Make It Less difficile: Understanding Genetic Evolution and Global Spread of Clostridioides difficile.

Clostridioides difficile is an obligate anaerobic pathogen among the most common causes of healthcare-associated infections. It poses a global threat due to the clinical outcomes of infection and resistance to antibiotics recommended by international guidelines for its eradication. In particular, C. difficile infection can lead to fulminant colitis associated with shock, hypotension, megacolon, and, in severe cases, death. It is therefore of the utmost urgency to fully characterize this pathogen and better understand its spread, in order to reduce infection rates and improve therapy success. This review aims to provide a state-of-the-art overview of the genetic variation of C. difficile, with particular regard to pathogenic genes and the correlation with clinical issues of its infection. We also summarize the current typing techniques and, based on them, the global distribution of the most common ribotypes. Finally, we discuss genomic surveillance actions and new genetic engineering strategies as future perspectives to make it less difficile.

Crosstalk Between the Gut Microbiota and Epithelial Cells Under Physiological and Infectious Conditions.

The gastrointestinal tract (GIT) is considered the largest immunological organ, with a diverse gut microbiota, that contributes to combatting pathogens and maintaining human health. Under physiological conditions, the crosstalk between gut microbiota and intestinal epithelial cells (IECs) plays a crucial role in GIT homeostasis. Gut microbiota and derived metabolites can compromise gut barrier integrity by activating some signaling pathways in IECs. Conversely, IECs can separate the gut microbiota from the host immune cells to avoid an excessive immune response and regulate the composition of the gut microbiota by providing an alternative energy source and releasing some molecules, such as hormones and mucus. Infections by various pathogens, such as bacteria, viruses, and parasites, can disturb the diversity of the gut microbiota and influence the structure and metabolism of IECs. However, the interaction between gut microbiota and IECs during infection is still not clear. In this review, we will focus on the existing evidence to elucidate the crosstalk between gut microbiota and IECs during infection and discuss some potential therapeutic methods, including probiotics, fecal microbiota transplantation (FMT), and dietary fiber. Understanding the role of crosstalk during infection may help us to establish novel strategies for prevention and treatment in patients with infectious diseases, such as C. difficile infection, HIV, and COVID-19.

Prevalence of Clostridioides difficile and Other Gastrointestinal Pathogens in Patients with COVID-19.

BACKGROUND: Gastrointestinal symptoms are common in patients with COVID-19, but prevalence of co-infection with enteric pathogens is unknown. AIMS: This study assessed the prevalence of enteric infections among hospitalized patients with COVID-19. METHODS: We evaluated 4973 hospitalized patients ≥ 18 years of age tested for COVID-19 from March 11 through April 28, 2020, at two academic hospitals. The primary exposure was a positive COVID-19 test. The primary outcome was detection of a gastrointestinal pathogen by PCR stool testing. RESULTS: Among 4973 hospitalized individuals, 311 were tested for gastrointestinal infections (204 COVID-19 positive, 107 COVID-19 negative). Patients with COVID-19 were less likely to test positive compared to patients without COVID-19 (10% vs 22%, p < 0.01). This trend was driven by lower rates of non-C.difficile infections (11% vs 22% in COVID-19 positive vs. negative, respectively, p = 0.04), but not C. difficile infection (5.1% vs. 8.2%, p = 0.33). On multivariable analysis, infection with COVID-19 remained significantly associated with lower odds of concurrent GI infection (aOR 0.49, 95% CI 0.24-0.97), again driven by reduced non-C.difficile infection. Testing for both C.difficile and non-C.difficile enteric infection decreased dramatically during the pandemic. CONCLUSIONS: Pathogens aside from C.difficile do not appear to be a significant contributor to diarrhea in COVID-19 positive patients.

Substantial reduction of healthcare facility-onset Clostridioides difficile infection (HO-CDI) rates after conversion of a hospital for exclusive treatment of COVID-19 patients.

Healthcare facility-onset Clostridioides difficile infection rates substantially dropped in a Mexican hospital after its conversion to a full COVID-19 setting, despite heavy contamination of the environment the previous year. Better adherence to hand hygiene and contact precautions may help explain this finding.

Clostridioides difficile infection in coronavirus disease 2019 (COVID-19): an underestimated problem?

INTRODUCTION: The use of antibiotics and possibility of microbiota disruption during the coronavirus disease 2019 (COVID­19) pandemic have raised questions about the incidence of Clostridioides difficile infection (CDI). OBJECTIVES: This study aimed to assess the frequency of and risk factors for CDI in patients with COVID­19. PATIENTS AND METHODS: We conducted a retrospective, single­center evaluation study on the frequency of and risk factors for CDI in patients with COVID­19 and in the prepandemic era. The analysis included 441 patients with severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infection and 2961 pa­ tients hospitalized before the pandemic. RESULTS: A significant increase in the incidence of CDI was noted during the COVID­19 pandemic compared with the prepandemic period: 10.9% versus 2.6%, P <0.001. Risk factors for CDI in patients with COVID­19 included: age, length of hospital stay, occurrence of diarrhea during hospitalization, use of antibiotics other than azithromycin, and coexistence of nervous system disease or chronic kidney disease-all of these factos had a weak association with CDI development. The multivariable logistic regression model indicated other unassessed variables that had an impact on the CDI incidence rate. CONCLUSIONS: We observed a higher incidence of CDI in patients with COVID­19. Antibiotic therapy was a relevant risk factor for CDI, although its effect was weak. Other drugs used during the pandemic were not found to have an impact on disease development. Possible causes of CDI may include fecal microbiota disruption by SARS­CoV­2 infection, but further research is needed to validate this hypothesis.

Maintaining standard volumes, efficacy and safety, of fecal microbiota transplantation for C. difficile infection during the COVID-19 pandemic: A prospective cohort study.

BACKGROUND: Fecal microbiota transplantation (FMT) can be a life-saving treatment against recurrent Clostridioides difficile infection (CDI). It is therefore necessary to maintain this procedure available for these patients during the COVID-19 pandemic while keeping high efficacy and safety standards. AIMS: To report outcomes of a FMT service that has adapted its operational workflow during COVID-19 pandemic to continue offering FMT to patients with CDI. METHODS: All patients with CDI referred to our center for FMT during pandemic were prospectively included. Each step of the FMT working protocol was adapted with specific security measures to prevent the transmission of SARS-CoV-2. RESULTS: Of 26 patients evaluated for FMT, 21 were treated for recurrent or refractory CDI. Eighteen patients completed the 8-week follow-up, and no one recurred after FMT. Follow-up is ongoing in 3 patients, although in all of them diarrhea disappeared after the first procedure. No serious adverse events were reported. Two patients had also COVID-19-related pneumonia, and were cured both from CDI and COVID-19. CONCLUSION: This is the first report to show that it is possible to maintain standard volumes, efficacy and safety of FMT for recurrent CDI during the COVID-19 pandemic, by adopting specific changes in the operational workflow.

Severe Clostridium difficile colitis as potential late complication associated with COVID-19.

Spain has been one of the most affected countries by the COVID-19 outbreak. After the high impact of the pandemic, a wide clinical spectrum of late complications associated with COVID-19 are being observed. We report a case of a severe Clostridium difficile colitis in a post-treatment and recovered COVID-19 patient. A 64-year-woman with a one-month hospital admission for severe bilateral pneumonia associated with COVID-19 and 10 days after discharge presented with diarrhoea and abdominal pain. Severe C. difficile-associated colitis is diagnosed according to clinical features and CT findings. An urgent pancolectomy was performed due to her bad response to conservative treatment. Later evolution slowly improved to recovery. C. difficile-associated colitis is one of the most common hospital-acquired infections. Significant patient-related risk factors for C. difficile infection are antibiotic exposure, older age, and hospitalisation. Initial therapeutic recommendations in our country included administration broad-spectrum antibiotics to all patients with bilateral pneumonia associated with SARS-CoV-2. These antibiotics are strongly associated with C. difficile infection. Our patient developed a serious complication of C. difficile due to the use of broad-spectrum antibiotics. The appearance of late digestive symptoms in patients diagnosed and treated for COVID-19 should alert clinicians to the possibility of C. difficile infection. The updated criteria for severe colitis and severe C. difficile infection should be considered to ensure an early effective treatment for the complication.

COVID-19 and Clostridioides difficile infection (CDI): Possible implications for elderly patients.

COVID-19 dramatically affects the elderly. Due to the large usage of antibiotics during the current pandemic and the gastrointestinal manifestations of COVID-19, the elderly population, hospitalized patients, residents in LTCFs and persons that survived the COVID-19 might be more prone to Clostridioides difficile infections (CDI). A renewed attention to CDI is necessary during the ongoing COVID-19 pandemic.