Escherichia coli (E. coli) bloodstream infections (BSIs) are among the most predominant causes of death in infants and children worldwide. NDM-5 (New Delhi Metallo-lactamase-5) is responsible for one of the main mechanisms of carbapenem resistance in E. coli. To analyze the phenotypic and genomic characteristics of NDM-5-producing E. coli from bloodstream infections (BSIs), a total of 114 E. coli strains was collected from a children’s hospital in Jiangsu province, China. Eight bla_NDM-5-carrying E. coli strains were identified which were all carbapenem-resistant and carried diverse antimicrobial resistance genes apart from bla_NDM-5. They belonged to six distinct sequence types (STs) and serotypes including one each for ST38/O7:H8, ST58/O?:H37, ST131/O25:H4, ST156/O11:H25 and ST361/O9:H30 and three strains are originating from a single clone belonging to ST410/O?:H9. Apart from bla_NDM-5, the E. coli strains isolated from BSIs also carried other β-lactamase genes, including bla_CMY-2 (n = 4), bla_CTX-M-14 (n = 2), bla_CTX-M-15 (n = 3), bla_CTX-M-65 (n = 1), bla_OXA-1 (n = 4) and bla_TEM-1B (n = 5). The bla_NDM-5 genes were located on three different types of plasmids, which were IncFII/I1 (n = 1), IncX3 (n = 4) and IncFIA/FIB/FII/Q1 (n = 3). The former two types were conjugatively transferable at frequencies of 10⁻³ and 10⁻⁶, respectively. The dissemination of NDM-producing strains, which exhibit resistance to the last-line antibiotics, carbapenems, may increase the muti-antimicrobial resistance burden among E. coli BSIs and further threaten public health.

Programmed death-ligand 1 (PD-L1) is a crucial negative costimulatory molecule expressed on both tumor and immune cells. It binds to programmed death-1, facilitating tumor escape. Tumor-infiltrating immune cells play a vital role in this process. However, the clinical relationship between PD-L1 expression and tumor-infiltrating immune cells remains uncertain. Immunohistochemistry (IHC) was utilized to assess PD-L1 expression and TIIC markers (CD3, CD4, CD8, CD19, CD31, CD68, CD11c, CD56, and α-smooth muscle actin) in gastric adenocarcinoma tissues from 268 patients. The aim was to explore the prognostic significance of PD-L1 and the infiltration of different immune cell types. The study analyzed overall survival and the correlations between PD-L1 expression, immune cell infiltration, and clinicopathological characteristics. Among the 268 patients, 52 (19.40%) exhibited high PD-L1 expression on tumor cells (TPD-L1), while 167 (62.31%) displayed high PD-L1 expression on immune cells (IPD-L1). Patients with high IPD-L1 expression showed improved survival compared to those with low IPD-L1 expression (P = .028). High TPD-L1 expression associated with various clinicopathological features, such as larger tumor size, poorer differentiation, deeper invasion depth, and higher tumor stage. Conversely, patients with high IPD-L1 expression exhibited shallower tumor invasion and lower mortality rates. Univariate analysis indicated that superficial tumor infiltration, absence of lymph node and distant metastasis, low tumor stage, high IPD-L1 expression, and elevated CD8 and CD19 expression were associated with a reduced risk of tumor progression. Multivariate analysis revealed that patients with high IPD-L1 and CD8 expression or high TPD-L1 and low CD31 expression experienced significantly better overall survival than patients with other combinations. The findings indicate that patients with high PD-L1 expression in immune cells have a substantially improved prognosis. Additionally, the combination of PD-L1 with CD8 or CD31 expression status can serve as an indicator of prognosis in patients with gastric adenocarcinoma.

Background: The emergence and spread of the tigecycline resistance gene tet(A)-v1 in carbapenem-resistant Klebsiella pneumoniae (CRKP) poses significant public health challenges. However, the prevalence of tet(A)-v1-positive CRKP, especially in pediatric patients, remains poorly understood. This study aims to address the gap by performing an in-depth analysis of isolates collected from a children’s hospital in China. Methods: A 4-year retrospective study was conducted in the children’s hospital in Suzhou, China. Non-duplicated specimens were obtained from pediatric patients, and antimicrobial susceptibility profiles were assessed. Whole-genome sequencing and bioinformatics analyses were conducted to characterize the genetic background, antimicrobial resistance determinants, hypervirulence-associated genes, diversity of tet(A)-v1-carrying plasmids, the genetic environment of tet(A)-v1, and the potential for clonal transmission. Conjugative transferability of tet(A)-v1-carrying plasmids was also evaluated via conjugation assays. Results: Of the 73 tet(A)-v1-positive CRKP isolates from pediatric patients, 10.96% were non-susceptible to tigecycline. These isolates exhibited high genetic diversity, spanning across 13 STs (sequence types), with ST17 being predominant. Three carbapenemases were identified, with IMP being the most common. Isolates from diverse backgrounds, such as ST17, ST20, ST323, ST792, and ST3157, demonstrated evidence of clonal transmission. The tet(A)-v1 gene was located on 14 distinct plasmids across seven replicon types, with IncFIA/IncHI1 and IncFII being most commonly detected. All tet(A)-v1-carrying plasmids were multidrug-resistant, and 68.49% were conjugatively transferable, indicating a high potential for horizontal transfer. Four genetic contexts bordering tet(A)-v1 were identified, which points to active clonal dissemination. Conclusions: Although limited to a single hospital, this study represents one of the first in-depth investigations of tet(A)-v1-positive CRKP in pediatric patients, providing valuable insights into the prevalence and spread of tet(A)-v1 in this vulnerable group. These findings emphasize the urgent need for enhanced surveillance and infection control measures to curb the spread of tet(A)-v1-positive CRKP in pediatric healthcare environments, offering critical insights to mitigate its public health impact.

In 2017, 553,000 clinical cases of Streptococcus pneumoniae in children were reported in China, although the pneumococcal conjugate vaccine (PCV), which targets the pneumococcal capsule, is not included in the Chinese National Immunization Program (NIP) for children. Therefore, the PCV uptake rate is very low. To investigate the S. pneumoniae population over the past 10 years in China, we collected 418 S. pneumoniae isolates from children with pneumococcal diseases in Suzhou, China, 2014–2023, and whole-genome sequenced them. A total of 27 serotypes expressed by 36 Global Pneumococcal Sequence Clusters (GPSCs) that encompassed 72 sequence types were identified, with serotype 19F (38.3%, n=160) and GPSC1 (60.8%, n=254) as the predominant serotype and lineage, respectively. We found that the majority (64.8%, n=271) of samples represented serotypes that are covered by the GSK 10-valent PCV (PCV10) formulation and that even more were covered by the SII PCV10 formulation (89.2%, n=373). Almost all (94.3%, n=394) samples represented serotypes that are included within the 13-valent PCV (PCV13) vaccine formulation. This suggests that the inclusion of the PCV in the NIP would lead to significant benefits for child health. Also, we observed that no significant differences were seen in the serotypes or lineages in cases of invasive and non-invasive pneumococcal diseases.Additionally, we investigated the prevalence of antimicrobial resistance within the population and found that 99.8% (n=417) of isolates were predicted to be resistant to at least one antibiotic tested. This again supports the need to increase PCV uptake to prevent infections with antibiotic-resistant S. pneumoniae and to reduce the number of infections in general, consequently lowering the consumption of antibiotics. In summary, the PCV13 vaccine could potentially cover over 90% of invasive and non-invasive S. pneumoniae isolates in Suzhou, China. Therefore, increasing the uptake of PCVs by including PCV13 in the NIP would lead to significant benefits for child health.

This study aimed to characterize the IncHI2 plasmids co-harbouring carbapenemase genes and mcr-9 genes in carbapenem-resistant Enterobacter hormaechei (CREH) isolated from a children's hospital in Suzhou, China. Whole-genome sequencing (WGS) was employed to determine the genome sequences of 12 non-duplicate CREH strains. The molecular features of CREH strains and IncHI2 plasmids harbouring carbapenemase genes with or without mcr-9 genes were characterized through genomic analysis. Conjugal transfer assay and plasmid stability testing were used to evaluate the transfer ability and stability of IncHI2 plasmids. The genomic analysis revealed that 12 CREH strains all carried carbapenemase genes bla_NDM-1, bla_NDM-5 or bla_IMP-26. Although the sequence types (STs) of these 12 strains were relatively diverse, most of the strains (11/12) carried IncHI2 and IncHI2A replicons. Further plasmid analysis showed that carbapenemase genes bla_IMP-26 and bla_NDM-1 could coexist with mcr-9.1 or mcr-9.2 on IncHI2 plasmids. While the backbones of these IncHI2 plasmids were relatively conserved, the accessory modules carrying the carbapenemase and mcr-9 genes exhibited diverse genetic contexts, involving transposon Tn125, Tn1696 and Tn6725, and integron In27-like, In615b, and In837. Conjugal transfer assay and plasmid stability testing confirmed the transferability and stability of IncHI2 plasmids. This study reports the emergence and diversity of IncHI2 plasmids that co-harbour carbapenemase genes and mcr-9.1/9.2 in E. hormaechei. To our knowledge, this is also the first report of bla_NDM-1 and mcr-9.2 being carried on a single plasmid in China. The prevalence of such evolutionarily diverse and conjugative carbapenemase-encoding IncHI2 plasmids warrants close monitoring.

Carbapenem resistance has a widespread globally. In this study, three bacterial strains including Escherichia coli (SXY-EC), Serratia marcescens (SXY-SM), and Klebsiella michiganensis (SXY-KM) were isolated from a pediatric patient in China. Whole-genome sequencing and resistome analysis revealed the appearance of bla_NDM-1 β-lactamase gene in all these three strains, and conjugation tests confirmed its transferability. Additionally, SXY-SM and SXY-KM harbored two to three other resistance genes, while SXY-EC carried eleven. Notably, the multidrug resistance region containing bla_NDM-1 in plasmid pSXY-EC_NDM1 from SXY-EC was flanked by mobile elements, potentially enabling intermolecular replicative transposition mediated by distinct insertion sequences.