Invasive pneumococcal disease (IPD) is a life-threatening infection caused by Streptococcus pneumoniae, particularly in immunocompromised individuals, such as those with asplenia. Although pneumococcal vaccination has reduced the incidence of vaccine-covered serotypes, non-vaccine serotypes, including serotype 23B, have emerged as the predominant cause of IPD. This case report describes a 67-year-old woman with asplenia who developed IPD caused by multidrug-resistant Streptococcus pneumoniae serotype 23B, which led to meningitis, septic arthritis, and endophthalmitis. The patient, who had declined pneumococcal vaccination after her splenectomy, presented with fever, pain in her left hip and right shoulder, and visual issues. The diagnosis confirmed S. pneumoniae serotype 23B, resistant to multiple antibiotics. The treatment involved a combination of vancomycin, ceftriaxone, and rifampicin, followed by vitrectomy for the eye infection. Despite severe complications, including worsening vision, the patient's vision in the right eye improved after surgery, and the joint pain subsided with long-term antibiotic therapy. This case underscores the challenges posed by non-vaccine S. pneumoniae serotypes, particularly in asplenic patients. Currently, we can use the 21-valent pneumococcal conjugate vaccine (PCV21), which includes the 23B serotype. Vaccination and early recognition, combined with a multidisciplinary treatment approach involving both antimicrobial therapy and surgical intervention, are crucial for improving the outcomes of patients with severe IPD.

Standardized processing of respiratory specimens and accurate identification and antimicrobial susceptibility testing (AST) of Streptococcus pneumoniae are crucial for clinical management. This study investigated laboratory practices for specimen processing, S. pneumoniae identification, and AST of S. pneumoniaeamong CARSS hospitals. A nationwide online survey was conducted in 2023. After data cleaning, 3,297 valid questionnaires were analyzed. The survey assessed specimen distribution, sputum/BALF processing, identification and quality control (QC). Sputum was the most common specimen(39.92%), followed by "others" (20.83%), blood (20.47%), urine (14.16%), and BALF (4.58%). Most laboratories performed routine Gram staining on sputum (71.55%) and BALF (66.88%). For sputum smears, 75.80% ~ 86.29% reported semi-quantitative cell/pathogen counts. The dominant acceptability criterion for sputum was > 25 WBCs/LPF and <10 SECs/LPF (98.88%). For unacceptable sputum specimens yielding S. pneumoniae 45.12% laboratories laboratories performed identification/AST only if the bacterial quantity was ≥ 2 + . Common identification methods were Optochin/bile solubility test (53.32%), Vitek GP card (42.74%) and MALDI-TOF MS (30.15%). AST methods included Vitek GP68 (38.76%), disk diffusion (32.91%), gradient diffusion (22.78%) and DL-96STREP cards (21.20%). Notably, 44.10% perform no routine AST QC and 44.62% lacked QC strain ATCC 49619. Only 49.65% used ATCC 49619 for QC.Significant variations exist in laboratory practices for respiratory specimen processing and S. pneumoniae workup across CARSS hospitals. While conventional methods remain prevalent, MALDI-TOF MS adoption is growing.The high proportion of laboratories lacking routine AST QC underscores the need for standardized protocols and enhanced quality assurance nationwide.

Prevotella species are an extremely common and abundant bacteria detected within the low microbial biomass of the lungs and are a core component of the oral microbiome. Clinical studies have drawn associations between Prevotella abundance and lung homeostasis, indicating potential relationships between Prevotella and lung inflammation, infection defense, and lung function. Across several studies in critically ill patients, the depletion of Prevotella and other obligate anaerobes is linked to significantly reduced survival, leading to calls for anaerobe preservation in empiric antibiotic therapy regimens. In recent years, mechanistic studies have provided new information regarding Prevotella-host relationships, highlighting several processes by which Prevotella exposure activates epithelial, innate, and adaptive immune responses. Prevotella species also have direct and indirect effects on important lung bacterial pathogens, including Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa, with Prevotella species-dependent consequences for pathogen infection and regulation of pathogen-induced inflammation. This review summarizes our current understanding regarding how Prevotella regulate lung immune homeostasis, with a discussion of key knowledge gaps necessary for the translation of these insights into new therapeutic approaches to reduce the burden of lung infection and disease.

Streptococcus pneumoniae remains a leading cause of lower respiratory tract infections and pneumonia-related mortality worldwide. Although neutrophil recruitment is essential for pneumococcal containment, excessive and dysregulated neutrophilic inflammation can drive severe lung injury and acute respiratory distress syndrome. Specialized pro-resolving mediators, such as Resolvin D5 (7S,17S-dihydroxy-4Z,8E,10Z,13Z,15E,19Z-docosahexaenoic acid; RvD5), are produced in the lungs and have the potential to promote pathogen clearance and limit inflammatory injury. Using a mouse model of severe pneumococcal pneumonia, we investigated the actions of RvD5 on disease progression. Exogenous RvD5 was administered either at the time of infection, or post-infection together with the antibiotic ceftriaxone. Outcomes measured included lung neutrophil accumulation, bacterial burden, neutrophil activation markers, and indices of alveolar barrier integrity. Complementary in vitro assays were performed to assess the effects of RvD5 on human neutrophil phagocytosis and activation by LTB4. When administered at the time of infection, RvD5 reduced neutrophil accumulation in bronchoalveolar lavage (BAL) and lung tissue and enhanced clearance of S. pneumoniae. RvD5 decreased neutrophil activation marker expression and lowered total protein levels in BAL fluid, consistent with reduced inflammatory lung injury. When administered post-infection together with ceftriaxone, RvD5 significantly reduced lung neutrophil numbers and barrier disruption compared to antibiotic treatment alone. In vitro, RvD5 enhanced phagocytic uptake and intracellular killing of bacteria by human neutrophils, and blunted secondary calcium mobilization responses to LTB4. In summary, these findings indicate that RvD5 can initiate pro-resolving mechanisms adjunctive to antibiotics to enhance bacterial clearance and limit inflammation-driven lung injury in severe pneumococcal pneumonia.

Streptococcus pneumoniae asymptomatically colonizes the nasopharynx but can also cause mucosal infections or invasive pneumococcal disease. Despite the significant positive impact of pneumococcal conjugate vaccines, the burden of pneumococcal disease persists, reflecting the inherent limitations of a strategy that elicits serotype-dependent humoral immunity against a pathogen with > 100 known serotypes.

Early life is characterized by heightened susceptibility to respiratory pathogens, yet the immune mechanisms that predispose infants to infection remain poorly defined. Using an infant mouse model of Streptococcus pneumoniae (Spn) colonization, we identify an age-dependent delay in IL-17 A production that was associated with prolonged bacterial colonization in infant mice. Consistent with a critical role for this pathway, IL-17 receptor A (IL-17RA)-deficient infant mice exhibited persistent Spn colonization of the upper respiratory tract (URT). Transcriptomic profiling of the URT from Spn-colonized IL-17RA-deficient infant mice revealed an enrichment of antiviral responses compared to WT controls and included increased expression of the interferon-stimulated gene Cxcl10, a chemokine whose expression is positively associated with Spn carriage in humans. These results suggested that IL-17RA signaling constrains the interferon response during URT Spn colonization. WT infant mice exhibited progressively increased expression of Cxcl10 during Spn colonization and was dependent on type 1 interferon (IFNAR1) signaling and the pore forming bacterial toxin, pneumolysin. Genetic deletion of Ifnar1 or Cxcl10, including myeloid cell-specific deletion of Ifnar1, accelerated bacterial clearance in infant mice. In contrast, adult mice exhibited earlier induction of IL-17 A, minimal induction of Cxcl10 expression, and no alteration in bacterial clearance rates following Ifnar1 or Cxcl10 deficiency. Taken together, our results reveal a developmental window in which delayed IL-17 A production postpones the IL-17RA-dependent restraint of the type I interferon/CXCL10 axis, thereby prolonging pneumococcal carriage through impaired myeloid cell-mediated bacterial clearance.