Implications of IFNγ SNP rs2069705 in primary Sjögren's syndrome: transcriptional activation and B cell infiltration.

Primary Sjögren's syndrome (pSS) is characterized by its autoimmune nature. This study investigates the role of the IFNγ SNP rs2069705 in modulating the susceptibility to pSS. Differential expression of IFNγ and BAFF was analyzed using the GEO database's mRNA microarray GSE84844. Genotyping of the IFNγ SNP rs2069705 was conducted via the dbSNP website. The JASPAR tool was used for predicting transcription factor bindings. Techniques such as dual-luciferase reporter assays, Chromatin immunoprecipitation, and analysis of a pSS mouse model were applied to study gene and protein interactions. A notable increase in the mutation frequency of IFNγ SNP rs2069705 was observed in MNCs from the exocrine glands of pSS mouse models. Bioinformatics analysis revealed elevated levels of IFNγ and BAFF in pSS samples. The model exhibited an increase in both CD20+ B cells and cells expressing IFNγ and BAFF. Knocking down IFNγ resulted in lowered BAFF expression and less lymphocyte infiltration, with BAFF overexpression reversing this suppression. Activation of the Janus kinase (JAK)/STAT1 pathway was found to enhance transcription in the BAFF promoter region, highlighting IFNγ's involvement in pSS. In addition, rs2069705 was shown to boost IFNγ transcription by promoting interaction between its promoter and STAT4. SNP rs2069705 in the IFNγ gene emerges as a pivotal element in pSS susceptibility, primarily by augmenting IFNγ transcription, activating the JAK/STAT1 pathway, and leading to B-lymphocyte infiltration in the exocrine glands.NEW & NOTEWORTHY The research employed a combination of bioinformatics analysis, genotyping, and experimental models, providing a multifaceted approach to understanding the complex interactions in pSS. We have uncovered that the rs2069705 SNP significantly affects the transcription of IFNγ, leading to altered immune responses and B-lymphocyte activity in pSS.

Diagnostic value of BHI-V4 for heterogeneous and vancomycin-intermediate Staphylococcus aureus isolates: a systematic review and meta-analysis.

BACKGROUND: Brain-heart infusion agar supplemented with 4 µg/mL of vancomycin (BHI-V4) was commonly used for the detection of heterogeneous (hVISA) and vancomycin-intermediate Staphylococcus aureus (VISA). However, its diagnostic value remains unclear. This study aims to compare the diagnostic accuracy of BHI-V4 with population analysis profiling with area under the curve (PAP-AUC) in hVISA/VISA. METHODS: The protocol of this study was registered in INPLASY (INPLASY2023120069). The PubMed and Cochrane Library databases were searched from inception to October 2023. Review Manager 5.4 was used for data visualization in the quality assessment, and STATA17.0 (MP) was used for statistical analysis. RESULTS: In total, eight publications including 2153 strains were incorporated into the meta-analysis. Significant heterogeneity was evident although a threshold effect was not detected across the eight studies. The summary receiver operating characteristic (SROC) was 0.77 (95% confidence interval [CI], 0.74-0.81). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic score and diagnostic odds ratio were 0.59 (95% CI: 0.46-0.71), 0.96 (95%CI: 0.83-0.99), 14.0 (95% CI, 3.4-57.1), 0.43 (95%CI, 0.32-0.57), 3.48(95%CI, 2.12-4.85) and 32.62 (95%CI, 8.31-128.36), respectively. CONCLUSION: Our study showed that BHI-V4 had moderate diagnostic accuracy for diagnosing hVISA/VISA. However, more high-quality studies are needed to assess the clinical utility of BHI-V4.

Adaptive physiological and metabolic alterations in Staphylococcus aureus evolution under vancomycin exposure.

Staphylococcus aureus can develop antibiotic resistance and evade immune responses, causing infections in different body sites. However, the metabolic changes underlying this process are poorly understood. A variant strain, C1V, was derived from the parental strain C1 by exposing it to increasing concentrations of vancomycin in vitro. C1V exhibited a vancomycin-intermediate phenotype and physiological changes compared to C1. It showed higher survival rates than C1 when phagocytosed by Raw264.7 cells. Metabolomics analysis identified significant metabolic differences pre- and post-induction (C1 + SC1 vs. C1V + SC1V: 201 metabolites) as well as pre- and post-phagocytosis (C1 vs. SC1: 50 metabolites; C1V vs. SC1V: 95 metabolites). The variant strain had distinct morphological characteristics, decreased adhesion ability, impaired virulence, and enhanced resistance to phagocytosis compared to the parental strain. Differential metabolites may contribute to S. aureus ' resistance to antibiotics and phagocytosis, offering insights into potential strategies for altering vancomycin nonsusceptibility and enhancing phagocyte killing by manipulating bacterial metabolism.

Effects of Omeprazole on Recurrent Clostridioides difficile Infection Caused by ST81 Strains and Their Potential Mechanisms.

Clostridioides difficile infection (CDI) is associated with high recurrence rates that have substantial effects on patients' quality of life. To investigate the risk factors and potential mechanisms contributing to recurrent CDI (rCDI), a total of 243 cases were enrolled in this study. The history of omeprazole (OME) medication and ST81 strain infection were considered the two independent risks with the highest odds ratios in rCDI. In the presence of OME, we detected concentration-dependent increases in the MIC values of fluoroquinolone antibiotics against ST81 strains. Mechanically, OME facilitated ST81 strain sporulation and spore germination by blocking the pathway of purine metabolism and also promoted an increase in cell motility and toxin production by turning the flagellar switch to the ON state. In conclusion, OME affects several biological processes during C difficile growth, which have fundamental impacts on the development of rCDI caused by ST81 strains. Programmed OME administration and stringent surveillance of the emerging ST81 genotype are matters of considerable urgency and significance in rCDI prevention.

Root phosphatase activity aligns with the collaboration gradient of the root economics space.

The adoption of diverse resource acquisition strategies is critical for plant growth and species coexistence. Root phosphatase is of particular importance in the acquisition of soil phosphorus (P), yet it is often overlooked in studies of root trait syndromes. Here, we evaluated the role of root phosphatase activity (RPA) within the root economics space and the order-based variation of RPA, as well as the correlations between RPA and a suite of leaf traits and soil properties over a range of evergreen tree species in a subtropical forest. Root phosphatase activity exhibited a high degree of inter-specific variation. We found that there were two leading dimensions of the multidimensional root economics space, the root diameter-specific root length axis (collaboration trait gradient) and the root tissue density-root nitrogen concentration axis (classical trait gradient), and RPA aligned with the former. Root phosphatase activity is used as a 'do it yourself' strategy of soil P acquisition, and was found to be inversely correlated with mycorrhizal colonization, which suggests a trade-off in plant P acquisition strategies. Compared with soil and foliar nutrient status, root traits mattered most for the large inter-specific changes in RPA. Furthermore, RPA generally decreased from first- to third-order roots. Taken together, such diverse P-acquisition strategies are conducive to plant coexistence within local forest communities. The use of easily measurable root traits and their tight correlations with RPA could be a feasible and promising approach to estimating species-specific RPA values, which would be helpful for better understanding plant P acquisition and soil P cycling.

Soil moisture regulates warming responses of autumn photosynthetic transition dates in subtropical forests.

Autumn phenology plays a key role in regulating the terrestrial carbon and water balance and their feedbacks to the climate. However, the mechanisms underlying autumn phenology are still poorly understood, especially in subtropical forests. In this study, we extracted the autumn photosynthetic transition dates (APTD) in subtropical China over the period 2003-2017 based on a global, fine-resolution solar-induced chlorophyll fluorescence (SIF) dataset (GOSIF) using four fitting methods, and then explored the temporal-spatial variations of APTD and its underlying mechanisms using partial correlation analysis and machine learning methods. We further predicted the APTD shifts under future climate warming conditions by applying process-based and machine learning-based models. We found that the APTD was significantly delayed, with an average rate of 7.7 days per decade, in subtropical China during 2003-2017. Both partial correlation analysis and machine learning methods revealed that soil moisture was the primary driver responsible for the APTD changes in southern subtropical monsoon evergreen forest (SEF) and middle subtropical evergreen forest (MEF), whereas solar radiation controlled the APTD variations in the northern evergreen-broadleaf deciduous mixed forest (NMF). Combining the effects of temperature, soil moisture and radiation, we found a significantly delayed trend in APTD during the 2030-2100 period, but the trend amplitude (0.8 days per decade) was much weaker than that over 2003-2017. In addition, we found that machine learning methods outperformed process-based models in projecting APTD. Our findings generate from different methods highlight that soil moisture is one of the key players in determining autumn photosynthetic phenological processes in subtropical forests. To comprehensively understand autumn phenological processes, in-situ manipulative experiments are urgently needed to quantify the contributions of different environmental and physiological factors in regulating plants' response to ongoing climate change.

Prevalence of Helicobacter pylori Virulence Genes and Their Association with Chronic Gastritis in Beijing, China.

Helicobacter pylori is closely related to chronic gastritis. The aim of the study was to investigate the correlation between H. pylori virulence genes and chronic gastritis in order to determine the pathogenic role of H. pylori virulence genes in chronic gastritis. Gastric mucosal tissues were obtained from 142 patients with chronic gastritis at three Beijing hospitals. The presence of virulence genes was determined by polymerase chain reaction (PCR) from H. pylori DNA. Multilocus sequence typing (MLST) and a phylogenetic tree were performed to characterize the overall genetic diversity. 91 new sequence types were identified by MLST in this study, and all strains showed high genetic diversity. The H. pylori isolates were divided into three types: hspEAsia strains (61 strains), hpEurope strains (15 strains), and mixed strains (16 strains). Some virulence genes were found to be significantly different between strains. The highest positive rates were found for dupA in chronic atrophic gastritis (AG), iceA1 in chronic non-atrophic gastritis with erosions, and iceA2 in chronic non-atrophic gastritis. The presence of dupA was found to be inversely related to the risk of AG. The H. pylori strains display high genetic diversity. Some virulence genes were found to be significantly different between diseases. The detection of various virulence genes is critical for screening high-risk populations for precancerous lesions and for the early prevention and control of gastric cancer.

Characterization of the Clinical Features in HBV-Related Acute-on-Chronic Liver Failure.

OBJECTIVE: Acute-on-chronic liver failure (ACLF) is a type of liver failure commonly found in China, and currently the mechanism of the disease remains unknown. This study aimed to investigate the epidemiology, clinical features and prognostic factors in ACLF. METHODS: This study retrospectively included 170 patients with ACLF admitted to Beijing Friendship Hospital in Beijing, China from November 2017 to May 2019. Patients were divided into 2 groups: the improved group and the deteriorated group, according to the severity of their disease. Patients' demographic data; clinical manifestations; complications; laboratory indicators including platelets (PLT), alanine aminotransferase (ALT), aspartate amino transferase (AST), total bilirubin (TBIL), prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), and alkaline phosphatase (ALP) were collected. The relationship between these factors and the patients' prognosis were analyzed by logistic multivariate regression analysis. RESULTS: The highest morbidity rate was in the age group 40 to 49 years (29.41%). The age group with the second highest morbidity was between 50 and 59 years (25.29%), followed by >60 (21.18%), 30 to 39 (20.59%), 20 to 29 (2.94%) and <20 years (0.59%). A total of 53 patients (31.18%) had a family history of hepatitis B virus infection. The patients' main clinical manifestations were ascites (77.65%) and weakness (68.23%). The most common complications were hypoalbuminemia (80%), infection (67.65%) and electrolyte imbalance (44.12%). In addition, the PTA (P = .009), hepatorenal syndrome (P = .005) and hepatic encephalopathy (level IV) (P = .005) were independently related to the prognosis of ACLF. There is a significant relationship between complications and prognosis (χ2 = 8.502; P = .004). CONCLUSION: This study showed that prothrombin activity, hepatorenal syndrome and hepatic encephalopathy were independently related to the prognosis of ACLF. This outcome provided more options for reducing patient mortality in clinic.

An Overview of Analytical Methodologies for Determination of Vancomycin in Human Plasma.

Vancomycin is regarded as the last resort of defense for a wide range of infections due to drug resistance and toxicity. The detection of vancomycin in plasma has always aroused particular concern because the performance of the assay affects the clinical treatment outcome. This article reviews various methods for vancomycin detection in human plasma and analyzes the advantages and disadvantages of each technique. Immunoassay has been the first choice for vancomycin concentration monitoring due to its simplicity and practicality, occasionally interfered with by other substances. Chromatographic methods have mainly been used for scientific research due to operational complexity and the particular requirement of the instrument. However, the advantages of a small amount of sample needed, high sensitivity, and specificity makes chromatography irreplaceable. Other methods are less commonly used in clinical applications because of the operational feasibility, clinical application, contamination, etc. Simplicity, good performance, economy, and environmental friendliness have been points of laboratory methodological concern. Unfortunately, no one method has met all of the elements so far.

Prevalence and genotype distribution of high-risk HPV infection among women in Beijing, China.

Cervical cancer (CC) is highly associated with high-risk human papillomavirus (HPV) infection and genotype distribution of high-risk HPV (HR-HPV) infection varies greatly in different regions. Clinical specimens were collected from 46 365 patients at Beijing Friendship Hospital, Capital Medical University from January 2017 to December 2020. HPV DNA genotype testing was performed using real-time PCR. The infection rates based on disease group were compared using the χ 2 test. The linear-by-linear association test and gamma value were used to assess the changes in HPV prevalence over calendar year and age group. A total of 10 514 women were infected with HR-HPV, with an overall positive rate of 22.7%. The most prevalent HR-HPV types were HPV52, 58, 16, 51, and 66, and HPV59 had a higher prevalence except for HPV16, 58, and 52 in the CC group. Single infection of HR-HPV was dominant among different disease groups. The infection rate of HR-HPV decreased first and then increased from below 20 years old to over 60 years old. There were significant differences in the HR-HPV infection rates among the age and disease groups. Our findings demonstrate that the genotype distribution of HR-HPV varied with age and diseases. The HR-HPV genotypes prevalence was found to be directly useful for local governments to promote HPV targeted vaccination in the study region.

Genomic characterization of an emerging Enterobacteriaceae species: the first case of co-infection with a typical pathogen in a human patient.

BACKGROUND: Opportunistic pathogens are important for clinical practice as they often cause antibiotic-resistant infections. However, little is documented for many emerging opportunistic pathogens and their biological characteristics. Here, we isolated a strain of extended-spectrum ß-lactamase-producing Enterobacteriaceae from a patient with a biliary tract infection. We explored the biological and genomic characteristics of this strain to provide new evidence and detailed information for opportunistic pathogens about the co-infection they may cause. RESULTS: The isolate grew very slowly but conferred strong protection for the co-infected cephalosporin-sensitive Klebsiella pneumoniae. As the initial laboratory testing failed to identify the taxonomy of the strain, great perplexity was caused in the etiological diagnosis and anti-infection treatment for the patient. Rigorous sequencing efforts achieved the complete genome sequence of the isolate which we designated as AF18. AF18 is phylogenetically close to a few strains isolated from soil, clinical sewage, and patients, forming a novel species together, while the taxonomic nomenclature of which is still under discussion. And this is the first report of human infection of this novel species. Like its relatives, AF18 harbors many genes related to cell mobility, various genes adaptive to both the natural environment and animal host, over 30 mobile genetic elements, and a plasmid bearing blaCTX-M-3 gene, indicating its ability to disseminate antimicrobial-resistant genes from the natural environment to patients. Transcriptome sequencing identified two sRNAs that critically regulate the growth rate of AF18, which could serve as targets for novel antimicrobial strategies. CONCLUSIONS: Our findings imply that AF18 and its species are not only infection-relevant but also potential disseminators of antibiotic resistance genes, which highlights the need for continuous monitoring for this novel species and efforts to develop treatment strategies.

Identification of the role of toxin B in the virulence of Clostridioides difficile based on integrated bioinformatics analyses.

PURPOSE: Clostridioides difficile toxin B (TcdB) plays a critical role in C. difficile infection (CDI), a common and costly healthcare-associated disease. The aim of the current study was to explore the intracellular and potent systemic effects of TcdB on human colon epithelial cells utilizing Gene Expression Omnibus and bioinformatic methods. METHODS: Two datasets (GSE63880 and GSE29008) were collected to extract data components of mRNA of TcdB-treated human colon epithelial cells; "limma" package of "R" software was used to screen the differential genes, and "pheatmap" package was applied to construct heat maps for the differential genes; Metascape website was utilized for protein-protein interaction network and Molecular Complex Detection analysis, and Genome Ontology (GO) was used to analyze the selected differential genes. Quantitative real-time PCR (qRT-PCR) and Western blot were performed to validate the expression of hub genes. RESULTS: GO terms involved in DNA replication and cell cycle were identified significantly enriched in TcdB-treated human colon epithelial cells. Moreover, the decreased expression of DNA replication-related genes, MCM complex, and CDC45 in C. difficile (TcdA-/TcdB+)-infected Caco-2 cells were validated via qRT-PCR and Western blot assays. CONCLUSIONS: In conclusion, the integrated analysis of different gene expression datasets allowed us to identify a set of genes and GO terms underlying the mechanisms of CDI induced by TcdB. It would aid in understanding of the molecular mechanisms underlying TcdB-exposed colon epithelial cells and provide the basis for developing diagnosis biomarkers, treatment, and prevention strategies.

Epstein-Barr Virus Infection and Increased Sporadic Breast Carcinoma Risk: A Meta-Analysis.

OBJECTIVE: An association of Epstein-Barr virus (EBV) infection with breast carcinoma (BC) risk has so far been disputed in the literature. Therefore, we performed a meta-analysis to clarify this relationship. MATERIALS AND METHODS: An electronic database search for eligible case-control studies was performed using PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang Data until May 17, 2018. The pooled OR and 95% CI were used to estimate the relationship between EBV infection and BC risk using a fixed or random-effects model depending on heterogeneity. Subgroup analysis and meta-regression were used to explore the heterogeneity. Publication bias was assessed using Egger's and Harbord's tests. RESULTS: A total of 16 studies with 1,279 patients and 814 controls were reviewed based on our inclusion and exclusion criteria. Compared with the control group, EBV infection had a significant association with BC risk (OR 4.75, 95% CI 2.53-8.92, p < 0.01) with significant heterogeneity observed (I2 = 65.3%). The subgroup analysis revealed that region and tissue type might explain potential sources of heterogeneity. The sensitivity analyses yielded stable results. No significant publication bias was observed. CONCLUSION: The current results suggest that EBV infection is significantly associated with increased risk of BC.

The current novel therapeutic regimens for Clostridium difficile infection (CDI) and the potentials of Traditional Chinese Medicine in treatment of CDI.

Clostridium difficile infection (CDI) is featured as the dysbiosis of gut microbiota and consequent mild diarrhoea or severe pseudomembranous colitis. However, the frequent recurrence of CDI following treatment course challenged the antibiotic therapy. Currently, to address the relapse of CDI, several novel therapeutic approaches have emerged, including Bezlotoxumab, SYN-004 (Ribaxamase), RBX2660, and faecal microbial transplant. Traditional Chinese Medicine (TCM) is an old medical system accumulated for thousands of years. Orientated by syndrome-based treatment, TCM functions in a multicomponent and multitarget mode. This old medical system showed superiority over conventional medical treatment, particularly in the treatment of complex disorders, including CDI. In the present review, we will elaborate the TCM intervention in the management of CDI and others disorders via restoring the gut microbiota dysbiosis. We hope that this review will deepen our understanding of TCM as an alternative to CDI treatment. However, more rigorously designed basic researches and randomised controlled trials need to conduct to appraise the function mechanisms and effects of TCM. Finally, it is concluded that the combined therapeutic potentials of TCM and western medicine could be harness to resolve the recurrence and improve the outcome of CDI.

Taxonomy, virulence genes and antimicrobial resistance of Aeromonas isolated from extra-intestinal and intestinal infections.

BACKGROUND: Clinical characteristics (taxonomy, virulence genes and antimicrobial resistance ) of Aeromonas in isolated from extra-intestinal and intestinal infections were investigated to describe epidemiology, associated virulence factors and optimal therapy options. METHODS: Clinical samples (n = 115) of Aeromonas were collected from a general hospital in Beijing between the period 2015 and 2017. Taxonomy was investigate by Multilocus phylogenetic analysis (MLPA), 10 putative virulence factors by use of polymerase chain reaction (PCR) and antimicrobial resistance to 15 antibiotics by use of the microbroth dilution method. RESULTS: The most common species of Aeromonas detected in samples of intestinal tract included; A. caviae (43.9%), A. veronii (35.7%), and A. dhakensis (12.2%). Prevalent species of Aeromonas collected from extra-intestinal infections included; A. hydrophila (29.4%), A. caviae (29.4%), and A. dhakensis (23.5%). A. hydrophila were detected in 1% of stool samples and 29.4% (5/17) of extra-intestinal infections. A. hydrophila strains in extra-intestinal infections were related to malignancy. The most common medical conditions among patients with Aeromonas infections included malignancy and liver-transplant related cholecystitis. Multiple drug resistance (MDR) was prevalent in extra-intestinal isolates (82.3%, 14/17) and was greater than the prevalence in intestinal isolates (30.6%, 30/98) (P < 0.05). Resistant rates of extra-intestinal isolates were 70.6, 35.3, 23.5 and 5.9% for ceftriaxone, ciprofloxacin, gentamicin and imipenem, respectively, and were higher than found in previous studies. Despite differences in the number and type of virulence genes among samples of Aeromonas, no significant correlation was found between invasion and virulent genes in intestinal or extra-intestinal infections. CONCLUSIONS: Overall results of this study support a role for Aeromonas spp. as a potential causative infectious agent of gastroenteritis, and malignancy, liver cirrhosis, post liver transplantation in immunocompromised patients. A. hydrophila was more prevalent in samples of extra-intestinal infections when compared to samples of intestinal infections, and was especially prominent in samples of patients presenting with malignancy. Aeromonas isolates from extra-intestinal samples had high rates of drug resistance but 3rd generation cephalosporins, fluoroquinolones and aminoglycosides remain as options to treat severe diarrhea. However, increasing MDR of extra-intestinal infection samples warrants monitoring.

Critical role of MAVS in the protection against Clostridium difficile-induced colitis.

Clostridium difficile (C. difficile) is an opportunistic bacteria that flourishes in intestinal flora is altered by antibiotic use and can cause large intestinal colitis if left untreated. The mechanism of MAVS-mediated innate immune signaling in response to C. difficile infection remains unclear. This knowledge gap was addressed in the present research by administration of an antibiotic cocktail to WT and MAVS-deficient (MAVS-/-) mice for five days, followed by the oral administration of C. difficile VPI 10,463 strain (1 × 107 colony forming units). Subjects were subsequently observed for another eight days for signs of colitis. Colon and cecum tissue samples were harvested from naive and infected mice two days post-infection for histopathologic analysis. Colon tissue samples were harvested to analyze cytokine gene expression and RegIIIß/γ gene expression. MAVS-deficient mice suffered significantly higher mortality rates as well as increased mucosal tissue inflammation and damage after C. difficile infection (P <0.05). MAVS-/- mice displayed a significantly greater increase in IL-6, IL-1ß, TNF-α and IFN-ß expression in colon tissues in contrast to WT mice challenged with C. difficile (P <0.05). RegIIIß/γ gene expression was severely attenuated in the colons of MAVS-/- mice (P <0.05). These findings underscore MAVS as a vital innate immune system mediator in the intestinal mucosa and further suggests that MAVS-mediated maintenance of the intestinal epithelial barrier is an important defense against enteric pathogens.

Antimicrobial susceptibilities of aerobic and facultative gram-negative bacilli isolated from Chinese patients with urinary tract infections between 2010 and 2014.

BACKGROUND: The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli isolated from Chinese patients with UTIs collected within 48 h (community acquired, CA) or after 48 h (hospital acquired, HA) of hospital admission. METHODS: From 2010 to 2014, the minimum inhibitory concentrations (MICs) of 12 antibiotics for 4,332 aerobic and facultative Gram-negative bacilli, sampled in 21 hospitals in 16 cities, were determined by the broth microdilution method. RESULTS: Enterobacteriaceae composed 88.5% of the total isolates, with Escherichia coli (E. coli) (63.2%) the most commonly isolated species, followed by Klebsiella pneumoniae (K. pneumoniae) (12.2%). Non-Enterobacteriaceae accounted for only 11.5% of all isolates and included mainly Pseudomonas aeruginosa (P. aeruginosa) (6.9%) and Acinetobacter baumannii (A. baumannii) (3.3%). Among the antimicrobial agents tested, the susceptibility rates of E.coli to the two carbapenems, ertapenem and imipenem as well as amikacin and piperacillin-tazobactam ranged from 92.5 to 98.7%. Against K. pneumonia, the most potent antibiotics were imipenem (92.6% susceptibility), amikacin (89.2% susceptibility) and ertapenem (87.9% susceptibility). Although non-Enterobacteriaceae did not show high susceptibilities to the 12 common antibiotics, amikacin exhibited the highest in vitro activity against P. aeruginosa over the 5-year study period, followed by piperacillin-tazobactam, imipenem, ceftazidime, cefepime, ciprofloxacin, and levofloxacin. The Extended Spectrum Beta-Lactamase (ESBL) rates decreased slowly during the 5 years in E. coli from 68.6% in 2010 to 59.1% in 2014, in K. pneumoniae from 59.7 to 49.2%, and in Proteus mirabilis (P. mirabilis) from 40.0 to 26.1%. However, the ESBL rates were different in 5 regions of China (Northeast, North, East, South and Middle-China). CONCLUSION: E. coli and K. pneumonia were the major pathogens causing UTIs and carbapenems and amikacin retained the highest susceptibility rates over the 5-year study period, indicating that they are good drug choices for empirical therapies, particularly of CA UTIs in China.

Update of incidence and antimicrobial susceptibility trends of Escherichia coli and Klebsiella pneumoniae isolates from Chinese intra-abdominal infection patients.

BACKGROUND: To evaluate in vitro susceptibilities of aerobic and facultative Gram-negative bacterial (GNB) isolates from intra-abdominal infections (IAIs) to 12 selected antimicrobials in Chinese hospitals from 2012 to 2014. METHODS: Hospital acquired (HA) and community acquired (CA) IAIs were collected from 21 centers in 16 Chinese cities. Extended spectrum beta-lactamase (ESBL) status and antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards. RESULTS: From all isolated strains the Enterobacteriaceae (81.1%) Escherichia coli accounted for 45.4% and Klebsiella pneumoniae for 20.1%, followed by Enterobacter cloacae (5.2%), Proteus mirabilis (2.1%), Citrobacter freundii (1.8%), Enterobacter aerogenes (1.8%), Klebsiella oxytoca (1.4%), Morganella morganii (1.2%), Serratia marcescens (0.7%), Citrobacter koseri (0.3%), Proteus vulgaris (0.3%) and others (1.0%). Non- Enterobacteriaceae (18.9%) included Pseudomonas aeruginosa (9.8%), Acinetobacter baumannii (6.7%), Stenotrophomonas maltophilia (0.9%), Aeromonas hydrophila (0.4%) and others (1.1%). ESBL-screen positive Escherichia coli isolates (ESBL+) showed a decreasing trend from 67.5% in 2012 to 58.9% in 2014 of all Escherichia coli isolates and the percentage of ESBL+ Klebsiella pneumoniae isolates also decreased from 2012 through 2014 (40.4% to 26.6%), which was due to reduced percentages of ESBL+ isolates in HA IAIs for both bacteria. The overall susceptibilities of all 5160 IAI isolates were 87.53% to amikacin (AMK), 78.12% to piperacillin-tazobactam (TZP) 81.41% to imipenem (IMP) and 73.12% to ertapenem (ETP). The susceptibility of ESBL-screen positive Escherichia coli strains was 96.77%-98.8% to IPM, 91.26%-93.16% to ETP, 89.48%-92.75% to AMK and 84.86%-89.34% to TZP, while ESBL-screen positive Klebsiella pneumoniae strains were 70.56%-80.15% susceptible to ETP, 80.0%-87.5% to IPM, 83.82%-87.06% to AMK and 63.53%-68.38% to TZP within the three year study. Susceptibilities to all cephalosporins and fluoroquinolones were less than 50% beside 66.5% and 56.07% to cefoxitin (FOX) for ESBL+ Escherichia coli and Klebsiella pneumoniae strains respectively. CONCLUSIONS: The total ESBL+ rates decreased in Escherichia coli and Klebsiella pneumoniae IAI isolates due to fewer prevalence in HA infections. IPM, ETP and AMK were the most effective antimicrobials against ESBL+ Escherichia coli and Klebsiella pneumoniae IAI isolates in 2012-2014 and a change of fluoroquinolone regimens for Chinese IAIs is recommended.

Antimicrobial Susceptibilities of Aerobic and Facultative Gram-Negative Bacilli from Intra-abdominal Infections in Patients from Seven Regions in China in 2012 and 2013.

To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum ß-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused by Escherichia coli (46.3%) and Klebsiella pneumoniae (19.7%). Rates of ESBL-producing E. coli (P = 0.031), K. pneumoniae (P = 0.017), and Proteus mirabilis (P = 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective against P. mirabilis (<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptible E. coli and K. pneumoniae were higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused by E. coli or K. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China.

Berberine blocks the relapse of Clostridium difficile infection in C57BL/6 mice after standard vancomycin treatment.

Vancomycin is a preferred antibiotic for treating Clostridium difficile infection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the family Enterobacteriaceae and counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI.