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Aims Adequately and accurately identifying carbapenemase-producing Enterobacterales (CPE) is vital for selecting appropriate antimicrobial therapy and implementing effective infection control measures. This study aims to optimize the phenotypic detection method of carbapenemase for routine diagnostics in clinical microbiology laboratories. Methods and Results Carbapenemase genes in 2665 non-duplicate CRE clinical strains collected from various regions of China were confirmed through whole-genome sequencing (WGS). The carbapenemase inhibition test (CIT) was conducted and interpreted using different methods and breakpoints, then compared with the NG-Test CARBA 5 for carbapenemase detection. The diagnostic performance of the CIT method was optimal when the carbapenemase types were determined by comparing the inhibition zone diameters of the imipenem disc with 3-aminophenylboronic acid (APB) plus ethylenediaminetetraacetic acid (EDTA) to those of the imipenem disc with either APB or EDTA alone, with a breakpoint of 4 mm. The overall sensitivities of the current CIT, the modified CIT, and NG-Test CARBA 5 were 91.4%, 94.9%, and 99.9%, respectively. For detecting isolates co-producing Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBLs), the modified CIT method had higher sensitivity than the current method (70.0% vs. 53.3%), though this difference was not statistically significant (P  = 0.063). The NG-Test CARBA 5 showed excellent performance for multi-carbapenemases diagnosis, with sensitivity and specificity of 97.1% and 100%, respectively. Conclusions Optimizing and standardizing the CIT method for clinical use is necessary. It has certain advantages in diagnosing multi-carbapenemase and rare carbapenemase production. However, for identifying common carbapenemase types, the NG-Test CARBA 5 demonstrated superior performance. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance poses a significant threat to global public health, especially for Enterobacterales. In this study, we investigated the distribution and antimicrobial resistance of Enterobacterales in children in the China Antimicrobial Surveillance Network (CHINET) in 2015–2021. In total, 81,681 strains isolated from children were collected in this period, accounting for 50.1% of Gram-negative organisms. The most frequently isolated Enterobacterales were Escherichia coli, Klebsiella spp., Salmonella spp., and Enterobacter spp. The main sources of the isolates were urine and the respiratory tract, accounting for 29.3% and 27.7% of isolates, respectively. The proportions of E. coli, Klebsiella pneumoniae, and Proteus mirabilis expressing extended-spectrum β-lactamase were 48.8%–57.6%, 49.3%–66.7%, and 23.1%–33.8%, respectively. The prevalence of carbapenem-resistant Enterobacterales was 5.7%–9.5%, which showed a decreasing trend from 2015 to 2021. The detection rates of carbapenem-resistant Klebsiella spp., carbapenem-resistant Enterobacter spp., and carbapenem-resistant E. coli were 14.1%–22.6%, 7.1%–15.7% and 2.0%–3.4%, respectively. In Enterobacterales, the resistance rates to ciprofloxacin were higher than to levofloxacin. However, the Enterobacterales strains were highly susceptible to amikacin, polymyxin B, and tigecycline. The resistance rate of Salmonella spp. to ampicillin was > 70%, whereas their resistance rate to ceftriaxone was < 30%. These findings indicate that the resistant rates of some Enterobacterales isolates in children to common antimicrobial agents show decreasing trends. Continuous monitoring of bacterial resistance should be strengthened to prevent and control the spread of drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Colonoscopy is the primary method to prevent CRC. However, traditional polyp detection methods face problems such as low image resolution and the possibility of missing polyps. In recent years, deep learning techniques have been extensively employed in the detection of colorectal polyps. However, these algorithms have not yet addressed the issue of detection in low-resolution images. In this study, we propose a novel YOLO-SRPD model by integrating SRGAN and YOLO to address the issue of low-resolution colonoscopy images. Firstly, the SRGAN with integrated ACmix is used to convert low-resolution images to high-resolution images. The generated high-resolution images are then used as the training set for polyp detection. Then, the C3_Res2Net is integrated into the YOLOv5 backbone to enhance multiscale feature extraction. Finally, CBAM modules are added before the prediction head to enhance attention to polyp information. The experimental results indicate that YOLO-SRPD achieves a mean average precision (mAP) of 94.2% and a precision of 95.2%. Compared to the original model (YOLOv5), the average accuracy increased by 1.8% and the recall rate increased by 5.6%. These experimental results confirm that YOLO-SRPD can address the low-resolution problem during colorectal polyp detection and exhibit exceptional robustness. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) are common urological diseases that easily relapse and have led to an increasing economic and health burdens. The China Antimicrobial Surveillance Network (CHINET) system is one of the most influential antimicrobial resistance surveillance networks in China. This study analyzed antimicrobial resistance and distribution trends of uropathogens from 2015 to 2021 using the CHINET system. A total of 261,893 non-duplicate strains were collected; Gram-positive bacteria accounted for 23.8% while Gram-negative bacteria accounted for 76.2%. Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, and Enterococcus faecalis were the most common species. The resistance to vancomycin, linezolid, and teicoplanin in E. faecalis and E. faecium was less than 3%. The prevalence of carbapenem-resistant strains of E. coli, K. pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii was 1.7%, 18.5%, 16.4%, and 40.3%, respectively. The prevalence of carbapenem-resistant A. baumannii increased from 27.6% in 2015 to 43.4% in 2021. The prevalence of methicillin-resistant Staphylococcus aureus decreased from 40.6% in 2015 to 22.9% in 2021. The resistance rates to most β-lactam antimicrobials, aminoglycosides and fluoroquinolones in E. coli, K. pneumoniae, P. aeruginosa and A. baumannii isolated from ICU inpatients were significantly higher than in those isolated from outpatients and non-ICU inpatients. This study indicates that E. coli, Enterococcus, and K. pneumoniae were the most commonly isolated uropathogens in China. The bacterial species isolated and their antimicrobial resistance patterns differed in different patient populations. More attention must be paid uropathogen resistance surveillance to provide data for the rational use of antimicrobial agents. [ABSTRACT FROM AUTHOR]

Accurate prediction of blood glucose levels is essential for type 1 diabetes optimizing insulin therapy and minimizing complications in patients with type 1 diabetes. Using ensemble learning algorithms is a promising approach. In this regard, this study proposes an improved stacking ensemble learning algorithm for predicting blood glucose level, in which three improved long short-term memory network models are used as the base model, and an improved nearest neighbor propagation clustering algorithm is adaptively weighted to this ensemble model. The OhioT1DM dataset is used to train and evaluate the performance of the proposed model. This study evaluated the performance of the proposed model using the Root Mean Square Error (RMSE), Mean Absolute Error (MAE), and Matthews Correlation Coefficient (MCC) as the evaluation metrics. The experimental results demonstrate that the proposed model achieves an RMSE of 1.425 mg/dL, MAE of 0.721 mg/dL, and MCC of 0.982 mg/dL for a 30-minute prediction horizon(PH), RMSE of 3.212 mg/dL, MAE of 1.605 mg/dL, and MCC of 0.950 mg/dL for a 45-minute PH; and RMSE of 6.346 mg/dL, MAE of 3.232 mg/dL, and MCC of 0.930 mg/dL for a 60-minute PH. Compared with the best non-ensemble model StackLSTM, the RMSE and MAE were improved by up to 27.92% and 65.32%, respectively. Clarke Error Grid Analysis and critical difference diagram revealed that the model errors were within 10%. The model proposed in this study exhibits state-of-the-art predictive performance, making it suitable for clinical decision-making and of significant importance for the effective treatment of diabetes in patients. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Salmonella has recently aroused increasing attention. In this study, a total of four sequence type 36 Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) isolates were consecutively isolated from an 11-month-old female patient with a gastrointestinal infection, of which one was sensitive to carbapenems and three were resistant to carbapenems. Via antibiotic susceptibility testing, a carbapenemases screening test, plasmid conjugation experiments, Illumina short-reads, and PacBio HiFi sequencing, we found that all four S. Typhimurium isolates contained a blaCTX-M-14-positive IncI1 plasmid. One carbapenem-sensitive S. Typhimurium isolate then obtained an IncHI2 plasmid carrying blaNDM-1 and an IncP plasmid without any resistance genes during the disease progression. The blaNDM-1 gene was located on a new 30 kb multiple drug resistance region, which is flanked by IS26 and TnAs2, respectively. In addition, the ST_F0903R isolate contained eight tandem copies of the ISCR1 unit (ISCR1-dsbD-trpF-ble-blaNDM-1-ISAba125Δ1), but an increase in MICs to carbapenems was not observed. Our work further provided evidence of the rapid spread and amplification of blaNDM-1 through plasmid. Prompting the recognition of carbapenem-resistant Enterobacterales and the initiation of appropriate infection control measures are essential to avoid the spread of these organisms. [ABSTRACT FROM AUTHOR]

The tractor is the primary power device of the agricultural production process. For the problem that the traditional electro-hydraulic hitch control method for tractors cannot simultaneously meet the requirements of maintaining a constant ploughing depth and improving traction performance and electric tractor overall efficiency, this paper proposes a hydraulic cylinder pressure control method of the electro-hydraulic hitch system for electric tractors. We establish a tractor-implement system dynamic model, calculate the rear axle load of the tractor in real-time according to the actual working parameters under the premise of ensuring the constant ploughing depth, construct a traction performance objective optimization function, and use the genetic algorithm to solve the optimal hydraulic cylinder pressure value of the electro-hydraulic hitch system. Hardware-in-the-loop (HIL) simulation results show that the electric tractor under the traditional position control method and the hydraulic cylinder pressure control method has an average wheel slip of 18.50% and 16.93%, an average traction efficiency of 71.35% and 73.08%, and an average overall efficiency of 50.81% and 52.40%. The hydraulic cylinder pressure control method proposed in this paper reduces the wheel slip by 9.27%, increases the traction efficiency by 2.42%, improves the electric tractor overall efficiency by 3.13%, and reduces the electric tractor overall energy loss by 7.67% compared with the traditional position-control method. Therefore, the hydraulic cylinder pressure control method of the electro-hydraulic hitch system proposed in this paper can achieve the purpose of effectively improving tractor traction performance and reducing tractor energy loss while maintaining a constant ploughing depth. This study offers technological references for electric tractors to improve traction performance and reduce the overall energy loss of electric tractors. [ABSTRACT FROM AUTHOR]

Objectives: To establish the epidemiological cut-off values (ECOFFs) for cefoselis against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis and Pseudomonas aeruginosa.Methods: We collected 2288 non-repetitive clinical isolates from five laboratories throughout four cities in China. The cefoselis MICs and inhibition zone diameters for all isolates were established using the broth microdilution method and the disc diffusion method following EUCAST guidelines. MIC ECOFFs were determined by visual estimation and ECOFFinder software. Zone diameter ECOFFs were set if a high correlation of MICs and inhibition zone diameters was found by Pearson correlation. Zone diameter ECOFFs were finally determined by the visual estimate method.Results: MICs of cefoselis were distributed from 0.008 to >256 mg/L for the four Enterobacterales species and from 0.25 to >256 mg/L for P. aeruginosa. MIC ECOFFs were 0.125 mg/L for E. coli, K. pneumoniae and P. mirabilis, 0.25 mg/L for E. cloacae and 32 mg/L for P. aeruginosa. A high correlation of MICs and zone diameters was observed for all Enterobacterales (|r| > 0.8, P < 0.001) and a relatively high correlation was found for P. aeruginosa (|r| = 0.71, P < 0.001). The zone diameter ECOFF was 24 mm for E. cloacae, E. coli and K. pneumoniae, 26 mm for P. mirabilis and 21 mm for P. aeruginosa.Conclusions: We determined MIC and zone diameter ECOFFs for cefoselis against four Enterobacterales species and P. aeruginosa. The establishment of ECOFFs for cefoselis provides clinicians with helpful guidance to differentiate WT and non-WT pathogens. [ABSTRACT FROM AUTHOR]

Background: Easily accessible tools that reliably stratify Mycobacterium tuberculosis (MTB) infection are needed to facilitate the improvement of clinical management. The current study attempts to reveal lymphocyte-related immune characteristics of active tuberculosis (ATB) patients and establish immunodiagnostic model for discriminating ATB from latent tuberculosis infection (LTBI) and healthy controls (HC). Methods: A total of 171 subjects consisted of 54 ATB, 57 LTBI, and 60 HC were consecutively recruited at Tongji hospital from January 2019 to January 2021. All participants were tested for lymphocyte subsets, phenotype, and function. Other examination including T-SPOT and microbiological detection for MTB were performed simultaneously. Results: Compared with LTBI and HC, ATB patients exhibited significantly lower number and function of lymphocytes including CD4+ T cells, CD8+ T cells and NK cells, and significantly higher T cell activation represented by HLA-DR and proportion of immunosuppressive cells represented by Treg. An immunodiagnostic model based on the combination of NK cell number, HLA-DR+CD3+ T cells, Treg, CD4+ T cell function, and NK cell function was built using logistic regression. Based on receiver operating characteristic curve analysis, the area under the curve (AUC) of the diagnostic model was 0.920 (95% CI, 0.867-0.973) in distinguishing ATB from LTBI, while the cut-off value of 0.676 produced a sensitivity of 81.48% (95% CI, 69.16%-89.62%) and specificity of 91.23% (95% CI, 81.06%-96.20%). Meanwhile, AUC analysis between ATB and HC according to the diagnostic model was 0.911 (95% CI, 0.855-0.967), with a sensitivity of 81.48% (95% CI, 69.16%-89.62%) and a specificity of 90.00% (95% CI, 79.85%-95.34%). Conclusions: Our study demonstrated that the immunodiagnostic model established by the combination of lymphocyte-related indicators could facilitate the status differentiation of MTB infection. [ABSTRACT FROM AUTHOR]

Background: The prompt diagnosis of pulmonary tuberculosis (PTB) remains a challenge in clinical practice. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting. Methods: 28,171 adult inpatients suspected of having PTB in China were retrospectively analyzed. Bronchoalveolar lavage fluid (BALF) and/or sputum were used for acid-fast bacilli (AFB) smear, Xpert MTB/RIF (Xpert), and culture. A positive mycobacterial culture was used as the reference standard. Peripheral blood mononuclear cells (PBMC) were used for T-SPOT. TB. We analyzed specimen types' effect on these assays' performance, determined the number of smears for diagnosing PTB, and evaluated the ability of these assays performed alone, or in combination, to diagnose PTB and nontuberculous mycobacteria (NTM) infections. Results: Sputum and BALF showed moderate to substantial consistency when they were used for AFB smear or Xpert, with a higher positive detection rate by BALF. 3-4 smears had a higher sensitivity than 1-2 smears. Moreover, simultaneous combination of AFB and Xpert correctly identified 44/51 of AFB+/Xpert+ and 6/7 of AFB+/Xpert- cases as PTB and NTM, respectively. Lastly, when combined with AFB/Xpert sequentially, T-SPOT showed limited roles in patients that were either AFB+ or Xpert+. However, T-SPOTMDC (manufacturer-defined cut-off) showed a high negative predicative value (99.1%) and suboptimal sensitivity (74.4%), and TBAg/PHA (ratio of Mycobacterium tuberculosis -specific antigens to phytohaemagglutinin spot-forming cells, which is a modified method calculating T-SPOT. TB assay results) ≥0.3 demonstrated a high specificity (95.7%) and a relatively low sensitivity (16.3%) in AFB-/Xpert- patients. Conclusions: Concurrently performing AFB smear (at least 3 smears) and Xpert on sputum and/or BALF could aid in rapid diagnosis of PTB and NTM infections in a real-world high-burden setting. If available, BALF is preferred for both AFB smear and Xpert. Expanding this algorithm, PBMC T-SPOTMDC and TBAg/PHA ratios have a supplementary role for PTB diagnosis in AFB-/Xpert- patients (moderately ruling out PTB and ruling in PTB, respectively). Our findings may also inform policy makers' decisions regarding prevention and control of TB in a high burden setting. [ABSTRACT FROM AUTHOR]

Background: To establish a risk prediction model for carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) in intestinal carriers. Methods: CRE screenings were performed every two weeks in hematology department and intensive care unit (ICU). Patients with positive CRE rectal swab screening were identified using electronic medical records from 15 May 2018 to 31 December 2019. Intestinal carriers who developed CRE BSI were compared with those who did not develop CRE infection. A 1:1 matched case-control study was conducted. The control group was selected by stratified random sampling based on the department to ensure that all the departments were represented. Univariate logistic analysis, multivariate logistic analysis and stepwise regression analysis were carried on a variety of patient factors and microbial factors. Results: A total of 42 cases were included. Multivariate analysis showed that gastrointestinal injury (OR 86.819, 95% CI 2.584– 2916.592, P=0.013), tigecycline exposure (OR 14.991, 95% CI 1.816– 123.737, P=0.012) and carbapenem resistance score (OR 11.236, 95% CI 1.811– 69.700, P=0.009) were independent risk factors for CRE BSI in intestinal carriers (P< 0.050). They were included in the Logistic regression model to predict BSI. According to receiver operating characteristic (ROC) curve analysis, the cut-off value of the model was 0.722, and the sensitivity, specificity and area under the curve (AUC) were 90.5%, 85.7% and 0.921, respectively. Conclusion: The risk prediction model based on gastrointestinal injury, tigecycline exposure and carbapenem resistance score of colonizing strain can effectively predict CRE BSI in patients with CRE colonization. Early CRE screening and detection for inpatients in key departments may promote early warning and reduce the risk of nosocomial infection of CRE. [ABSTRACT FROM AUTHOR]

Objectives: To determine the epidemiological cut-off values (ECOFFs) of norvancomycin for Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus hominis.Methods: We collected 1199 clinical isolates of Staphylococcus species from five laboratories located in four cities in China. MICs and inhibitory zone diameters of norvancomycin were determined by broth microdilution and the disc diffusion method, separately. ECOFFs of norvancomycin for four species were calculated by ECOFFinder software following EUCAST principles. Methicillin and vancomycin resistance genes (mecA/mecC and vanA/vanB/vanC/vanD/vanE) were screened for by PCR in all isolates. Pearson correlation and χ2 test were used to calculate the correlation of MICs and inhibition zone diameters, and MICs and resistance genes, respectively.Results: MICs of norvancomycin for all strains from five laboratories fell in the range of 0.12-2 mg/L. ECOFFs of norvancomycin were determined to be 2 mg/L for S. epidermidis and S. haemolyticus and 1 mg/L for S. aureus and S. hominis. A weak correlation was observed between MIC values and zone diameters for S. haemolyticus (r = -0.36) and S. hominis (r = -0.26), while no correlation was found for S. epidermidis and S. aureus. The mecA gene was detected in 63.1% of Staphylococcus, whereas no isolate carried mecC, vanA, vanB, vanC, vanD or vanE. ECOFFs of norvancomycin were not correlated with mecA gene carriage in Staphylococcus species.Conclusions: ECOFFs of norvancomycin for four Staphylococcus species were determined, which will be helpful to differentiate WT strains. The correlation of MICs and zone diameters of norvancomycin was weak in Staphylococcus species. [ABSTRACT FROM AUTHOR]

Background: Acute diarrhea is a leading cause of morbidity and mortality in children, particularly in those under the age of 5 years. Rotavirus is recognized as the leading cause of acute diarrhea in children, however, the contribution of bacterial pathogens as causative agents varies throughout the world. Here we report a hospital-based prospective study to analyze the characteristics of bacterial pathogens associated with acute diarrhea in children under 5 years of age.Methods: Stool samples were collected from 508 patients with acute diarrhea under 5 years of age who presented at our hospital. Nine pathogens were isolated and identified by culturing, serology or PCR, these included Salmonella spp., Shigella spp., Vibrio cholerae, diarrheagenic Escherichia coli (DEC), Aeromonas spp., Plesiomonas spp., Vibrio parahaemolyticus, Campylobacter spp. and Yersinia enterocolitica. Antimicrobial sensitivity tests of these pathogens were conducted. The most commonly detected pathogen, Salmonella spp., was further investigated by PCR and sequencing of antibiotic resistance-related genes.Results: Pathogens were identified in 20.1 % of the 508 samples. The most commonly detected pathogens were Salmonella spp. (8.5 %), followed by DEC (4.7 %), Campylobacter jejuni (3.0 %) and Aeromonas spp. (2.0 %). The resistance rates to ampicillin and tetracycline in Salmonella spp. were >60 %, but were <30 % to cephalosporins and quinolones. More than 50 % of DEC strains displayed resistance to ampicillin, cefotaxime and tetracycline, and 60 % of C. jejuni strains were resistant to ciprofloxacin but highly sensitive to the other antibiotics. Among 12 cephalosporin-resistant Salmonella isolates, TEM-1 and CTX-M-14 determinants were present in two (16.7 %) isolates. PCR screening for plasmid-mediated quinolone resistance genes revealed gyrA mutations in one of three highly quinolone resistant isolates.Conclusions: Salmonella spp., DEC, Campylobacter spp. and Aeromonas spp. were the most commonly detected bacterial pathogens in children under the age of 5 years with acute diarrhea. Our findings indicate that ampicillin and tetracycline are not suitable as first line therapeutic drugs against Salmonella spp. Resistance to third generation cephalosporins and quinolones was also detected. TEM-1 and CTX-M-14 genetic determinants, and gyrA mutations, were the major mechanisms associated with high levels of cephalosporin and quinolone resistance, respectively, in Salmonella isolates. [ABSTRACT FROM AUTHOR]

Aims: To describe the identification of two carbapenem-resistant, NDM-1 and IMP-4, carbapenemases coproducing Enterobacteriaceae isolates recovered from hospitalized patients in China. Both Klebsiella pneumoniae clinical isolates ( Kpn922 and Kpn9599) were resistant to meropenem and imipenem and were subjected to additional antibiotic susceptibility testing. Polymerase chain reaction (PCR) and sequence analyses were used to characterize bacterial carbapenemase resistance genes, extended-spectrum β-lactamases, plasmid-mediated AmpC enzymes, quinolone resistance, and 16s RNA methylase. Genetic relatedness was determined using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Plasmids were analyzed by S1-PFGE and Southern blot. Results: PCR analyses revealed that the Kpn922 isolate carried blaNDM-1, blaIMP-4, blaTEM-1, and blaSHV-1 genes, while Kpn9599 carried blaNDM-1, blaIMP-4, blaTEM-1, and blaSHV-12 genes. MLST determined that the two isolates were ST1043 and ST571 sequence types. Southern blot analyses revealed that metallo-β-lactamase genes were plasmid borne in both isolates. Plasmids ∼300 kb simultaneously carried blaNDM-1 and blaIMP-4. Conclusions: Coexistence of blaNDM-1 and blaIMP-4 in these clinical isolates may herald the emergence of a new pattern of drug resistance. Surveillance of carbapenemases, particularly metallo-β-lactamases, in Enterobacteriaceae is urgently needed to control and prevent the spread of these resistance determinants in China. [ABSTRACT FROM AUTHOR]

Abstract: For providing the government with effective monitoring of the trends of the economic variables in the future and good reference for developing a reasonable policy, in this paper, we establish a time series model on China''s Foreign Direct Investment (FDI) by using wavelet analysis and intervention analysis and time series analysis and predict the trend of FDI in the next several years. This model eliminates the interference of noise for predicting by using wavelet analysis, and describes the autocorrelation and time-varying volatility of the financial time series by using ARIMA- GARCH-M model. The simulation results show that this model explains the dynamic structure of China''s FDI trends well. [Copyright &y& Elsevier]

Salmonella is a pathogenic bacterium contributing to food poisoning and acute infectious intestinal disease. The traditional standard detection method is based on the principle of liquid phase enrichment and has a low sensitivity on targeted bacteria. We previously developed a visual immunosensor technique for efficient detection and isolation of Salmonella by applying fluorescent nanobioprobes on a specially-designed cellulose-based swab. In this study, a whole-sample solid-phase enrichment assay (WSEA) was established by optimization of the enrichment medium using response surface methodology (RSM), a powerful statistical tool for regression analysis. The optimal formula was determined as: 0.60% polyvalent poly peptone, 0.40% buffered peptone water, 0.09% ferric citrate amine, 0.24% sodium hyposulfite, 0.035% cystine, 0.01 µg mL−1 super absorbing polymer, 0.011% sodium deoxycholate, 15.00 µg mL−1 ethyl green and 30.00 µg mL−1 sodium selenite. Using this formula, Salmonella was visualized with naked eyes by relying on the indication of black spots formed on the swab. The analytic sensitivity of the assay was determined as 101 cells mL−1 with a concentration of interfering bacteria (Escherichia coli) at 105 cells mL−1. This optimized formula was confirmed with 4006 patients' fecal samples, in which the positive rate was 0.42% by the conventional culture-based method and 2.12% by WSEA. The optimized formulation on solid phase enrichment by RSM allows relatively quick, low-cost, and large-scale detection of Salmonella, and could be used in grassroots medical institutions. [ABSTRACT FROM AUTHOR]

Bloodstream infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) is a severe and challenging complication in the early post-transplantation period. Pulmonary infection secondary to sepsis caused by CRKP has been reported only rarely in kidney transplant recipients. Here we report an interesting and complicated case in which CRKP was initially isolated in a culture of renal graft preservation solution, yet was not detected in the daily cultures from collection of surgical drainage. Prophylactic tigecycline was terminated at post-transplantation day 10 because of the occurrence of acute pancreatitis. Five days later, the patient suddenly developed a multisite infection with CRKP involving the bloodstream, urinary tract, and lungs, indicating probable transmission from the donor. Fortunately, the infection was controlled quickly and effectively with a combination therapy consisting of ceftazidime-avibactam (CZA) and carbapenem, which was suggested by the results of disc diffusion susceptibility testing. However, the CRKP infection reappeared in the bloodstream and urinary tract soon after the treatment of acute rejection. The combination regimen was continued for another 15 days, and the patient ultimately recovered. During the following 15 months of observation, the patient's renal graft function remained stable, without recurrence of the CRKP infection. In conclusion, the combined use of CZA and carbapenem was safe and produced an optimal therapeutic effect on the severe multisite infection caused by CRKP in a renal transplant recipient, thus providing a reference case for treating such patients. [ABSTRACT FROM AUTHOR]

Summary Background With the abuse of antibiotics, the methicillin-resistant Staphylococcus aureus (MRSA) strain became prevalent. Furthermore, Staphylococcus aureus with a character of vancomycin intermediate-resistance (VISA) has been found globally since the first report in Japan. The main objectives of this study were to report a case of VISA isolated from a Chinese patient who had never undergone Vancomycin treatment, and to determine its molecular character. Methods A total of 9 strains were recovered from a patient during the therapeutic process. Antimicrobial susceptibility testing was performed to determine their antibiotic susceptibility patterns. To detect the VISA strain's molecular epidemiological features, growth and morphological characters, we used multilocus sequence typing, autolysis assay and transmission electric microscope tests. Pulsed-field gel electrophoresis (PFGE) was performed to characterize the heterogeneities of all isolates. Results One isolate was found to exhibit vancomycin intermediated-resistant with MIC of 8 μg/ml. It was ST239-T030-agr-1, had thickened cell wall, and displayed a slower growth rate and reduced susceptibility to Triton X-100-induced autolysis than other strains. All 9 strains exhibited the same PFGE pattern. Conclusion This is the first report of VISA found in central China from a patient who had never received vancomycin treatment. [ABSTRACT FROM AUTHOR]

Background: In China, there have been instances of sudden cardiac death among university students, with a significant number of students being at risk of cardiovascular diseases. This risk is often attributed to sub-health conditions such as weight gain and obesity, which are triggered by sedentary lifestyles, irregular living habits, and unregulated diets. Therefore, it is crucial to enhance the guidance for participation in physical activities, encouraging students to actively reduce their risk of cardiovascular diseases (CVD). Jogging, characterized by its convenience, simplicity, and low-risk participation, has been widely accepted by university students. This study takes the impact of jogging on the cardiovascular function of university students as a starting point. It aims to explore the content of the changing process suitable for the development of cardiovascular function in university students. The ultimate goal is to promote the healthy development of the cardiovascular system function in university students and improve their adherence to physical activities., Methods: The study recruited 60 university students with no exercise habits through on-campus poster advertisements. These 60 participants were randomly divided into two groups. The students in the experimental group were required to jog no less than three times a week, with each session lasting at least 30 minutes. The organizers of the experiment would remind the students daily in a WeChat group to complete their weekly exercise plan and persist in jogging, promoting the benefits of this activity. During jogging, the students used the Keep mobile application to record their jogging time and heart rate, which they then uploaded to the WeChat group. Follow-ups were conducted with students who did not complete their exercise plan, providing encouragement and guidance to continue participating in the experiment. The study employed a comparative research approach between the experimental group and the control group., Results: According to the experimental protocol, after 12 weeks of jogging intervention, the cardiovascular health indicators of both male and female students in the experimental group showed positive changes. Measurements of cardiac function indicators in the experimental group of boys SPTI, DPTI, ED has decreased, SEVR has increased, the relevant indicators compared with the relevant indicators of the control group (P < .05) is significant; in the experimental group of girls, SPTI, DPTI, SEVR indicators decreased, ED increased, and compared with the relevant indicators of the control group (P < .01) has a very significant significance. Changes in vascular indicators in the experimental and control groups after the experiment, SBP, DBP, PP, CAP decreased in the experimental group, and DBP, CAP in the male and female groups were found to be (P < .01), with highly significant changes; while SBP, PP intergroup comparison (P < .05), with significant changes., Conclusion: Jogging is a good aerobic exercise program characterized by convenient ways of carrying out simple methods and low risk of participation. The benefits of jogging are not only reflected physiologically but also psychologically; it can make participants enhance their self-confidence and make their moods more pleasant. It can also improve sleep quality and maintain a good mental state. Long-term jogging habits can effectively improve endothelial function and heart contraction function, reduce blood pressure effectively prevent atherosclerosis and prevent CVD by reducing the incidence of CVD risk factors.

Carbapenem-resistant Salmonella has recently aroused increasing attention. In this study, a total of four sequence type 36 Salmonella enterica subsp. enterica serovar Typhimurium ( S. Typhimurium) isolates were consecutively isolated from an 11-month-old female patient with a gastrointestinal infection, of which one was sensitive to carbapenems and three were resistant to carbapenems. Via antibiotic susceptibility testing, a carbapenemases screening test, plasmid conjugation experiments, Illumina short-reads, and PacBio HiFi sequencing, we found that all four S. Typhimurium isolates contained a bla CTX-M-14 -positive IncI1 plasmid. One carbapenem-sensitive S. Typhimurium isolate then obtained an IncHI2 plasmid carrying bla NDM-1 and an IncP plasmid without any resistance genes during the disease progression. The bla NDM-1 gene was located on a new 30 kb multiple drug resistance region, which is flanked by IS 26 and TnAs2, respectively. In addition, the ST&#95;F0903R isolate contained eight tandem copies of the IS CR1 unit (IS CR1 - dsbD - trpF - ble - bla NDM-1 -IS Aba125 Δ1), but an increase in MICs to carbapenems was not observed. Our work further provided evidence of the rapid spread and amplification of bla NDM-1 through plasmid. Prompting the recognition of carbapenem-resistant Enterobacterales and the initiation of appropriate infection control measures are essential to avoid the spread of these organisms.

Background: Bloodstream infections (BSIs), especially hospital-acquired BSIs, are a major cause of morbidity and mortality. However, the details about the pathogens and antimicrobial resistance profile of BSIs across China are still lacking., Methods: An investigation was conducted in 10 large teaching hospitals from seven geographic regions across China in 2016 based on China Antimicrobial Surveillance Network (CHINET) to profile the clinical and etiological features of BSIs., Results: A total of 2,773 cases of BSIs were identified, a majority (97.3%) of which were monomicrobial. Overall, 38.4% (1,065/2,773) were community-acquired BSIs (CABSIs), and 61.6% (1,708/2,773) were hospital-acquired BSIs (HABSIs). Of the 2,861 pathogenic BSI isolates, 67.5% were Gram-negative bacteria, 29.6% were Gram-positive bacteria, and 2.9% were fungi. The top BSI pathogens were Escherichia coli , Klebsiella pneumoniae , coagulase-negative Staphylococci (CNS), Staphylococcus aureus , Enterococci , and Acinetobacter baumannii . Escherichia coli and K. pneumoniae isolates showed low susceptibility to penicillins, cephalosporins (except ceftazidime and cefepime), and ampicillin-sulbactam (13.1%-43.4% susceptible); moderate susceptibility (about 60% susceptible) to ceftazidime, cefepime, and aztreonam; and high susceptibility (>90%) to β-lactam/β-lactamase inhibitor combinations other than ampicillin-sulbactam, except K. pneumoniae strains to piperacillin-tazobactam (59.2% susceptible). HABSIs were associated with significantly higher prevalence of carbapenem-resistant and extended-spectrum β-lactamases-producing K. pneumoniae , methicillin-resistant S. aureus , methicillin-resistant CNS, and ampicillin-resistant Enterococci than CABSIs. Overall, 42.0% of the BSI due to S. aureus strains were resistant to methicillin., Conclusions: The findings about BSIs in teaching hospitals across China add more scientific evidence to inform the appropriate management of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor YWT declared a past co-authorship with the authors FH and YY., (Copyright © 2022 Hu, Yuan, Yang, Xu, Huang, Hu, Ai, Zhuo, Su, Shan, Du, Yu, Lin, Sun, Chen, Xu, Zhang, Wang, He, Ni, Zhang, Lin, Zhu and Zhang.)

Cefiderocol is a novel siderophore cephalosporin exhibiting potent antimicrobial activities. Although cefiderocol has not been approved in China, resistance is emerging. A multicenter study was performed to evaluate the cefiderocol resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP) strains from bloodstream infections in patients with hematologic malignancies in China. Clinical data analysis and whole-genome sequencing were conducted for collected cefiderocol-resistant CRKP strains. CRISPR-Cas9 system was employed to construct site-specific mutagenesis for gene cirA . Plasmid curing and cloning were performed to assess the effect of β-lactamases on cefiderocol resistance. Total 86 CRKP strains were collected. The MICs of cefiderocol ranged from 0.06 to >256 mg/L. Among four cefiderocol-nonsusceptible strains (4/86, 4.7%), two cefiderocol-resistant strains AR8538 (MIC = 32 mg/L) and AR8416 (MIC > 256 mg/L) were isolated from two patients with acute lymphocytic leukemia (frequency of resistance, 2/86, 2.3%). Metallo- and serine-β-lactamase inhibitors addition would decrease the MIC of cefiderocol from 32 to 1 mg/L in AR8538, which harbors bla SHV-12 , bla DHA-1 , and two copies of bla NDM-1 in different plasmids. Avibactam did not impact cefiderocol susceptibility of AR8416, which produces NDM-5. However, we found a deficient CirA in AR8416. Using the same K serotype strain D3, we proved CirA deficiency or carrying NDM individually reduced cefiderocol susceptibility, but their simultaneously existence rendered a high-level cefiderocol resistance. In summary, the resistance of CRKP against cefiderocol is mediated by multiple factors, including the deficiency of CirA, metallo- or serine-β-lactamases, while a high-level cefiderocol resistance could be rendered by the combined effect of NDM expression and CirA deficiency. IMPORTANCE Cefiderocol-resistant CRKP strains are emerging in bloodstream infections in Chinese patients with hematologic malignancies, although cefiderocol has not been approved for clinical use in China. Our study proved that the resistance of CRKP against cefiderocol is mediated by multiple factors, including the deficiency of CirA, metallo- or serine-β-lactamases, while a high-level cefiderocol resistance could be rendered by the combined effect of NDM expression and CirA deficiency. As NDM production is one of the most critical mechanisms resulting in carbapenem resistance, it would pose great challenges on the clinical efficacy of cefiderocol in future.

Klebsiella pneumoniae carbapenemase (KPC)-producing Pseudomonas aeruginosa (KPC-PA) has been reported sporadically. However, epidemiological and antimicrobial susceptibility data specific for KPC-PA are lacking. We collected 374 carbapenem-resistant P. aeruginosa (CRPA) isolates from seven hospitals in China from June 2016 to February 2019 and identified the bla KPC-2 gene in 40.4% ( n  = 151/374) of the isolates. Approximately one-half of all KPC-PA isolates ( n  = 76/151; 50.3%) were resistant to ceftazidime-avibactam (CAZ-AVI). Combining Kraken2 taxonomy identification and Nanopore sequencing, we identified eight plasmid types, five of which carried bla KPC-2 , and 13 combination patterns of these plasmid types. In addition, we identified IS 26 -ΔTn 6296 and Tn 1403 -like-ΔTn 6296 as the two mobile genetic elements that mediated bla KPC-2 transmission. bla KPC-2 plasmid curing in 28 strains restored CAZ-AVI susceptibility, suggesting that bla KPC-2 was the mediator of CAZ-AVI resistance. Furthermore, the bla KPC-2 copy number was found to correlate with KPC expression and, therefore, CAZ-AVI resistance. Taken together, our results suggest that KPC-PA is becoming a clinical threat and that using CAZ-AVI to treat this specific pathogen should be done with caution. IMPORTANCE Previous research has reported several cases of KPC-PA strains and three KPC-encoding P. aeruginosa plasmid types in China. However, the prevalence and clinical significance of KPC-PA are not available. In addition, the susceptibility of the strains to CAZ-AVI remains unknown. Samples in this study were collected from seven tertiary hospitals prior to CAZ-AVI clinical approval in China. Therefore, our results represent a retrospective study establishing the baseline efficacy of the novel β-lactam/β-lactamase combination agent for treating KPC-PA infections. The observed correlation between the bla KPC copy number and CAZ-AVI resistance suggests that close monitoring of the susceptibility of the strain during treatment is required. It would also be beneficial to screen for the bla KPC gene in CRPA strains for antimicrobial surveillance purposes.

Objectives: The aim of this study was to characterise carbapenem-resistant Klebsiella pneumoniae isolates recovered from neonatal clinical specimens over a 4-month period., Methods: Seven carbapenem-resistant K. pneumoniae isolates were analysed. Antibiotic susceptibilities of the isolates were determined by the agar dilution method, and the drug resistance genes were evaluated by PCR. Clonal relatedness of the isolates was assessed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Conjugation experiments and Southern blot hybridisation were performed to determine the transferability of the plasmids., Results: All of the K. pneumoniae isolates carried the bla NDM-1 gene but were negative for all other carbapenemases tested. All of the isolates harboured bla SHV-12 , and five isolates also carried bla CTX-M-15 and/or bla TEM-1 . All of the isolates exhibited multidrug resistance. The isolates belonged to sequence types ST1419 and ST101 and formed three different PFGE patterns. Plasmids carrying bla NDM-1 were successfully transferred from six of the seven isolates to the Escherichia coli recipient. These six NDM-1-producing K. pneumoniae were clonal and carried bla NDM-1 on the same plasmid, but one isolate possibly carried chromosomal bla NDM-1 ., Conclusions: This is the first report of NDM-1-positive K. pneumoniae ST1419 from neonates in China. Closer attention should be paid to monitoring bla NDM-1 gene dissemination because it is potentially transferred horizontally., (Copyright © 2017. Published by Elsevier Ltd.)

Background: The spread of resistance to carbapenems among Enterobacteriaceae has become a major public health problem in recent years. In this study, we describe an outbreak of Klebsiella pneumoniae in the neonatal ward. First, we aimed to study the drug resistance, genetic relatedness, and transmission mechanism of carbapenem-resistant K. pneumoniae; second, we implemented infection control measures to contain the outbreak., Methods: We investigated 27 non-repetitive strains isolated from neonates and five strains cultured from around the neonatal ward. Polymerase chain reaction (PCR), the agar dilution method, and multilocus sequence typing (MLST) were used to analyze the resistance gene(s), antimicrobial susceptibility, and homology, respectively. Health-care personnel education, hand hygiene, outer gown changing, and infected patient isolation were strictly enforced., Results: Our antimicrobial susceptibility results show that all strains were multidrug-resistant. MLST and PCR results revealed that, in this study, all of the KPC-2-producing strains are Sequence Type (ST) 11 (ST11) (n = 22) and all of the NDM-1-producing strains are ST20 (n = 4) or ST888 (n = 1). The environmental strains were identified as KPC-2-positive K. pneumoniae ST11 (n = 3) and NDM-1-positive K. pneumoniae ST20 (n = 2). The percentages of isolates with the extended-spectrum-β-lactamases CTX-M-15, blaCTX-M-14, blaTEM-1 were 9.4, 84.3, and 68.8 %, respectively. AmpC β-lactamase genes were not detected in our isolates., Conclusions: KPC-2-positive K. pneumoniae ST11 and NDM-1-positive K. pneumoniae ST20 were associated with this outbreak. The identification of these isolates in samples from radiant warmers and nurses suggests that hospital cross-transmission played a role in this outbreak. Active infection control measures were effective for controlling this multidrug-resistant K. pneumoniae outbreak.

Background: Acute diarrhea is a leading cause of morbidity and mortality in children, particularly in those under the age of 5 years. Rotavirus is recognized as the leading cause of acute diarrhea in children, however, the contribution of bacterial pathogens as causative agents varies throughout the world. Here we report a hospital-based prospective study to analyze the characteristics of bacterial pathogens associated with acute diarrhea in children under 5 years of age., Methods: Stool samples were collected from 508 patients with acute diarrhea under 5 years of age who presented at our hospital. Nine pathogens were isolated and identified by culturing, serology or PCR, these included Salmonella spp., Shigella spp., Vibrio cholerae, diarrheagenic Escherichia coli (DEC), Aeromonas spp., Plesiomonas spp., Vibrio parahaemolyticus, Campylobacter spp. and Yersinia enterocolitica. Antimicrobial sensitivity tests of these pathogens were conducted. The most commonly detected pathogen, Salmonella spp., was further investigated by PCR and sequencing of antibiotic resistance-related genes., Results: Pathogens were identified in 20.1 % of the 508 samples. The most commonly detected pathogens were Salmonella spp. (8.5 %), followed by DEC (4.7 %), Campylobacter jejuni (3.0 %) and Aeromonas spp. (2.0 %). The resistance rates to ampicillin and tetracycline in Salmonella spp. were >60 %, but were <30 % to cephalosporins and quinolones. More than 50 % of DEC strains displayed resistance to ampicillin, cefotaxime and tetracycline, and 60 % of C. jejuni strains were resistant to ciprofloxacin but highly sensitive to the other antibiotics. Among 12 cephalosporin-resistant Salmonella isolates, TEM-1 and CTX-M-14 determinants were present in two (16.7 %) isolates. PCR screening for plasmid-mediated quinolone resistance genes revealed gyrA mutations in one of three highly quinolone resistant isolates., Conclusions: Salmonella spp., DEC, Campylobacter spp. and Aeromonas spp. were the most commonly detected bacterial pathogens in children under the age of 5 years with acute diarrhea. Our findings indicate that ampicillin and tetracycline are not suitable as first line therapeutic drugs against Salmonella spp. Resistance to third generation cephalosporins and quinolones was also detected. TEM-1 and CTX-M-14 genetic determinants, and gyrA mutations, were the major mechanisms associated with high levels of cephalosporin and quinolone resistance, respectively, in Salmonella isolates.

Aims: To describe the identification of two carbapenem-resistant, NDM-1 and IMP-4, carbapenemases coproducing Enterobacteriaceae isolates recovered from hospitalized patients in China. Both Klebsiella pneumoniae clinical isolates (Kpn922 and Kpn9599) were resistant to meropenem and imipenem and were subjected to additional antibiotic susceptibility testing. Polymerase chain reaction (PCR) and sequence analyses were used to characterize bacterial carbapenemase resistance genes, extended-spectrum β-lactamases, plasmid-mediated AmpC enzymes, quinolone resistance, and 16s RNA methylase. Genetic relatedness was determined using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Plasmids were analyzed by S1-PFGE and Southern blot., Results: PCR analyses revealed that the Kpn922 isolate carried blaNDM-1, blaIMP-4, blaTEM-1, and blaSHV-1 genes, while Kpn9599 carried blaNDM-1, blaIMP-4, blaTEM-1, and blaSHV-12 genes. MLST determined that the two isolates were ST1043 and ST571 sequence types. Southern blot analyses revealed that metallo-β-lactamase genes were plasmid borne in both isolates. Plasmids ∼300 kb simultaneously carried blaNDM-1 and blaIMP-4., Conclusions: Coexistence of blaNDM-1 and blaIMP-4 in these clinical isolates may herald the emergence of a new pattern of drug resistance. Surveillance of carbapenemases, particularly metallo-β-lactamases, in Enterobacteriaceae is urgently needed to control and prevent the spread of these resistance determinants in China.

The vanC₁ gene, which is chromosomally located, confers resistance to vancomycin and serves as a species marker for Enterococcus gallinarum. Enterococcus faecium TJ4031 was isolated from a blood culture and harbours the vanC₁gene. Polymerase chain reaction (PCR) assays were performed to detect vanXYc and vanTc genes. Only the vanXYc gene was found in the E. faecium TJ4031 isolate. The minimum inhibitory concentrations of vancomycin and teicoplanin were 2 µg/mL and 1 µg/mL, respectively. Real-time reverse transcription-PCR results revealed that the vanC₁ and vanXYc genes were not expressed. Pulsed-field gel electrophoresis and southern hybridisation results showed that the vanC₁ gene was encoded in the chromosome. E. faecalis isolated from animals has been reported to harbour vanC₁gene. However, this study is the first to report the presence of the vanC₁gene in E. faecium of human origin. Additionally, our research showed the vanC₁gene cannot serve as a species-specific gene of E. gallinarum and that it is able to be transferred between bacteria. Although the resistance marker is not expressed in the strain, our results showed that E. faecium could acquire the vanC₁gene from different species.