Emerging Options for the Prevention and Management of Clostridioides difficile Infection

Gonzales-Luna, Anne J; Carlson, Travis J; Garey, Kevin W.

doi:10.1007/s40265-022-01832-x

Cited by 17 publications

(3 citation statements)

References 80 publications

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“…The strategies against CDI adopted so far have shown notable limitations and can be summarized as follows: (a) new, more specific drugs that have less impact on the host's microbiota, (b) effective vaccines directed towards Tcds, and (c) faecal transplant [43][44][45][46][47][48].…”

Section: Discussionmentioning

confidence: 99%

Pro-Inflammatory Cytokines Enhanced In Vitro Cytotoxic Activity of Clostridioides difficile Toxin B in Enteric Glial Cells: The Achilles Heel of Clostridioides difficile Infection?

Fettucciari,

Spaterna,

Marconi

et al. 2024

IJMS

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Bacterial infections are characterized by an inflammatory response, which is essential for infection containment but is also responsible for negative effects on the host. The pathogen itself may have evolved molecular mechanisms to antagonize the antimicrobial effects of an inflammatory response and to enhance its pathogenicity using inflammatory response mediators, such as cytokines. Clostridioides difficile (C. difficile) infection (CDI) causes gastrointestinal diseases with markedly increasing global incidence and mortality rates. The main C. difficile virulence factors, toxin A and B (TcdA/TcdB), cause cytopathic/cytotoxic effects and inflammation. We previously demonstrated that TcdB induces enteric glial cell (EGC) apoptosis, which is enhanced by the pro-inflammatory cytokine tumor necrosis factor alpha plus interferon gamma (CKs). However, it is unknown whether CKs-enhanced TcdB cytotoxicity (apoptosis/necrosis) is affected by the timing of the appearance of the CKs. Thus, we simulated in vitro, in our experimental model with TcdB and EGCs, three main situations of possible interactions between TcdB and the timing of CK stimulation: before TcdB infection, concomitantly with infection, or at different times after infection and persisting over time. In these experimental conditions, which all represent situations of possible interactions between C. difficile and the timing of CK stimulation, we evaluated apoptosis, necrosis, and cell cycle phases. The CKs, in all of these conditions, enhanced TcdB cytotoxicity, which from apoptosis became necrosis when CK stimulation persisted over time, and was most relevant after 48 h of TcdB:EGCs interaction. Particularly, the enhancement of apoptosis by CKs was dependent on the TcdB dose and in a less relevant manner on the CK stimulation time, while the enhancement of necrosis occurred always independently of the TcdB dose and CK stimulation time. However, since in all conditions stimulation with CKs strongly enhanced the TcdB cytotoxicity, it always had a negative impact on C. difficile pathogenicity. This study might have important implications for the treatment of CDI.

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Section: Discussionmentioning

confidence: 99%

Pro-Inflammatory Cytokines Enhanced In Vitro Cytotoxic Activity of Clostridioides difficile Toxin B in Enteric Glial Cells: The Achilles Heel of Clostridioides difficile Infection?

Fettucciari,

Spaterna,

Marconi

et al. 2024

IJMS

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“…In current clinical practice, prebiotics, probiotics, and synbiotics are often used for the treatment of IBD without oversight I [27,30]. Probiotics are defined as any live microorganism(s) that confers a health benefit when administered in adequate amounts, and they can be found in foods or dietary supplements available over-the-counter.…”

Section: Current Microbiome-based Interventionsmentioning

confidence: 99%

“…Live biotherapeutic products (LBPs), as defined by the US Federal Drug Administration (FDA), are nonvaccine biological products that contain live organisms, are applicable to the prevention, treatment, or cure of a disease or condition [27]. Based on this broad definition, LBPs encompass a wide range of agents including probiotics, intestinal microbiota transplant, probiotics, symbiotics (prebiotics + probiotics), bacteriophages, and synthetic products [28].…”

Section: Current Microbiome-based Interventionsmentioning

confidence: 99%

Current and future microbiome-based therapies in inflammatory bowel disease

Montrose,

Kurada,

Fischer

2024

Current Opinion in Gastroenterology

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Purpose of review The role of the microbiome and dysbiosis is increasingly recognized in the pathogenesis of inflammatory bowel disease (IBD). Intestinal microbiota transplant (IMT), previously termed fecal microbiota transplant has demonstrated efficacy in restoring a healthy microbiome and promoting gut health in recurrent Clostridioides difficile infection. Several randomized trials (RCTs) highlighted IMT's potential in treating ulcerative colitis, while smaller studies reported on its application in managing Crohn's disease and pouchitis. Recent findings This review delves into the current understanding of dysbiosis in IBD, highlighting the distinctions in the microbiota of patients with IBD compared to healthy controls. It explores the mechanisms by which IMT can restore a healthy microbiome and provides a focused analysis of recent RCTs using IMT for inducing and maintaining remission in IBD. Lastly, we discuss the current knowledge gaps that limit its widespread use. Summary The body of evidence supporting the use of IMT in IBD is growing. The lack of a standardized protocol impedes its application beyond clinical trials. Further research is needed to identify patient profile and disease phenotypes that benefit from IMT, to delineate key donor characteristics, optimize the delivery route, dosage, and frequency.

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European Practice for CDI Treatment

Fitzpatrick,

Brennan,

van Prehn

et al. 2024

Advances in Experimental Medicine and Biology

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Clostridium difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used routinely for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases CDI treatment guidelines outline the treatment options for a variety of CDI clinical scenarios, including use of the more traditional anti-CDI therapies (e.g., metronidazole, vancomycin), the role of newer anti-CDI agents (e.g., fidaxomicin), indications for surgical intervention and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). A 2017 survey of 20 European countries found that while the majority (n=14) have national CDI guidelines that provide a variety of recommendations for CDI treatment, only five have audited guideline implementation. A variety of restrictions are in place in 13 (65%) countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. Novel anti-CDI agents are being evaluated in Phase III trials; it is not yet clear what will be the roles of these agents. Prophylaxis is an optimum approach to reduce the impact of CDI especially in high-risk populations; monoclonal antibodies, antibiotic blocking approaches and multiple vaccines are currently in advanced clinical trials. The treatment of recurrent CDI is particularly troublesome, and several different live bio therapeutics are being developed, in addition to FMT.

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Emerging Options for the Prevention and Management of Clostridioides difficile Infection

Cited by 17 publications

References 80 publications

Pro-Inflammatory Cytokines Enhanced In Vitro Cytotoxic Activity of Clostridioides difficile Toxin B in Enteric Glial Cells: The Achilles Heel of Clostridioides difficile Infection?

Pro-Inflammatory Cytokines Enhanced In Vitro Cytotoxic Activity of Clostridioides difficile Toxin B in Enteric Glial Cells: The Achilles Heel of Clostridioides difficile Infection?

Current and future microbiome-based therapies in inflammatory bowel disease

European Practice for CDI Treatment

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