Distributions of candidate vaccine Targets, virulence Factors, and resistance features of invasive group B Streptococcus using Whole-Genome Sequencing: A Multicenter, population-based surveillance study.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants. METHODS: We used whole-genome sequencing to characterize invasive GBS isolates from infants < 3 months of age obtained from a multicenter population-based study conducted from 2015 to 2021 in China. RESULTS: Overall, seven serotypes were detected from 278 GBS isolates, four (Ia, Ib, III, V) of which accounted for 97.8 %. We detected 30 sequence types (including 10 novel types) that were grouped into six clonal complexes (CCs: CC1, CC10, CC17, CC19, CC23 and CC651); three novel ST groups in CC17 were detected, and the rate of CC17, considered a hyperinvasive neonatal clone complex, was attached to 40.6 % (113/278). A total of 98.9 % (275/278) of isolates harbored at least one alpha-like protein gene. All GBS isolates contained at least one of three pilus backbone determinants and the pilus types PI-2b and PI-1 + PI-2a accounted for 79.8 % of the isolates. The 112 serotype III/CC17 GBS isolates were all positive for hvgA. Most of the isolates (75.2 %) were positive for serine-rich repeat glycoprotein determinants (srr1or srr2). Almost all isolates possessed cfb (99.6 %), c1IE (100 %), lmb (95.3 %) or pavA (100 %) gene. Seventy-seven percent of isolates harboured more than three antimicrobial resistance genes with 28.4 % (79/278) gyrA quinoloneresistancedeterminants mutation, 83.8 % (233/278) carrying tet cluster genes and 77.3 % (215/278) carrying erm genes which mediated fluoroquinolone, tetracycline and clindamycin resistance, respectively." CONCLUSIONS: The findings from this large whole-genome sequence of GBS isolates establish important baseline data required for further surveillance and evaluating the impact of future vaccine candidates.

Analysis of the incidence, characteristics, and risk factors of complications during induction chemotherapy in children with high-risk neuroblastoma.

Patients with high-risk neuroblastoma (HR-NB) exhibit suboptimal 5-year survival rates, leading to a widespread international preference for high-intensity chemotherapeutic regimens in these children. We analyzed the incidence and risk factors for complications during induction chemotherapy in children with HR-NB and tried to assist clinicians in predicting such complications and optimizing therapeutic strategy. The clinical data of children with HR-NB admitted to our hospital from January 2007 to December 2019 were retrospectively analyzed. The incidence, characteristics, and risk factors of complications (infection, hemorrhage, and chemotherapy-related adverse reactions (CRAR)) requiring hospitalization during induction chemotherapy in these children were explored. (1) A total of 108 patients with HR-NB were included in the final analysis. The overall infection rate was 92.6% (100/108), with the highest incidence of 71.3% observed during the first cycle. FN, bacterial infection, as well as fungal infection were common infectious complications in children with HR-NB during induction chemotherapy. (2) The overall hemorrhage rate was 24.1% (26/108), with the highest incidence of 14.8% also observed in the first cycle. Among the children with hemorrhage, there were 72% with bone marrow involved, while 65.0% of them had a high vanillylmandelic acid (VMA) value. And children with hemorrhage also exhibited neuron-specific enolase (NSE) ≥ 200 µg/L in 88.5% of cases and lactic dehydrogenase (LDH) ≥ 1000U/L in 73.1% of cases. (3) The incidence of CRAR rate was 100%, and 99.1% (107/108) patients experienced myelosuppression. The incidence of myelosuppression peaked in the third cycle, reaching up to 85.2%. Most children suffered severe myelosuppression existed with bone marrow metastases (76.3%), abnormal VMA (67.5%), and LDH ≥ 1000 U/L (60%). (4) Non-myelosuppressive adverse effects were observed in 75.9% children (82/108), with the highest incidence occurring in the third cycle at 42.6%. (5) Patients who experienced three types of complications had a lower median survival time (MST) of 54.4 months, a 3-year event-free survival (EFS) rate of (44.2 ± 10.7)%, and a 3-year overall survival (OS) rate of (75.8 ± 8.6)%, in comparison to those with only one or two complications, who had a higher MST of 59.5 months, a 3-year EFS rate of (73.5 ± 5.2)% (X2 = 10.457, P = 0.001), and a 3-year OS rate of (84.8 ± 4.1)% (X2 = 10.511, P = 0.001). CONCLUSION: The presence of bone marrow involved and increased VMA were high-risk factors for infection, while NSE ≥ 200 µg/L and LDH ≥ 1000 U/L were high-risk factors for hemorrhage. For those children who had experienced severe myelosuppression, the presence of bone marrow metastases, increased VMA, and LDH ≥ 1000 U/L were their risk factors. The presence of bone involvement was a high-risk factor for children to have non-myelosuppressive adverse effects. Complications that arise during induction chemotherapy could negatively impact the children's prognosis and overall quality of life. WHAT IS KNOWN: • The high-risk neuroblastoma (HR-NB) had a worse prognosis; there was a general international preference for high-intensity chemotherapeutic regimens in the induction phase to these children. WHAT IS NEW: • We analyzed the incidence and risk factors of complications during induction chemotherapy in children with HR-NB and tried to help clinicians predict such complications and adopt optimized therapeutic strategy.

Perceptions and preparedness of senior medical students about antimicrobial stewardship programs: are we providing adequate training to future prescribers?

BACKGROUND: Senior medical students will become one of the key partners in antimicrobial stewardship efforts in the future, yet the level of education and their perceptions toward this topic are not well documented in China. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional, anonymous, online survey between December 2021 and February 2022. The students came from six universities of all five provinces/autonomous regions in northwest China. Students completed the survey by using WeChat. RESULTS: More than half of students agreed/strongly agreed that antimicrobials are overused (53.1%) and that antimicrobial resistance is a significant problem nationally (50.2%). Most of the respondents (70%) were interested in learning more about antimicrobials. Around 60% of the respondents thought they were well prepared for future use of antimicrobials. Only 30% of the respondents were familiar with the term 'Antimicrobial Stewardship,' but 80.7% were interested in taking part in an antimicrobial stewardship program training. More than half of the senior medical students thought that courses in antibacterial is suitable for second and third academic years. CONCLUSIONS: It is therefore suggested to provide specific curriculum and strengthen training of antimicrobial use for medical students in the future, as well as more rotation practice in infectious diseases related departments.

Preferences of pregnant women toward a future maternal Group B Streptococcus vaccine in China: A cross-sectional survey with a discrete choice experiment.

Group B streptococcus (GBS) is a major cause of neonatal death worldwide. A GBS vaccine for pregnant women is under development and is expected to be available in the near future. The perceptions and preferences of pregnant women in China of GBS vaccines has not been investigated, and this study aimed to investigate pregnant women's awareness of GBS and their potential preferences for the GBS vaccine. A discrete choice experiment was conducted among pregnant women in hospitals from Shaanxi, Hunan, and Zhejiang provinces located in Western, Central, and Eastern China, respectively. A conditional logit model was used to analyze the data and calculate willingness to pay values and choice probabilities of different GBS vaccine programs. A total of 354 pregnant women were included in the final analysis, 45.8% of whom were willing to receive a GBS vaccine if it were licensed. Vaccine safety was the most important attribute of a future vaccine, while cost was the least important attribute. Compared with no vaccination, pregnant women had a strong preference for future GBS vaccination (ASC = 1.267, p < .001). Pregnant women's decisions were highly influenced by those of other pregnant women. Improving the safety, efficacy, and vaccination rate of the GBS vaccine in China is of great significance for future GBS vaccine development and vaccination. Compared to other variable options, the cost of a GBS vaccine was of the least importance among pregnant women in mainland China. These findings can inform public health policy decisions related to GBS vaccination in China.

Serotype Distribution, Virulence Determinants and Antimicrobial Susceptibility of Streptococcus agalactiae Isolated from Young Infants

Background: Streptococcus agalactiae (Group B Streptococcus, GBS) is the most common cause of serious infections in the first 3 months of life worldwide. The pathogenicity of GBS is closely related to serotypes, surface proteins and virulence factors, and the distribution of them may vary temporally and geographically. However, data related to GBS surface proteins and virulence determinants in China are very few. The aim of this study is to investigate the genetic characteristics of clinical GBS isolates from infected infants. Methods: We recovered GBS isolates from infected infants younger than 3 months during 2017−2021 at Maternal and Child Health Hospital of Hubei Province in China. We assessed the GBS serotypes, surface proteins, virulence determinants and antibiotic resistance genes distribution, by Multilocus sequence typing (MLST) and whole-genome sequencing analysis. Results: Among 97 isolates (81 EOD and 16 LOD), 5 serotypes were detected. Serotype III was the most represented (49.5%), followed by type Ib (20.6%). The isolates belonged to 17 different sequence types (STs) that grouped into the 8 clonal complexes (CCs). The most frequently identified ST was ST17 (23.7%). The most predominant surface protein of alpha-protein-like (alp) family (one of the protein components of the GBS surface antigen, resistant to trypsin) present was Rib (41.2%), which was mainly detected in serotype III. The srr1, which encodes Srr1 protein, was identified in 54.6% of isolates. The hvgA encoding for hypervirulent GBS adhesin can be detected in all 24 serotype III GBS. Among the pilus islands genes, 50% and 58.8% of the isolates were positive for pi-1 and pi-2a genes, respectively. The presence of pi-2b was mainly associated with serotype III/CC17 strains; 56.7% of isolates carried tetM, tetO/tetL, ermB antibiotic resistant genes. Among all the virulence genes detected, the cfb-cylE-lmb-pavA pattern was the main virulence gene profile (81.4%), mainly in serotype III/CC17. Conclusions: The whole genomic sequencing data revealed the high variation in surface proteins, determining virulence and antibiotic resistance in clinical isolates from 97 GBS infected infants. These data provide insightful characteristics of genetic features of GBS. Constant epidemiological surveillance is warranted to provide information on the GBS pathogenic dynamics and antibiotic resistance profiles in the surveyed areas for improving therapeutic outcomes.

The Impact of a National Stewardship Policy on the Usage Patterns of Key Monitoring Drugs in a Tertiary Teaching Hospital: An Interrupted Time Series Analysis.

Background: The management of Key Monitoring Drugs has become one of important aspects to control the growth of pharmaceutical expenditures in China. The first batch of the China National Key Monitoring Drugs (NKMDs) policy was released in July 2019. However, little is known about the impact of the national stewardship on the trends of NKMDs prescribing practice in hospitals, especially in the Northwestern China. Methods: We collected 8-years of monthly NKMDs usage data from a tertiary hospital between 2014 and 2021. A segmented regression model of interrupted time series (ITS) analysis was used to evaluate the Defined Daily Doses (DDDs) and spending trends of ten NMKDs in the hospital throughout the study period. The pre-implementation period was from January 2014 to November 2019 and the post-implementation period was from December 2019 to June 2021. Results: Prior to the implementation of the NKMDs policy, there was an increasing trend both in DDDs and spending for 8 of 10 NKMDs. The interventions managed by clinical pharmacists after the implementation of the national stewardship policy led to a significant decreasing trend of DDDs in the 19 months following implementation, of 430 fewer DDDs per month in total, compared to the pre-implementation period (p < 0.001). A similar decrease in spending was seen in the post-implementation period, with a trend of $4,682 less total spending on medications in those months compared to the pre-implementation trend (p = 0.003). There was a significant decrease in both monthly DDDs and spending for 6 of the 10 medications in the post-implementation period, while there was a significant increased trend both in monthly DDDs and spending on 1 medication in that period. Conclusion: Using ITS analysis, the total DDDs and spending on 10 NKMDs in this hospital indicated sustained reductions over 19 months after multidimensional interventions under the implementation of the national policy guidance. The national stewardship policy could therefore be considered an effective strategy. Additional comprehensive policies should be introduced to further improve the rational use of NKMDs.

Correlation analysis between IL-35, IL-36γ, CCL27 and psoriasis vulgaris.

OBJECTIVE: Evaluating the serum level of IL-35, IL-36γ and CCL27 cytokines expression in patients with psoriasis and to explore their correlation with disease severity. To explore the role of these cytokines in the pathogenesis of psoriasis vulgaris and to guide clinical practice. METHODS: Thirty patients with psoriasis vulgaris (PV) were treated with routine drug treatment for7 weeks, and 30 healthy controls were used as control group. Peripheral blood of the PV group before and after treatment and control group were detected by double-antibody sandwich ELISA. The expression levels of IL-35, IL-36γ and CCL27 in peripheral blood were analyzed statistically. RESULTS: The expression of IL-35 in the peripheral blood of the pre-PV group (187.54 ± 172.41) was significantly lower than that of the control group (310.52 ± 174.22) and the PV treatment group (417.75 ± 47.07). The level of IL-36γ in peripheral blood of pre-PV group (295.11 ± 27.91) was higher than that of control group (155.40 ± 45.66) and PV treatment group (209.86 ± 27.91). The level of CCL27 in peripheral blood of patients pre-PV treatment (479.06 ± 285.80) was significantly higher than that of the control group (341.53 ± 98.72) and the group after PV treatment (316.56 ± 245.53). There was a negative correlation between IL-35 and IL-36γ levels in serum (r= -0.826, p < .001); IL-36γ was positively correlated with CCL27 level (r = 0.906, p < .001); IL-35 and CCL27 levels were negative correlation (r= -0.810, p < .001). CONCLUSION: IL-36γ and CCL27 may be involved in the pathogenesis of psoriasis as a pro-inflammatory factor. IL-35 may be involved in the pathogenesis of psoriasis as an anti-inflammatory factor.