Streptococcus pneumoniae infections cause community-acquired pneumonia and invasive pneumococcal disease such as sepsis and acute meningitis. In the adult population, the risk of severe infections, which can be lethal, is particularly high among people aged above 65 years and subgroups with comorbidities. Pneumococcal vaccines underwent progressive improvement and a new conjugated vaccine targeting 20 serotypes (PCV20) is now available. The Belgian Superior Health Council has recently reiterated the importance of vaccinating at-risk individuals against S. pneumoniae and now recommends vaccination with PCV20 (Apexxnar®) as the preferred primary vaccination regimen in all at-risk adults. The present article reminds the risk of severe pneumococcal infections among patients with comorbidities, by targeting five of them, chronic respiratory diseases, heart failure, chronic kidney disease, diabetes mellitus and cirrhosis. It emphasizes the too low rate of pneumococcal vaccination in these at-risk subgroups and summarizes the last guidelines of the Belgian Superior Health Council in favor of pneumococcal vaccination in at-risk patients with comorbidities. Finally, it describes the Belgian reimbursement criteria recently granted to people aged 65-85 years with comorbidities.
Les infections par le Streptococcus pneumoniae sont responsables de pneumonies communautaires et de maladies invasives à pneumocoques telles que sepsis et méningites aiguës. Dans la population adulte, le risque d’infections graves, potentiellement léthales, est particulièrement élevé chez les personnes âgées de plus de 65 ans et parmi des sous-groupes avec comorbidités. Les vaccins antipneumococciques ont été progressivement améliorés et un nouveau vaccin conjugué ciblant 20 sérotypes (PCV20) est désormais disponible. Le Conseil Supérieur de la Santé (CSS) belge a rappelé, en 2022, l’importance de vacciner contre S. pneumoniae les personnes à risque et privilégie le PCV20 (Apexxnar®) pour la primo-vaccination chez les personnes adultes dans tous les groupes à risque. Cet article rappelle le risque d’infections pneumococciques graves chez les patients avec comorbidités, en ciblant plus particulièrement quatre d’entre elles, les maladies respiratoires chroniques, l’insuffisance cardiaque, la maladie rénale chronique, le diabète sucré et la cirrhose. Il insiste sur le trop faible taux de vaccination antipneumococcique dans ces populations à risque et résume les dernières recommandations du CSS en faveur de la vaccination antipneumococcique des groupes à risque en fonction de la présence de comorbidités. Enfin, il fait état des conditions de remboursement récemment accordées à la vaccination antipneumococcique dans les groupes à risque chez les personnes âgées de 65 à 85 ans.

OBJECTIVE: To determine whether a novel intervention improves the adherence to guideline-based preventive measures in asplenic patients at risk of post-splenectomy sepsis (PSS).
METHODS: We used a prospective controlled, two-armed historical control group design to compare a novel, health action process approach (HAPA)-based telephonic intervention involving both patients and their general practitioners to usual care. Eligible patients were identified in cooperation with the insurance provider AOK Baden-Wuerttemberg, Germany. Patients with anatomic asplenia (n = 106) were prospectively enrolled and compared to a historical control group (n = 113). Comparisons were done using a propensity-score-based overlap-weighting model. Adherence to preventive measures was quantified by the study-specific \'Preventing PSS score\' (PrePSS score) which includes pneumococcal and meningococcal vaccination status, the availability of a stand-by antibiotic and a medical alert card.
RESULTS: At six months after the intervention, we estimated an effect of 3.96 (95% CI 3.68-4.24) points on the PrePSS score scale (range 0-10) with mean PrePSS scores of 3.73 and 7.70 in control and intervention group, respectively. Substantial improvement was seen in all subcategories of the PrePSS score with the highest absolute gains in the availability of stand-by antibiotics. We graded the degree of participation by the general practitioner (no contact, short contact, full intervention) and noted that the observed effect was only marginally influenced by the degree of physician participation.
CONCLUSIONS: Patients who had received the intervention exhibited a significantly higher adherence to guideline-based preventive measures compared to the control group. These data suggest that widespread adoption of this pragmatic intervention may improve management of asplenic patients. Health insurance provider-initiated identification of at-risk patients combined with a patient-focused intervention may serve as a blueprint for a wide range of other preventive efforts leading to patient empowerment and ultimately to better adherence to standards of care.

BACKGROUND: The incidence of community-acquired acute bacterial meningitis has decreased during the last decades. However, outcome remains poor with a significant proportion of patients not surviving and up to 50% of survivors suffering from long-term sequelae. These guidelines were developed by the Deutsche Gesellschaft für Neurologie (DGN) under guidance of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) to guide physicians through diagnostics and treatment of adult patients with acute bacterial meningitis.
CONCLUSIONS: The most important recommendations are: (i) In patients with suspected acute bacterial meningitis, we recommend that lumbar cerebrospinal fluid (with simultaneous collection of serum to determine the cerebrospinal fluid-serum glucose index and blood cultures) is obtained immediately after the clinical examination (in the absence of severely impaired consciousness, focal neurological deficits, and/or new epileptic seizures). (ii) Next, we recommend application of dexamethasone and empiric antibiotics intravenously. (iii) The recommended initial empiric antibiotic regimen consists of ampicillin and a group 3a cephalosporin (e.g., ceftriaxone). (iv) In patients with severely impaired consciousness, new onset focal neurological deficits (e.g. hemiparesis) and/or patients with newly occurring epileptic seizures, we recommend that dexamethasone and antibiotics are started immediately after the collection of blood; we further recommend that -if the imaging findings do not indicate otherwise -a lumbar CSF sample is taken directly after imaging. (v) Due to the frequent occurrence of intracranial and systemic complications, we suggest that patients with acute bacterial meningitis are treated at an intensive care unit in the initial phase of the disease. In the case of impaired consciousness, we suggest that this is done at an intensive care unit with experience in the treatment of patients with severe CNS diseases.
CONCLUSIONS: The German S2k-guidelines give up to date recommendations for workup, diagnostics and treatment in adult patients with acute bacterial meningitis.

To report on the therapy used for penicillin- and cephalosporin-resistant pneumococcal meningitis, we conducted an observational cohort study of patients admitted to our hospital with pneumococcal meningitis between 1977 and 2018. According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations, we defined pneumococci as susceptible and resistant to penicillin with MIC values of ≤0.06 mg/L and > 0.06 mg/L, respectively; the corresponding values for cefotaxime (CTX) were ≤0.5 mg/L and >0.5 mg/L. We treated 363 episodes of pneumococcal meningitis during the study period. Of these, 24 had no viable strain, leaving 339 episodes with a known MIC for inclusion. Penicillin-susceptible strains accounted for 246 episodes (73%), penicillin-resistant strains for 93 (27%), CTX susceptible for 58, and CTX resistant for 35. Nine patients failed or relapsed and 69 died (20%), of whom 22% were among susceptible cases and 17% were among resistant cases. During the dexamethasone period, mortality was equal (12%) in both susceptible and resistant cases. High-dose CTX (300 mg/Kg/day) helped to treat failed or relapsed cases and protected against failure when used as empirical therapy (P = 0.02), even in CTX-resistant cases. High-dose CTX is a good empirical therapy option for pneumococcal meningitis in the presence of a high prevalence of penicillin and cephalosporin resistance, effectively treating pneumococcal strains with MICs up to 2 mg/L for either penicillin or CTX.

Streptococcus pneumoniae can commonly cause otitis media, sinusitis, pneumonia, or meningitis; however, these infections less frequently can develop into invasive pneumococcal disease (IPD). Vaccination for the prevention of pneumococcal disease has significantly decreased complications from severe infections, including pneumonia, meningitis, and IPD, in patients with certain risk factors. In this case study, we describe a unique presentation of disseminated S. pneumoniae meningitis and bacteremia in a patient who initially presented with acute otitis media (AOM). Due to the patient\'s multiple comorbidities of obesity, tobacco use, pre-diabetes, coronary artery disease, and lack of pneumococcal vaccination, their AOM rapidly progressed to life-threatening, an invasive pneumococcal infection which was successfully treated with timely initiation of antibiotics. In addition to discussing the patient\'s clinical course and treatment regimen, we will review pertinent updates to the pneumococcal vaccination guidelines for high-risk patients and their efficacy in preventing severe disease.

Streptococcus pneumoniae (pneumococcus) remains a significant cause of both mild infections such as otitis media, sinusitis, and bronchitis and more severe manifestations such as bacteremia, pneumonia, and invasive pneumococcal disease. Several key serotypes have been targeted in vaccine development due to their association with increased infectivity. Pneumococcal vaccines are available in two formulations, the unconjugated purified polysaccharide (PPSV) and the conjugated formulation (PCV), which leads to a more robust and prolonged immune response. There have been dramatic reductions in mortality attributed to invasive pneumococcal disease over the past 2 decades due to improved vaccination rates and improved serotype coverage with the existing arsenal of vaccines (PCV13 and PPSV23). Utilizing both conjugate and purified polysaccharide modalities in series has produced greater and lasting immunity. The development of both the PCV15 and the PCV20 vaccines provides an opportunity to use conjugated vaccines against a wider spectrum of pneumococcal serotypes. National guidelines have been updated to incorporate the new pneumococcal vaccines into clinical practice.

Pneumococcal disease is a serious global public health problem and a leading cause of morbidity and mortality of children and adults in China. Antibiotics are commonly used to treat pneumococcal disease. However, antibiotic resistance to Streptococcus pneumoniae has become a severe problem around the world due to widespread antibiotic use. Immunoprophylaxis of pneumococcal disease with pneumococcal vaccines is therefore of great importance. In this article, we review the etiology, clinical presentation, epidemiology, and disease burden of pneumococcal disease and the vaccinology of pneumococcal vaccines. Our review is based on the Expert Consensus on Immunoprophylaxis of Pneumococcal Disease (2017 version), the Pneumococcal Vaccines WHO Position Paper (2019), and recent national and international scientific advances. This consensus article aims to provide public health and vaccination staff with appropriate evidence for pneumococcal vaccine use and to improve professional capacity for pneumococcal disease prevention and control.
肺炎球菌性疾病是全球严重的公共卫生问题之一，也是导致中国儿童及成人发病和死亡的重要原因。肺炎球菌性疾病的临床治疗用药以抗生素为主，由于抗生素的广泛应用，肺炎球菌的耐药性问题日益严重。采用肺炎球菌疫苗预防肺炎球菌性疾病并减少细菌耐药性，尤为必要和迫切。本文在《肺炎球菌性疾病免疫预防专家共识（2017版）》基础上，结合WHO肺炎球菌疫苗立场文件（2019年）和国内外最新研究进展，对肺炎球菌性疾病的病原学、临床学、流行病学、疾病负担、疫苗学等方面进行系统综述，目的是为公共卫生和预防接种专业人员在科学使用疫苗与发挥疫苗最佳预防作用方面提供证据，提高肺炎球菌性疾病防控水平。.

Pneumococcal disease is a serious global public health problem and a leading cause of morbidity and mortality of children and adults in China. Antibiotics are commonly used to treat pneumococcal disease. However, antibiotic resistance to Streptococcus pneumoniae has become a severe problem around the world due to widespread antibiotic use. Immunoprophylaxis of pneumococcal disease with pneumococcal vaccines is therefore of great importance. In this article, we review the etiology, clinical presentation, epidemiology, and disease burden of pneumococcal disease and the vaccinology of pneumococcal vaccines. Our review is based on the Expert Consensus on Immunoprophylaxis of Pneumococcal Disease (2017 version), the Pneumococcal Vaccines WHO Position Paper (2019), and recent national and international scientific advances. This consensus article aims to provide public health and vaccination staff with appropriate evidence for pneumococcal vaccine use and to improve professional capacity for pneumococcal disease prevention and control.
肺炎球菌性疾病是全球严重的公共卫生问题之一，也是导致中国儿童及成年人发病和死亡的重要原因。肺炎球菌性疾病的临床治疗用药以抗生素为主，由于抗生素的广泛应用，肺炎球菌的耐药性问题日益严重。采用肺炎球菌疫苗预防肺炎球菌性疾病并减少细菌耐药性，尤为必要和迫切。本文在《肺炎球菌性疾病免疫预防专家共识（2017版）》基础上，结合WHO肺炎球菌疫苗立场文件（2019年）和国内外最新研究进展，对肺炎球菌性疾病的病原学、临床学、流行病学、疾病负担、疫苗学等方面进行系统综述，目的是为公共卫生和预防接种专业人员在科学使用疫苗与发挥疫苗最佳预防作用方面提供证据，提高肺炎球菌性疾病防控水平。.

Copper is broadly toxic to bacteria. As such, bacteria have evolved specialized copper export systems (cop operons) often consisting of a DNA-binding/copper-responsive regulator (which can be a repressor or activator), a copper chaperone, and a copper exporter. For those bacteria using DNA-binding copper repressors, few studies have examined the regulation of this operon regarding the operator DNA sequence needed for repressor binding. In Streptococcus pneumoniae (the pneumococcus), CopY is the copper repressor for the cop operon. Previously, homologs of pneumococcal CopY have been characterized to bind a 10-base consensus sequence T/GACANNTGTA known as the cop box. Using this motif, we sought to determine whether genes outside the cop operon are also regulated by the CopY repressor, which was previously shown in Lactococcus lactis We found that S. pneumoniae CopY did not bind to cop operators upstream of these candidate genes in vitro During this process, we found that the cop box sequence is necessary but not sufficient for CopY binding. Here, we propose an updated operator sequence for the S. pneumoniae cop operon to be ATTGACAAATGTAGAT binding CopY with a dissociation constant (Kd ) of ∼28 nM. We demonstrate strong cross-species interaction between some CopY proteins and CopY operators, suggesting strong evolutionary conservation. Taken together with our binding studies and bioinformatics data, we propose the consensus operator RNYKACANNYGTMRNY for the bacterial CopR-CopY copper repressor homologs.IMPORTANCE Many Gram-positive bacteria respond to copper stress by upregulating a copper export system controlled by a copper-sensitive repressor, CopR-CopY. The previous operator sequence for this family of proteins had been identified as TACANNTGTA. Here, using several recombinant proteins and mutations in various DNA fragments, we define those 10 bases as necessary but not sufficient for binding and in doing so, refine the cop operon operator to the 16-base sequence RNYKACANNTGTMRNY. Due to the sheer number of repressors that have been said to bind to the original 10 bases, including many antibiotic resistance repressors such as BlaI and MecI, we feel that this study highlights the need to reexamine many of these sites of the past and use added stringency for verifying operators in the future.

Pneumococcal disease constitutes a major global health problem. Adults aged over 50 years and younger adults with specific chronic health conditions are at risk for invasive pneumococcal disease, associated with substantial morbidity and mortality. In Europe, two vaccine types are used in adults for pneumococcal immunization: pneumococcal polysaccharide vaccine (PPV23) and pneumococcal conjugate vaccine (PCV13). To provide an overview and to compare the national guidelines for pneumococcal immunization for adults in Europe. In November 2016, national guidelines on pneumococcal vaccination for adults of 31 European countries were obtained by Google search, the website of European Centre for Disease Prevention and Control, and contacting public health officials. In our analysis, we distinguished between age-based and risk-based guidelines. In October 2017, we used the same method to retrieve guideline updates. We observed great variability regarding age, risk groups, vaccine type, and use of boosters. In age-based guidelines, vaccination is mostly recommended in adults aged over 65 years using PPV23. Boosters are generally not recommended. An upper age limit for vaccination is reported in three countries. In the immunocompromised population, vaccination with both vaccines and administration of a booster is mostly recommended. In the population with chronic health conditions, there is more heterogeneity according vaccine type, sequence, and administration of boosters. Asplenia is the only comorbidity for which all countries recommend vaccination. The great variability in European pneumococcal vaccination guidelines warrants European unification of the guidelines for better control of pneumococcal disease.