Comparison of Risk Stratification Approaches to Identify Patients with Clostridioides difficile Infection at Risk for Multidrug-Resistant Organism Gut Microbiota Colonization.

Introduction: Multidrug-resistant organisms (MDRO) commonly colonize the gut microbiota of patients with Clostridioides difficile infection (CDI). This increases the likelihood of systemic infections with these MDROs. To help guide MDRO screening and/or empiric antibiotic therapy, we derived and compared predictive indices for MDRO gut colonization in patients with CDI.

High-level ceftazidime-avibactam resistance in conferred by the novel plasmid-mediated beta-lactamase CMY-185 variant.

Objectives: To characterize a variant associated with ceftazidime-avibactam (CZA) resistance from a serially collected isolate.

Methods: A patient with an intra-abdominal infection due to recurrent was treated with CZA. On day 48 of CZA therapy, with a CZA MIC of >256 mg/L was identified from abdominal drainage.

Fusobacteria behaving badly: Masquerading strains of strictly anaerobic Escherichiacoli misidentified due to the deletion of the hemB gene.

Three strictly anaerobic strains of Escherichia coli were misidentified as Fusobacterium mortiferum, due to a deletion of the hemB gene which is involved in anaerobic respiration. An unusual antimicrobial susceptibility pattern sparked the further diagnostic strategies that eventually identified these strains as true anaerobic E. coli This phenomenon is more common than appreciated and can have an impact on clinical practice including persistent and relapsing infections.

Systems biology evaluation of refractory Clostridioides difficile infection including multiple failures of fecal microbiota transplantation.

Background: Fecal microbiota transplantation (FMT) aims to cure Clostridioides difficile infection (CDI) through reestablishing a healthy microbiome and restoring colonization resistance. Although often effective after one infusion, patients with continued microbiome disruptions may require multiple FMTs. In this N-of-1 study, we use a systems biology approach to evaluate CDI in a patient receiving chronic suppressive antibiotics with four failed FMTs over two years.

The metabolic profile of Bifidobacterium dentium reflects its status as a human gut commensal.

Background: Bifidobacteria are commensal microbes of the mammalian gastrointestinal tract. In this study, we aimed to identify the intestinal colonization mechanisms and key metabolic pathways implemented by Bifidobacterium dentium.

Results: B.

Visualization of fidaxomicin association with the exosporium layer of Clostridioides difficile spores.

Background: Fidaxomicin has novel pharmacologic effects on C. difficile spore formation including outgrowth inhibition and persistent spore attachment. However, the mechanism of fidaxomicin attachment on spores has not undergone rigorous microscopic studies.

Fusobacteriumnucleatum Adheres to Clostridioides difficile via the RadD Adhesin to Enhance Biofilm Formation in Intestinal Mucus.

Background & Aims: Although Clostridioides difficile infection (CDI) is known to involve the disruption of the gut microbiota, little is understood regarding how mucus-associated microbes interact with C difficile. We hypothesized that select mucus-associated bacteria would promote C difficile colonization and biofilm formation.

Methods: To create a model of the human intestinal mucus layer and gut microbiota, we used bioreactors inoculated with healthy human feces, treated with clindamycin and infected with C difficile with the addition of human MUC2-coated coverslips.

Human intestinal enteroids as a model of -induced enteritis.

is an important nosocomial pathogen that produces toxins to cause life-threatening diarrhea and colitis. Toxins bind to epithelial receptors and promote the collapse of the actin cytoskeleton. toxin activity is commonly studied in cancer-derived and immortalized cell lines.

Eosinopenia and Binary Toxin Increase Mortality in Hospitalized Patients With Infection.

Background: Patients with infection (CDI) with either eosinopenia or infected with a binary toxin strain have increased likelihood of mortality. However, the relationship between binary toxin and eosinopenia to synergistically increase mortality has not been studied in humans. We hypothesized that patients with CDI due to binary toxin strains and concomitant peripheral eosinopenia would have a higher likelihood of inpatient mortality.

Constitutive expression of the cryptic vanGCd operon promotes vancomycin resistance in Clostridioides difficile clinical isolates.

Objectives: To describe, for the first time (to the best of our knowledge), the genetic mechanisms of vancomycin resistance in clinical isolates of Clostridioides difficile ribotype 027.

Methods: Clinical isolates and laboratory mutants were analysed: genomically to identify resistance mutations; by transcriptional analysis of vanGCd, the vancomycin resistance operon encoding lipid II d-alanine-d-serine that is less bound by vancomycin than native lipid II d-alanine-d-alanine; by imaging of vancomycin binding to cell walls; and for changes in vancomycin bactericidal activity and autolysis.

Results: Vancomycin-resistant laboratory mutants and clinical isolates acquired mutations to the vanSR two-component system that regulates vanGCd.

Bifidobacterium dentium Fortifies the Intestinal Mucus Layer via Autophagy and Calcium Signaling Pathways.

Much remains unknown about how the intestinal microbiome interfaces with the protective intestinal mucus layer. species colonize the intestinal mucus layer and can modulate mucus production by goblet cells. However, select strains can also degrade protective glycans on mucin proteins.

Epidemic Ribotype 027 Lineages: Comparisons of Texas Versus Worldwide Strains.

Background: The epidemic e ribotype 027 strain resulted from the dissemination of 2 separate fluoroquinolone-resistant lineages: FQR1 and FQR2. Both lineages were reported to originate in North America; however, confirmatory large-scale investigations of ribotype 027 epidemiology using whole genome sequencing has not been undertaken in the United States.

Methods: Whole genome sequencing and single-nucleotide polymorphism (SNP) analysis was performed on 76 clinical ribotype 027 isolates obtained from hospitalized patients in Texas with infection and compared with 32 previously sequenced worldwide strains.

Ridinilazole for the treatment of Clostridioides difficile infection.

Ridinilazole is a novel antibiotic being developed for the treatment of Clostridioides difficile infection (CDI). Ridinilazole has completed two phase II trials and phase III trials which are denoted Ri-CoDIFy 1 and 2, are planned (ClinicalTrials.gov identifiers: NCT03595553 and NCT03595566).

Environmental transmission of Clostridioides difficile ribotype 027 at a long-term care facility; an outbreak investigation guided by whole genome sequencing.

Objective: This article describes a CDI outbreak in a long-term care (LTC) facility that used molecular typing techniques and whole-genome sequencing to identify widespread dissemination of the clonal strain in the environment which was successfully removed after terminal cleaning.

Setting: This study was conducted in a long-term care facility in Texas.

Methods: A recently hospitalized LTC patient was diagnosed with CDI followed shortly thereafter by 7 subsequent CDI cases.

Clostridioides (Formerly Clostridium) difficile Infection During Hospitalization Increases the Likelihood of Nonhome Patient Discharge.

Background: Clostridioides (formerly Clostridium) difficile infection (CDI) is associated with significant morbidity and mortality, including frequent hospitalizations. However, the impact of CDI after hospital discharge is poorly understood. The purpose of this study was to assess patient discharge disposition and understand CDI-related risk factors for nonhome discharge.

Nitric oxide production by glomerular podocytes.

Nitric Oxide (NO), a potent vasodilator and vital signaling molecule, has been shown to contribute to the regulation of glomerular ultrafiltration. However, whether changes in NO occur in podocytes during the pathogenesis of salt-sensitive hypertension has not yet been thoroughly examined. We showed here that podocytes produce NO, and further hypothesized that hypertensive animals would exhibit reduced NO production in these cells in response to various paracrine factors, which might contribute to the damage of glomeruli filtration barrier and development of proteinuria.

A Protocol to Characterize the Morphological Changes of Clostridium difficile in Response to Antibiotic Treatment.

Assessment of antibiotic action with new drug development directed towards anaerobic bacteria is difficult and technically demanding. To gain insight into possible MOA, morphologic changes associated with antibiotic exposure can be visualized using scanning electron microscopy (SEM). Integrating SEM imaging with traditional kill curves may improve our insight into drug action and advance the drug development process.

Community Environmental Contamination of Toxigenic .

Background: infection is often considered to result from recent acquisition of a isolate in a healthcare setting. However, spores can persist for long periods of time, suggesting a potentially large community environmental reservoir. The objectives of this study were to assess community environmental contamination of toxigenic and to assess strain distribution in environmental versus clinical isolates.

Intravital imaging of the kidney in a rat model of salt-sensitive hypertension.

Hypertension is one of the most prevalent diseases worldwide and a major risk factor for renal failure and cardiovascular disease. The role of albuminuria, a common feature of hypertension and robust predictor of cardiorenal disorders, remains incompletely understood. The goal of this study was to investigate the mechanisms leading to albuminuria in the kidney of a rat model of hypertension, the Dahl salt-sensitive (SS) rat.

The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling.

Podocytes are becoming a primary focus of research efforts due to their association with progressive glomeruli damage in disease states. Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca flux in podocytes. We showed here with patch-clamp electrophysiology that Ang II activates TRPC channels; then using confocal calcium imaging we demonstrated that Ang II-dependent stimulation of Ca influx in the podocytes is precluded by blocking either AT or AT receptors (ATRs).

Cadazolid for the treatment of Clostridium difficile.

Antibiotic development goals for CDI include potent antimicrobial effect against C. difficile, limited killing of host microbiota, potential effect on spores, and ability to interfere with toxin production. Cadazolid, a novel, non-absorbable hybrid antibiotic has many of these criteria.

Novel antibiotics in development to treat Clostridium difficile infection.

Purpose Of Review: Clostridium difficile infections (CDI) remain a challenge to treat clinically due primarily to limited number of antibiotics available and unacceptably high recurrence rates. Because of this, there has been significant demand for creating innovative therapeutics, which has resulted in the development of several novel antibiotics.

Recent Findings: This review updates seven different antibiotics that are currently in development to treat CDI including fidaxomicin, surotomycin, ridinilazole, ramoplanin, cadazolid, LFF571, and CRS3123.

A novel method for imaging the pharmacological effects of antibiotic treatment on Clostridium difficile.

Clostridium difficile is a significant cause of nosocomial-acquired infection that results in severe diarrhea and can lead to mortality. Treatment options for C. difficile infection (CDI) are limited, however, new antibiotics are being developed.