Establishment of epidemiological cut-off values for eravacycline, against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii and Staphylococcus aureus.

OBJECTIVES: To establish the epidemiology cut-off (ECOFF) values of eravacycline against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii and Staphylococcus aureus, from a multi-centre study in China. METHODS: We collected 2500 clinical isolates from five hospitals in China from 2017 to 2020. The MICs of eravacycline were determined using broth microdilution. The ECOFF values of eravacycline against the five species commonly causing cIAIs were calculated using visual estimation and ECOFFinder following the EUCAST guideline. RESULTS: The MICs of eravacycline against all the strains were in the range of 0.004-16 mg/L. The ECOFF values of eravacycline were 0.5 mg/L for E. coli, 2 mg/L for K. pneumonia and E. cloacae, and 0.25 mg/L for A. baumannii and S. aureus, consistent with the newest EUCAST publication of eravacycline ECOFF values for the populations. No discrepancy was found between the visually estimated and 99.00% ECOFF values calculated using ECOFFinder. CONCLUSIONS: The determined ECOFF values of eravacycline against the five species can assist in distinguishing wild-type from non-wild-type strains. Given its promising activity, eravacycline may represent a member of the tetracycline class in treating cIAIs caused by commonly encountered Gram-negative and Gram-positive pathogens.

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.

Synthesis, Crystal Structures and Catalytic Oxidation Property of Two Oxidovanadium(V) Complexes with Schiff bases.

Two new oxidovanadium(V) complexes, [VO2L1] (1) and [V2O2(µ-O)2L2)] (2), where L1 and L2 are the deprotonated form of 5-bromo-2-(((2-(pyrrolidin-1-yl)ethyl)imino)methyl)phenol (HL1) and 5-bromo-2-(((2-((2-hydroxyethyl)amino)ethyl)imino)methyl)phenol (HL2), respectively, have been synthesized and structurally characterized by physico-chemical methods and single crystal X-ray determination. X-ray analysis indicates that the V atom in complex 1 is in square pyramidal coordination, and those in complex 2 are in octahedral coordination. Crystal structures of the complexes are stabilized by hydrogen bonds. The catalytic property for epoxidation of styrene by the complexes was evaluated.

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.

The role of coffee and potential mediators in subclinical atherosclerosis: insights from Mendelian randomization study.

Background and aims: Coffee contains many bioactive compounds, and its inconsistent association with subclinical atherosclerosis has been reported in observational studies. In this Mendelian randomization study, we investigated whether genetically predicted coffee consumption is associated with subclinical atherosclerosis, as well as the role of potential mediators. Methods: We first conducted a two-sample Mendelian randomization analysis to examine the causal effect of coffee and its subtypes on subclinical atherosclerosis inferred from coronary artery calcification (CAC). Next, the significant results were validated using another independent dataset. Two-step Mendelian randomization analyses were utilized to evaluate the causal pathway from coffee to subclinical atherosclerosis through potential mediators, including blood pressure, blood lipids, body mass index, and glycated hemoglobin. Mendelian randomization analyses were performed using the multiplicative random effects inverse-variance weighted method as the main approach, followed by a series of complementary methods and sensitivity analyses. Results: Coffee, filtered coffee, and instant coffee were associated with the risk of CAC (ß = 0.79, 95% CI: 0.12 to 1.47, p = 0.022; ß = 0.66, 95% CI: 0.17 to 1.15, p = 0.008; ß = 0.66, 95% CI: 0.20 to 1.13, p = 0.005; respectively). While no significant causal relationship was found between decaffeinated coffee and CAC (ß = -1.32, 95% CI: -2.67 to 0.04, p = 0.056). The association between coffee and CAC was validated in the replication analysis (ß = 0.27, 95% CI: 0.07 to 0.48, p = 0.009). Body mass index mediated 39.98% of the effect of coffee on CAC (95% CI: 9.78 to 70.19%, p = 0.009), and 5.79% of the effect of instant coffee on CAC (95% CI: 0.54 to 11.04%, p = 0.030). Conclusion: Our study suggests that coffee other than decaffeinated coffee increases the risk of subclinical atherosclerosis inferred from CAC. Body mass index mediated 39.98 and 5.79% of the causal effects of coffee and instant coffee on CAC, respectively. Coffee should be consumed with caution, especially in individuals with established cardiovascular risk factors, and decaffeinated coffee appears to be a safer choice.

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.

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.

Metagenomic next-generation sequencing for detecting Aspergillosis pneumonia in immunocompromised patients: a retrospective study.

Purpose: The identification of Aspergillus by metagenomic next-generation sequencing (mNGS) remains a challenging task due to the difficulty of nucleic acid extraction. The objective of this study was to determine whether mNGS could provide an accurate and efficient method for detecting invasive pulmonary aspergillosis (IPA) in immunocompromised patients (ICP). Methods: A total of 133 ICP admitted to the ICU between January 2020 and September 2022 were enrolled in the study, of which 46 were diagnosed with IPA and 87 were non-IPA cases. The bronchoalveolar lavage fluid (BALF) was analyzed for the presence of Aspergillosis and other co-pathogens using mNGS, and its diagnostic performance was compared to conventional microbial tests (CMTs) that included smear, cultures, serum and BALF galactomannan (GM) test. Clinical composite diagnosis was used as the reference standard. Results: mNGS had a sensitivity, specificity, and accuracy of 82.6%, 97.7%, and 92.5%, respectively, in diagnosing IPA. These findings were comparable to those of the combination of multiple CMTs. Interestingly, the sensitivity of mNGS was superior to that of any single CMT method, as demonstrated by comparisons with smears (8.7%, P < 0.001), culture (39.1%, P < 0.001), serum GM (23.9%, P < 0.001) and BALF GM (69.6%, P = 0.031). mNGS was capable of accurately distinguish strains of Aspergillus genus, with a consistency of 77.8% with culture. Furthermore, mNGS also identified A. fumigatus, A. flavus, A. terrestris, A. oryzae and Mucor spp. in culture-negative cases. The sequencing reads of Aspergillus by mNGS exhibited extensive variation, ranging from 11 to1702. A positive correlation was observed between the optical density index of BALF GM and unique reads by mNGS (r = 0.607, P = 0.001) in BALF-GM positive patients. Notably, mNGS was able to diagnose 35 out of 37 cases with mixed infection, with P. jirovecii and cytomegalovirus being the most common co-pathogens. Conclusions: mNGS presents a feasible and remarkably sensitive approach for detecting Aspergillus in ICP, thereby serving as a valuable adjunctive tool to CMT. Furthermore, mNGS's ability to accurately identify fungal species and co-pathogens can assist in guiding appropriate antimicrobial therapy.

Metabolic changes before and after weaning in Dezhou donkey foals in relation to gut microbiota.

Weaning is undoubtedly one of the most crucial stages in the growth and development of all mammalian animals, including donkey foals. Weaning is a dynamic and coordinated process of the body, which is closely associated with the health, nutrition, and metabolism of the host. Many studies have shown that the intestinal microbiota and serum metabolites of mammals exhibit different changes during lactation, weaning, and postweaning. However, the alterations in serum metabolites in donkey foals before and postweaning and the correlation between serum metabolites and intestinal microbiota are largely unknown. This study is based on the fecal 16S rRNA and serum metabolomes of Dezhou donkey foals. In total, 10 samples (fecal and serum) were collected during the following three stages: before weaning (F.M.1), during weaning (F.M.3), and postweaning (F.M.6). To study the alterations in intestinal microflora, serum metabolites, and their correlation before and postweaning. We found that with the growth and weaning progress of donkey foals, the intestinal microbiota of donkey foals underwent obvious changes, and the diversity of fecal bacteria increased (Chao1 and Shannon indexes). The main intestinal microbial flora of donkey foals include Bacteroides and Firmicutes. We found many microbiota that are associated with immunity and digestion in the postweaning group, such as Verrucomicrobiales, Clostridia, Oscillospiraceae, Akkermansia, and Rikenellaceae, which can be considered microbial markers for the transition from liquid milk to solid pellet feed. Clostridia and Oscillospiraceae can produce organic acids, including butyric acid and acetic acid, which are crucial for regulating the intestinal microecological balance of donkeys. Furthermore, the metabolome showed that the serum metabolites enriched before and postweaning were mainly related to arachidonic acid metabolism and riboflavin metabolism. Riboflavin was associated with the development of the small intestine and affected the absorption of the small intestine. We also found that the changes in the gut microbiome of the foals were significantly correlated with changes in serum metabolites, including lysophosphatidylcholine (LPC; 12,0) and positively correlated with Lachnoclostridium and Roseburia. To summarize, this study provides theoretical data for the changes in the intestinal microbiome and serum metabolism during the entire weaning period of donkey foals.

Rapid, automated, and reliable antimicrobial susceptibility test from positive blood culture by CAST-R.

Antimicrobial susceptibility tests (ASTs) are pivotal in combating multidrug resistant pathogens, yet they can be time-consuming, labor-intensive, and unstable. Using the AST of tigecycline for sepsis as the main model, here we establish an automated system of Clinical Antimicrobials Susceptibility Test Ramanometry (CAST-R), based on D2O-probed Raman microspectroscopy. Featuring a liquid robot for sample pretreatment and a machine learning-based control scheme for data acquisition and quality control, the 3-h, automated CAST-R process accelerates AST by >10-fold, processes 96 paralleled antibiotic-exposure reactions, and produces high-quality Raman spectra. The Expedited Minimal Inhibitory Concentration via Metabolic Activity is proposed as a quantitative and broadly applicable parameter for metabolism-based AST, which shows 99% essential agreement and 93% categorical agreement with the broth microdilution method (BMD) when tested on 100 Acinetobacter baumannii isolates. Further tests on 26 clinically positive blood samples for eight antimicrobials, including tigecycline, meropenem, ceftazidime, ampicillin/sulbactam, oxacillin, clindamycin, vancomycin, and levofloxacin reveal 93% categorical agreement with BMD-based results. The automation, speed, reliability, and general applicability of CAST-R suggest its potential utility for guiding the clinical administration of antimicrobials.