Phase I trial comparing bile acid and short-chain fatty acid alterations in stool collected from human subjects treated with omadacycline or vancomycin.

Unlabelled: Omadacycline, an aminomethylcycline tetracycline, has a low propensity to cause infection (CDI) in clinical trials. Omadacycline exhibited a reduced bactericidal effect compared with vancomycin on key microorganisms implicated in bile acid homeostasis and short-chain fatty acids (SCFAs), key components of CDI pathogenesis. The purpose of this study was to assess bile acid and SCFA changes in stool samples from healthy volunteers given omadacycline or vancomycin.

Proton pump inhibitor effect on macrophage and neutrophil function: a systematic review.

Background: Proton pump inhibitors (PPIs) are one of the most used drugs worldwide. While generally considered safe, the usage of PPIs is associated with several adverse outcomes including acute infectious diseases. PPIs influence macrophage and neutrophil function although a systematic review has never been undertaken.

A quantitative PCR to detect non-toxigenic .

species lacking toxin genes (non-toxigenic or NTCD) may confer protection against CDI. However, current diagnostic tests detect either toxin proteins or toxin genes and cannot detect NTCD. This study developed a molecular testing method that uniquely identified NTCD and assessed its prevalence in a clinical cohort.

Microbiome impact of ibezapolstat and other infection relevant antibiotics using humanized mice.

Background: Ibezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for treatment of infection (CDI). Previous studies demonstrated IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done.

From Chaos to Clarity? The Quest for Effective Probiotics in Antibiotic-Associated Diarrhea.

Antibiotic-associated diarrhea (AAD) frequently complicates treatment of infections. A recent randomized, double-blind, placebo-controlled trial tested a proprietary probiotic mixture and found that it reduced the incidence of AAD by 16%. This is encouraging for patients, but future progress on probiotics for AAD and other conditions depends on transparency around strain selection, probiotic design guided by preclinical mechanistic studies, and rigorously conducted human studies.

Reduced Vancomycin Susceptibility in Is Associated With Specific Ribotypes.

Background: Reduced vancomycin (VAN) susceptibility in clinical isolates is correlated with poor clinical outcomes. However, factors associated with infection with these strains are unknown. The goal of this study was to determine risk factors for reduced VAN susceptibility among clinical isolates of .

Fidaxomicin resistance in : a systematic review and predictive modeling with RNA polymerase binding sites.

Fidaxomicin (FDX), an RNA polymerase (RNAP) inhibitor antibiotic, is a guideline-recommended therapy for infection. Mutations associated with reduced FDX minimum inhibitory concentrations (MICs) have been identified. However, the molecular characterization of these mutations on FDX binding and the development of FDX resistance have not been studied.

Emerging ribotypes have divergent metabolic phenotypes.

Unlabelled: is a gram-positive spore-forming pathogen that commonly causes diarrheal infections in the developed world. Although is a genetically diverse species, certain ribotypes are overrepresented in human infections. It is unknown if metabolic adaptations are essential for the emergence of these epidemic ribotypes.

Estimating infection-associated readmission rates: A systematic review and meta-analysis.

Background: The economic burden of infection (CDI) is considerable and mostly associated with a high frequency of hospitalizations. Numerous publications have demonstrated that CDI is associated with a higher risk of hospital readmission, but not always a specific rate or attributable to disease recurrence.

Methods: In this systematic review, we describe the incidence of 30-day CDI-associated readmission rates and the effect of active interventions.

Development and validation of LC-MS/MS for quantifying omadacycline from stool for gut microbiome studies.

This study developed and validated a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify omadacycline and its epimerization in stool to facilitate microbiome studies. Omadacycline was extracted in a methanol-water-ethylenediaminetetraacetic acid (ETDA) solvent containing deuterated omadacycline as internal standard, followed by dilution. In an optimal gradient elution mode, omadacycline and its C4 epimer were separated within 5 min on reversed-phase C18 column.

Reduced Vancomycin Susceptibility in Clostridioides difficile Is Associated With Lower Rates of Initial Cure and Sustained Clinical Response.

Background: Epidemiologic studies have shown decreasing vancomycin susceptibility among clinical Clostridioides difficile isolates, but the impact on patient outcomes is unknown. We hypothesized that reduced vancomycin susceptibility would be associated with decreased rates of sustained clinical response (SCR).

Methods: This multicenter cohort study included adults with C.

Antibacterial activity of ibezapolstat against antimicrobial-resistant clinical strains of .

Antimicrobial resistance is emerging in clinical strains of . Ibezapolstat (IBZ) is a DNA polymerase IIIC inhibitor that has completed phase II clinical trials. IBZ has potent activity against wild-type, susceptible strains but its effect on strains with reduced susceptibility to metronidazole (MTZ), vancomycin (VAN), or fidaxomicin (FDX) has not been tested.

Microscopy methods for Clostridioides difficile.

Microscopic technologies including light and fluorescent, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and cryo-electron microscopy have been widely utilized to visualize Clostridioides difficile at the molecular, cellular, community, and structural biology level. This comprehensive review summarizes the microscopy tools (fluorescent and reporter system) in their use to study different aspects of C. difficile life cycle and virulence (sporulation, germination) or applications (detection of C.

A Randomized, Double-Blind, Phase 3 Safety and Efficacy Study of Ridinilazole Versus Vancomycin for Treatment of Clostridioides difficile Infection: Clinical Outcomes With Microbiome and Metabolome Correlates of Response.

Background: Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI.

Efficacy and Health-Related Quality of Life Impact of Fecal Microbiota, Live-jslm: A Post Hoc Analysis of PUNCH CD3 Patients at First Recurrence of Clostridioides difficile Infection.

Introduction: Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients' health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments.

Healthcare Resource Utilization and Discharge Readiness in Adult Hospitalized Patients With Candidemia or Invasive Candidiasis Who Received an Echinocandin: An Analysis of United States Hospitals.

Background: Scant real-world outcomes data are available among hospitalized patients with candidemia (C) or invasive candidiasis without candidemia (IC) who were treated with an echinocandin and few have assessed if there is an opportunity to accelerate the transition of their care to the outpatient setting. This study described the outcomes associated with echinocandin therapy for C/IC and determined the proportion of patients on an echinocandin at hospital discharge (HD) who were potentially eligible for an earlier HD.

Methods: A retrospective, multicenter observational study was performed using the PINC AI Healthcare Database (January 2016-April 2019) of hospitalized adult patients with C/IC who received ≥3 days of an echinocandin.

Increased Prevalence of Clostridioides difficile Infection Among Pediatric Oncology Patients: Risk Factors for Infection and Complications.

Background: Pediatric oncology patients, who are typically immunosuppressed, exposed to medications associated with increased Clostridioides difficile infection (CDI) risk and hospitalized, are expected to be at substantial risk for infection and complications. Although certain C. difficile ribotypes have been associated with more severe infection in adults, such an association has not been described in children.

Review Article: Safety of Live Biotherapeutic Products Used for the Prevention of Clostridioides difficile Infection Recurrence.

Live biotherapeutic products (LBPs) represent a new class of therapeutics indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in adults. However, microbiota-based therapies have been used in CDI management before the Food and Drug Administration (FDA) designated this new drug class. The regulation of these microbiome-based therapies has varied, and several safety concerns have arisen over time.

Fecal Pharmacokinetics and Gut Microbiome Effects of Oral Omadacycline Versus Vancomycin in Healthy Volunteers.

Background: Clostridioides difficile infection (CDI) is a common healthcare-associated infection with limited treatment options. Omadacycline, an aminomethylcycline tetracycline, has potent in vitro activity against C difficile and a low propensity to cause CDI in clinical trials. We aimed to assess fecal pharmacokinetics and gut microbiome effects of oral omadacycline compared to oral vancomycin in healthy adults.

Effect of Fecal Microbiota, Live-Jslm (REBYOTA [RBL]) on Health-Related Quality of Life in Patients With Recurrent Infection: Results From the PUNCH CD3 Clinical Trial.

Background: Recurrence of infection (rCDI) is common, prolonging disease morbidity and leading to poor quality of life. We evaluated disease-specific health-related quality of life (HRQL) in patients with rCDI treated with fecal microbiota, live-jslm (REBYOTA [RBL]; Rebiotix) versus placebo.

Methods: This was a secondary analysis of a randomized, double-blind, placebo-controlled phase 3 study (PUNCH CD3).

Donor-recipient specificity and age-dependency in fecal microbiota therapy and probiotic resolution of gastrointestinal symptoms.

Fecal microbiota transplantation (FMT) has proven to be an effective treatment for recurrent Clostridioides difficile infection (rCDI) in both adult and pediatric patients. However, as microbiome development is a critical factor in children, it remains unclear whether adult fecal donors can provide age-appropriate functional restoration in pediatric patients. To address this issue, we conducted an integrated systems approach and found that concordant donor strain engraftment, along with metabolite restoration, are associated with FMT outcomes in both adult and pediatric rCDI patients.

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.