Disease burden and antimicrobial resistance of invasive group B streptococcus among infants in China: a protocol for a national prospective observational study
Abstract:BackgroundGroup B Streptococcus (GBS) is a cause of neonatal sepsis, pneumonia, and meningitis that can lead to neurological sequelae in infants less than 3 months of age. The GBS disease burden is not known in China, therefore it cannot receive major attention. The main objectives of this study are the evaluation of the incidence of neonatal GBS infection, GBS case-fatality ratio, its serotypes and genotypes, bacterial resistance, clinical treatment and outcomes in China.MethodsWe are conducting a nation-wide… Show more
“…Participating hospitals met the following inclusion criteria ( 8 ): large, urban, tertiary-care center; adequate research capabilities and facilities to conduct the study, including laboratory facilities and the ability to identify, process, and store GBS isolates; investigators willing to devote time to the study; and location, to ensure > 1 hospital from each region. Trained site investigators in each participating hospital collected clinical data by using a standardized case report form.…”
Invasive group B Streptococcus (GBS) remains a leading cause of illness and death among infants globally. We conducted prospective and retrospective laboratory-based surveillance of GBS-positive cultures from infants <3 months of age in 18 hospitals across China during January 1, 2015–December 31, 2017. The overall incidence of GBS was 0.31 (95% CI 0.27–0.36) cases/1,000 live births; incidence was 0–0.76 cases/1,000 live births across participating hospitals. The case-fatality rate was 2.3%. We estimated 13,604 cases of GBS and 1,142 GBS–associated deaths in infants <90 days of age annually in China. GBS isolates were most commonly serotype III (61.5%) and clonal complex 17 (40.6%). Enhanced active surveillance and implementation of preventive strategies, such as maternal GBS vaccination, warrants further investigation in China to help prevent these infections.
“…Participating hospitals met the following inclusion criteria ( 8 ): large, urban, tertiary-care center; adequate research capabilities and facilities to conduct the study, including laboratory facilities and the ability to identify, process, and store GBS isolates; investigators willing to devote time to the study; and location, to ensure > 1 hospital from each region. Trained site investigators in each participating hospital collected clinical data by using a standardized case report form.…”
Invasive group B Streptococcus (GBS) remains a leading cause of illness and death among infants globally. We conducted prospective and retrospective laboratory-based surveillance of GBS-positive cultures from infants <3 months of age in 18 hospitals across China during January 1, 2015–December 31, 2017. The overall incidence of GBS was 0.31 (95% CI 0.27–0.36) cases/1,000 live births; incidence was 0–0.76 cases/1,000 live births across participating hospitals. The case-fatality rate was 2.3%. We estimated 13,604 cases of GBS and 1,142 GBS–associated deaths in infants <90 days of age annually in China. GBS isolates were most commonly serotype III (61.5%) and clonal complex 17 (40.6%). Enhanced active surveillance and implementation of preventive strategies, such as maternal GBS vaccination, warrants further investigation in China to help prevent these infections.
“…In addition to structure-activity relationship (SAR) studies, we found that HMOs potentiate the activity of select intracellular targeting antibiotics (32). This included three antibiotics to which GBS has evolved resistance, aminoglycosides, macrolides, and tetracyclines (33)(34)(35)(36)(37)(38)(39)(40)(41)(42). At their 50% inhibitory concentration (IC 50 ), HMO extracts reduced the MICs of certain intracellular targeting antibiotics up to 32-fold (Table 1).…”
Adjuvants can be used to potentiate the function of antibiotics whose efficacy has been reduced by acquired or intrinsic resistance. In the present study, we discovered that human milk oligosaccharides (HMOs) sensitize strains of group B Streptococcus (GBS) to trimethoprim (TMP), an antibiotic to which GBS is intrinsically resistant. Reductions in the MIC of TMP reached as high as 512-fold across a diverse panel of isolates. To better understand HMOs’ mechanism of action, we characterized the metabolic response of GBS to HMO treatment using ultrahigh-performance liquid chromatography–high-resolution tandem mass spectrometry (UPLC-HRMS/MS) analysis. These data showed that when challenged by HMOs, GBS undergoes significant perturbations in metabolic pathways related to the biosynthesis and incorporation of macromolecules involved in membrane construction. This study represents reports the metabolic characterization of a cell that is perturbed by HMOs.
IMPORTANCE Group B Streptococcus is an important human pathogen that causes serious infections during pregnancy which can lead to chorioamnionitis, funisitis, premature rupture of gestational membranes, preterm birth, neonatal sepsis, and death. GBS is evolving antimicrobial resistance mechanisms, and the work presented in this paper provides evidence that prebiotics such as human milk oligosaccharides can act as adjuvants to restore the utility of antibiotics.
“…Severe inflammation and MODS greatly threat patients' life. The increasing prevalence of drug resistant compels us to find new and effective approaches for the diagnosis and therapy of severe inflammation [26]. MicroRNAs such as miR-9 have been reported to be involved in inflammation and to play an important role in preventing inflammation developing to MODS, while the specific mechanism is still unclear [27][28][29][30].…”
Severe inflammation may lead to multiple organs dysfunction syndrome, which has a high mortality. MicroRNA is found participated in this process. In this study we developed a lipopolysaccharide-induced inflammation cell model on macrophages and a lipopolysaccharide-induced inflammation mouse model. It was found that during inflammation, microRNA-9 was increased, accompanied with the up-regulation of pro-inflammatory cytokines and anti-inflammatory cytokines. Down-regulation of microRNA-9 inhibited the up-regulation of inflammatory cytokines, promoted the up-regulation of anti-inflammatory cytokines and induced the remission of organ damage, showing a protective effect in inflammation. Bioinformatics analysis combined with luciferase reporter assay showed that SIRT1 was the target gene of microRNA-9. Transfection of microRNA-9 inhibitor could increase the level of SIRT1 and decrease the activation of NF-κB pathway in macrophages. Myeloid specific sirt1 knockout mice were included and we found that lack of SIRT1 in mice macrophages led to aggravated inflammation, cell apoptosis and organ injury, and eliminated the protective property of microRNA-9 inhibitor. In conclusion, we demonstrated that inhibition of microRNA-9 could alleviate inflammation through the up-regulation of SIRT1 and then suppressed the activation of NF-κB pathway. This is a meaningful explore about the specific mechanism of microRNA-9 in inflammation.
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