THE NOVEL CORONAVIRUS INFECTION (COVID-19) CONCURRENT WITH PSEUDOMEMBRANOUS COLITIS IN THE EARLY POSTPARTUM PERIOD: A CLINICAL CASE.

Background: Women are most at risk for Clostridium difficile infection in the early postpartum period. Clostridium difficile-associated colitis may be mistaken for the intestinal form of COVID-19 during the ongoing novel coronavirus infection pandemic. Case report: The paper describes a clinical case of a female patient diagnosed with the novel coronavirus infection and Clostridium difficile-associated pseudomembranous colitis in the early postpartum period. It depicts the diagnosis and treatment of the identified concurrent pathology. It demonstrates data from of an endoscopic examination of the colon and spiral computed tomography of the chest and provides laboratory confirmation of the infectious etiology of comorbidity. There are data available in the literature on the high rate and recurrent course of pseudomembranous colitis in the early postpartum period. It is noted that timely C. difficile eradication and pathogenetic treatment for the novel coronavirus infection allow relief of clinical symptoms. Conclusion(s): The case of the novel coronavirus infection concurrent with Clostridium difficile-associated pseudomembranous colitis in the early postpartum period is of interest in connection with the need for differential diagnosis of the etiology of diarrheal syndrome, the precise identification of which determines the further tactics of patient management and the nature of anti-epidemic measures.Copyright © A group of authors, 2021.

Clostridium perfringens spores in urology hospital

Background: Clostridium spp. spores are resistant to many factors, including alcohol-based disinfectants. The presence of clostridial spores in a hospital environment may lead to infection outbreaks among patients and health care workers. Background: This study is aimed to detect clostridial spores in the aurology hospital using C diff Banana BrothTM and assess the antibiotic sensitivity and toxinotypes of isolates. Methods: After diagnosing COVID-19 in medical staff and closing an 86-bed urology hospital in 2020 for H2O2 fogging, 58 swabs from the hospital environment were inoculated to C diff Banana BrothTM, incubated at 37 degrees C for 14 days, checked daily, and positive broths were sub-cultured anaerobically for 48 h at 37 degrees C. After identification, multiplex PCR (mPCR) was performed for Clostridium perfringens, C. difficile toxin genes, and minimum inhibitory concentration (MIC) determination. Results: In this study, 16 out of 58 (~ 28%) strains of Clostridium spp. were cultured: 11 - C. perfringens, 2 - C. baratii, and 1 each of C. paraputrificum, C. difficile, and C. clostridioforme. 11 C. perfringens were positive for the cpa, 7 - the cpb2, 2 - cpiA, and 1 - cpb toxin genes. All isolates were sensitive to metronidazole, vancomycin, moxifloxacin, penicillin/tazobactam, and rifampicin. Two out of the 11 C. perfringens strains were resistant to erythromycin and clindamycin. Conclusions: Regardless of the performed H2O2 fogging, antibiotic-resistant, toxigenic strains of C. perfringens (69%) obtained from the urology hospital environment were cultured using C diff Banana BrothTM, indicating the need to develop the necessary sanitary and epidemiological procedures in this hospital.

Loss of Bifidobacteria in Lyme Disease: Cause or Effect

Introduction: Lyme disease is a poorly understood condition which starts with a rash but may continue with chronic fatigue and neurological symptoms. Approximately 1 in 5 early Lyme disease patients have GI symptoms, such as nausea, anorexia, abdominal pain, or diarrhea. Lyme disease is thought to be cased by microbes in the spirochetes phylum transmitted by black legged ticks. Lyme-related healthcare costs in America exceed 1.3 billion dollars annually. Bifidobacteria are known for their beneficial probiotic actions within the human gut microbiome. Their numbers are reduced in severe COVID-19, Clostridioides difficile infection and Inflammatory Bowel Disease. To our knowledge Bifidobacteria levels have not been studied in Lyme disease patients. Given the importance of Bifidobacterium abundance in other diseases, we focused on relative abundance of Bifidobacterium in fecal samples of patients with Lyme disease compared to controls. Method(s): Fecal samples were assessed for relative abundance of Bifidobacterium in Healthy Control subjects without Lyme disease (n=20) compared to patients with Lyme disease (n=39). The average symptom duration in patients with Lyme disease was 5 years and none were on antibiotics 2 weeks prior to sample collection (range of symptoms from 1 month to 20 years, all treated initially with antibiotics).Metagenomics Next Generation sequencing was performed on fecal samples, where DNA samples were extracted and normalized for library downstream analysis using Shotgun Methodology. Mann- Whitney Statistical test was used for comparison. This study was IRB approved. Result(s): Relative Abundance of bifidobacteria was significantly decreased (p< 0.0001) in patients with Lyme disease. Median and interquartile range (IQR) were: Control (Median:4.175%;IQR:1.72-10.27%) and Lyme disease (Median:0.0014%;IQR:0.00%-0.96%)(Figure). 30/39 Lyme disease patients (77%) were found to possess < 1% relative abundance of Bifidobacterium in their stool sample. Of interest only 1/39 samples showed presence of Spirochetes in stool samples. Conclusion(s): This is the first study that demonstrates low levels of Bifidobacteria in patients with chronic Lyme disease. These results raise three questions;whether the disease was caused by 1. the original microbe creating loss of Bifidobacterium 2. baseline low Bifidobacteria due likely to either diet or medications or 3. excessive treatment. Given Lyme disease comprises a gut dysbiosis issue, therapies should also aim at restoration of depleted Bifidobacteria. (Figure Presented).

Clostridium Difficillae Infection in Post-Covid Patients

Intro: The ongoing pandemic caused by the SARS-CoV-2 virus has brought many new insights into medicine. During the first months of the pandemic, when there were no comprehensive guidelines for precise antimicrobial therapy, empirical overuse of broad-spectrum antibiotics was observed. Which resulted in the development of clostidium infection in certain cases. In our report, we address 83 cases of clostridial colitis in post-covid patients from 3/2020 to 3/2021 and their specific therapy. Method(s): Retrospective analysis of risk factors for clostridial infection and therapy of clostridial colitis. Finding(s): In the period 3/2020-3/2021, 9617 patients were diagnosed with SARS-CoV-2 virus infection in our hospital, of which 1247 were hospitalized. In 83 cases, clostridial colitis occurred during or after the covid infection had resolved. Mortality in this group was 17%, which corresponds to 14 patients. Previous empirical administered antiobiotics in COVID-19 infection contributed to the development of clostridial colitis in case of 22 patients (27%) by clarithromycin, in 14 pacients (17%) by penicillins and by 3rd generation cephalosporins in 9 patients (11%). The average duration of therapy with broad-spectrum antibiotics was 15.63 days (+-8.99). Other risk factors we observed are: PPI use (25%), active malignant disease (10%), previous glucocorticoid therapy (22%). Vancomycin was used in clostridial infection therapy in 47% (39), metronidazole in 31% (25) and fidaxonicin in 7% (6). In the group, we observed recurrence of clostridium difficile infection in 14% of patients and FMT was performed in 6 patients. Conclusion(s): This study shows a higher percentage of clostridial infection in cases of long-term therapy with broad-spectrum antibiotics. It also points to the effect of specific antimicrobial therapy for infection caused by the bacterium Clostridium difficile and the possibility of using fecal bacteriotherapy.Copyright © 2023

Outcomes of Patients Receiving Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infection - A Multicenter Study

Introduction: Clostridioides difficile infection (CDI) is the most common healthcare-associated infection in the United States (US). Treatment guidelines have evolved resulting in better outcomes however recurrent disease remains a major issue associated with significant morbidity despite best practices. Bezlotoxumab (BEZ) is a fully humanized monoclonal antibody approved by FDA in 2017 for prevention of recurrent CDI (rCDI). Limited real-world data are available regarding BEZ usage outside of clinical trials. In this multicenter study, we aim to report our experience with BEZ at a large healthcare system in northeast US. Method(s): We retrospectively reviewed all consecutive adult patients who received BEZ from 1/2017 until 12/2021 at Yale-New Haven Health System and had at least 90 days of follow up. Data collected for each patient included demographics, medical co-morbidities, adverse events to BEZ and rates of rCDI following BEZ. Result(s): A total of 114 patients were included with a mean age of 67.3 years (range 25-97);74 (64.9%) were female. There has been a recent increased utilization of BEZ with more than half of our sample (n=73, 64%) being since the beginning of COVID-19 pandemic and 38.6% in 2021 alone. Most patients were treated with vancomycin (88.6%) while 11 (9.7%) received fidaxomicin. Median time from most recent CDI episode to BEZ infusion was 22.5 days. Notably, 17.5% were not on active CDI treatment when they received BEZ. 30 (26.3%) received BEZ after initial CDI, 52 (45.6%) had one prior recurrent episode while 32 (28.1%) had 2 or more previous recurrences. Among those who received BEZ, 10 patients (8.8%) experienced 90-day rCDI, of these 9 (90%) had history of at least 1 episode of rCDI. There were no statistically significant differences in baseline characteristics between r-CDI and non-rCDI groups (Table). Furthermore, no statistical difference in rCDI between those who were on CDI treatment at the time of BEZ and those who completed it before BEZ [9/94 (9.6%) vs 1/20 (5.0%);p=0.511]. Conclusion(s): Our real-life data confirms that Bezlotoxumab appears to be safe and effective in preventing rCDI in this population whether given during CDI treatment or after. BEZ represents an important treatment option in this highly morbid population. Further studies are needed to determine the benefit of early administration of BEZ after index CDI in those at risk and to consider utilization shifts following the 2021 ACG updated guideline recommendations advising it's usage.

Improving care for patients with Clostridioides difficile infection: A clinical practice and healthcare systems perspective.

Introduction: Arriving at a C. difficile infection (CDI) diagnosis, treating patients and dealing with recurrences is not straightforward, but a comprehensive and well-rounded understanding of what is needed to improve patient care is lacking. This manuscript addresses the paucity of multidisciplinary perspectives that consider clinical practice related and healthcare system-related challenges to optimizing care delivery. Methods: We draw on narrative review, consultations with clinical experts and patient representatives, and a survey of 95 clinical and microbiology experts from the UK, France, Italy, Australia and Canada, adding novel multi-method evidence to the knowledge base. Results and discussion: We examine the patient pathway and variations in clinical practice and identify, synthesize insights on and discuss associated challenges. Examples of key challenges include the need to conduct multiple tests for a conclusive diagnosis, treatment side-effects, the cost of some antibiotics and barriers to access of fecal microbiota transplantation, difficulties in distinguishing recurrence from new infection, workforce capacity constraints to effective monitoring of patients on treatment and of recurrence, and ascertaining whether a patient has been cured. We also identify key opportunities and priorities for improving patient care that target both clinical practice and the wider healthcare system. While there is some variety across surveyed countries' healthcare systems, there is also strong agreement on some priorities. Key improvement actions seen as priorities by at least half of survey respondents in at least three of the five surveyed countries include: developing innovative products for both preventing (Canada, Australia, UK, Italy, and France) and treating (Canada, Australia, and Italy) recurrences; facilitating more multidisciplinary patient care (UK, Australia, and France); updating diagnosis and treatment guidelines (Australia, Canada, and UK); and educating and supporting professionals in primary care (Italy, UK, Canada, and Australia) and those in secondary care who are not CDI experts (Italy, Australia, and France) on identifying symptoms and managing patients. Finally, we discuss key evidence gaps for a future research agenda.

Cilta-Cel Efficacy and Safety in Patients with Progressive Multiple Myeloma after Exposure to Non-Cellular Anti-BCMA Immunotherapy

Introduction: CARTITUDE-2 (NCT04133636) is a phase 2, multicohort study evaluating cilta-cel, an anti-BCMA CAR-T therapy, in several multiple myeloma (MM) patient (pt) populations. Objective(s): To report updated results with longer follow-up on cohort C pts with previous exposure to a non-cellular anti- BCMA immunotherapy. Method(s): Cohort C pts had progressive MM after treatment (tx) with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and non-cellular BCMA-targeting agent. A single cilta-cel infusion (target dose 0.75x106 CAR+ viable T cells/kg) was administered 5-7 days post lymphodepletion. Primary endpoint was minimal residual disease (MRD) negativity at 10-5. Secondary endpoints included overall response rate (ORR), duration of response (DOR), and adverse events (AEs). Result(s): As of June 1, 2022, 20 pts (13 ADC exposed;7 BsAb exposed) were treated with cilta-cel;4 pts did not receive cilta-cel due to either low cellular yield (n=2, 1 in each group) or death due to progressive disease (PD) prior to dosing (n=2, 1 in each group) and 6 pts received anti-BCMA tx as their last line of therapy (n=4 ADC, n=2 BsAb). During prior anti-BCMA tx, best responses included VGPR (ADC: 2 pts;BsAb: 1 pt), sCR (ADC: 1 pt), and CR (BsAb: 1 pt);the rest had best response of stable disease or PD (1 pt not evaluable). Baseline characteristics are presented in Figure 1A. Median time from last anti- BCMA agent to cilta-cel infusion was 195 d;median administered dose of cilta-cel was 0.65x106 CAR+ viable T cells/kg. At a median follow-up of 18.0 mo, 7/10 evaluable pts (70%) were MRD negative at 10-5 (ADC: 5/7 [71.4%], BsAb: 2/3 [66.7%]). ORR: full cohort, 60%;ADC, 61.5%;BsAb, 57.1% (Figure 1B). Median DOR: full cohort, 12.8 mo;ADC, 12.8 mo;BsAb, 8.2 mo. Median PFS: full cohort, 9.1 mo;ADC, 9.5 mo;BsAb, 5.3 mo. Cilta-cel responders had a shorter median duration of last anti- BCMA agent exposure (29.5 d) compared with non-responders (63.5 d). Responders also had a longer median time from last anti-BCMA tx exposure to apheresis (161.0 d) than non-responders (56.5 d). Most common AEs were hematologic. CRS: n=12 (60%;all Gr1/2), median time to onset 7.5 d, median duration 6.0 d. ICANS: n=4 (20%, 2 Gr3/4), median time to onset 9.0 d, median duration 7.0 d. No patient had movement or neurocognitive tx emergent AE/parkinsonism. There were 12 deaths (PD: 8;COVID-19 pneumonia: 2 [not tx related];subarachnoid hemorrhage: 1 [not tx related];C. difficile colitis: 1 [tx related]). (Figure Presented)(Figure Presented)Conclusions: Pts with heavily pretreated MM and previous exposure to a non-cellular anti-BCMA therapy had favorable responses to cilta-cel. However, depth and DOR appear lower than that seen in anti-BCMA-naive pts treated with cilta-cel (at 27.7 mo, median DOR was not reached in heavily pre-treated but anti-BCMA naive CARTITUDE-1 pts). These data may inform tx plans, including sequencing and washout period between BCMA-targeting agentsCopyright © 2023 American Society for Transplantation and Cellular Therapy

L-Ornithine-L-Aspartate and Intermittent Renal Replacement Therapy in Fulminant Hepatitis A: A Case Report

Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. Since the introduction of an efficient vaccine, the incidence of infection has decreased but the number of cases has risen due to widespread community outbreaks among unimmunized individuals. Classic symptoms include fever, malaise, dark urine, and jaundice, and are more common in older children and adults. People are often most infectious 14 days prior to and 7 days following the onset of jaundice. We will discuss the case of a young male patient, diagnosed with acute hepatitis A, leading to fulminant hepatitis refractory to conventional therapy and the development of subsequent kidney injury. The medical treatment through the course of hospitalization was challenging and included the use of L-ornithine-L-aspartate and prolonged intermittent hemodialysis, leading to a remarkable outcome. Hepatitis A is usually self-limited and vaccine-preventable;supportive care is often sufficient for treatment, and chronic infection or chronic liver disease rarely develops. However, fulminant hepatitis, although rare, can be very challenging to manage as in the case of our patient.Copyright © 2023 The Author(s).

IDWeek 2022

IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). For the first time since the COVID-19 public health emergency began, IDWeek 2022 returned to in-person attendance. It was held in Washington, D.C., and the meeting comprised 5 days of live sessions and on-demand content that included posters and oral presentations.Copyright © 2023 Clarivate.

Care for an elderly frail woman with double infection by Clostridium difficile and COVID-19 in the hospital setting

The objective was to present an individualized nursing plan of care for a 94-year-old woman, presenting frailty, without cognitive deterioration, coming from a nursing home and admitted to the Internal Medicine Unit by referral from the Emergency Unit, due to presenting infection by Clostridium difficile and respiratory infection by COVID-19. After assessment at admission, following Marjory Gordon's functional health patterns, the following NANDA diagnoses were prioritized: frailty syndrome of the elderly, skin integrity deterioration, and chronic pain. The desired NOC outcomes were determined for each: nutritional status, mobility, knowledge: prevention of falls, tissue integrity: skin and mucous membranes, pain: harmful effects, pain;adverse psychological response. The NIC interventions and their corresponding activities achieved an improvement in the basal score of all indicators, reaching the target score. It is essential to address care for elderly patients from the physical, mental, functional and social areas. © 2023 DAE Editorial, Grupo Paradigma. All rights reserved.

Some issues of safety of antimicrobial therapy in COVID-19 patients.

Currently, there is a lack of evidence for empiric use of antimicrobial agents in most patients with COVID-19 in outpatient and hospital settings as the overall proportion of secondary bacterial infections in COVID-19 is quite low. This literature review summarizes data on changes in antimicrobial resistance over the course of COVID-19 pandemic, especially in nosocomial ESKAPE pathogens. The other significant consequences of excessive and unnecessary administration of antibiotics to COVID-19 patients including risk of Clostridioides difficile infection and adverse effects of antimicrobial agents are also discussed.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Clostridioides difficile, a New "Superbug".

Clostridioides difficile is a Gram-positive, spore-forming, anaerobic bacterium. The clinical features of C. difficile infections (CDIs) can vary, ranging from the asymptomatic carriage and mild self-limiting diarrhoea to severe and sometimes fatal pseudomembranous colitis. C. difficile infections (CDIs) are associated with disruption of the gut microbiota caused by antimicrobial agents. The infections are predominantly hospital-acquired, but in the last decades, the CDI patterns have changed. Their prevalence increased, and the proportion of community-acquired CDIs has also increased. This can be associated with the appearance of hypervirulent epidemic isolates of ribotype 027. The COVID-19 pandemic and the associated antibiotic overuse could additionally change the patterns of infections. Treatment of CDIs is a challenge, with only three appropriate antibiotics for use. The wide distribution of C. difficile spores in hospital environments, chronic persistence in some individuals, especially children, and the recent detection of C. difficile in domestic pets can furthermore worsen the situation. "Superbugs" are microorganisms that are both highly virulent and resistant to antibiotics. The aim of this review article is to characterise C. difficile as a new member of the "superbug" family. Due to its worldwide spread, the lack of many treatment options and the high rates of both recurrence and mortality, C. difficile has emerged as a major concern for the healthcare system.

Lorigerlimab, a bispecific PD-13CTLA-4 DART molecule in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A phase 1 expansion (exp) cohort

Background: Lorigerlimab (MGD019) is an investigational, bispecific Fc-bearing (IgG4) DART molecule designed to enhance CTLA-4 blockade on dual expressing, tumor infiltrating lymphocytes, while maintaining maximal PD-1 blockade on PD-1 expressing cells. Lorigerlimab has approximate dose proportional PK across 1-10 mg/kg IV dosing Q3W, with sustained PD-1 receptor occupancy evident at doses >=1 mg/kg Q3W. MGD019-01 is a global first-in-human dose finding and activity estimating study of lorigerlimab in advanced solid tumors (AST). Method(s): The exp phase of MGD019-01 evaluates single agent safety, PK, and antitumor effects of lorigerlimab at the recommended dose for exp of 6 mg/ kg IV Q3W in 4 tumor specific cohorts. Confirmed responses were noted in each cohort. Preliminary results of the mCRPC cohort are reported here. Response evaluable pts received >=1 dose and had >=1 postbaseline imaging evaluation. Measurable lesions were evaluated per RECIST v1.1 and skeletal metastases assessed by bone scan. Prostate specific antigen (PSA) response was defined as a >=50% (PSA50) or>=90% (PSA90) PSA decline from baseline with confirmation>=3 weeks later. Expression of proliferation marker, Ki67, and inducible costimulator (ICOS) by peripheral T cells was assessed by flow cytometry. Result(s): At data cutoff (9/10/22), 127 pts with AST received >=1 dose of lorigerlimab 6 mg/ kg. Median exposure was 10 weeks (range, 0.1, 94.4) with median of 4 infusions. 6 pts remain on therapy;36 discontinued for PD (n=13), AEs (n=17), or patient/physician decision (n=6). Treatment related adverse events (TRAE) occurred in 109/127 (85.8%) pts. TRAEs occurring in>=15% of pts were fatigue, pruritus, hypothyroidism, pyrexia. Rates of grade >=3 TRAEs and immune-related AEs were 32.3% and 7.9%, respectively. AEs leading to drug discontinuation occurred in 22.8% of pts. There were no fatal AEs related to lorigerlimab. In the mCRPC exp cohort (n=42), pts had a median of 2 prior lines of therapy for CRPC, >80% received prior ART or taxanes;88% had visceral (liver, 26%;lung, 26%) or nodal disease and 95% had bone metastases. 42 pts were PSA response evaluable;35 were RECIST evaluable. ORR was 25.7% (9/35;9 confirmed PRs). Median duration of response was 16.1 weeks (range 6-25+ weeks). 5 responders remain on study, 4 discontinued for unrelated fatal AEs: COVID-19 (2) cardiac arrest (1) C. difficile infection (1). Confirmed PSA50 and PSA90 response rates were 28.6%(12/42) and 21.4% (9/42), respectively. Increased frequencies of Ki67+ and ICOS+ T cells were observed on day 8 posttreatment compared to pretherapy per the flow cytometry analyses from 35 pts. Conclusion(s): Lorigerlimab demonstrates a manageable safety profile with evidence of encouraging and durable antitumor activity in a chemotherapy refractory mCRPC population. Randomized evaluation of lorigerlimab in mCRPC is warranted.

Accommodating ''History Effects'' in Long Duration, Multisite Clinical Trials to Ensure Relevant and Compelling Evidence

Over the course of a clinical trial, changes in the practice environment have the potential to reduce internal and external validity and impact change in patient outcomes. Such ''history effects''1 can take the form of changes in standard of care, clinical guidelines and recommendations, new drug/device availability in the marketplace, testing and screening procedures, and, as recently experienced, a global pandemic. Clinical trials conducted over many years are particularly susceptible to history effects. Such effects can impact foundational ability to continue a trial, including clinician equipoise and ability to implement trial interventions, necessitating awareness and action planning. For example, Curtis et al.2 acknowledged challenges with clinical guideline history effects and issued recommendations for addressing them such as consideration of participant wellbeing, stakeholder engagement, safety monitoring, review of guideline and policy changes, and development of rules for protocol changes. This session will explore how four multisite clinical trials conducted with VA Cooperative Studies Program sponsorship and coordination have weathered history effects during prolonged periods of enrollment. Topics to be covered include the implementation of pragmatic designs, monitoring of clinical guidelines, assessing control group treatment conditions, modifying protocols, adjusting quality assurance procedures, refining recruitment pathways, and training site investigators. The speakers, Study Chairs, will describe best practices and provide recommendations for navigating history effects in prolonged multisite clinical trials that can ensure outcomes remain relevant and compelling to inform public health at trial commencement. The CSP 2008/PTXRx study is a pragmatic, randomized, double-blind, placebo-controlled, multicenter clinical trial of Veteran patients with diabetic kidney disease (DKD) examining whether pentoxifylline (PTX), when added to usual care, can delay time to end-stage renal disease or death. Enrollment for the study began in 2019, and it is anticipated that 9 years of follow-up will be required to observe the required number of primary events. Given the long duration of the study, changes in clinical guidelines were anticipated and have occurred, including the approval of new DKD therapies and introduction of a new formula for estimated glomerular filtration rate (eGFR) calculation. In anticipation of these changes, the study design allows for whatever standard of care is extant at any time during the course of the study. PTXR's pragmatic trial design and protocol leverage the VA's research infrastructure and remote platforms allowing the study to be responsive to external changes and to safely continue during a global pandemic. The CSP 596/OPTION study is a randomized, double- blind, multicenter trial of Veteran patients with a first or second recurrent Clostridium difficile infection (CDI) comparing (1) fidaxomicin and (2) vancomycin, followed by a taper and pulse to (3) a standard vancomycin regimen. Since enrollment began in 2016, significant changes in CDI epidemiology and clinical management have impacted the study. The COVID-19 pandemic also resulted in an administrative hold on all trial activity followed by staggered reopening of sites due to variable COVID-19 activity and clinical priorities. Many clinical laboratories switched to algorithms that included free toxin assays in addition to polymerase chain reaction (PCR) tests out of concern for overdiagnosis based on PCR testing alone, reducing the number of potentially enrollable cases. There has been increased empirical vancomycin treatment for recurrent CDI without confirmation by stool testing, a requirement for enrollment, and a recruitment strategy for identifying potential cases. Finally, conflicting clinical guidelines for recurrent CDI has created potential equipoise when considering enrollment. Ongoing educational efforts have been made to clarify the protocol and emphasize the validity of the research question as well as protoco changes to allow safe enrollment and follow-up of participants in the face of the ongoing COVID-19 pandemic. The CSP 2005/VALOR is a phase III randomized, open label, multicenter clinical trial of Veteran patients with operable stage I non-small cell lung cancer that compares stereotactic radiotherapy and anatomic pulmonary resection with a primary outcome measure of overall survival. The study was activated in 2017 and recruitment to the trial has been affected by ongoing changes in public and clinician perceptions about stereotactic radiotherapy and surgery that have interfered with equipoise and willingness of participants to enroll. The study team perpetually addresses this challenge through group conversations with local site investigators, study coordinators, and other research personnel to preserve group equipoise across the study. Since the study's activation, new safety information about stereotactic radiotherapy has emerged necessitating protocol modifications while aiming to preserve internal and external validity. The includes modifying standard operating procedures for the study's centralized quality assurance program that has had to adapt its process to remain contemporary. STARPORT, funded by VA CSRD with CSP collaboration, is a randomized, open label, multicenter clinical trial of Veteran patients with oligorecurrent prostate cancer comparing the effects of standard systemic therapy (SST) alone or with PET-directed local therapy using surgery or radiation. Although enrollment was initiated in 2021, changes are already evident in clinical practice guidelines regarding the use of imaging in workup in this patient population. Shortly before the start of accrual, 18F-DCFPyL PSMA PET/CT received FDA-approval. Consequently, it is being rapidly adopted at the STARPORT VA medical centers and the use of conventional imaging using CT or bone scan prior to PET/CT imaging-part of the original eligibility criteria-quickly is falling out of favor. Furthermore, shortly after the start of enrollment, NCCN guidelines adopted the stance that conventional imaging was no longer required in the setting of PSMA PET/CT imaging, solidifying the transition away from conventional imaging. Thus, the protocol is being amended to remove the requirement for conventional imaging as part of workup for oligorecurrence. In addition, to be generalizable, the study is designed to integrate future PSMA radiotracers that are incorporated into practice as well as changes in SST regimens over the time of the study.

Inflammatory Bowel Disease in the elderly, a survey of elderly patient demographics, diseaserelated complications and compliance with vaccination and screening services

Background: Inflammatory Bowel Disease (IBD) in the elderly (>60yrs) is becoming more prevalent in concordance with the ageing population and the rising incidence of IBD. An increasing number of patients are receiving a diagnosis of IBD in later years in addition to those with known IBD transitioning to elderly. The presentation, disease course, risk of complications and choice of medical therapies differ in this group from younger cohorts. We aimed to examine patient demographics and the incidence of adverse effects/complications amongst elderly IBD patients. We also sought to identify appropriate vaccination rates and uptake with screening services. Method(s): In a single tertiary centre, IBD patients aged >60 attending the outpatient clinic or admitted acutely were invited to complete an anonymous written survey. Result(s): 28 patients surveyed to date. 61% (n=17) had a diagnosis of UC. 54% were female (n=15). Mean age was 67.5, while mean age at diagnosis was 50 (range 19-65). 25% (n=7) received a diagnosis of IBD after 60 years, of which 57% were female. Mean BMI was 25.9. 25% (n=7) reported an infection in the last 6 months, all of whom required treatment with antibiotics. There was only one case of infection requiring hospitilisation, a patient on biologic therapy who developed a clostridium difficile infection. COVID-19 affected 39% (n=11), none required hospitilisation. 21% (n=6) report 2 or more comorbidities, of which 50% report a recent infection requiring treatment. All patients who required IBD surgery (n=5) had a high BMI. 57% (n=16) had a smoking history, with 14% (n=4) being active smokers. Infliximab and salofalk granules were the most prescribed IBD treatments. 46% were on biologics (n=13), with anti-TNF being the most common (29%). 25% (n=7) reported steroid use in the last year while 14% were not currently on IBD treatment. 21.4% (n=6) reported prior malignancy, skin cancer being most common. 50% of cancer sufferers were smokers. 100% have had a minimal of two COVID-19 vaccines. 64% (n=18) have had a flu-vaccine in the last 12 months with 75% (n=21) report annual flu-vaccine uptake. 61% (n=17) had the pneumococcal vaccine. Bowel screening participation was 46.5% (n=13). Conclusion(s): Smoking, high BMI and multiple comorbidities were common in elderly IBD patients. Infections were common in this cohort and typically required treatment with antibiotics, however, were rarely severe or required hospitalisation. Severe infections were seen in those on biologic therapy. Biologics were commonly prescribed to elderly IBD patients. Skin cancer was the most common malignancy. There was suboptimal uptake with vaccinations and bowel screening. (Figure Presented).

Health Care-Associated Infections: Best Practices for Prevention

Health care-associated infections (HAIs) are a significant cause of morbidity and mortality in the United States. Common examples include catheter-associated urinary tract infections, central line-associated bloodstream infections, ventilator-associated pneumonia, surgical site infections, and Clostridioides difficile infections. Standardized infection control processes and precautions have been shown to reduce the rate of HAIs, and targeted practices for HAIs have shown further reductions. Patient safety tools have been developed for various HAIs to help guide administrators and are free for public use through the Centers for Disease Control and Prevention STRIVE (States Targeting Reduction in Infections via Engagement) initiative. The Choosing Wisely initiative makes best practice recommendations for physicians to improve quality of care and reduce costs;targeted recommendations were developed to reduce the risk of HAIs. For example, using invasive devices only when indicated and for the shortest time possible reduces the risk of device-related HAIs. The goal of antibiotic stewardship is to reduce C. difficile infections and further development of multidrug-resistant organisms such as vancomycin-resistant Enterococcus and carbapenem-resistant Enterobacteriaceae. Antibiotic stewardship targets physician behaviors such as reviewing antibiotic therapy choices every 48 to 72 hours, reviewing culture results as soon as available, de-escalating antibiotic therapy when appropriate, and documenting the indications for initiating and continuing antibiotic therapy.Copyright © 2022 American Academy of Family Physicians.

Depression and anxiety in Clostridioides difficile infection compared with inflammatory bowel disease during the Covid-19 pandemic

Background: Numerous studies and their meta-analysis have shown a high prevalence of anxiety and depression in patients with inflammatory bowel disease (IBD): Up to a third of patients with anxiety symptoms and a quarter with depression symptoms. These rates increase even more with high disease activity: Up to half of patients with anxiety criteria and up to a third with depression symptoms. Data on the frequency and severity of depression and anxiety in patients with Clostridioides difficile infection (CDI) are not so numerous and unambiguous. During the Covid-19 pandemic, the frequency of depression and anxiety increased among healthy individuals and, even more so, among patients with intestinal diseases. The aim of the study was to evaluate the degree of anxiety and depression in patients with IBD and those with CDI during the Covid-19 pandemic. Method(s): Thirty patients with IBD and 30 patients with CDI were included in the study. IBD was confirmed by endoscopy and histology. CDI was confirmed by enzyme analysis for glutamate dehydrogenase and toxins A and B in the feces of patients with nosocomial infection. Hamilton scale (17 items) was used in order to assess the depression grade. This scale divides patients into four groups: No depression, mild, moderate and severe depression. Anxiety was diagnosed by the Spielberger scale (40 items) which includes analysis of State anxiety (SA) and Trait anxiety (TA). Result(s): Depression was determined in 56.7% of patients in the IBD group: 46.7% had mild depression, and 10% moderate depression. In the CDI group depression was diagnosed significantly more frequently - 86.7% of cases: Mild grade in 76.6% and moderate in 10%, predominantly among women. SA was identified in 46.7% of patients in IBD group, and severe SA in 10.0%. In CDI group the frequency and grade of SA were similar: 40.0% and 13.3% respectively. The of TA was extremely high in both groups: 93.3% in the IBD group, of which 50.0% with severe TA, and 96.7% in the CDI group, of which 40.0% with severe TA. Conclusion(s): The results of the study confirm the presence of anxiety and depression in an extremely large number of patients with IBD and CDI during the Covid-19 pandemic. The frequency of anxiety and depression in this study is significantly higher than previously reported. Patients with IBD and CDI should be monitored for early diagnosis and adequate treatment of depression and anxiety.

Antibiotic Use in Acute Upper Respiratory Tract Infections

Upper respiratory tract infections are responsible for millions of physician visits in the United States annually. Although viruses cause most acute upper respiratory tract infections, studies show that many infections are unnecessarily treated with antibiotics. Because inappropriate antibiotic use results in adverse events, contributes to antibiotic resistance, and adds unnecessary costs, family physicians must take an evidence-based, judicious approach to the use of antibiotics in patients with upper respiratory tract infections. Antibiotics should not be used for the common cold, influenza, COVID-19, or laryngitis. Evidence supports antibiotic use in most cases of acute otitis media, group A beta-hemolytic streptococcal pharyngitis, and epiglottitis and in a limited percentage of acute rhinosinusitis cases. Several evidence-based strategies have been identified to improve the appropriateness of antibiotic prescribing for acute upper respiratory tract infections.Copyright © 2022 American Academy of Family Physicians.

COVID-19 and Fulminant Clostridium difficile Colitis Co-Infection.

The development of Clostridium difficile infection in COVID-19 patients is an understudied complication of the disease. Herein, we present the case of a 46-year-old man who developed severe healthcare-associated C. difficile infection leading to toxic megacolon and perforation in the setting of COVID-19 infection. It is important to continue to follow guidelines regarding antibiotics in healthcare settings to prevent such complications. LEARNING POINTS: Co-infection with Clostridium difficile and COVID-19 leads to poor outcomes with high mortality.C. difficile infection should be ruled out in COVID-19 patients who develop diarrhoea on antibiotic therapy.We should continue to follow the established guidelines of antimicrobial stewardship and remain vigilant for unexpected adverse effects.

Managing infection prevention and control in the emergency care setting: an overview for emergency nurses.

The control and prevention of infection in emergency departments (EDs) remains challenging because of the complexity of the environment and the consistently high attendance in many EDs. Emergency nurses play an essential role in infection prevention and control in this clinical area. The COVID-19 pandemic has refocused the need for emergency nurses to have a good knowledge and understanding of infection control processes and the clinical skills to protect themselves and patients alike. This article provides an overview of UK epidemiological perspectives, the main pathogens associated with healthcare infections, the importance of reducing pathogen transmission and the emergency nurse's role in antibiotic stewardship.