Clinical and Genomic Characterization of Recalcitrant Enterococcal Bacteremia: A Multicenter Prospective Cohort Study (VENOUS).

Background: Patients with recalcitrant enterococcal bloodstream infections are at greater risk of adverse outcomes. We identified patients in the 2016-2022 Vancomycin-Resistant Enterococcal Bacteremia Outcomes Study (VENOUS) cohort experiencing recalcitrant bloodstream infections for further clinical and genomic characterization.

Methods: Bacteremia episodes were considered "persistent" if there was a lack of clearance on day four while receiving ≥ 48 hours of active therapy and recurrent if there was clearance during hospitalization with a subsequent positive culture (collectively, "recalcitrant" bacteremia).

Clinical and Genomic Characterization of Recalcitrant Enterococcal Bacteremia: A Multicenter Prospective Cohort Study (VENOUS).

Background: Patients with recalcitrant enterococcal bloodstream infections are at greater risk of adverse outcomes. We identified patients in the 2016-2022 Vancomycin-Resistant Enterococcal Bacteremia Outcomes Study (VENOUS) cohort experiencing recalcitrant bloodstream infections for further clinical and genomic characterization.

Methods: Bacteremia episodes were considered "persistent" if there was a lack of clearance on day four while receiving ≥ 48 hours of active therapy and recurrent if there was clearance during hospitalization with a subsequent positive culture (collectively, "recalcitrant" bacteremia).

Comprehensive Assessment of Initial Adaptation of Extended-Spectrum β-Lactamase-Positive ST131 Escherichia coli to Carbapenem Exposure.

Background: It remains unclear how high-risk Escherichia coli lineages, like sequence type (ST) 131, initially adapt to carbapenem exposure in their progression to carbapenem resistance.

Methods: Carbapenem mutation frequency was measured in multiple subclades of extended-spectrum β-lactamase (ESBL)-positive ST131 clinical isolates using a fluctuation assay followed by whole genome sequencing (WGS) characterization. Genomic, transcriptomic, and porin analyses of the ST131 C2/H30Rx isolate MB1860, under prolonged, increasing carbapenem exposure was performed using 2 experimental evolutionary platforms to measure fast versus slow adaptation.

Comprehensive Assessment of Initial Adaptation of ESBL Positive ST131 to Carbapenem Exposure.

Background: It remains unclear how high-risk lineages, like sequence type (ST) 131, initially adapt to carbapenem exposure in their progression to becoming carbapenem resistant.

Methods: Carbapenem mutation frequency was measured in multiple subclades of extended-spectrum β-lactamase (ESBL) positive ST131 clinical isolates using a fluctuation assay followed by whole genome sequencing (WGS) characterization. Genomic, transcriptomic, and porin analyses of ST131 C2/ 30Rx isolate, MB1860, under prolonged, increasing carbapenem exposure was performed using two distinct experimental evolutionary platforms to measure fast vs.

Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in of clinical origin.

The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression.

ATP-dependent citrate lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling of the Heart.

Background: Metabolic remodeling is a hallmark of the failing heart. Oncometabolic stress during cancer increases the activity and abundance of the ATP-dependent citrate lyase (ACL, ), which promotes histone acetylation and cardiac adaptation. ACL is critical for the de novo synthesis of lipids, but how these metabolic alterations contribute to cardiac structural and functional changes remains unclear.

Autophagic signaling promotes systems-wide remodeling in skeletal muscle upon oncometabolic stress by D2-HG.

Objectives: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG).

Membrane Lipids Augment Cell Envelope Stress Signaling via the MadRS System to Defend Against Antimicrobial Peptides and Antibiotics in Enterococcus faecalis.

Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated.

Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in of clinical origin.

The siderophore-cephalosporin cefiderocol(FDC) presents a promising treatment option for carbapenem-resistant (CR) (PA). FDC circumvents traditional porin and efflux mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression.

Membrane Lipids Augment Cell Envelope Stress Signaling and Resistance to Antibiotics and Antimicrobial Peptides in .

Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated.

Developing and validating noninvasive prenatal testing for autosomal dominant monogenic diseases in Vietnam.

Over 60% of single-gene diseases in newborns are autosomal dominant variants. Noninvasive prenatal testing for monogenic conditions (NIPT-SGG) is cost-effective and timesaving, but not widely applied. This study introduces and validates NIPT-SGG in detecting 25 monogenic conditions.

Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA.

Background: Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR . This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts.

Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America.

Background: Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) compromise the clinical efficacy of vancomycin. The hVISA isolates spontaneously produce vancomycin-intermediate Staphylococcus aureus (VISA) cells generated by diverse and intriguing mechanisms.

Objective: To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches.

Unravelling complex transposable elements surrounding bla in a Pseudomonas aeruginosa ExoU strain.

Objectives: We characterised the complex surrounding regions of bla in a Pseudomonas aeruginosa exoU+ strain (P-10.226) in Brazil.

Methods: Species identification was performed by MALDI-TOF MS, and the antimicrobial susceptibility profile was determined by broth microdilution based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints.

Accessory Genomes Drive Independent Spread of Carbapenem-Resistant Klebsiella pneumoniae Clonal Groups 258 and 307 in Houston, TX.

Carbapenem-resistant Klebsiella pneumoniae (CR) is an urgent public health threat. Worldwide dissemination of CR has been largely attributed to clonal group (CG) 258. However, recent evidence indicates the global emergence of a CR CG307 lineage.

Ring Contraction of Tropylium Ions into Benzenoid Derivatives.

We report a method to convert substituted tropylium ions into benzenoid derivatives.

Contemporary Clinical and Molecular Epidemiology of Vancomycin-Resistant Enterococcal Bacteremia: A Prospective Multicenter Cohort Study (VENOUS I).

Background: Vancomycin-resistant enterococci (VRE) are major therapeutic challenges. Prospective contemporary data characterizing the clinical and molecular epidemiology of VRE bloodstream infections (BSIs) are lacking.

Methods: The Vancomycin-Resistant Enterococcal BSI Outcomes Study (VENOUS I) is a prospective observational cohort of adult patients with enterococcal BSI in 11 US hospitals.

Efficacy, Safety, Pharmacokinetics, and Microbiome Changes of Ibezapolstat in Adults with Clostridioides difficile Infection: A Phase 2a Multicenter Clinical Trial.

Background: This study was the first human validation of the gram-positive bacterial DNA polymerase IIIC target in patients with Clostridioides difficile infection. The primary objectives were to assess clinical cure rates and adverse events (AEs). Secondary objectives were to evaluate plasma/fecal pharmacokinetics, microbiologic eradication, microbiome and bile acid effects, and sustained clinical cure (SCC) with ibezapolstat.

Invasive Infections during a COVID-19 Case Surge.

Clinical cases of C. auris noted during a COVID-19 surge led to an epidemiological, clinical, and genomic investigation. Evaluation identified a close genetic relationship but inconclusive epidemiologic link between all cases.

Selective digestive decontamination with oral colistin plus gentamicin for persistent bacteraemia caused by non-carbapenemase-producing carbapenem-resistant in a neutropenic patient.

Background: Carbapenem-resistant (CR) have become an increasing public health problem worldwide. While most CR around the world harbour a carbapenemase enzyme, the clinical relevance of non-carbapenemase-producing CR (non-CP-CR) is increasingly recognized. Selective digestive decontamination (SDD) has been proven successful as a decolonization strategy for patients colonized with Gram-negatives in the ICU.