Anemia in Heart Failure: A Perspective from 20-Year Bibliometric Analysis.

Background & Objective: Anemia in patients with heart failure (HF) is a growing concern. However, there has no bibliometric analysis in this area up to now. The aim of this study is to explore the status and trends in the field of anemia in HF through the bibliometric analysis, and to provide an outlook on future research. Methods: We retrieved publications from the Web of Science Core Collection database, and the following data analysis and visualization tools were utilized to perform data processing, statistical computing and graphics generation: VOSviewer (v.1.6.18), CiteSpace (v.6.2 R5), Scimago Graphica (v.1.0.36), Biblimatrix and Microsoft Excel. Results: We identified a total of 3490 publications from 2004 to 2023. The publications in the field of anemia in HF are growing steadily. The United States, the United Kingdom, and Italy were the leading countries in this area. Stefan D Anker, as the most influential author, held the most total citations and publications. Harvard University was the most productive institution in this area. The European Journal of Heart Failure had published the most papers. Through the analysis of co-citations, 14 major clusters based on cluster labels were identified. Keyword analysis showed that mortality, outcome, prevalence, and risk were the most frequent keywords, and the potential research hotspots in the future will be intravenous iron and iron deficiency. Conclusion: This study provides a comprehensive analysis of countries, authors, institutions, journals, co-cited references, and keywords in the field of anemia in HF through bibliometric analysis and data visualization. The status, hotspots and future trends in this field offer a reference for in-depth research. Further studies are necessary in the future to broaden the spectrum of research in this field, to evaluate comprehensive approaches to treating anemia in patients with HF, and to find rational targets for the management of anemia.

Effect of ceftazidime-avibactam combined with different antimicrobials against carbapenem-resistant Klebsiella pneumoniae.

This study aimed to assess the in vitro efficacy of ceftazidime-avibactam (CZA) in combination with various antimicrobial agents against carbapenem-resistant Klebsiella pneumoniae (CRKP). We selected 59 clinical CRKP isolates containing distinct drug resistance mechanisms. The minimum inhibitory concentrations (MICs) of meropenem (MEM), colistin (COL), eravacycline (ERA), amikacin (AK), fosfomycin (FOS), and aztreonam (ATM), both individually and in combination with CZA, were tested using the checkerboard method. The interactions of antimicrobial agent combinations were assessed by fractional inhibitory concentration index (FICI) and susceptible breakpoint index (SBPI). The time-kill curve assay was employed to dynamically evaluate the effects of these drugs alone and in combination format. In the checkerboard assay, the combination of CZA+MEM showed the highest level of synergistic effect against both KPC-producing and carbapenemase-non-producing isolates, with synergy rates of 91.3% and 100%, respectively. Following closely was the combination of FOS+CZA . For metallo-beta-lactamases (MBLs) producing strains, ATM+CZA displayed complete synergy, while the combination of MEM+CZA showed a synergy rate of only 57.14% for NDM-producing strains and 91.67% for IMP-producing strains. In the time-kill assay, MEM+CZA also demonstrated significant synergistic effects against the two KPC-2-producing isolates (Y070 and L70), the two carbapenemase-non-producing isolates (Y083 and L093), and the NDM-1-producing strain L13, with reductions in log10 CFU/mL exceeding 10 compared to the control. Against the IMP-producing strain Y047, ATM+CZA exhibited the highest synergistic effect, resulting in a log10 CFU/mL reduction of 10.43 compared to the control. The combination of CZA and MEM exhibited good synergistic effects against KPC-producing and non-enzyme-producing strains, followed by the FOS+CZA combination. Among MBL-producing strains, ATM+CZA demonstrated the most pronounced synergistic effect. However, the combinations of CZA with ERA, AK, and COL show irrelevant effects against the tested clinical isolates. IMPORTANCE: Our study confirmed the efficacy of the combination CZA+MEM against KPC-producing and non-carbapenemase-producing strains. For metalloenzyme-producing strains, CZA+ATM demonstrated the most significant synergy. Additionally, CZA exhibited a notable synergy effect when combined with FOS. These combination therapies present promising new options for the treatment of CRKP infection.

Utility of paired plasma and drainage fluid mNGS in diagnosing acute intra-abdominal infections with sepsis.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has been increasingly applied in sepsis. We aimed to evaluate the diagnostic and therapeutic utility of mNGS of paired plasma and peritoneal drainage (PD) fluid samples in comparison to culture-based microbiological tests (CMTs) among critically ill patients with suspected acute intra-abdominal infections (IAIs). METHODS: We conducted a prospective study from October 2021 to December 2022 enrolling septic patients with suspected IAIs (n = 111). Pairwise CMTs and mNGS of plasma and PD fluid were sent for pathogen detection. The mNGS group underwent therapeutic regimen adjustment based on mNGS results for better treatment. The microbial community structure, clinical features, antibiotic use and prognoses of the patients were analyzed. RESULTS: Higher positivity rates were observed with mNGS versus CMTs for both PD fluid (90.0% vs. 48.3%, p < 0.005) and plasma (76.7% vs. 1.6%, p < 0.005). 90% of enrolled patients had clues of suspected pathogens combining mNGS and CMT methods. Gram-negative pathogens consist of most intra-abdominal pathogens, including a great variety of anaerobes represented by Bacteroides and Clostridium. Patients with matched plasma- and PD-mNGS results had higher mortality and sepsis severity. Reduced usage of carbapenem (30.0% vs. 49.4%, p < 0.05) and duration of anti-MRSA treatment (5.1 ± 3.3 vs. 7.0 ± 8.4 days, p < 0.05) was shown in the mNGS group in our study. CONCLUSIONS: Pairwise plasma and PD fluid mNGS improves microbiological diagnosis compared to CMTs for acute IAI. Combining plasma and PD mNGS could predict poor prognosis. mNGS may enable optimize empirical antibiotic use.

Impact of Immunosuppressed Status on Prognosis of Carbapenem-Resistant Organisms Bloodstream Infections.

INTRODUCTION: The impact of immunosuppression on prognosis of carbapenem-resistant organism (CRO) bloodstream infection (BSI) remains unclear. The aim of this study was to clarify the relationship between immunosuppression and mortality of CRO-BSI and to identify the risk factors associated with mortality in immunosuppressed patients. METHODS: This retrospective study included 279 patients with CRO-BSI from January 2018 to March 2023. Clinical characteristics and outcomes were compared between the immunosuppressed and immunocompetent patients. The relationship between immunosuppression and 30-day mortality after BSI onset was assessed through logistic-regression analysis, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Factors associated with mortality in immunosuppressed patients were analyzed using multivariable logistic regression analysis. RESULTS: A total of 88 immunocompetent and 191 immunosuppressed patients were included, with 30-day all-cause mortality of 58.8%. Although the 30-day mortality in immunosuppressed patients was significantly higher than in immunocompetent patients (46.6% vs. 64.4%, P = 0.007), immunosuppression was not an independent risk factor for mortality in multivariate logistic regression analysis (odds ratio [OR] 3.53, 95% confidence interval [CI] 0.74-18.89; P = 0.123), PSM (OR 1.38, 95% CI 0.60-3.18; P = 0.449,) or IPTW (OR 1.40, 95% CI 0.58-3.36; P = 0.447). For patients with CRO-BSI, regardless of immune status, appropriate antibiotic therapy was associated with decreased 30-day mortality, while Charlson comorbidity index (CCI), intensive care unit (ICU)-acquired infection and thrombocytopenia at CRO-BSI onset were associated with increased mortality. CONCLUSION: Despite the high mortality rate of CRO-BSI, immunosuppression did not affect the mortality. Appropriate antibiotic therapy is crucial for improving the prognosis of CRO-BSI, regardless of the immune status.

Genome-wide analyses based on a novel donkey 40K liquid chip reveal the gene responsible for coat color diversity in Chinese Dezhou donkey.

Dezhou donkey is one of the representative local breeds in China, which is mainly divided into two strains: Sanfen and Wutou. There are obvious differences in coat color between the two strains. The former shows light points around the eyes, around the muzzle and under the belly, while the latter is completely solid black. In this study, genome-wide association analysis was performed for the differences in coat color traits between the Sanfen (n = 97) and Wutou (n = 108) strains using a novel donkey 40K liquid chip developed based on GenoBaits technology, to identify genomic regions and causal genes that could explain this variation. We also used FST and The cross-population composite likelihood ratio test (XPCLR) analyses to explore selected regions related to coat color differences. We identified one significant region on chromosome 15, with the most significant SNP located within the agouti signaling protein (ASIP) gene. At the same time, both FST and XPCLR methods detected the same selected region on chromosome 15, and ASIP was the gene with the strongest signal. ASIP and melanocortin 1 receptor (MC1R) control the ratio of eumelanin to pheomelanin through their protein activity. They are deeply involved in the process of melanosome organation and melanogenesis, thus affecting mammals' coat color variation. We used a range of genome-wide approach to identify the genetic basis of coat color variation in Dezhou donkeys. The results provide a supplement to the color variation study in Chinese donkeys at the genome-wide level, and preliminarily verified the reliability of the Molbreeding Donkey No. 1 40K liquid chip.

Bta-miR-127 inhibits secretion, proliferation and promotes apoptosis by targeting ITGA6 in bovine Sertoli cell.

Sertoli cell (SC) play a critical role in the spermatogenesis process involved in male fecundity and reproductive potential. SC development is regulated by microRNAs (miRNAs). However, the effect and molecular mechanism of miRNAs and target genes on bovine immature SC remains poorly understood. In this study, bta-miR-127 overexpression in SC inhibited cell secretion, proliferation, cell viability, and S-phase cells number. However, inhibition of bta-miR-127 had the opposite effect. An over-expression of bta-miR-127 significantly promotes SC apoptosis, and bta-miR-127 inhibition can significantly inhibit this process. These results reveal that bta-miR-127 is an inhibitor of SC proliferation and secretion. A combination of transcriptome sequencing, bioinformatics analysis, and dual-luciferase reporter assay showed that ITGA6 was targeted by bta-miR-127. The small interfering RNA of ITGA6 (si-ITGA6) inhibits SC proliferation and secretion, as well as promotes apoptosis. The SC proliferation and secretion marker genes, cell viability, and S phase cell number in co-transfected si-ITGA6 + miR-127 inhibitor was significantly lower than those of the bta-miR-127 inhibitor group. These results further confirmed that bta-miR-127 targeting ITGA6 inhibits the SC proliferation and secretion, and promotes SC apoptosis. These findings proposed a novel miRNA (bta-miR-127) that impeded bovine SC proliferation and promoted SC apoptosis through downregulation of ITGA6.

mRNA sequencing provides new insights into the pathogenesis of Hirschsprung's disease in mice.

PURPOSE: The aim of this study is to use RNA sequencing and RT-qPCR to identify the main susceptibility genes linked to the occurrence and development of Hirschsprung disease in the colonic tissues of EDNRBm1yzcm and wild mice. METHODS: RNA was extracted from colon tissues of 3 mutant homozygous mice and 3 wild mice. RNA degradation, contamination concentration, and integrity were then measured. The extracted RNA was then sequenced using the Illumina platform. The obtained sequence data are filtered to ensure data quality and compared to the reference genome for further analysis. DESeq2 was used for gene expression analysis of the raw data. In addition, graphene oxide enrichment analysis and RT-qPCR validation were also performed. RESULTS: This study identified 8354 differentially expressed genes in EDNRBm1yzcm and wild mouse colon tissues by RNA sequencing, including 4346 upregulated genes and 4005 downregulated genes. Correspondingly, the results of RT-qPCR analysis showed good correlation with the transcriptome data. In addition, GO and KEGG enrichment results suggested that there were 8103 terms and 320 pathways in all DEGs. When P < 0.05, 1081 GO terms and 320 KEGG pathways reached a significant level. Finally, through the existing studies and the enrichment results of differentially expressed genes, it was determined that axon guidance and the focal adhesion pathway may be closely related to the occurrence of HSCR. CONCLUSIONS: This study analyzed and identified the differential genes in colonic tissues between EDNRBm1yzcm mice and wild mice, which provided new insight for further mining the potential pathogenic genes of Hirschsprung's disease.

Comorbidity of Pulmonary Fibrosis and COPD/Emphysema: Research Status, Trends, and Future Directions --------- A Bibliometric Analysis from 2004 to 2023.

Objective: The comorbidity of pulmonary fibrosis and COPD/emphysema has garnered increasing attention. However, no bibliometric analysis of this comorbidity has been conducted thus far. This study aims to perform a bibliometric analysis to explore the current status and cutting-edge trends in the field, and to establish new directions for future research. Methods: Statistical computing, graphics, and data visualization tools such as VOSviewer, CiteSpace, Biblimatrix, and WPS Office were employed. Results: We identified a total of 1827 original articles and reviews on the comorbidity of pulmonary fibrosis and COPD/emphysema published between 2004 and 2023. There was an observed increasing trend in publications related to this comorbidity. The United States, Japan, and the United Kingdom were the countries with the highest contributions. Professor Athol Wells and the University of Groningen had the highest h-index and the most articles, respectively. Through cluster analysis of co-cited documents, we identified the top 17 major clusters. Keyword analysis predicted that NF-κB, oxidative stress, physical activity, and air pollution might be hot spots in this field in the future. Conclusion: This bibliometric analysis demonstrates a continuous increasing trend in literature related to the comorbidity of pulmonary fibrosis and COPD/emphysema. The research hotspots and trends identified in this study provide a reference for in-depth research in this field, aiming to promote the development of the comorbidity of pulmonary fibrosis and COPD/emphysema.

Oocytes orchestrate protein prenylation for mitochondrial function through selective inactivation of cholesterol biosynthesis in murine species.

Emerging research and clinical evidence suggest that the metabolic activity of oocytes may play a pivotal role in reproductive anomalies. However, the intrinsic mechanisms governing oocyte development regulated by metabolic enzymes remain largely unknown. Our investigation demonstrates that geranylgeranyl diphosphate synthase1 (Ggps1), the crucial enzyme in the mevalonate pathway responsible for synthesizing isoprenoid metabolite geranylgeranyl pyrophosphate from farnesyl pyrophosphate, is essential for oocyte maturation in mice. Our findings reveal that the deletion of Ggps1 that prevents protein prenylation in fully grown oocytes leads to subfertility and offspring metabolic defects without affecting follicle development. Oocytes that lack Ggps1 exhibit disrupted mitochondrial homeostasis and the mitochondrial defects arising from oocytes are inherited by the fetal offspring. Mechanistically, the excessive farnesylation of mitochondrial ribosome protein, Dap3, and decreased levels of small G proteins mediate the mitochondrial dysfunction induced by Ggps1 deficiency. Additionally, a significant reduction in Ggps1 levels in oocytes is accompanied by offspring defects when females are exposed to a high-cholesterol diet. Collectively, this study establishes that mevalonate pathway-protein prenylation is vital for mitochondrial function in oocyte maturation and provides evidence that the disrupted protein prenylation resulting from an imbalance between farnesyl pyrophosphate and geranylgeranyl pyrophosphate is the major mechanism underlying impairment of oocyte quality induced by high cholesterol.

Antimicrobial Susceptibility Among Gram-Negative Isolates in Pediatric Patients in Latin America, Africa-Middle East, and Asia From 2016-2020 Compared to 2011-2015: Results From the ATLAS Surveillance Study.

BACKGROUND: Antimicrobial resistance (AMR) data in the pediatric population are limited, particularly in developing countries. This study assessed the AMR profile and key resistance phenotypes and genotypes for Gram-negative bacteria (GNB) isolates collected as part of the Antimicrobial Testing Leadership and Surveillance program from pediatric patients in Latin America, Africa-Middle East, and Asia in 2016-2020 versus 2011-2015. METHODS: Minimum inhibitory concentrations by broth microdilution methodology were interpreted per the Clinical and Laboratory Standards Institute. European Committee on Antimicrobial Susceptibility Testing breakpoints were used for interpreting colistin activity. ß-lactamase genes were screened by polymerase chain reaction and sequencing. RESULTS: For Acinetobacter baumannii, low susceptibility (<60.0%) was observed for all antimicrobials, except colistin (≥92.9%), across regions and year periods. Ceftazidime-avibactam, amikacin, colistin, and meropenem were mostly active (78.6%-100.0%) against Enterobacter cloacae, Escherichia coli, and Klebsiella pneumoniae. For Pseudomonas aeruginosa, susceptibility to ceftazidime-avibactam, amikacin, and colistin was ≥85.9%. Among resistance phenotypes, carbapenem-resistant (CR, ≥44.8%) and difficult-to-treat resistant (DTR, ≥37.1%) rates were the highest in A. baumannii. A consistent increase in CR and DTR K. pneumoniae was noted across regions over time. Extended-spectrum ß-lactamases (ESBL)-producing K. pneumoniae (32.6%-55.6%) were more frequent than ESBL-producing E. coli (25.3%-37.1%). CTX-M was the dominant ESBL among Enterobacterales. NDM-positive Enterobacterales species and VIM-positive P. aeruginosa were identified across regions. CONCLUSIONS: This study identified high susceptibility to few agents for key GNB in pediatric patients. Continued surveillance of resistance phenotypes and genotypes at regional levels may help to guide appropriate treatment decisions.

Diagnostic value of metagenomic next-generation sequencing of lower respiratory tract specimen for the diagnosis of suspected Pneumocystis jirovecii pneumonia.

AIM: To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for Pneumocystis jirovecii pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori methenamine silver (GMS) staining and serum 1,3-ß-d-Glucan (BG) assay. METHODS: 52 PCP patients and 103 patients with non-pneumocystic jirovecii pneumonia (non-PCP) were enrolled, and comparative analysis was conducted of different diagnostic tests. Clinical features and co-pathogen characteristics were reviewed. RESULTS: The diagnostic sensitivity (92.3%) and specificity (87.4%) of mNGS did not show significant differences compared with that of PCR while mNGS had the advantage over PCR in the detection of co-pathogens. Despite its excellent specificity, the sensitivity of GMS staining (9.3%) was inferior to that of mNGS (p < .001). The combination of mNGS with serum BG statistically outperformed mNGS or serum BG alone in the areas under the receiver operating characteristic curves (AUCs, p = .0013 and p = .0015, respectively). Notably, all the blood samples showing positive mNGS for Pneumocystis jirovecii came from PCP patients. The leading co-pathogens among patients with PCP were cytomegalovirus, Epstein-Barr virus and Torque teno virus. CONCLUSIONS: mNGS shows superiority over several common clinical methods in the diagnosis of suspected PCP. Serum BG in conjunction with mNGS further improved the diagnostic efficacy of mNGS.

Prognostic Biomarkers Based on Proteomic Technology in COPD: A Recent Review.

Chronic obstructive pulmonary disease (COPD) is a common heterogeneous respiratory disease which is characterized by persistent and incompletely reversible airflow limitation. Due to the heterogeneity and phenotypic complexity of COPD, traditional diagnostic methods provide limited information and pose a great challenge to clinical management. In recent years, with the development of omics technologies, proteomics, metabolomics, transcriptomics, etc., have been widely used in the study of COPD, providing great help to discover new biomarkers and elucidate the complex mechanisms of COPD. In this review, we summarize the prognostic biomarkers of COPD based on proteomic studies in recent years and evaluate their association with COPD prognosis. Finally, we present the prospects and challenges of COPD prognostic-related studies. This review is expected to provide cutting-edge evidence in prognostic evaluation of clinical patients with COPD and to inform future proteomic studies on prognostic biomarkers of COPD.

Application of metagenomic sequencing of drainage fluid in rapid and accurate diagnosis of postoperative intra-abdominal infection: a diagnostic study.

BACKGROUND: Postoperative intra-abdominal infection (PIAI) is one of the most serious complications of abdominal surgery, increasing the risk of postoperative morbidity and mortality and prolonging hospital stay. Rapid diagnosis of PIAI is of great clinical value. Unfortunately, the current diagnostic methods of PIAI are not fast and accurate enough. METHODS: The authors performed an exploratory study to establish a rapid and accurate diagnostic method of PIAI. The authors explored the turnaround time and accuracy of metagenomic next-generation sequencing (mNGS) in diagnosing PIAI. Patients who underwent elective abdominal surgery and routine abdominal drainage with suspected PIAI were enroled in the study. The fresh midstream abdominal drainage fluid was collected for mNGS and culturing. RESULTS: The authors found that the median sample-to-answer turnaround time of mNGS was dramatically decreased than that of culture-based methods (<24 h vs. 59.5-111 h). The detection coverage of mNGS was much broader than culture-based methods. The authors found 26 species from 15 genera could only be detected by mNGS. The accuracy of mNGS was not inferior to culture-based methods in the 8 most common pathogens detected from abdominal drainage fluid (sensitivity ranged from 75 to 100%, specificity ranged from 83.3 to 100%, and kappa values were higher than 0.5). Moreover, the composition of the microbial spectrum established by mNGS varied between upper and lower gastrointestinal surgery, enhancing the understanding of PIAI pathogenesis. CONCLUSION: This study preliminarily revealed the clinical value of mNGS in the rapid diagnosis of PIAI and provided a rationale for further research.

Emergence of ST463 exoU-Positive, Imipenem-Nonsusceptible Pseudomonas aeruginosa Isolates in China.

This study investigated the resistance mechanisms and the distribution and proportions of virulence genes, including exoU, in 182 imipenem-nonsusceptible Pseudomonas aeruginosa (INS-PA) strains collected from China in 2019. There was no obvious prevalent sequence type or concentrated evolutionary multilocus sequence typing (MLST) type on the INS-PA phylogenetic tree in China. All of the INS-PA isolates harbored ß-lactamases with/without other antimicrobial mechanisms, such as gross disruption of oprD and overexpression of efflux genes. Compared with exoU-negative isolates, exoU-positive isolates (25.3%, 46/182) presented higher virulence in A549 cell cytotoxicity assays. The southeast region of China had the highest proportion (52.2%, 24/46) of exoU-positive strains. The most frequent exoU-positive strains belonged to sequence type 463 (ST463) (23.9%, 11/46) and presented multiple resistance mechanisms and higher virulence in the Galleria mellonella infection model. The complex resistance mechanisms in INS-PA and the emergence of ST463 exoU-positive, multidrug-resistant P. aeruginosa strains in southeast China indicated a challenge that might lead to clinical treatment failure and higher mortality. IMPORTANCE This study investigates the resistance mechanisms and distribution and proportions of virulence genes of imipenem-nonsusceptible Pseudomonas aeruginosa (INS-PA) isolates in China in 2019. Harboring PDC and OXA-50-like genes is discovered as the most prevalent resistance mechanism in INS-PA, and the virulence of exoU-positive INS-PA isolates was significantly higher than that of exoU-negative INS-PA isolates. There was an emergence of ST463 exoU-positive INS-PA isolates in Zhejiang, China, most of which presented multidrug resistance and hypervirulence.

A-to-I RNA Editing in Klebsiella pneumoniae Regulates Quorum Sensing and Affects Cell Growth and Virulence.

Millions of adenosine (A) to inosine (I) RNA editing events are reported and well-studied in eukaryotes; however, many features and functions remain unclear in prokaryotes. By combining PacBio Sequel, Illumina whole-genome sequencing, and RNA Sequencing data of two Klebsiella pneumoniae strains with different virulence, a total of 13 RNA editing events are identified. The RNA editing event of badR is focused, which shows a significant difference in editing levels in the two K. pneumoniae strains and is predicted to be a transcription factor. A hard-coded Cys is mutated on DNA to simulate the effect of complete editing of badR. Transcriptome analysis identifies the cellular quorum sensing (QS) pathway as the most dramatic change, demonstrating the dynamic regulation of RNA editing on badR related to coordinated collective behavior. Indeed, a significant difference in autoinducer 2 activity and cell growth is detected when the cells reach the stationary phase. Additionally, the mutant strain shows significantly lower virulence than the WT strain in the Galleria mellonella infection model. Furthermore, RNA editing regulation of badR is highly conserved across K. pneumoniae strains. Overall, this work provides new insights into posttranscriptional regulation in bacteria.

Artificial intelligence-aided rapid and accurate identification of clinical fungal infections by single-cell Raman spectroscopy.

Integrating artificial intelligence and new diagnostic platforms into routine clinical microbiology laboratory procedures has grown increasingly intriguing, holding promises of reducing turnaround time and cost and maximizing efficiency. At least one billion people are suffering from fungal infections, leading to over 1.6 million mortality every year. Despite the increasing demand for fungal diagnosis, current approaches suffer from manual bias, long cultivation time (from days to months), and low sensitivity (only 50% produce positive fungal cultures). Delayed and inaccurate treatments consequently lead to higher hospital costs, mobility and mortality rates. Here, we developed single-cell Raman spectroscopy and artificial intelligence to achieve rapid identification of infectious fungi. The classification between fungi and bacteria infections was initially achieved with 100% sensitivity and specificity using single-cell Raman spectra (SCRS). Then, we constructed a Raman dataset from clinical fungal isolates obtained from 94 patients, consisting of 115,129 SCRS. By training a classification model with an optimized clinical feedback loop, just 5 cells per patient (acquisition time 2 s per cell) made the most accurate classification. This protocol has achieved 100% accuracies for fungal identification at the species level. This protocol was transformed to assessing clinical samples of urinary tract infection, obtaining the correct diagnosis from raw sample-to-result within 1 h.

Guidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli.

The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, clinical microbiology, clinical pharmacology, infection control, and guideline methodology experts jointly developed the present clinical practice guidelines based on best available scientific evidence to address the clinical issues regarding laboratory testing, antimicrobial therapy, and prevention of CRGNB infections. This guideline focuses on carbapenem-resistant Enterobacteriales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Sixteen clinical questions were proposed from the perspective of current clinical practice and translated into research questions using PICO (population, intervention, comparator, and outcomes) format to collect and synthesize relevant evidence to inform corresponding recommendations. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate the quality of evidence, benefit and risk profile of corresponding interventions and formulate recommendations or suggestions. Evidence extracted from systematic reviews and randomized controlled trials (RCTs) was considered preferentially for treatment-related clinical questions. Observational studies, non-controlled studies, and expert opinions were considered as supplementary evidence in the absence of RCTs. The strength of recommendations was classified as strong or conditional (weak). The evidence informing recommendations derives from studies worldwide, while the implementation suggestions combined the Chinese experience. The target audience of this guideline is clinician and related professionals involved in management of infectious diseases.

In-vitro activity of ceftolozane/tazobactam against Pseudomonas aeruginosa collected in the Study for Monitoring Antimicrobial Resistance Trends (SMART) between 2016 and 2019 in China.

Ceftolozane/tazobactam (an antipseudomonal cephalosporin) in combination with a well-established ß-lactamase inhibitor has not been approved to date in clinical practice in China. The aim of this study was to evaluate the in-vitro activity of ceftolozane/tazobactam and comparator agents against Pseudomonas aeruginosa with various resistance patterns. P. aeruginosa (n=2178) specimens were collected from multiple sources in seven geographic regions of China between 2016 and 2019. All isolates were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and minimum inhibitory concentrations of various antimicrobial agents (ceftolozane/tazobactam, amikacin, tobramycin, ceftazidime, cefepime, colistin, levofloxacin, aztreonam, meropenem, imipenem and piperacillin/tazobactam) were determined using the Clinical and Laboratory Standards Institute's broth microdilution method. P. aeruginosa demonstrated considerably high rates of multi-drug resistance (MDR, 57.3%), extensive drug resistance (XDR, 43.5%) and difficult-to-treat resistance (DTR, 16.8%). The overall susceptibility of P. aeruginosa to ceftolozane/tazobactam was 81.9%, and ceftolozane/tazobactam showed diverse activity against the three resistant subsets, ranging from 28.5% against DTR P. aeruginosa to 68.9% against MDR P. aeruginosa. P. aeruginosa, MDR P. aeruginosa, XDR P. aeruginosa and DTR P. aeruginosa derived from the East (Jiangzhe area) region maintained significantly lower susceptibility to ceftolozane/tazobactam compared with P. aeruginosa, MDR P. aeruginosa, XDR P. aeruginosa and DTR P. aeruginosa from other regions. The susceptibility rates of P. aeruginosa isolated from diverse sources to ceftolozane/tazobactam were similar to isolates from bloodstream infections, with the highest being 88.6%. Compared with other antimicrobial agents, ceftolozane/tazobactam was more active than the ß-lactams tested but was slightly less active than amikacin. Amikacin demonstrated the best activity against P. aeruginosa and the three resistant subsets. Ceftolozane/tazobactam demonstrated considerable in-vitro activity against P. aeruginosa, MDR P. aeruginosa, XDR P. aeruginosa and DTR P. aeruginosa, indicating that it could be an optional therapeutic agent against P. aeruginosa.

Setting of the tentative epidemiological cut-off values of contezolid for Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae and Streptococcus agalactiae.

OBJECTIVES: To set the tentative epidemiological cut-off values (TECOFFs) of contezolid for Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae and Streptococcus agalactiae based on the distributions of inhibition zone diameters and MICs. METHODS: A total of 1358 non-duplicate clinical isolates of Gram-positive bacteria were collected from the patients across China from 2017 to 2020. The isolates were tested for susceptibility to contezolid and the comparator linezolid by broth microdilution and disc diffusion methods in three microbiology laboratories. The zone diameters and MICs of linezolid WT strains were used to set the WT TECOFFs of contezolid by normalized resistance interpretation calculations. RESULTS: Contezolid showed an aggregate MIC range from 0.03 to 8 mg/L and MIC90 value of 1-2 mg/L against all of the Gram-positive bacterial strains tested. The TECOFF of contezolid based on MIC distributions was 4 mg/L for both S. aureus and Enterococcus species, and 2 mg/L for S. pneumoniae and S. agalactiae. The TECOFF of contezolid based on zone diameter was 24 mm for S. aureus, 18 mm for E. faecalis, 20 mm for E. faecium and S. pneumoniae, and 17 mm for S. agalactiae. CONCLUSIONS: The epidemiological cut-off values of contezolid were set tentatively for selected Gram-positive bacteria using the MIC and zone diameter distributions. These data are helpful for clinical microbiologists and clinicians to interpret the antimicrobial susceptibility results of contezolid.