccinated against pneumococcal diseases in South Korea. Despite this, the pneumococcal serotype distribution is evolving, which impedes efficient roll-out of vaccines. METHODS: This prospective cohort study included patients aged ≥ 19 years with community-acquired pneumonia (CAP) from five university hospitals in South Korea between September 2018 and July 2021. The outcomes of interest were the demographic and clinical characteristics of patients with CAP, pneumococcal serotype distribution, and risk factors of 30-day mortality in patients with pneumococcal CAP (pCAP). Considering the high seroprevalence, we analyzed the clinical characteristics of serotype 3 pCAP. RESULTS: A total of 5,009 patients hospitalized with CAP was included (mean age ± standard deviation, 70.3 ± 16.0 years; 3,159 [63.1%] men). Streptococcus pneumoniae was the leading causative agent of CAP (11.8% overall, 17.7% in individuals aged < 65 years with chronic medical conditions). Among the 280 serotyped Streptococcus pneumococcus, serotype 3 was the most common (10.0%), followed by serotypes 19A (8.9%), 34 (8.9%), and 35B (8.9%). Non-vaccine serotypes (serotype 35B [13.9%] and 34 [12.0%]) were the most prevalent in 108 individuals vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23). Serotype 3 was prevalent, irrespective of PPSV23 vaccination status, and more common in individuals with chronic lung disease (P = 0.008). Advanced age (adjusted odds ratio [aOR], 1.040; 95% confidence interval [CI], 1.011-1.071), long-term care facility residence (aOR, 2.161; 95% CI, 1.071-4.357), and bacteremia (aOR, 4.193; 95% CI, 1.604-10.962) were independent risk factors for 30-day mortality in patients with pCAP. PPSV23 vaccination reduced the risk of mortality (aOR, 0.507; 95% CI, 0.267-0.961). CONCLUSION: Serotype 3 and 19A were still the most common serotypes of pCAP in South Korea despite the national immunization program of 13-valent pneumococcal conjugated vaccine in children and PPSV23 in old adults. PPSV23 vaccination might reduce the risk of mortality in patients with pCAP.

Impact of the new membrane-targeting lipoglycopeptide antibiotic MCC5145 on the treatment of bacteremic pneumococcal pneumonia in mice.

Bacteremic Streptococcus pneumoniae pneumonia is one of the most severe forms of invasive pneumococcal disease (IPD) and with particularly high case-fatality rates among the elderly and individuals with comorbidities, exacerbated by rising antibiotic resistance and time to initiation of therapy. Here, we examined the efficacy of the preclinical "vancapticin" glycopeptide MCC5145 against fulminant infection by S. pneumoniae serotype 2 strain D39 in a bioluminescent, neutropenic mouse model of bacteremic pneumonia. MCC5145 is a semisynthetic vancomycin derivative chemically modified at the C-terminus with a membrane-targeting motif designed to preferentially bind the anionic bacterial surface. We show that similar to vancomycin, subcutaneous administration of MCC5145 to mice 1 day after intranasal infection with a bioluminescent derivative of S. pneumoniae D39 elicited time and concentration-dependent reduction in total flux in the lungs and blood. Together, our finding supports the further development of MCC5145 as a potential new treatment option for pneumonia and/or bacteremic pneumonia in clinical settings, particularly for immunocompromised individuals. IMPORTANCE S. pneumoniae (the pneumococcus) causes severe community acquired lung and blood infection, especially among the elderly and people with underlying medical conditions and/or weakened immune systems. The rising incidence of antibiotic resistance and delays between diagnosis of infection and commencement of effective therapy make treatment difficult and result in high mortality rates. In this work, we show that a new derivative (MCC5145) of an existing antibiotic (vancomycin) rapidly eradicated lethal pneumococcal challenge from the lungs and blood of mice with a suppressed immune system. Our findings support that MCC5145 is a promising option for the treatment of lung and blood infections caused by the pneumococcus at point-of-care settings, particularly for the elderly and individuals with a weakened immune system.

Cost-Effectiveness of Pneumococcal Vaccination in Adults in Italy: Comparing New Alternatives and Exploring the Role of GMT Ratios in Informing Vaccine Effectiveness.

In Italy, a sequential pneumococcal vaccination with conjugate vaccine (PCV) and polysaccharide vaccine (PPSV23) is recommended for individuals aged ≥ 65 years and those at risk for pneumococcal disease (PD) aged ≥ 6 years. The aim of this study was to assess the cost-effectiveness of the new vaccines, i.e., approved 15-valent and 20-valent PCVs. A published Markov model was adapted to evaluate the lifetime cost-effectiveness of vaccination with PCV15 + PPSV23 versus PCV13 + PPSV23, PCV20 alone, PCV20 + PPSV23, and No Vaccination. Simulated cohorts representing the Italian population, including individuals aged ≥ 65 years, those at risk aged 50-100 years, and those deemed high risk aged 18-100 years were assessed. Outcomes were accrued in terms of incremental PD cases, costs, quality-adjusted life years, life years, and the cost-utility ratio relative to PCV13 + PPSV23. The conservative base case analysis, including vaccine efficacy based on PCV13 data, showed that sequential vaccination with PCV15 or PCV20 in combination with PPSV23 is preferred over sequential vaccination with PCV13 + PPSV23. Especially in the high-risk group, PCV15 + PPSV23 sequential vaccination was dominant over No Vaccination and resulted in an ICUR of €3605 per QALY gained. Including PCV20 + PPSV23 into the comparison resulted in the domination of the PCV15 + PPSV23 and No Vaccination strategies. Additionally, explorative analysis, including the geometric mean titer (GMT) informed vaccine effectiveness (VE) was performed. In the low-risk and high-risk groups, the results of the GMT scenarios showed PCV15 + PPSV23 to be dominant over the other sequential vaccines. These findings suggest that if real-world studies would confirm a difference in vaccine effectiveness of PCV15 and PCV20 versus PCV13 based on GMT ratios, PCV15 + PPSV23 could prove a highly immunogenic and effective vaccination regime for the Italian adult population.

Outcomes among Thai children with risk conditions hospitalized for pneumococcal disease (invasive or non-bacteraemic pneumonia): A multi-centre, observational study.

Objective: To describe the risk condition status and clinical outcomes among Thai children hospitalized with pneumococcal disease. Methods: In this retrospective analysis, children with invasive pneumococcal disease (IPD) or x-ray-confirmed non-bacteraemic pneumococcal pneumonia (NBPP) were identified from nine hospitals in Thailand between 2010 and 2019. Data on risk factors and outcomes were extracted from medical records. Results: In total, 413 cases were identified: 319 IPD and 94 NBPP. Overall, 133 (32.2%) patients were admitted to intensive care units and 11/406 (2.7%) died. Twenty-seven percent of IPD cases had at-risk conditions and 15% had high-risk conditions. Most IPD cases (32.9%) occurred in children aged 2-4 years, and most NBPP cases (28.7%) occurred in infants aged 0-11 months. Of 51 Streptococcus pneumoniae isolates collected, 41 (80%) were pneumococcal 13-valent conjugate vaccine serotypes. Only 5.1% of children had received a pneumococcal vaccine. Conclusions: Most children with IPD and NBPP did not have high-risk or at-risk conditions, while 42% had at-risk or high-risk conditions for pneumococcal disease. Very few children in the cohort had received any type of pneumococcal vaccine. Increasing the availability of pneumococcal conjugate vaccines should be considered to reduce the burden of pneumococcal disease among children in Thailand.

Epidemiología de la neumonía neumocócica en adultos mayores de 50 años: estudio de cohortes en Cataluña, 2017-2018 / Epidemiology of pneumococcal pneumonia among middle-aged and older adults in Catalonia, 2017–2018

Objetivo: Analizar la incidencia y letalidad de la neumonía neumocócica (NN) en adultos tras la implementación de la vacunación universal en los niños. Diseño: Estudio de cohortes de base poblacional. Emplazamiento: Atención primaria/hospital, Cataluña. Participantes: 2.059.645 personas≥50 años afiliadas al Institut Català de la Salut, con seguimiento retrospectivo entre 01/01/2017-31/12/2018. Mediciones principales: El Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP) de Cataluña fue usado para establecer las características basales de los miembros de la cohorte, clasificados en 3 estratos de riesgo: bajo (inmunocompetentes sin condiciones de riesgo), medio (inmunocompetentes con alguna condición de riesgo) y alto (inmunocompromiso/asplenia). La ocurrencia de NN entre los miembros de la cohorte fue identificada mediante Conjunto Mínimo Básico de Datos de los 64 hospitales catalanes de referencia. Resultados: Se registraron 3592 episodios de NN, con una incidencia de 90,7 casos por 100.000 personas-año (IC 95%: 85,2-96,5), siendo 11,9 bacteriémicas (IC 95%: 10,8-13,1) y 78,8 no bacteriémicas (IC 95%: 74,0-83,8). La incidencia aumentó sustancialmente según edad (37,3 en 50-64; 98,3 en 65-79 y 259,8 en ≥80 años) y estrato de riesgo basal (42,1; 120,7 y 238,6 en bajo, medio y alto riesgo, respectivamente). La letalidad global fue del 7,6% (10,8% en casos invasivos vs. 7,1%en no invasivos; p=0,004). En modelos multivariantes, estrato de riesgo alto y edad avanzada (>80 años) fueron los más fuertes predictores para padecer episodios invasivos y no invasivos, respectivamente. Conclusión: La incidencia y letalidad de la NN fue moderada en la población>50 años de Cataluña durante 2017-2018.(AU)

Objective: To analyse population-based incidence and lethality of pneumococcal pneumonia (PP) requiring hospitalisation among Catalonian adults after universal vaccination implementation in infants. Design: Population-based cohort study. Setting: Primary care/hospital, Catalonia. Participants: 2,059,645 individuals ≥50 years old affiliated to the Institut Catala de la Salut retrospectively followed between 01/01/2017 and 31/12/2018. Main outcome measures: The Catalonian information system for the development of research in primary care (SIDIAP, Sistema de Información para el Desarrollo de la Investigación en Atención Primaria) was used to establish baseline characteristics and risk-strata of cohort members at study start: low-risk (immunocompetent persons without risk conditions), intermediate-risk (immunocompetent persons with at-risk condition) and high-risk (immunocompromising conditions). PP requiring hospitalisation among cohort members across study period were collected from CMBD (Conjunto Mínimo Básico de Datos) discharge data of 64 reference Catalonian hospitals. Results: An amount of 3592 episodes of HPP were observed, with an incidence density of 90.7 cases per 100,000 person-years (95% CI: 85.2-96.5), being 11.9 bacteremic (95% CI: 10.8-13.1) and 78.8 non-bacteremic (95% CI: 74.0-83.8). Incidence rates substantially increased by age (37.3 in 50-64 years vs. 98.3 in 65-79 years vs. 259.8 in ≥80 years) and baseline-risk stratum (42.1, 120.7 and 238.6 in low-, intermediate- and high-risk stratum, respectively). Overall case-fatality rate was 7.6% (10.8% in invasive cases vs. 7.1% in non-invasive cases; pP=.004). In multivariable analyses, high-risk stratum and oldest age were the strongest predictors for invasive and non-invasive cases, respectively. Conclusion: Incidence and lethality of PP remained moderate among adults >50 years in Catalonia during 2017–2018 (earlier period after universal vaccination introduction for infants).(AU)

Pneumococcal Disease: Global Disease Prevention Strategies with a Focus on the Challenges in Iraq.

Pneumococcal disease is a global public health concern that significantly contributes to clinical disease burden and economic burden. Patients frequently afflicted are young children and older adults, as well as the immunocompromised population. Immunization is the most effective public health strategy to combat pneumococcal disease and several vaccine formulations have been developed in this regard. Although vaccines have had a significant global impact in reducing pneumococcal disease, there are several barriers to its success in Iraq. The war and conflict situation, increasing economic crises and poverty, poor vaccine accessibility in the public sector, and high vaccine costs are a few of the major obstacles that impede a successful immunization program. The last reported third dose pneumococcal conjugate vaccine coverage for Iraq was 37% in 2019, which is expected to reduce even further owing to the COVID-19 pandemic. Thus, strategies and policies to improve pneumococcal vaccine availability and coverage need to be strengthened to achieve maximum benefits of immunization. In the current review, we provide an overview of the existing knowledge on pneumococcal disease-prevention strategies across the globe. The main aim of this manuscript is to discuss the current status and challenges of pneumococcal vaccination in Iraq as well as the strategies to prevent pneumococcal infections.

A Retrospective Study of Pneumococcal Pneumonia in Hospitalized Patients Aged ≥65 Years in Izumo, Japan: 2010 to 2014.

Purpose: In Japan, both a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a 13-valent pneumococcal conjugate vaccine (PCV13) are available. Although randomized controlled trials have examined the effects of pneumococcal vaccines, few epidemiological studies have investigated the onset of pneumococcal pneumonia in general practice. In Izumo, Shimane Prefecture, Japan, a public subsidy for PPSV23 inoculation began in November 2012. Patients and Methods: The subjects were pneumonia patients aged 65 and over who were admitted to a hospital in Izumo. This retrospective study analyzed the following data extracted from medical records: pneumococcal pneumonia prevalence, pneumonia severity, mortality rate, PPSV23 vaccination rate, and length of hospital stay. The 2 years before the start of the public subsidy were defined as the early phase, and the 2 years after the subsidy initiation were defined as the late phase. We compared the two phases in terms of PPSV23 vaccination rate, prevalence and severity of pneumococcal pneumonia, and mortality rate. Results: We investigated data from a total of 1188 and 1086 patients in the early and late phases, respectively. The prevalence of pneumococcal pneumonia was 21.0% and 21.3% in the early and late phases, respectively. The mortality rate from pneumococcal pneumonia was 10.4% and 5.4% in the early and late phases, respectively (p = 0.080), indicating a 50% reduction. The PPSV23 vaccination rate (p < 0.001) and the comorbidity rates of chronic respiratory disease (p = 0.022) and chronic renal disease (p < 0.001) were significantly different between the early and late phases. Conclusion: This study showed that the rate of in-hospital deaths due to pneumococcal pneumonia was halved after the PPSV23 vaccine was subsidized. The causal relationship between the pneumococcal vaccination rate and the mortality rate of pneumococcal disease was unclear. Further investigation is deemed necessary.

Evaluation of Plasma Lipocalin-2 as a Predictor of Etiology and Severity in Adult Patients with Community-Acquired Pneumonia.

The aim of this study was to evaluate the diagnostic performance of plasma Lipocalin-2 (LCN2) concentration in adult patients with community-acquired pneumonia (CAP) to determine its etiology, severity and prognosis. A prospective observational study involving adults with CAP from November 2015 to May 2017 was conducted. Plasma LCN2 concentration was measured upon admission by a modified enzyme immunoassay coupled with chemiluminescence (Architect, Abbott Laboratories). The diagnostic performance of LCN2, C-reactive protein (CRP) and white blood cell to predict bacterial CAP was assessed. A total of 130 patients with CAP were included: 71 (54.6%) bacterial CAP, 42 (32.3%) unknown origin CAP and 17 (13.1%) viral CAP. LCN2 was higher in bacterial CAP than in non-bacterial CAP (122.0 vs. 89.7 ng/mL, respectively) (p = 0.03) with a limited ability to distinguish bacterial and non-bacterial CAP (AUROC: 0.62 [95% CI 0.52-0.72]). The LCN2 cutoff ≥ 204 ng/mL predicted the presence of pneumococcal bacteremia with an AUROC of 0.74 (sensitivity 70%, specificity 79.1%). Regarding severity, as defined by CURB-65 and PSI scores, there was a significant linear trend in the mean concentration of LCN2, exhibiting a shift from the low-risk to the intermediate-risk and high-risk group (p < 0.001 and 0.001, respectively). LCN2 concentration was associated with severity in adult patients with CAP. However, its utility as a biomarker to discriminate viral and bacterial etiology in CAP is limited.

Incidence and risk factors of pneumococcal pneumonia in adults: a population-based study.

BACKGROUND: Infection caused by Streptococcus pneumoniae, mainly invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP), are a major public health problem worldwide. This study investigated population-based incidence and risk of PP among Catalonian persons ≥ 50 years-old with and without specific underlying conditions/comorbidities, examining the influence of single and multi-comorbidities in the risk of suffering PP. METHODS: Population-based cohort study involving 2,059,645 persons ≥ 50 years-old in Catalonia, Spain, who were retrospectively followed between 01/01/2017-31/12/2018. The Catalonian information system for development of research in primary care (SIDIAP) was used to establish baseline characteristics of the cohort (comorbidities/underlying conditions), and PP cases were collected from discharge codes (ICD-10: J13) of the 68 referral Catalonian hospitals. RESULTS: Global incidence rate (IR) was 90.7 PP cases per 100,000 person-years, with a 7.6% (272/3592) case-fatality rate (CFR). Maximum IRs emerged among persons with history of previous IPD or all-cause pneumonia, followed by haematological neoplasia (475.0), HIV-infection (423.7), renal disease (384.9), chronic respiratory disease (314.7), liver disease (232.5), heart disease (221.4), alcoholism (204.8), solid cancer (186.2) and diabetes (159.6). IRs were 42.1, 89.9, 201.1, 350.9, 594.3 and 761.2 in persons with 0, 1, 2, 3, 4 and ≥ 5 comorbidities, respectively. In multivariable analyses, HIV-infection (hazard ratio [HR]: 5.16; 95% CI: 3.57-7.46), prior all-cause pneumonia (HR: 3.96; 95% CI: 3.45-4.55), haematological neoplasia (HR: 2.71; 95% CI: 2.06-3.57), chronic respiratory disease (HR: 2.66; 95% CI: 2.47-2.86) and prior IPD (HR: 2.56; 95% CI: 2.03-3.24) were major predictors for PP. CONCLUSION: Apart of increasing age and immunocompromising conditions (classically recognised as high-risk conditions), history of prior IPD/pneumonia, presence of chronic pulmonary/respiratory disease and/or co-existing multi-comorbidity (i.e., two or more underlying conditions) are major risk factors for PP in adults, with an excess risk near to immunocompromised subjects. Redefining risk categories for PP, including all the above-mentioned conditions into the high-risk category, could be necessary to improve prevention strategies in middle-aged and older adults.

Discordance of the Urinary and Pleural Fluid Antigen Test and False Positive for Streptococcus pneumoniae in Empyema Secondary to Necrotizing Bacterial Pneumonia.

Empyema is a severe complication of pneumonia with high morbidity and mortality rates. Rapid diagnosis and tailoring of antibiotic therapy are crucial to treatment success for these severe bacterial lung infections. A Streptococcus pneumoniae (S. pneumonia) antigen test drawn from the pleural fluid rather than a urine sample has been found to have equivalent diagnostic utility to the urinary antigen test. Discordance between these tests is rare. We report a case of a 69-year-old female with CT imaging findings consistent with empyema and a bronchopulmonary fistula. A rapid S. pneumonia antigen test was negative from the urinary sample but positive when drawn from a patient's pleural fluid sample. Final pleural fluid cultures resulted in Streptococcus constellatus (S. constellatus). This case demonstrates discordance between the results of urinary and pleural fluid S. pneumoniae antigen tests, representing a potential pitfall in using rapid antigen testing on pleural fluid samples. False positives for the S. pneumoniae antigen in patients with viridans streptococci infections have been documented due to the cross-reactivity of cell wall proteins in different streptococcal species. Physicians encountering bacterial pneumonia of unknown etiology complicated by empyema should understand the potential for discordance and false positives using this diagnostic method.

[Epidemiology of pneumococcal pneumonia among middle-aged and older adults in Catalonia, 2017-2018]. / Epidemiología de la neumonía neumocócica en adultos mayores de 50 años: estudio de cohortes en Cataluña, 2017-2018.

OBJECTIVE: To analyse population-based incidence and lethality of pneumococcal pneumonia (PP) requiring hospitalisation among Catalonian adults after universal vaccination implementation in infants. DESIGN: Population-based cohort study. SETTING: Primary care/hospital, Catalonia. PARTICIPANTS: 2,059,645 individuals ≥50 years old affiliated to the Institut Catala de la Salut retrospectively followed between 01/01/2017 and 31/12/2018. MAIN OUTCOME MEASURES: The Catalonian information system for the development of research in primary care (SIDIAP, Sistema de Información para el Desarrollo de la Investigación en Atención Primaria) was used to establish baseline characteristics and risk-strata of cohort members at study start: low-risk (immunocompetent persons without risk conditions), intermediate-risk (immunocompetent persons with at-risk condition) and high-risk (immunocompromising conditions). PP requiring hospitalisation among cohort members across study period were collected from CMBD (Conjunto Mínimo Básico de Datos) discharge data of 64 reference Catalonian hospitals. RESULTS: An amount of 3592 episodes of HPP were observed, with an incidence density of 90.7 cases per 100,000 person-years (95% CI: 85.2-96.5), being 11.9 bacteremic (95% CI: 10.8-13.1) and 78.8 non-bacteremic (95% CI: 74.0-83.8). Incidence rates substantially increased by age (37.3 in 50-64 years vs. 98.3 in 65-79 years vs. 259.8 in ≥80 years) and baseline-risk stratum (42.1, 120.7 and 238.6 in low-, intermediate- and high-risk stratum, respectively). Overall case-fatality rate was 7.6% (10.8% in invasive cases vs. 7.1% in non-invasive cases; pP=.004). In multivariable analyses, high-risk stratum and oldest age were the strongest predictors for invasive and non-invasive cases, respectively. CONCLUSION: Incidence and lethality of PP remained moderate among adults >50 years in Catalonia during 2017-2018 (earlier period after universal vaccination introduction for infants).