Emergence and Spread of Clostridioides difficile Isolates With Reduced Fidaxomicin Susceptibility in an Acute Care Hospital.

Background: There have been several recent reports of Clostridioides difficile infection (CDI) due to isolates with reduced fidaxomicin susceptibility (minimum inhibitory concentration [MIC] ≥ 2 µg/mL). However, the clinical implications are uncertain because fidaxomicin achieves high concentrations in the intestinal tract.

Methods: In an acute care hospital, we conducted a 3-year cohort study of patients with CDI to determine the frequency of infection with isolates with reduced fidaxomicin susceptibility and the impact on response to fidaxomicin treatment.

Enteritis necroticans and Clostridium perfringens type C; Epidemiological and pathological findings over the past 20 years.

Enteritis necroticans (EN) in humans caused by infection with Clostridium perfringens type C, once thought limited to the highlands of Papua New Guinea has been identified sporadically worldwide. Outbreaks still occur among children in low-income countries and isolated cases occur among children and adults in other countries. Here the disease seems to be associated with diabetes mellitus and other risk factors.

Informing estimates of probability of infection for testing and treatment: expert consensus from a modified-Delphi procedure.

Background: infection (CDI) may be misdiagnosed if testing is performed in the absence of signs or symptoms of disease. This study sought to support appropriate testing by estimating the impact of signs, symptoms, and healthcare exposures on pre-test likelihood of CDI.

Methods: A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI.

Risk of rehospitalization due to infection among hospitalized patients with : a cohort study.

Background: Reducing rehospitalization has been a primary focus of hospitals and payors. Recurrence of infection (CDI) is common and often results in rehospitalization. Factors that influence rehospitalization for CDI are not well understood.

Efficacy of Fecal Microbiota, Live-jslm (REBYOTA®), Among Patients Exposed to Non- Infection Antibiotics: Post Hoc Subgroup Analysis of a Phase 2 Open-Label Study.

Background: Antibiotic use is a major risk factor for recurrent infection (CDI) due to the associated disruption in gut microbiota. Fecal microbiota, live-jslm (REBYOTA®; RBL, previously RBX2660), is the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent CDI in adults following standard-of-care antibiotic treatment. To investigate the impact of non-CDI antibiotics on the durability of RBL, a subgroup analysis was conducted on PUNCH™ Open-Label study participants who received non-CDI antibiotics during the period between RBL administration and up to 2 years after.

Epidemiology of infection at one hospital 10 years after an outbreak of the epidemic strain BI/027: changing strain prevalence, antimicrobial susceptibilities, and patient antibiotic exposures.

In contrast to the epidemiology 10 years earlier at our hospital when the epidemic restriction endonuclease analysis (REA) group strain BI accounted for 72% of isolates recovered from first-episode infection (CDI) cases, BI represented 19% of first-episode CDI isolates in 2013-2015. Two additional REA group strains accounted for 31% of isolates (Y, 16%; DH, 12%). High-level resistance to fluoroquinolones and azithromycin was more common among BI isolates than among DH, Y, and non-BI/DH/Y isolates.

Management and Outcomes of Patients at a Specialty Clinic for Infection.

Vancomycin and fidaxomicin taper regimens were the most common treatment strategies employed but nearly half of patients (40/83) referred to our infection (CDI) clinic did not require further treatment. The overall 60-day CDI recurrence rate was 16.9% (11/65).

Fecal Microbiota, Live-jslm for the Prevention of Recurrent Clostridioides difficile Infection : Subgroup Analysis of PUNCH CD2 and PUNCH CD3.

Goals: To assess fecal microbiota, live-jslm (REBYOTA, abbreviated as RBL, formerly RBX2660) efficacy and safety in participants grouped by recurrent Clostridioides difficile infection (rCDI) risk factors and treatment-related variables.

Background: RBL is the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration for the prevention of rCDI in adults after antibiotic treatment for rCDI.

Study: Treatment success rates across subgroups for PUNCH CD3 (NCT03244644) were estimated using a Bayesian hierarchical model, borrowing data from PUNCH CD2 (NCT02299570).

Efficacy of bezlotoxumab to prevent recurrent Clostridioides difficile infection (CDI) in patients with multiple prior recurrent CDI.

Among 23 patients with multiply recurrent Clostridioides difficile infection (mrCDI) who received bezlotoxumab at the end of antibiotic treatment a sustained clinical response of 91 % at 30 days and 78 % at 90 days was achieved. Bezlotoxumab administered at the end of antibiotic treatment was effective in patients with mrCDI.

Effect of the COVID-19 Pandemic on Rates and Epidemiology of Infection in One VA Hospital.

The COVID-19 pandemic was associated with increases in some healthcare-associated infections. We investigated the impact of the pandemic on the rates and molecular epidemiology of infection (CDI) within one VA hospital. We anticipated that the potential widespread use of antibiotics for pneumonia during the pandemic might increase CDI rates given that antibiotics are a major risk for CDI.

Characteristics and outcomes of infection after a change in the diagnostic testing algorithm.

Background: Polymerase chain reaction (PCR) testing for the detection of is a highly sensitive test. Some clinical laboratories have included a 2-step testing algorithm utilizing PCR plus toxin enzyme immunoassays (EIAs) to increase specificity.

Objective: To determine the risk factors and outcomes of PCR-positive/toxin-positive encounters compared to PCR-positive/toxin-negative encounters.

Antimicrobial susceptibility of Clostridioides difficile to omadacycline and comparator antimicrobials.

Background: Omadacycline is a novel aminomethylcycline tetracycline antimicrobial that was approved for the treatment of community-associated bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in 2018. Omadacycline has demonstrated a high degree of in vitro activity towards Clostridioides difficile and previous data have hypothesized that use of omadacycline for CABP or ABSSSI may decrease the risk of C. difficile infections.

Effective Colonization by Nontoxigenic Clostridioides difficile REA Strain M3 (NTCD-M3) Spores following Treatment with Either Fidaxomicin or Vancomycin.

Colonization with nontoxigenic Clostridioides difficile strain M3 (NTCD-M3) has been demonstrated in susceptible hamsters and humans when administered after vancomycin treatment. NTCD-M3 has also been shown to decrease risk of recurrent C. difficile infection (CDI) in patients following vancomycin treatment for CDI.

Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults.

This clinical practice guideline is a focused update on management of Clostridioides difficile infection (CDI) in adults specifically addressing the use of fidaxomicin and bezlotoxumab for the treatment of CDI. This guideline was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). This guideline is intended for use by healthcare professionals who care for adults with CDI, including specialists in infectious diseases, gastroenterologists, hospitalists, pharmacists, and any clinicians and healthcare providers caring for these patients.

Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults.

This clinical practice guideline is a focused update on management of Clostridioides difficile infection (CDI) in adults specifically addressing the use of fidaxomicin and bezlotoxumab for the treatment of CDI. This guideline was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). This guideline is intended for use by healthcare professionals who care for adults with CDI, including specialists in infectious diseases, gastroenterologists, hospitalists, pharmacists, and any clinicians and healthcare providers caring for these patients.

Translating nanoparticle dosimetry from conventional systems to occupational inhalation exposures.

As encouraged by st , researchers increasingly apply high-throughput approaches to identify and characterize nanoparticle hazards, including conventional aqueous cell culture systems to assess respiratory hazards. Translating nanoparticle dose from conventional toxicity testing systems to relevant human exposures remains a major challenge for assessing occupational risk of nanoparticle exposures. Here, we explored existing computational tools and data available to translate nanoparticle dose metrics from cellular test systems to inhalation exposures of silver nanoparticles in humans.

A Tapered-pulsed Fidaxomicin Regimen Following Treatment in Patients With Multiple Clostridioides difficile Infection Recurrences.

We treated 46 patients with multiple recurrent Clostridioides difficile infections (mrCDI) using a tapered-pulsed (T-P) fidaxomicin regimen, the majority of whom failed prior T-P vancomycin treatment. Sustained clinical response rates at 30 and 90 days were 74% (34/46) and 61% (28/46). T-P fidaxomicin shows promise for management of mrCDI.

The Relative Role of Toxins A and B in the Virulence of .

Most pathogenic strains of possess two large molecular weight single unit toxins with four similar functional domains. The toxins disrupt the actin cytoskeleton of intestinal epithelial cells leading to loss of tight junctions, which ultimately manifests as diarrhea in the host. While initial studies of purified toxins in animal models pointed to toxin A (TcdA) as the main virulence factor, animal studies using isogenic mutants demonstrated that toxin B (TcdB) alone was sufficient to cause disease.

Fidaxomicin for the treatment of in children.

Fidaxomicin is an oral narrow-spectrum novel 18-membered macrocyclic antibiotic that was initially approved in 2011 by the US FDA for the treatment of infections (CDI) in adults. In February 2020, the FDA approved fidaxomicin for the treatment of CDI in children age >6 months. In adults, fidaxomicin is as efficacious as vancomycin in treating CDI and reduces the risk of recurrent CDI.

Sequential introduction of a multistep testing algorithm and nucleic acid amplification testing leading to an increase in detection and a trend toward increased strain diversity.

Background: Most clinical microbiology laboratories have replaced toxin immunoassay (EIA) alone with multistep testing (MST) protocols or nucleic acid amplification testing (NAAT) alone for the detection of C. difficile.

Objective: Study the effect of changing testing strategies on C.