Humoral Immunity and Antibody Responses against Diphtheria, Tetanus, and Pneumococcus after Immune Effector Cell Therapies: A Prospective Study.

Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT and the patients' response to vaccination. We enrolled patients who underwent IECT from January 2020 to March 2022.

LiaX is a surrogate marker for cell envelope stress and daptomycin non-susceptibility in .

Daptomycin (DAP) is often used as a first-line therapy to treat vancomycin-resistant infections, but emergence of DAP non-susceptibility threatens the effectiveness of this antibiotic. Moreover, current methods to determine DAP minimum inhibitory concentrations (MICs) have poor reproducibility and accuracy. In enterococci, DAP resistance is mediated by the LiaFSR cell membrane stress response system, and deletion of encoding the response regulator results in hypersusceptibility to DAP and antimicrobial peptides.

Genetic determinants underlying the progressive phenotype of β-lactam/β-lactamase inhibitor resistance in .

The increased feasibility of whole-genome sequencing has generated significant interest in using such molecular diagnostic approaches to characterize difficult-to-treat, antimicrobial-resistant (AMR) infections. Nevertheless, there are current limitations in the accurate prediction of AMR phenotypes based on existing AMR gene database approaches, which primarily correlate a phenotype with the presence/absence of a single AMR gene. Our study utilized a large cohort of cephalosporin-susceptible bacteremia samples to determine how increasing the dosage of narrow-spectrum β-lactamase-encoding genes in conjunction with other diverse β-lactam/β-lactamase inhibitor (BL/BLI) genetic determinants contributes to progressively more severe BL/BLI phenotypes.

Young-onset Rectal Cancer: Unique Tumoral Microbiome and Correlation With Response to Neoadjuvant Therapy.

Objective: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology.

Background: YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years.

Contribution of the Oral and Gastrointestinal Microbiomes to Bloodstream Infections in Leukemia Patients.

Bloodstream infections (BSIs) pose a significant mortality risk for acute myeloid leukemia (AML) patients. It has been previously reported that intestinal domination (>30% relative abundance [RA] attributed to a single taxon) with the infecting taxa often precedes BSI in stem cell transplant patients. Using 16S rRNA amplicon sequencing, we analyzed oral and stool samples from 63 AML patients with BSIs to determine the correlation between the infectious agent and microbiome composition.

Oral and Stool Microbiome Coalescence and Its Association With Antibiotic Exposure in Acute Leukemia Patients.

Failure to maintain segregation of oral and gut microbial communities has been linked to several diseases. We sought to characterize oral-fecal microbiome community coalescence, ectopic extension of oral bacteria, clinical variables contributing to this phenomenon, and associated infectious consequences by analyzing the 16S rRNA V4 sequences of longitudinal fecal (n=551) and oral (n=737) samples from 97 patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC). Clustering observed in permutation based multivariate analysis of variance (PERMANOVA) of Bray-Curtis dissimilarity and PCoA plot of UniFrac distances between intra-patient longitudinal oral-stool sample pairs suggested potential oral-stool microbial community coalescence.

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.

Population Genomics of Group A Streptococcus Reveals Progressive Replacement with a Hypervirulent Clone in North America.

Clonal replacement is a major driver for changes in bacterial disease epidemiology. Recently, it has been proposed that episodic emergence of novel, hypervirulent clones of group A Streptococcus (GAS) results from acquisition of a 36-kb DNA region leading to increased expression of the cytotoxins Nga (NADase) and SLO (streptolysin O). We previously described a gene fusion event involving the gene encoding the GAS M protein () and an adjacent M-like protein () in the GAS population, a GAS type that lacks the hyaluronic acid capsule.

IS26-mediated amplification of blaOXA-1 and blaCTX-M-15 with concurrent outer membrane porin disruption associated with de novo carbapenem resistance in a recurrent bacteraemia cohort.

Background: Approximately half of clinical carbapenem-resistant Enterobacterales (CRE) isolates lack carbapenem-hydrolysing enzymes and develop carbapenem resistance through alternative mechanisms.

Objectives: To elucidate development of carbapenem resistance mechanisms from clonal, recurrent ESBL-positive Enterobacterales (ESBL-E) bacteraemia isolates in a vulnerable patient population.

Methods: This study investigated a cohort of ESBL-E bacteraemia cases in Houston, TX, USA.

Alterations of the Oral Microbiome and Cumulative Carbapenem Exposure Are Associated With Stenotrophomonas maltophilia Infection in Patients With Acute Myeloid Leukemia Receiving Chemotherapy.

Background: Stenotrophomonas maltophilia is increasingly common in patients with acute myeloid leukemia (AML). Little is known about factors that drive S. maltophilia infection.

Observational Cohort Study of Oral Mycobiome and Interkingdom Interactions over the Course of Induction Therapy for Leukemia.

Although the term "microbiome" refers to all microorganisms, the majority of microbiome studies focus on the bacteriome. Here, we characterize the oral mycobiome, including mycobiome-bacteriome interactions, in the setting of remission-induction chemotherapy (RIC) for acute myeloid leukemia (AML). Oral samples ( = 299) were prospectively collected twice weekly from 39 AML patients during RIC until neutrophil recovery.

Gut Microbiome Signatures Are Predictive of Infectious Risk Following Induction Therapy for Acute Myeloid Leukemia.

Background: The majority of studies that provide insights into the influence of the microbiome on the health of hematologic malignancy patients have concentrated on the transplant setting. Here, we sought to assess the predictive capacity of the gastrointestinal microbiome and its relationship to infectious outcomes in patients with acute myeloid leukemia (AML).

Methods: 16s rRNA-based analysis was performed on oral swabs and stool samples obtained biweekly from baseline until neutrophil recovery following induction chemotherapy (IC) in 97 AML patients.

Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study.

Background: Accumulating evidence suggests that the intestinal microbiome may dramatically affect the outcomes of hematopoietic stem cell transplant (HSCT) recipients. Providing 16S ribosomal RNA based microbiome characterization in a clinically actionable time frame is currently problematic. Thus, determination of microbial metabolites as surrogates for microbiome composition could offer practical biomarkers.

Associations of inflammation with symptom burden in patients with acute myeloid leukemia.

The aim of the study was to assess the association inflammation with symptom burden in patients with acute myeloid leukemia (AML), assessed before and during remission induction chemotherapy (IC). Patients with AML (n = 95) were followed from baseline (before IC) to the third week of IC for severity of self-reported somatic symptoms (assessed with the MD Anderson Symptom Inventory) and plasma levels of 13 inflammation-related biomarkers (n = 64). A composite symptom burden severity score was computed as the average score of the six most severe somatic symptoms i.

Whole-Genome Sequencing Accurately Identifies Resistance to Extended-Spectrum β-Lactams for Major Gram-Negative Bacterial Pathogens.

Background: There is marked interest in using DNA-based methods to detect antimicrobial resistance (AMR), with targeted polymerase chain reaction (PCR) approaches increasingly being incorporated into clinical care. Whole-genome sequencing (WGS) could offer significant advantages over targeted PCR for AMR detection, particularly for species where mutations are major drivers of AMR.

Methods: Illumina MiSeq WGS and broth microdilution (BMD) assays were performed on 90 bloodstream isolates of the 4 most common gram-negative bacteria causing bloodstream infections in neutropenic patients.

Use of a Phosphorylation Site Mutant To Identify Distinct Modes of Gene Repression by the Control of Virulence Regulator (CovR) in Streptococcus pyogenes.

Control of the virulence regulator/sensor kinase (CovRS) two-component system (TCS) serves as a model for investigating the impact of signaling pathways on the pathogenesis of Gram-positive bacteria. However, the molecular mechanisms by which CovR, an OmpR/PhoB family response regulator, controls virulence gene expression are poorly defined, partly due to the labile nature of its aspartate phosphorylation site. To better understand the regulatory effect of phosphorylated CovR, we generated the phosphorylation site mutant strain 10870-CovR-D53E, which we predicted to have a constitutive CovR phosphorylation phenotype.

Characterization of oral and gut microbiome temporal variability in hospitalized cancer patients.

Background: Understanding longitudinal variability of the microbiome in ill patients is critical to moving microbiome-based measurements and therapeutics into clinical practice. However, the vast majority of data regarding microbiome stability are derived from healthy subjects. Herein, we sought to determine intra-patient temporal microbiota variability, the factors driving such variability, and its clinical impact in an extensive longitudinal cohort of hospitalized cancer patients during chemotherapy.

Identification and Whole Genome Sequencing of the First Case of Causing a Human Bloodstream Infection.

The taxonomy of species is rapidly changing. Herein we report a bloodstream infection isolate originally identified as by Vitek2 methodology that we found to be using genetic means. Comparative whole genome sequencing of our isolate and other published genomes revealed these organisms lack the AmpC β-lactamase present on the chromosome of sp.

The role of the gastrointestinal microbiome in infectious complications during induction chemotherapy for acute myeloid leukemia.

Background: Despite increasing data on the impact of the microbiome on cancer, the dynamics and role of the microbiome in infection during therapy for acute myelogenous leukemia (AML) are unknown. Therefore, the authors sought to determine correlations between microbiome composition and infectious outcomes in patients with AML who were receiving induction chemotherapy (IC).

Methods: Buccal and fecal specimens (478 samples) were collected twice weekly from 34 patients with AML who were undergoing IC.

Complete Genome Sequence of Streptococcus mitis Strain SVGS_061 Isolated from a Neutropenic Patient with Viridans Group Streptococcal Shock Syndrome.

Streptococcus mitisfrequently causes invasive infections in neutropenic cancer patients, with a subset of patients developing viridans group streptococcal (VGS) shock syndrome. We report here the first complete genome sequence ofS. mitisstrain SVGS_061, which caused VGS shock syndrome, to help elucidate the pathogenesis of severe VGS infection.

Sequence type 1 group B Streptococcus, an emerging cause of invasive disease in adults, evolves by small genetic changes.

The molecular mechanisms underlying pathogen emergence in humans is a critical but poorly understood area of microbiologic investigation. Serotype V group B Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive serotype V GBS disease significantly increased starting in the early 1990s. We found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream of nonpregnant adults in the United States and Canada between 1992 and 2013 were multilocus sequence type (ST) 1.