Monitoring the long-term spatiotemporal transmission dynamics and ecological surveillance of multidrug-resistant Salmonella enterica serovar Goldcoast: A multicenter genomic epidemiology study.

The emergence of multidrug-resistant Salmonella enterica serovar Goldcoast poses a significant threat to the effective treatment and control of salmonellosis within the ecological environment. Here, we conducted a genomic epidemiological study delineate the global dissemination scenarios of the multidrug-resistant S. Goldcoast originated from 11 countries for over 20 years. The population structure and evolutionary history of multidrug-resistant S. Goldcoast was investigated through phylogenomic and long-term spatiotemporal transmission dynamic analysis. ST358 and ST2529 are the predominant lineages of S. Goldcoast. Multidrug-resistant S. Goldcoast strains have mainly been identified in the ST358 lineage from human and the ST2529 lineage from livestock. ST358 S. Goldcoast was estimated to have emerged in the United Kingdom in 1969, and then spread to China, with both countries serve as centers for the global dissemination of the ST358 lineage. After its emergence and subsequent spread in Chinese clinical and environmental samples, occasional instances of this lineage have been reported in Canada, the United Kingdom, and Ireland. Clonal transmission of ST358 and ST2529 S. Goldcoast have occurred not only on an international and intercontinental scale but also among clinical, environmental and livestock samples. These data indicated that international circulation and local transmission of S. Goldcoast have occurred for over a decade. Continued surveillance of multidrug-resistant S. Goldcoast from a global "One Health" perspective is urgently needed to facilitate monitoring the spread of the antimicrobial resistant high-risk clones.

Genomic and epidemiological characterization of a blaCTX-M-27-carrying ST34 Salmonella enterica serotype Typhimurium in China.

OBJECTIVES: Consuming contaminated food and water is a leading cause of food poisoning, with Salmonella being one of the primary culprits. The aim of this study is to elucidate the genomic characteristics of a blaCTX-M-27-carrying S. enterica strain recovered from a patient with diarrhoea in China. METHODS: Antimicrobial susceptibility of S. enterica strain 123 was determined by microdilution broth assay. Whole-genome sequencing was performed using both long-read MinION and short-read Illumina platforms to fully characterize the genetic structure of the blaCTX-M-27-carrying plasmid of the S. enterica 123. In silico multilocus sequence typing (MLST), antimicrobial resistance genes and genomic epidemiological analysis of 69 Salmonella strains carrying the blaCTX-M-27 gene stored in NCBI GenBank were further analysed by BacWGSTdb 2.0 server. RESULTS: The isolate was resistant to ampicillin, ampicillin/sulbactam, ceftazidime, ceftriaxone, cefepime, aztreonam, azithromycin, but still susceptible to ciprofloxacin, levofloxacin, imipenem, amikacin, trimethoprim-sulfamethoxazole and gentamicin. The complete genome sequence of Salmonella 123 is made up of one chromosome and three plasmids, which could be assigned as sequence type (ST)34. The blaCTX-M-27 gene was found in the 65 644 bp IncFII-type plasmid with IS26 and IS5 exist upstream of blaCTX-M-27 gene, and IS26 and IS1B are located downstream as a truncated fragment. The closest relative of Salmonella 123 was Salmonella strain La89, another ST34 strain recovered in 2011, which differed by only 52 SNPs. CONCLUSION: This study reports the complete genome of a blaCTX-M-27-carrying S. enterica that can be used for gaining insights into the antimicrobial resistance mechanisms and dissemination patterns of the emerging pandemic lineage ST34.

The Application Value of Esketamine and Dexmedetomidine in Preventing Postoperative Delirium and Hyperalgesia in Elderly Patients with Thoracic Anesthesia.

Objective: Our aim was to evauate the application value of esesketamine and dexmedetomidine in preventing postoperative hyperalgesia in elderly patients who received thoracic anesthesia. Methods: A total of 94 elderly patients who underwent thoracic anesthesia in Sanmen People's Hospital from January 2021 to October 2022 were selected and divided into a dexmedetomidine group (n = 47) and an esketamine group (n = 47) by the random number table method. All patients were continuously received intravenous (IV) remifentanil. In the dexmedetomidine group, dexmedetomidine 0.7 µg/kg was administered IV, followed by 0.2 to 0.5 µg/kg/h to maintain anesthesia, while in the esketamine group, esketamine 0.5 mg/kg was given IV 20 min after induction of anesthesia was completed. Results: Visual analogue scale (VAS) scores in the esketamine group were lower than in the dexmedetomidine group at 1, 6, 12 and 24 h postoperatively (P < .05), and Ramsay sedation scores were not statistically different from those in the dexmedetomidine group (P > .05). At 3 d postoperatively, the Mini-Mental State Examination (MMSE) scores in the dexmedetomidine group were lower than 1 d preoperatively; at 5 d postoperatively, the negative mood and Pittsburgh Sleep Quality Index (PSQI) scores were significantly higher in both groups than 1 d preoperatively; at 14 d postoperatively, the PSQI scores were higher in both groups than 1 d preoperatively, and there was no statistical difference between the negative mood scores at 1 d before surgery (P > .05). At 5 d postoperatively in the esketamine group, the negative mood scores were lower than in the dexmedetomidine group at 5 d postoperatively and the PSQI scores at 5 and 14 d postoperatively were lower than in the dexmedetomidine group (P < .05). Conclusion: Both esketamine and dexmedetomidine can be used to prevent postoperative delirium and nociceptive hypersensitivity after anesthesia in elderly patients with thoracic surgery. However, esketamine is superior to dexmedetomidine in analgesic effect, improvement of negative mood and sleep and stabilization of intraoperative hemodynamics, leading to better effect in preventing delirium and hyperalgesia after anesthesia.

Genomic epidemiology of mcr carrying multidrug-resistant ST34 Salmonella enterica serovar Typhimurium in a one health context: The evolution of a global menace.

The rapid global dissemination of Salmonella enterica sequence type 34 (ST34) has sparked significant concern due to its resistance to critical antimicrobials and its ability to spread across various sectors. In order to investigate the evolution and transmission dynamics of this epidemic clonal lineage, as well as the horizontal transfer of mcr-carrying plasmids within the One Health framework, we conducted a comprehensive genomic epidemiological study. This study focused on the 11 mcr-carrying S. enterica isolates obtained from clinical settings in China, while also considering 2337 publicly available genomes of mcr-carrying S. enterica collected from 20 countries and diverse sources spanning over a 22-year period. Among the mcr-positive Salmonella isolates, ST34 was found to be the predominant lineage, comprising 30.12 % (704/2337) of the total collection. These isolates were identified as either serovar Typhimurium or its monophasic variant, which were obtained from both clinical and non-clinical sources. Phylogeographic analyses traced the global spread of the mcr-carrying ST34 lineage, which was divided into three distinct clusters, with 83.10 % of them carrying mcr-1 or/and mcr-9 genes. Notably, the mcr-1 positive ST34 isolates were primarily found in China (190/298, 63.76 %), with only four from the United States. Conversely, mcr-9 positive ST34 isolates were predominantly identified in the United States (261/293, 89.08 %), while none were observed in China. The mcr-1 positive ST34 isolates was predicted to have originated from clinical sources in United Kingdom, whereas mcr-9 positive ST34 isolates was likely derived from environmental sources in Germany. The most recent common ancestor for mcr-1 and mcr-9 carrying ST34 S. enterica was estimated to have emerged around 1983 and 1951. These findings provided thorough and intuitive insights into the intercontinental spread of mcr-carrying S. enterica ST34 lineage in a One Health context. Ongoing surveillance is crucial for effectively monitoring the worldwide dissemination of this multidrug-resistant high-risk clone.

Clostridium ramosum Bacteremia in an Immunocompetent Patient with SARS-CoV-2 Infection: A Case Report.

We report a case of Clostridium ramosum bacteremia in a 73-year-old patient with SARS-CoV-2 infection and right lower abdominal tenderness in China. The microbiological features and genomic epidemiological characteristics of C. ramosum worldwide were investigated to identify the possible sources of infection. Whole-genome sequencing of C. ramosum WD-I2 was performed using an Illumina NovaSeq 6000 platform. Phylogenetic analysis of C. ramosum WD-I2 and other publicly available C. ramosum isolates was performed and visualized using the interactive Tree of Life (iTOL) web server. The resistome of C. ramosum WD-I2 consists of two antimicrobial resistance genes (tetM and ermB), which explains the antimicrobial resistance trait to tetracycline and macrolides. Phylogenetic analysis showed that the strain closest to our isolated strain WD-I2 was SUG1069, recovered from a pig feces sample from Canada, which differed by 589 SNPs. To our knowledge, this is the first report of C. ramosum bacteremia in China. Our findings highlight the potential risk of invasive C. ramosum infections during the COVID-19 pandemic.

Bacteremia Caused by a Serotype Ob5 Vibrio cholerae Strain in a Cirrhotic Patient in China.

The increasing incidence of non-O1/non-O139 Vibrio cholerae (NOVC) has been observed worldwide. However, septicemia caused by NOVC remains a rare condition that has received limited attention. Currently, there are no established treatment guidelines for bloodstream infections caused by NOVC, and the understanding of this condition mainly relies on individual case reports. Although NOVC bacteremia can be fatal in a small percentage of cases, knowledge about its microbiological features remains limited. Here, we present a case of V. cholerae septicemia caused by NOVC in a 46-year-old man with chronic viral hepatitis and liver cirrhosis. The isolated strain, named V. cholerae VCH20210731 and classified as a new sequence type (ST), ST1553, was found to be susceptible to most of the antimicrobial agents tested. O-antigen serotyping of V. cholerae VCH20210731 revealed that it belonged to serotype Ob5. Interestingly, the ctxAB genes, which are typically associated with V. cholerae, were absent in VCH20210731. However, the strain possessed 25 other potential virulence genes, such as hlyA, luxS, hap, and rtxA. The resistome of V. cholerae VCH20210731 included several genes, including qnrVC4, crp, almG, and parE. Nevertheless, susceptibility testing demonstrated that the isolate was susceptible to most of the antimicrobial agents tested. Phylogenetic analysis indicated that the closest strain to VCH20210731 was strain 120 from Russia, differing by 630 single-nucleotide polymorphisms (SNPs). Our findings contribute to the understanding of the genomic epidemiological characteristics and antibiotic resistance mechanisms of this invasive bacterial pathogen. IMPORTANCE This study highlights the discovery of a novel ST1553 V. cholerae strain in China, providing valuable insights into the genomic epidemiology and global transmission dynamics of V. cholerae. It is important to note that clinical presentations of NOVC bacteremia can vary significantly, and the isolates demonstrate genetic diversity. Consequently, health care professionals and public health experts should remain vigilant about the potential for infection with this pathogen, particularly considering the elevated prevalence of liver disease in China.

Global population structure and genomic surveillance framework of carbapenem-resistant Salmonella enterica.

Due to the frequent international and intercontinental transmission of multidrug-resistant bacteria, it is imperative to understand the epidemiology, phylogeography, and population structure of carbapenem-resistant Salmonella enterica (CRSE) across the globe. During the period of 2015-2022, two blaNDM-carrying S. enterica strains were recovered from 3695 Salmonella strains in four hospitals in China. The global phylogenetic framework and geographical distribution of CRSE were defined by our recently updated bacterial whole genome sequence typing and source tracking database BacWGSTdb 2.0 to measure the diversity and evolutionary relatedness in context with epidemiological metadata. Phylogeny for all carbapenemase gene-harboring plasmids in S. enterica based on the pairwise Mash differences was also constructed to evaluate the potential transmission of these plasmids in a global context. A large-scale phylogenetic analysis grouped global CRSE into nine distinct clades. The small genetic distance (< 20 SNPs) between 198 pairs of CRSE suggested the presence of clonal transmission. Global CRSE have significant geographical variations, which was associated with the clonal lineages and carbapenemase genes. Carbapenemase gene-carrying plasmids with a high degree of similarity have surfaced in various hosts and countries. The widespread of multiple-replicon plasmids that offer a great capacity to accommodate multiple antimicrobial resistance genes is continuously enhancing the potential risk of CRSE isolates to propagate globally. Both clonal spread of strains and horizontal transfer of carbapenemase gene-harboring plasmids contribute to the global dissemination of CRSE. Our findings on the worldwide spread and transmission dynamics of this emerging bacterium has increased the knowledge of its global epidemics. Continued epidemiological surveillance is necessary to prevent global outbreak of multidrug-resistant Salmonella infections.

First Identification of a Multidrug-Resistant Pseudomonas putida Co-Carrying Five ß-Lactam Resistance Genes Recovered from a Urinary Tract Infection in China.

The emergence of multidrug-resistant Pseudomonas spp. in the clinical settings has heightened public awareness. Here, we described the genomic characteristics of a P. putida isolate co-carrying five ß-lactam resistance genes recovered from a urinary tract infection in China. Whole-genome sequencing was performed using Illumina NovaSeq 6000 and Oxford Nanopore MinION platforms. The genome sequence was annotated and further subjected to identify the sequence type (ST), antibiotic resistance and virulence genes. Phylogenetic analysis of 193 P. putida strains stored in NCBI public database based on core genome single nucleotide polymorphism (cgSNP) strategy were also performed and visualized. Our study indicated that P. putida PP_2463 was resistant to a wide range of antimicrobial agents tested, including aminoglycosides, carbapenems and fluoroquinolones. The complete genome sequence of P. putida PP_2463 is made up of one chromosome and two plasmids, which could be assigned to a new sequence type (ST) 148. The co-occurrence of ß-lactam resistance genes bla IPM-15, bla PME-1, bla CARB-2, and bla NDM-1 were first identified in P. putida, and a novel ß-lactamase gene located in the chromosome were among the antimicrobial resistance genes discovered. The closest relative of P. putida PP_2463 was identified in 2012 from a urine sample in China, with a difference of 143 SNPs. Along with the presence of multiple ß-lactamase genes and mobile genetic elements, the multidrug-resistant phenotype suggests a significant potential as an antibiotic resistance reservoir for Pseudomonas spp.

Emergence of a Multidrug-Resistant Escherichia coli Co-Carrying a New mcr-1.33 Variant and bla NDM-5 Genes Recovered from a Urinary Tract Infection.

Background: Carbapenem-resistant Enterobacterales (CRE) are a significant threat to worldwide public health, resulting in increased morbidity, death, hospitalization time and healthcare expenses. Here, the genomic and phylogenetic characteristics of a multidrug-resistant Escherichia coli isolate carrying both the new mcr-1.33 variant and bla NDM-5 gene obtained from a urinary tract infection in China are investigated. Methods: Antimicrobial susceptibility of E. coli 779 was evaluated by using the broth microdilution method. Short-read Illumina NovaSeq 6000 and long-read Oxford Nanopore MinION platforms were applied to sequence the bacterial whole genomic DNA and then de novo assembled. The genome sequence was annotated using the NCBI Prokaryotic Genome Annotation Pipeline and further subjected to identify the sequence type (ST), capsular type, and antibiotic resistance genes. BacWGSTdb 2.0 was used to perform the core genome multilocus sequence typing (cgMLST) analysis with other closely related E. coli isolates deposited in the public database. Results: E. coli 779 was resistant to aztreonam, levofloxacin, fosfomycin, cefoxitin, cefepime, cefotaxime, imipenem, meropenem, polymyxin, and tigecycline. The complete genome sequence of E. coli 779 is made up of nine contigs totaling 5,667,876 bp, including one chromosome and eight plasmids. The isolate was assigned to ST101, serotype O-:H31, and phylogroup B1. The colistin resistance gene mcr-1.33 (located in a 242,460 bp IncHI2/IncHI2A plasmid) and the ß-lactam resistance gene bla NDM-5 (located in a 46,161 bp IncX3 plasmid) were among the 27 antimicrobial resistance genes discovered. The closest relative of E. coli 779, another ST101 strain (E. coli 443) obtained from a sewage sample in Shandong, China in 2015, differs by only 24 cgMLST alleles. Conclusion: We discovered the first multidrug-resistant ST101 E. coli strain with plasmid-mediated mcr-1.33 variant and bla NDM-5 gene in China. These findings would help us to better understanding the genomic traits, antimicrobial resistance mechanisms and epidemiological aspects of this bacterial pathogen.

Use of acid-suppressive drugs and risk of fracture in children and young adults: a meta-analysis of observational studies.

BACKGROUND: Acid-suppressive drugs (ASDs) are being used by increasing number of children and young adults. However, evidence for a relationship between ASD use and the risk of fracture in these groups of patients is conflicting. We conducted a meta-analysis to evaluate the risk of fracture in children and young adults exposed to ASDs. METHODS: A literature search was performed using the PUBMED, EMBASE, and Cochrane Library databases from inception to November 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to determine the relationship of ASD use with fracture risk in children and young adults. RESULTS: Six studies reporting the outcomes of more than 900,000 children and young adults with ASD use were included in the meta-analysis. The pooled RR for fracture with the use of proton pump inhibitors (PPIs) versus non-use of these medications was 1.17 (95% CI = 1.1-1.25; P < 0.001) in children and 1.2 (95% CI = 0.87-1.65; P = 0.272) in young adults. By contrast, the use of histamine H2-receptor antagonists (H2RAs) was not significantly associated with fracture risk in children (RR, 1.08, 95% CI = 0.99-1.17; P = 0. 083) or young adults (RR, 1.08, 95% CI = 0.82-1.42; P = 0.589). Significant statistical and clinical heterogeneity among studies were determined for the main analysis and most of the subgroup analyses. CONCLUSIONS: Our study provides evidence linking PPI use to an increased risk of fracture in children. Thus, the use of PPIs in these patients should be carefully considered. However, randomized controlled studies are needed to determine causality and the role of unmeasured/residual confounding factors in this association.

Maternal non-steroidal anti-inflammatory drug exposure during pregnancy and risk of miscarriage: a systematic review and meta-analysis.

BACKGROUND: Numerous studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) might be associated with increased risk of miscarriage. However, these results are conflicting and inconclusive. METHODS: We performed this systematic review and meta-analysis to assess the relationship between NSAIDs exposure and risk of miscarriage. A systematic literature search was conducted to identify relevant studies published from the time of database inception until June 2021. RESULTS: A total of ten studies involving 207,341 pregnant women were subjected to meta-analysis. There was no statistically significantly increased risk of miscarriage with the use of NSAIDs during pregnancy (OR = 1.37, 95% CI 0.99-1.88, p = 0.057). However, our findings showed that women exposed to NSAIDs around the time of conception were at increased risk of miscarriage (OR 2.32, 95% CI 1.16-4.66, p = 0.018). Furthermore, no significant association between NSAID use and miscarriage was evident during the first trimester of pregnancy (OR = 1, 95% CI = 0.83-1.2, p = 0.996), possibly attributable to the small sample size. CONCLUSION: Our findings indicate that NSAID exposure around the time of conception might be a risk factor for miscarriage. Further studies are needed to evaluate whether the risk varies by the type, dosage, or timing of NSAID exposure.

KIF18b-dependent hypomethylation of PARPBP gene promoter enhances oxaliplatin resistance in colorectal cancer.

As the new platinum drug oxaliplatin has been widely used in clinical treatment of colorectal cancer (CRC), oxaliplatin resistance has become a burning problem. In this study, higher expression of PARP-1 binding protein (PARPBP) was detected in oxaliplatin-resistant CRC (OR-CRC) cells than in non-resistant cells. Further research showed that kinesin family member 18 b (KIF18b) induced the overexpression of PARPBP, sustaining oxaliplatin resistance in OR-CRC cells. Through exploring the PARPBP gene promoter, we found that SP1-recruited DNMT3b methylated PARPBP promoter to suppress transcription in CRC cells, and increased KIF18b attenuated the recruitment of DNMT3b to PARPBP promoter by directly interacting with SP1 in OR-CRC cells. Clinical analysis suggested a positive relationship between KIF18b and PARPBP in CRC tissues and indicated poor prognosis in CRC patients with high level of KIF18b or PARPBP. In summary, KIF18b-induced PARPBP contributes to the resistant phenotype of OR-CRC.

MicroRNA-139-5p inhibits inflammatory and oxidative stress responses of Salmonella-infected macrophages through modulating TRAF6.

Evidence indicates that macrophages play an important role in the immune system. Therefore, research involving inflammatory and oxidative stress responses in macrophages is of great significance. Many factors contribute to inflammation and oxidative stress, including Salmonella. We investigated the effect of the miR-139-5p/TRAF6 axis on the inflammatory and oxidative stress responses of Salmonella -infected macrophages. Our findings revealed that miR-139-5p decreased IL-1ß and TNF-α levels to inhibit Salmonella-induced inflammatory responses in the RAW264.7 macrophage cell line. Furthermore, miR-139-5p inhibited Salmonella-induced oxidative stress by strengthening SOD, CAT and GSH-PX activity, as well as lowering the malondialdehyde level in the RAW264.7 macrophages cell line. Subsequently, it was verified that TRAF6 was a downstream target of miR-139-5p in RAW264.7 cells. Rescue assays indicated that the over-expression of miR-139-5p inhibits the effects of TRAF6 on inflammatory and oxidative stress responses including Salmonella infection in RAW264.7 cells. To our knowledge, this study is the first to verify that miR-139-5p inhibits inflammatory and oxidative stress responses of Salmonella-infected macrophages through regulating TRAF6. This discovery may offer new insights on inflammatory and oxidative stress responses in macrophages.

Maternal anti-tumour necrosis factor-α drug use during pregnancy and risk of infection in the offspring: A systematic review and meta-analysis.

BACKGROUND: Anti-tumour necrosis factor (TNF)-α drugs are used by increasing numbers of reproductive-age women. Although the neonatal outcomes have been described, there are concerns regarding the risk of infection in offspring following exposure to anti-TNF-α. METHODS: A literature search was conducted using Pubmed, EMBASE, and the Cochrane Database, from inception through August 2020. We evaluated the risk of infection in autoimmune disease (AID) offspring unexposed to anti-TNF-α compared to AID offspring exposed to anti-TNF-α, as well as to unexposed non-AID offspring. RESULTS: Our primary analysis showed that both AID offspring unexposed to anti-TNF-α [risk ratio (RR) 1.09; 95% confidence interval (CI), 1.03-1.16; I2=0%] and AID offspring exposed to anti-TNF-α (RR 1.39; 95% CI, 1.2-1.61; I2=0%] was associated with an increased risk of infection during the first year of life compared with the unexposed non-AID offspring. However, our secondary analysis demonstrated that AID offspring exposed to anti-TNF-α was not associated with an increased risk of infection when compared with AID offspring unexposed to anti-TNF-α (RR=1.1; 95% CI, 0.86-1.4). CONCLUSION: Our results suggest that in utero exposure to anti-TNF-α does not appear to increase the risk of infection during the first year of life in the offspring; however, AID itself was associated with a marked excess risk of infection in the children.

Clinical Significance of Hemostatic Parameters in the Prediction for Type 2 Diabetes Mellitus and Diabetic Nephropathy.

It would be important to predict type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). This study was aimed at evaluating the predicting significance of hemostatic parameters for T2DM and DN. Plasma coagulation and hematologic parameters before treatment were measured in 297 T2DM patients. The risk factors and their predicting power were evaluated. T2DM patients without complications exhibited significantly different activated partial thromboplastin time (aPTT), platelet (PLT), and D-dimer (D-D) levels compared with controls (P < 0.01). Fibrinogen (FIB), PLT, and D-D increased in DN patients compared with those without complications (P < 0.001). Both aPTT and PLT were the independent risk factors for T2DM (OR: 1.320 and 1.211, P < 0.01, resp.), and FIB and PLT were the independent risk factors for DN (OR: 1.611 and 1.194, P < 0.01, resp.). The area under ROC curve (AUC) of aPTT and PLT was 0.592 and 0.647, respectively, with low sensitivity in predicting T2DM. AUC of FIB was 0.874 with high sensitivity (85%) and specificity (76%) for DN, and that of PLT was 0.564, with sensitivity (60%) and specificity (89%) based on the cutoff values of 3.15 g/L and 245 × 109/L, respectively. This study suggests that hemostatic parameters have a low predicting value for T2DM, whereas fibrinogen is a powerful predictor for DN.