Molecular epidemiology of Acinetobacter baumannii during COVID-19 at a hospital in northern China.

BACKGROUND: The wide spread of carbapenem-resistance clones of Acinetobacter baumannii has made it a global public problem. Some studies have shown that the prevalence of Acinetobacter baumannii clones can change over time. However, few studies with respect to the change of epidemiological clones in Acinetobacter baumannii during Corona Virus Disease 2019 (COVID-19) were reported. This study aims to investigate the molecular epidemiology and resistance mechanisms of Acinetobacter baumannii during COVID-19. RESULTS: A total of 95 non-replicated Acinetobacter baumannii isolates were enrolled in this study, of which 60.0% (n = 57) were identified as carbapenem-resistant Acinetobacter baumannii (CRAB). The positive rate of the blaOXA-23 gene in CRAB isolates was 100%. A total of 28 Oxford sequence types (STs) were identified, of which the most prevalent STs were ST540 (n = 13, 13.7%), ST469 (n = 13, 13.7%), ST373 (n = 8, 8.4%), ST938 (n = 7, 7.4%) and ST208 (n = 6, 6.3%). Differently, the most widespread clone of Acinetobacter baumannii in China during COVID-19 was ST208 (22.1%). Further study of multidrug-resistant ST540 showed that all of them were carrying blaOXA-23, blaOXA-66, blaADC-25 and blaTEM-1D, simultaneously, and first detected Tn2009 in ST540. The blaOXA-23 gene was located on transposons Tn2006 or Tn2009. In addition, the ST540 strain also contains a drug-resistant plasmid with msr(E), armA, sul1 and mph(E) genes. CONCLUSION: The prevalent clones of Acinetobacter baumannii in our organization have changed during COVID-19, which was different from that of China. ST540 strains which carried multiple drug-resistant mobile elements was spreading, indicating that it is essential to strengthen the molecular epidemiology of Acinetobacter baumannii.

Clinical and bacteriological features and prognosis of ascitic fluid infection in Chinese patients with cirrhosis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) and bacterascites (BA) represent frequent and serious complications in cirrhosis patients with ascites. However, few detailed data are available regarding the clinical and bacteriological feature of SBP or BA patients in China. METHODS: We retrospectively analyzed bacteriological and clinical characteristics of patients with SBP and BA at Beijing 302 Hospital in China from January 2012 to December 2015. RESULTS: A total of 600 patients with SBP (n = 408) or BA (n = 192) were enrolled. Patients with BA appeared to have a less severe clinical manifestation and lower mortality rate than patients with SBP. Gram-negative bacteria formed the majority of pathogens in SBP (73.9%) and BA (55.8%) cases. Higher ascitic fluid polymorphonuclear leucocytes (PMN) count and hepatocellular carcinoma were independent risk factors for BA episode progressing to SBP. The concentration of blood urea nitrogen (BUN) was independent risk factor for 30-day mortality of BA patients. For patients with SBP, the independent risk factors for 30-day mortality were age, Model for End-Stage Liver Disease (MELD) score, septic shock and hepatocellular carcinoma. Patients with third-generation cephalosporin or carbapenems resistant infection had a significantly lower survival probability. There were significant differences in clinical characteristics and outcome among the major bacteria. Multivariate analysis showed that patients infected with Klebsiella spp. had higher hazard ratio of 30-day mortality. CONCLUSION: Our study reported the bacteriological and clinical characteristics of patients with SBP and BA. Higher ascitic fluid PMN count and hepatocellular carcinoma were found to be independent risk factors for BA episode progressed to SBP. Outcome of ascitic fluid infection in patients with cirrhosis was influenced by the type of bacteria and antimicrobial susceptibility.

Molecular epidemiology of bla OXA-23 -producing carbapenem-resistant Acinetobacter baumannii in a single institution over a 65-month period in north China.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii poses a significant threat to hospitalized patients, as few therapeutic options remain. Thus, we investigated the molecular epidemiology and mechanism of resistance of carbapenem-resistant A.baumannii isolates in Beijing, China. METHODS: Carbapenem-resistant A.baumannii isolates (n = 101) obtained between June 2009 and November 2014 were used. Multilocus sequence typing (MLST) and PCR assays for class C and D ß-lactamase were performed on all isolates. S1 nuclease pulsed-field gel electrophoresis (PFGE) and Southern blot hybridization were performed to identify the resistance gene location. RESULTS: All 101 A.baumannii isolates were highly resistant to frequently used antimicrobials, and were considered multidrug resistant. A total of 12 sequence types (STs) were identified, including 10 reported STs and 2 novel STs. Eighty-seven isolates were classified to clonal complex 92 (CC92), among which ST191 and ST195 were the most common STs. The bla OXA-23 gene was positive in most (n = 95) of the A.baumannii isolates. Using S1-nuclease digestion PFGE and Southern blot hybridization, 3 patterns of plasmids carrying bla OXA-23 were confirmed. ST191 and ST195 (both harboring bla OXA-23 ) caused outbreaks during the study period, and this is the first report of outbreaks caused by ST191 and ST195 in north China. CONCLUSION: bla OXA-23 -producing A.baumannii ST191 and ST 195 isolates can disseminate in a hospital and are potential nosocomial outbreak strains. Surveillance of imipenem-resistant A.baumannii and antimicrobial stewardship should be strengthened.

Detection of the mcr-1 Colistin Resistance Gene in Carbapenem-Resistant Enterobacteriaceae from Different Hospitals in China.

The spread of the plasmid-mediated colistin resistance gene, mcr-1, into carbapenem-resistant Enterobacteriaceae (CRE) clinical isolates poses a significant threat to global health. Here we report the identification of three mcr-1-harboring carbapenem-resistant Escherichia coli strains, collected from three patients in two provinces in China. Our results show that mcr-1-harboring CRE strains have started to spread in different hospitals in China. In addition, this report presents the first description of chromosomal integration of mcr-1 into a carbapenem-resistant E. coli strain.

HBeAg induces neutrophils activation impairing NK cells function in patients with chronic hepatitis B.

BACKGROUND: The role of neutrophils in hepatitis B virus (HBV) infection has been a subject of debate due to their involvement in antiviral responses and immune regulation. This study aimed to elucidate the neutrophil characteristics in patients with chronic hepatitis B (CHB). METHODS: Through flow cytometry and ribonucleic acid-sequencing analysis, the phenotypes and counts of neutrophils were analyzed in patients with CHB. Moreover, the effects of HBeAg on neutrophils and the corresponding pattern recognition receptors were identified. Simultaneously, the cross-talk between neutrophils and natural killer (NK) cells was investigated. RESULTS: Neutrophils were activated in patients with CHB, characterized by higher expression levels of programmed death-ligand 1 (PD-L1), cluster of differentiation 86, and interleukin-8, and lower levels of CXC motif chemokine receptor (CXCR) 1 and CXCR2. Hepatitis B e antigen (HBeAg) partially induces neutrophil activation through the Toll-like receptor 2 (TLR2). A consistent upregulation of the TLR2 and HBeAg expression was observed in patients with CHB. Notably, the genes encoding molecules pivotal for NK-cell function upon NK receptor engagement enriched in neutrophils after HBeAg activation. The HBeAg-activated neutrophils demonstrated the ability to decrease the production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in NK cells, while the PD-1 and PD-L1 pathways partially mediated the immunosuppression. CONCLUSIONS: The immunosuppression of neutrophils induced by HBeAg suggests a novel pathogenic mechanism contributing to immune tolerance in patients with CHB.

Replicon-Based Typing About IncG Plasmids and Molecular Characterization of Five IncG Plasmids Carrying Carbapenem Resistance Gene bla KPC-2.

Purpose: To investigate the genetic diversity of IncG plasmids, we have proposed a typing scheme based on replicon repA and performed comparative genomic analysis of five IncG plasmids from China. Methods: p30860-KPC, p116965-KPC, pA1705-KPC, pA1706-KPC and pNY5520-KPC total in five IncG plasmids from clinical isolates of Pseudomonas and Enterobacteriaceae, respectively, were fully sequenced and were compared with the previously collected reference plasmid p10265-KPC. Results: Based on phylogeny, IncG-type plasmids are divided into IncG-I to IncG-VIII, the five plasmids belong to IncG-VIII. A detailed sequence comparison was then presented that the IncG plasmid involved accessory region I (Tn5563a/b/c/d/e), accessory region II (ISpa19), and accessory region III (bla KPC-2-region). Expect for the pNY5520-KPC, the rest of the plasmids had the same backbone structure as the reference one. Within the plasmids, insertion sequences Tn5563d and Tn5563e were identified, a novel unknown insertion region was found in Tn5563b/c/d/e. In addition, Tn6376b and Tn6376c were newly designated in the study. Conclusion: The data presented here including a typing scheme and detailed genetic comparison which provide an insight into the diversification and evolution history of IncG plasmids.

Omicron neutralization character in patients with breast cancer and liver cancer after the nationwide omicron outbreak.

BACKGROUND: The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. METHODS: In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. RESULTS: Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. CONCLUSION: Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

First report of liver abscess caused by Salmonella enterica serovar Dublin.

This is the first reported case of liver abscess attributable to Salmonella serovar Dublin infection and also the fourth case of Salmonella liver abscess complicated with hepatocellular carcinoma reported since 1990. Drainage combined with intravenous antibiotics resulted in improvement, but recovery regressed again. Subsequent hepatic left lobectomy led to full recovery.

Acinetobacter baumannii adaptation to the host pH microenvironment is mediated by allelic variation in a single residue of BauA protein.

Acinetobacter baumannii has been listed as one of the most critical pathogens in nosocomial infections; however, the key genes and mechanisms to adapt to the host microenvironment lack in-depth understanding. In this study, a total of 76 isolates (from 8 to 12 isolates per patient, spanning 128 to 188 days) were longitudinally collected from eight patients to investigate the within-host evolution of A. baumannii. A total of 70 within-host mutations were identified, 80% of which were nonsynonymous, indicating the important role of positive selection. Several evolutionary strategies of A. baumannii to increase its potential to adapt to the host microenvironment were identified, including hypermutation and recombination. Six genes were mutated in isolates from two or more patients, including two TonB-dependent receptor genes (bauA and BJAB07104_RS00665). In particular, the siderophore receptor gene bauA was mutated in multiple isolates from four patients with three MLST types, and all mutations were at amino acid 391 in ligand-binding sites. With 391T or 391A, BauA was more strongly bound to siderophores, which promoted the iron-absorption activity of A. baumannii at acidic or neutral pH, respectively. Through the A/T mutation at site 391 of BauA, A. baumannii displayed two reversible phases to adapt to distinct pH microenvironments. In conclusion, we demonstrated the comprehensive within-host evolutionary dynamics of A. baumannii, and discovered a key mutation of BauA site 391 as a genetic switch to adapt to different pH values, which may represent a model in the pathogen evolutionary adaption of the host microenvironment.

Clinical features, microbial spectrum, and antibiotic susceptibility patterns of spontaneous bacterial peritonitis in cirrhotic patients.

BACKGROUND AND AIMS: The microbial spectrum and antimicrobial resistance patterns change over time and vary across regions in patients with spontaneous bacterial peritonitis (SBP). There is an urgent need to clarify the factors associated with in-hospital mortality in these patients. METHODS: In this study, 377 patients with SBP and 794 patients with bacterascites were analyzed for the microbial spectrum, antimicrobial resistance profiles, and laboratory findings. RESULTS: The most common pathogens were Escherichia coli (96, 25.5%), Staphylococcus epidermidis (55, 14.6%), and Enterococcus faecium (42, 11.1%). Multidrug-resistant (MDR) bacteria comprised 49.7% of gram-positive bacteria (GPB) and 48.8% of gram-negative bacteria (GNB). The most sensitive antibiotics were amikacin (91.5%), meropenem (89.8%) and piperacillin/tazobactam (87.6%). Extensively drug-resistant (XDR) (OR=51.457, p < 0.001), neutrophil count (OR=1.088, p < 0.001), and the model for end-stage liver disease (MELD) score (OR=1.124, p < 0.001) were independent predictive factors of in-hospital mortality in patients with SBP. CONCLUSION: MDR represented nearly half of the bacteria isolated from patients with SBP, of which the high prevalence of extended-spectrum ß-lactamase-producing and Carbapenem-resistant bacteria is concerning. The presence of XDR, higher MELD score, and neutrophil count were independent predictive factors associated with higher in-hospital mortality in patients with SBP, indicating that intensive care should be provided to these patients.

Genetic Characterization of Four Groups of Chromosome-Borne Accessory Genetic Elements Carrying Drug Resistance Genes in Providencia.

Purpose: The aim of this study was to gain a deeper genomics and bioinformatics understanding of diversification of accessory genetic elements (AGEs) in Providencia. Methods: Herein, the complete genome sequences of five Providencia isolates from China were determined, and seven AGEs were identified from the chromosomes. Detailed genetic dissection and sequence comparison were applied to these seven AGEs, together with additional 10 chromosomal ones from GenBank (nine of them came from Providencia). Results: These 17 AGEs were divided into four groups: Tn6512 and its six derivatives, Tn6872 and its two derivatives, Tn6875 and its one derivative, and Tn7 and its four derivatives. These AGEs display high-level diversification in modular structures that had complex mosaic natures, and particularly different multidrug resistance (MDR) regions were presented in these AGEs. At least 52 drug resistance genes, involved in resistance to 15 different categories of antimicrobials and heavy metal, were found in 15 of these 17 AGEs. Conclusion: Integration of these AGEs into the Providencia chromosomes would contribute to the accumulation and distribution of drug resistance genes and enhance the ability of Providencia isolates to survive under drug selection pressure.

[Construction and application of lentivirus overexpression vector with two labeling genes fused with CopGFP and PuroR].

Objective: To construct the lentivirus overexpression vector with two label genes fused with CopGFP and PuroR and to detect the emission of green fluorescence as well as resistance to puromycin in liver cancer cells infected with lentivirus packaged with the above vector. Methods: Firstly, two fragments containing copGFP and PuroR coding sequences were amplified from pCDH-CMV-MCS-copGFP and pLKO.1 respectively; secondly, the two amplified regions were fused with each other by recombinant PCR; thirdly, the fusion DNA fragment was cut and inserted into pCDH-CMV-MCS-copGFP vector, which was linearized with the same restriction endonuclease as used to digest fusion DNA fragment: BamH Ⅰ and Sal Ⅰ. The fusion region in the constructed vector was confirmed by DNA sequencing. The checked vector was co-transfected with package assistant plasmids, namely PLP1, PLP2 and VSVG into in 293T cells and the culture supernatant was subjected to centrifuge and infect liver cancer MHCC97H cells, which were then used to detect their resistance to puromycin (infected cells were treated with 1 mg/ml puromycin for 7 days after infection) and to observe green fluorescence emission in microscope. To determine its efficiency in expressing foreign target protein, the Sp1 coding region was inserted into the MCS sites of the vector, and Sp1 mRNA and protein expression levels were compared with the vehicle vector by RT-qPCR and Western blot. Results: The lentivirus overexpression vector with two label genes fused with CopGFP and PuroR was successfully constructed, and the liver cancer cells infected with lentivirus packaged with the vector expressing two labeling genes fused with CopGFP and PuroRshowed both emission of green fluorescence and resistance to puromycin simultaneously, while cells containing with the vector inserted with Sp1 coding region improved Sp1 mRNA level with 3.3 fold and protein level with 2.2 fold higher in comparison with cells containing the vehicle vector (P＜0.01). Conclusion: The fused label genes consisting of copGFP and PuroR are correctly cloned into the lentivirus vector and confer cells with the ability to emission of green fluorescence and resistance to puromycin, besides, the vector may promote the expression of the target gene with long coding sequence.

Listeriosis Cases and Genetic Diversity of Their L. monocytogenes Isolates in China, 2008-2019.

Listeriosis, caused by Listeria monocytogenes, is a severe food-borne infection. The nationwide surveillance in China concerning listeriosis is urgently needed. In the present study, 144 L. monocytogenes isolates were collected from the samples of blood, cerebrospinal fluid (CSF), and fetal membrane/placenta in China for 12 years from 2008 to 2019. We summarized these listeriosis patients' demographical and clinical features and outcomes. The susceptibility profile for 12 antibiotics was also determined by the broth microdilution method. Multilocus sequence typing (MLST) and serogroups of these listeria isolates were analyzed to designate epidemiological types. We enrolled 144 cases from 29 healthcare centers, including 96 maternal-neonatal infections, 33 cases of bacteremia, 13 cases of neurolisteriosis, and two cutaneous listeriosis. There were 31 (59.6%) fetal loss in 52 pregnant women and four (9.8%) neonatal death in 41 newborns. Among the 48 nonmaternal-neonatal cases, 12.5% (6/48) died, 41.7% (20/48) were female, and 64.6% (31/48) occurred in those with significant comorbidities. By MLST, the strains were distinguished into 23 individual sequence types (STs). The most prevalent ST was ST87 (49 isolates, 34.0%), followed by ST1 (18, 12.5%), ST8 (10, 6.9%), ST619 (9, 6.3%), ST7 (7, 4.9%) and ST3 (7, 4.9%). Furthermore, all L. monocytogenes isolates were uniformly susceptible to penicillin, ampicillin, and meropenem. In summary, our study highlights a high genotypic diversity of L. monocytogenes strains causing clinical listeriosis in China. Furthermore, a high prevalence of ST87 and ST1 in the listeriosis should be noted.

Nasal colonization of and clonal transmission of methicillin-susceptible Staphylococcus aureus among Chinese military volunteers.

Military facilities provide unique opportunities for studying Staphylococcus aureus nasal colonization and transmission patterns. In this cross-sectional observational study, we assessed the prevalence of S. aureus nasal colonization among Chinese military volunteers in two camps in the Beijing area. Antimicrobial resistance patterns, risk factors for colonization, and transmission patterns using pulsed-field gel electrophoresis were also evaluated. From May to July 2007, 1,044 nasal swabs were collected from military volunteers from suburban (560) and urban (484) camps. A total of 209 S. aureus isolates were recovered, of which all were methicillin susceptible. Independent factors associated with methicillin-susceptible S. aureus (MSSA) nasal colonization included younger age (odds ratio [OR] = 1.51, 95% confidence interval [95% CI] = 1.03 to 2.21, P = 0.0347), higher education (OR = 1.38, 95% CI = 1.10 to 1.73, P = 0.0056), shorter length of service (OR = 1.74, 95% CI = 1.28 to 2.36, P = 0.0004), nonsmoking (OR = 1.61, 95% CI = 1.14 to 2.28, P = 0.0069), and inactive participation in social events (OR = 2.40, 95% CI = 1.25 to 5.49, P = 0.0082). Among 209 MSSA isolates, 126 (60.3%) were determined to be epidemic and a total of 12 genotypes were identified, of which four (90 isolates [71.4%]) represented the majority of strains. Length of service and camp location were statistically related to the four major MSSA genotype clonal transmissions. Our data indicated that MSSA, not methicillin-resistant S. aureus (MRSA), nasal colonization and clonal transmission occur in healthy military volunteers in Beijing. Younger, female, nonsmoking volunteers with higher education, little or no participation in social events, and less time in service are at higher risk for nasal MSSA carriage.

Mechanism of berberine in treating Helicobacter pylori induced chronic atrophic gastritis through IRF8-IFN-γ signaling axis suppressing.

AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.

Palmatine ameliorates Helicobacter pylori-induced chronic atrophic gastritis by inhibiting MMP-10 through ADAM17/EGFR.

Palmatine (Pal), a plant-based isoquinoline alkaloid, was initially isolated from Coptidis Rhizoma (CR, Huanglian in Chinese) and considered to be a potential non-antibiotic therapeutic agent that can safely and effectively improve Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). However, underlying mechanisms are unclear. In this study, we explored the protective effect of Pal on H. pylori induced CAG in vivo and in vitro. As a result, Pal alleviated the histological damage of gastric mucosa and the morphological changes of gastric epithelial cell (GES-1) caused by H. pylori. Furthermore, Pal significantly inhibited the expression of EGFR-activated ligand genes, including a disintegrin and metalloproteinase 17 (ADAM17) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), and the proinflammatory factors, such as chemokine 16 (CXCL-16) and interleukin 8 (IL-8), were suppressed. In addition, Pal attenuated inflammatory infiltration of CD8+ T cells while promoted Reg3a expression to enhance host defense. Taken together, we concluded that Pal attenuated the MMP-10 dependent inflammatory response in the gastric mucosa by blocking ADAM17/EGFR signaling, which contributed to its gastrointestinal protective effect.

UPLC-Q-TOF/MS-Based Serum and Urine Metabonomics Study on the Ameliorative Effects of Palmatine on Helicobacter pylori-Induced Chronic Atrophic Gastritis.

OBJECTIVE: The main objective of this study was to investigate the ameliorative effects of Palmatine (Pal) on Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). METHOD: Body function, serum biochemical indicators and histopathology were used to evaluate the pharmacodynamics of Pal on CAG rats. The target genes expression levels were verified and assessed by RT-PCR and immunohistochemistry (IHC). Moreover, UPLC-Q-TOF/MS analysis based on urine and serum was performed to identify the potential metabolites in the pathological process of CAG induced by H. pylori. Metabolic pathway analysis was performed to elucidate the metabolic network associated with Pal treatment of CAG. RESULTS: Pal (10, 20, 40 mg/kg/day) significantly restored the body function of CAG rats, reduced the serum biochemical indicators, and maintained the integrity of the gastric mucosal epithelial barrier while alleviated gastric histological damage. Metabolomics analysis shows that the therapeutic effect of Pal on CAG involves 10 metabolites and 10 metabolic pathways, of which the Taurine and hypotaurine metabolism, Glycerophospholipid metabolism and Pentose and glucuronate interconversions are closely related to the gastrointestinal protection of Pal, and these metabolic pathways crosstalk with each other due to the internet hub of citric acid cycle. CONCLUSIONS: Metabolomics was used for the first time to identify potential biomarkers of CAG and to illuminate the therapeutic mechanism of Pal on CAG induced by H. pylori. The results provided a new insight for further research on CAG treatment.

Species Distribution and Antifungal Susceptibility of Invasive Candidiasis: A 2016-2017 Multicenter Surveillance Study in Beijing, China.

OBJECTIVE: Invasive candidiasis (IC), a life-threatening fungal infection prevalent among hospitalized patients, has highly variable regional epidemiology. We conducted a multicenter surveillance study to investigate recent trends in species distribution and antifungal susceptibility patterns among IC-associated Candida spp. in Beijing, China, from 2016 to 2017. MATERIALS AND METHODS: A total of 1496 non-duplicate Candida isolates, recovered from blood and other sterile body fluids of IC patients, were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry combined with ribosomal DNA internal transcribed spacer (ITS) region sequencing. Broth microdilution-based susceptibility testing using six antifungal agents was also conducted. RESULTS: Candida albicans was the most frequently isolated species (49.9%), followed by Candida tropicalis (15.5%), Candida glabrata (14.7%) and Candida parapsilosis (14.2%). No significant differences in species distribution were observed when compared with a 2012-2013 dataset. Overall, the rates of susceptibility to fluconazole and voriconazole were high among C. albicans (98% and 97.2%, respectively) and C. parapsilosis species complex (91.1% and 92%, respectively) isolates but low among C. tropicalis (81.5% and 81.1%, respectively) isolates. In addition, the rate of azole resistance among C. tropicalis isolates increased significantly (1.8-fold, P<0.05) compared with that observed in 2012-2013, while micafungin resistance rates were <5% for all tested Candida species. CONCLUSION: Our results suggest that species distribution has remained stable among IC-associated Candida isolates in Beijing. Resistance to micafungin was rare, but increased azole resistance among C. tropicalis isolates was noted. Our study provides information on local epidemiology that will be important for the selection of empirical antifungal agents and contributes to global assessments of antifungal resistance.

[The distribution and antimicrobial resistance tendency of pathogens associated with diarrhea in Beijing].

OBJECTIVE: To monitor the constituents and resistant tendency of bacterial pathogens isolated from diarrheal patients in our hospital form 1994 to 2005 to offer the basis for guiding epidemiologic study, vaccination research and clinical treatment. METHODS: Enteric pathogenic bacteria were cultured and identified to species, group and serotype with biochemical and serologic methods and the susceptibility of bacteria to antimicrobial agents were tested. RESULTS: Enteric pathogenic bacteria were isolated predominantly in male patients and mainly in children and youngsters. It reached a peak from July to September every year. Shigella spp. (75.11%) was the most frequently isolated pathogens and followed by Vibrio spp. (12.7%), Salmonella spp. (6.28%), Aeromonas spp. (4.43%) and Escherichia coli (1.25%). During the period from 1994 to 2005, diarrheal pathogens had a trend of decrease especially Shigella spp. and Salmonella spp. Of the 6329 isolates of Shigella spp., 75.62% was S. flexneri and S. sonnei, S. dysenteriae and S. boydii constituted 23.98%, 0.22% and 0.01% respectively. The sensitivity of different species, group or serotype to different antimicrobial agents was not the same. S. flexneri and Aeromonas spp. were highly resistant to most of antibiotics. However, S. sonnei and Vibrio spp. had good susceptibility to antibiotics tested except trimethoprim/sulfamethoxazole and ampicillin. CONCLUSION: There are many species and serotypes of enteric pathogenic bacteria causing infective diarrhea and the distribution changes gradually in Beijing. The resistance rate of enteric pathogenic bacteria to antibiotics is not the same in different species and serotypes, so strict surveillance is always needed.

Microbiological characterisation of Klebsiella pneumoniae isolates causing bloodstream infections from five tertiary hospitals in Beijing, China.

OBJECTIVES: Klebsiella pneumoniae is prevalent in China. Little is known about the microbiological characteristics of clinical K. pneumoniae isolates causing bloodstream infections (BSIs). METHODS: BSI-causing K. pneumoniae (BSI-Kpn) were collected from five tertiary-care hospitals in Beijing. Genetic relatedness was analysed by PFGE, antimicrobial susceptibility was determined by agar dilution, and sequence types (STs) were evaluated by MLST. Hypermucoviscosity (HV) phenotype was identified by positive string test. Carbapenemase, capsular serotype and HV-associated genes were detected by PCR. RESULTS: A total of 219 non-duplicate BSI-Kpn were collected from December 2013 to December 2014 and were categorised into 203 types (strains) with unique PFGE patterns. Among 203 BSI-Kpn, 105 STs were identified. Overall, ST11 and ST23 were the predominant clones (14 strains each; 6.9%), followed by ST412 (n=13), ST37 (n=9), ST65 (n=7), ST15 (n=6), ST86 (n=6), ST592 (n=5) and ST29 (n=4). There were 74 STs containing only a single strain. Approximately 8.4% (17/203) of the strains exhibited carbapenem resistance, most producing KPC carbapenemase. The majority (75.9%; 154/203) of isolates were associated with non-K1/K2/K5/K20/K54/K57 serotypes. Only 16.3% (33/203) of the strains had K1/K2 serotypes. A total of 66 (32.5%) of the BSI-Kpn strains exhibited a HV phenotype. rmpA was a predominant factor in determining a HV phenotype. CONCLUSIONS: The majority of BSI-Kpn strains exhibited high genetic diversity and low resistance to commonly used antimicrobials. The specific capsular serotype and HV phenotype were not major features of BSI-Kpn strains in China.