Non-Toxin-Based Clostridioides difficile Vaccination Approaches

Razim, Agnieszka; Górska, Sabina; Gamian, Andrzej

doi:10.3390/pathogens12020235

Cited by 9 publications

(6 citation statements)

References 68 publications

(71 reference statements)

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“…Ultimately, an effective vaccine would be the most effective way of preventing CDI-associated morbidity and mortality. No FDA-approved C. difficile vaccine currently exists; however, clinical trials and research into the development of an effective vaccine against CDI are ongoing [ 125 , 126 , 127 ].…”

Section: Discussionmentioning

confidence: 99%

Clostridioides difficile Infection: Diagnosis and Treatment Challenges

Markantonis,

Fallon,

Madan

et al. 2024

Pathogens

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Clostridioides difficile is the most important cause of healthcare-associated diarrhea in the United States. The high incidence and recurrence rates of C. difficile infection (CDI), associated with high morbidity and mortality, pose a public health challenge. Although antibiotics targeting C. difficile bacteria are the first treatment choice, antibiotics also disrupt the indigenous gut flora and, therefore, create an environment that is favorable for recurrent CDI. The challenge of treating CDI is further exacerbated by the rise of antibiotic-resistant strains of C. difficile, placing it among the top five most urgent antibiotic resistance threats in the USA. The evolution of antibiotic resistance in C. difficile involves the acquisition of new resistance mechanisms, which can be shared among various bacterial species and different C. difficile strains within clinical and community settings. This review provides a summary of commonly used diagnostic tests and antibiotic treatment strategies for CDI. In addition, it discusses antibiotic treatment and its resistance mechanisms. This review aims to enhance our current understanding and pinpoint knowledge gaps in antimicrobial resistance mechanisms in C. difficile, with an emphasis on CDI therapies.

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Section: Discussionmentioning

confidence: 99%

Clostridioides difficile Infection: Diagnosis and Treatment Challenges

Markantonis,

Fallon,

Madan

et al. 2024

Pathogens

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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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“…Although effective at reducing the incidence of recurrence, there is a distinct lack of preventive options. C. difficile vaccines to prevent primary CDI would offer a huge economic benefit; however, vaccine candidates are currently limited [ 46 , 47 ] and the failure of a bivalent C. difficile toxoid vaccine [ 48 ] and the vaccine candidate VLA84 [ 47 ] on hold after phase 2 trials further compounds this [ 49 ].…”

Section: Increasing Patient Immunitymentioning

confidence: 99%

Clostridioides difficile infections; new treatments and future perspectives

Normington,

Chilton,

Buckley

2023

Current Opinion in Gastroenterology

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Purpose of review As a significant cause of global morbidity and mortality, Clostridioides difficile infections (CDIs) are listed by the Centres for Disease Control and prevention as one of the top 5 urgent threats in the USA. CDI occurs from gut microbiome dysbiosis, typically through antibiotic-mediated disruption; however, antibiotics are the treatment of choice, which can result in recurrent infections. Here, we highlight new treatments available and provide a perspective on different classes of future treatments. Recent findings Due to the reduced risk of disease recurrence, the microbiome-sparing antibiotic Fidaxomicin has been recommended as the first-line treatment for C. difficile infection. Based on the success of faecal microbiota transplantations (FMT) in treating CDI recurrence, defined microbiome biotherapeutics offer a safer and more tightly controlled alterative as an adjunct to antibiotic therapy. Given the association between antibiotic-mediated dysbiosis of the intestinal microbiota and the recurrence of CDI, future prospective therapies aim to reduce the dependence on antibiotics for the treatment of CDI. Summary With current first-in-line antibiotic therapy options associated with high levels of recurrent CDI, the availability of new generation targeted therapeutics can really impact treatment success. There are still unknowns about the long-term implications of these new CDI therapeutics, but efforts to expand the CDI treatment toolbox can offer multiple solutions for clinicians to treat this multifaceted infectious disease to reduce patient suffering.

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Non-Toxin-Based Clostridioides difficile Vaccination Approaches

Cited by 9 publications

References 68 publications

Clostridioides difficile Infection: Diagnosis and Treatment Challenges

Clostridioides difficile Infection: Diagnosis and Treatment Challenges

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

Clostridioides difficile infections; new treatments and future perspectives

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