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Objectives: This study aims to understand the magnitude of and mechanisms underlying the development of cardiovascular events (CVEs) in patients with invasive pneumococcal disease (IPD). We aimed to identify factors that contribute to the occurrence of CVEs within 1 year after admission and discuss implications for patient care., Methods: A multicentered cohort study included adult patients from four Dutch hospitals who had a positive blood culture for Streptococcus pneumoniae and any type of clinical manifestation between 2012 and 2020. Disease characteristics and microbiological data were systematically collected from electronic patient files. The main outcome measures were the occurrence of stroke and acute coronary syndromes (ACS)., Results: Of 914 eligible patients, 4.2% experienced a CVE within 1 year after admission for IPD. ACS mainly occurred in the first 2 weeks, whereas stroke developed throughout follow-up. Although ACS was positively associated with disease severity, the sole independent predictor was alcohol abuse (odds ratio [OR] 3.840, 95% confidence interval [CI] 1.108-13.303). Although stroke occurred in 6.3% of meningitis cases, the best clinical predictor of stroke was a body temperature >39.5 °C at admission (OR 3.117 [1.154-8.423]). In the adult IPD population aged <70 years, pneumococcal serotypes were the primary predictors of ACS (7F; OR 15.733 [1.812-136.632]) and stroke (22F; OR 7.320 [1.193-44.903])., Conclusions: Adverse CVEs were not uncommon after IPD diagnosis and deserve attention, especially in the high-risk groups we identified in our study population. Whether specific serotypes play a role in the development of CVE requires substantiation in further research., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The Streptococcus pneumoniae capsule is regarded as indispensable in bacteremia. We report an infant with a ventricular septal defect and infective endocarditis caused by nontypeable S. pneumoniae. In-depth investigation confirmed a deficient capsule yet favored pneumococcal fitness for causing infective endocarditis, rather than a host immune disorder, as the cause of infective endocarditis in this case., Competing Interests: Potential conflicts of interest. N. M. v. S. reports that patent WO 2013/020090 A3 has been licensed by the company Vaxcyte, generating royalties when milestones are reached and royalties from a patent on vaccine development against Streptococcus pyogenes, not part of the work submitted here (licensee University of California San Diego inventors, N. M. v. S. and Victor Nizet). N. M. v. S. also reports consulting fees from MSD (fee for service paid directly to the institution, related to pneumococcal invasive disease, and consulting fee for an expert panel) and GlaxoSmithKline (fee for service paid directly to the institution, related to pneumococcal invasive disease); payment or honoraria from MSD for expert meeting contribution on pneumococcal disease); and personal stocks from GenMab, Bank of America, and exchange-traded funds. 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) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: To explore the negative predictive value (NPV) of C-reactive protein (CRP) at admission to exclude complicated disease manifestations of pneumococcal disease., Methods: A Dutch multicentre retrospective cohort study was conducted between 01-01-2012 and 30-06-2020. Adults with positive blood cultures for Streptococcus pneumoniae, whose CRP was measured at admission and whose infection focus was known, were included. Electronic medical and microbiological records were reviewed., Results: Of the 832 bacteraemic patients enrolled, 30% had complicated manifestations of pneumococcal disease; most frequent were pleural effusion (8.9%), pleural empyema (5.4%) and meningitis (7.5%). Compared to solitary pneumonia, patients with pleural effusion and empyema presented with higher CRP levels. Although low CRP levels did not exclude complicated disease in general, a CRP level < 114 mg/L at admission could reliably exclude empyema among adult pneumonia patients with an NPV of 93% and a specificity of 26%. However, in cases where pleural fluid was present, CRP levels were mostly > 114 mg/L, such that suspicion of empyema could only be ruled out in a minority of cases (10%)., Conclusions: Complicated manifestations are prevalent in adult pneumococcal bacteraemia. Low blood CRP levels can reliably exclude the development of pulmonary empyema. Practical value may be largest in settings without thoracic imaging at hand., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Streptococcus pneumoniae is the leading bacterial pathogen causing respiratory infections. Since the COVID-19 pandemic emerged, less invasive pneumococcal disease (IPD) was identified by surveillance systems worldwide. Measures to prevent transmission of SARS-CoV-2 also reduce transmission of pneumococci, but this would gradually lead to lower disease rates., Design: Here, we explore additional factors contributing to the instant drop in pneumococcal disease cases captured in surveillance., Results: Our observations on referral practices and other impediments to diagnostic testing indicate that residual IPD has likely occurred but remained undetected by conventional hospital-based surveillance., Conclusions: Depending on the setting, we discuss alternative monitoring strategies that could improve understanding of pneumococcal disease dynamics., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Different clinical manifestations of invasive pneumococcal disease (IPD) have thus far mainly been explained by patient characteristics. Here we studied the contribution of pneumococcal genetic variation to IPD phenotype., Methods: The index cohort consisted of 349 patients admitted to 2 Dutch hospitals between 2000-2011 with pneumococcal bacteremia. We performed genome-wide association studies to identify pneumococcal lineages, genes, and allelic variants associated with 23 clinical IPD phenotypes. The identified associations were validated in a nationwide (n = 482) and a post-pneumococcal vaccination cohort (n = 121). The contribution of confirmed pneumococcal genotypes to the clinical IPD phenotype, relative to known clinical predictors, was tested by regression analysis., Results: Among IPD patients, the presence of pneumococcal gene slaA was a nationwide confirmed independent predictor of meningitis (odds ratio [OR], 10.5; P = .001), as was sequence cluster 9 (serotype 7F: OR, 3.68; P = .057). A set of 4 pneumococcal genes co-located on a prophage was a confirmed independent predictor of 30-day mortality (OR, 3.4; P = .003). We could detect the pneumococcal variants of concern in these patients' blood samples., Conclusions: In this study, knowledge of pneumococcal genotypic variants improved the clinical risk assessment for detrimental manifestations of IPD. This provides us with novel opportunities to target, anticipate, or avert the pathogenic effects related to particular pneumococcal variants, and indicates that information on pneumococcal genotype is important for the diagnostic and treatment strategy in IPD. Ongoing surveillance is warranted to monitor the clinical value of information on pneumococcal variants in dynamic microbial and susceptible host populations.

In many low- and middle-income countries (LMICs), a poor link between antibiotic policies and practices exists. Numerous contextual factors may influence the degree of antibiotic access, appropriateness of antibiotic provision, and actual use in communities. Therefore, improving appropriateness of antibiotic use in different communities in LMICs probably requires interventions tailored to the setting of interest, accounting for cultural context. Here we present the ABACUS study (AntiBiotic ACcess and USe), which employs a unique approach and infrastructure, enabling quantitative validation, contextualization of determinants, and cross-continent comparisons of antibiotic access and use. The community infrastructure for this study is the INDEPTH-Network (International Network for the Demographic Evaluation of Populations and Their Health in Developing Countries), which facilitates health and population research through an established health and demographic surveillance system. After an initial round of formative qualitative research with community members and antibiotic suppliers in three African and three Asian countries, household surveys will assess the appropriateness of antibiotic access, provision and use. Results from this sample will be validated against a systematically conducted inventory of suppliers. All potential antibiotic suppliers will be mapped and characterized. Subsequently, their supply of antibiotics to the community will be measured through customer exit interviews, which tend to be more reliable than bulk purchase or sales data. Discrepancies identified between reported and observed antibiotic practices will be investigated in further qualitative interviews. Amartya Sen's Capability Approach will be employed to identify the conversion factors that determine whether or not, and the extent to which appropriate provision of antibiotics may lead to appropriate access and use of antibiotics. Currently, the study is ongoing and expected to conclude by 2019. ABACUS will provide important new insights into antibiotic practices in LMICs to inform social interventions aimed at promoting optimal antibiotic use, thereby preserving antibiotic effectiveness., Competing Interests: Competing interests: No competing interests were disclosed.

Introduction: The clinical severity and course of invasive pneumococcal disease (IPD) differs substantially between patients. Streptococcus pneumoniae harbors large genetic variability. Zinc metalloproteinase C (ZmpC), a secreted pneumococcal protein involved in neutrophil extravasation, inflammation and tissue remodeling, is present in a minority of IPD isolates. We investigated whether the presence of zmpC was associated with the clinical manifestation of IPD., Material and Methods: IPD patients admitted to two Dutch hospitals between 2000 and 2013 were included in the study. Detailed clinical data were collected and the serotype and presence of zmpC were determined in the corresponding blood culture isolates., Results: ZmpC was present in 21% of the 542 included IPD cases and was mainly associated with serotypes 8, 4, 33A/F and 11A/D. Infection with S. pneumoniae positive for zmpC was more frequently observed in females (p=0.048) and patients with a history of smoking (p=0.033). Although no relation to clinical syndrome was observed, zmpC positive cases more often presented with cough, dyspnea and sepsis (p-values 0.026, 0.001 and 0.018), and more frequently required ICU admission (p=0.011) compared to zmpC negative cases., Conclusion: The presence of zmpC was associated with a more severe clinical manifestation of IPD. This study demonstrates that information on pneumococcal genetic background may be useful to identify vulnerable individuals, to monitor clinical presentation and to predict the course of IPD., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Purpose: The introduction of a 7-valent conjugate pneumococcal vaccine (PCV7) in children largely affected the prevalence of adult pneumococcal pneumonia. In this study we investigated whether the clinical severity of adult bacteremic pneumococcal pneumonia has also altered following the introduction of pediatric PCV7 vaccination., Methods: Adults hospitalized with bacteremic pneumococcal pneumonia between 2001 and June 2011 at two Dutch hospitals were included retrospectively. Clinical data on patient characteristics, comorbidities and severity of disease were obtained and pneumococcal serotypes were determined., Results: Among 343 patients investigated, those infected with PCV7 serotypes had a higher PSI score (p=0.0072) and mortality rate (p=0.0083) compared with the remainder of the cohort. Since the introduction of PCV7 the proportion of pneumococcal pneumonias caused by serotypes 1 and 7F (p-values 0.037 and 0.025) increased, as well as the rate of pleural effusion and empyema (p-values 0.011 and 0.049). Whilst de proportion of adults infected with PCV7 serotypes decreased after the introduction of PCV7 (p=0.015), PSI scores in these patients remained higher (p=0.030), although mortality rates between PCV7 and non PCV7 types equalized. After the introduction of PCV7 a marked shortening in hospital stay was observed only among patients infected with non PCV7 serotypes (p=0.019)., Conclusions: The introduction of pediatric PCV7 vaccination was accompanied by subtle changes in clinical severity of adult bacteremic pneumococcal pneumonia. Expansion of serotypes covered by pneumococcal vaccination may again influence the clinical presentation of disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)