Microbiota restoration for recurrent <i>Clostridioides difficile</i>: Getting one step closer every day!

Khanna, Sahil

doi:10.1111/joim.13290

Cited by 15 publications

(21 citation statements)

References 76 publications

(148 reference statements)

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“…We fully share the enthusiasm shown by Khanna [ 74 ] in a recent article in which he summarized the four ongoing trials of capsule therapies (CP101, RBX7455, SER-109, VE303) plus the one based on the use of enema (RBX2660), again related to remodeling the microbiota to cope with CDI .…”

Section: New Therapeutic Strategiesmentioning

confidence: 70%

Gut Microbiota and Clostridium difficile: What We Know and the New Frontiers

Piccioni

Rosa

Manca

et al. 2022

IJMS

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Our digestive system, particularly our intestines, harbors a vast amount of microorganisms, whose genetic makeup is referred to as the microbiome. Clostridium difficile is a spore-forming Gram-positive bacterium, which can cause an infection whose symptoms range from asymptomatic colonization to fearsome complications such as the onset of toxic megacolon. The relationship between gut microbiota and Clostridium difficile infection has been studied from different perspectives. One of the proposed strategies is to be able to specifically identify which types of microbiota alterations are most at risk for the onset of CDI. In this article, we understood once again how crucial the role of the human microbiota is in health and especially how crucial it becomes, in the case of its alteration, for the individual’s disease. Clostridium difficile infection is an emblematic example of how a normal and physiological composition of the human microbiome can play a very important role in immune defense against such a fearsome disease.

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Section: New Therapeutic Strategiesmentioning

confidence: 70%

Gut Microbiota and Clostridium difficile: What We Know and the New Frontiers

Piccioni

Rosa

Manca

et al. 2022

IJMS

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“…In addition, laboratories within and across countries can apply diverse testing strategies due to different guidelines [( 20 , 22 ) Int2–3, 5, 7] and so there is a lack of standardized practice. There are also both advantages and disadvantages to individual diagnostic tools, related to accuracy, turnaround time and distinguishing colonization from toxigenic infection [( 2 , 4 , 16 , 20 , 21 , 23 , 24 ), Int2–3].…”

Section: Resultsmentioning

confidence: 99%

“…Ensuring appropriate and effective treatment that is optimal for an individual patient comes with a set of challenges. For example, anti-CDI antibiotics are the first-line treatment for CDI, but can have side-effects such as a further imbalance of the gut microbiome [( 2 , 7 , 16 , 23 , 33 , 36 , 44 , 45 ); Int1, 3, 5–6]. Although the evidence base is inconclusive, there is also some concern about risks of resistance to mainstream therapies ( 18 , 33 , 36 ).…”

Section: Resultsmentioning

confidence: 99%

“…A review by Khanna ( 23 ) states that CDI recurrence occurs in an estimated 20–30% of cases after the first CDI episodes, increasing to approximately 60% of cases after three or more episodes ( 23 ). Should CDI recurrence be suspected in a patient of any age, it is important to distinguish whether it is actual recurrence or if symptoms are due to something else, such as post-infection irritable bowel syndrome (IBS) ( 23 ). While distinguishing between recurrence and an entirely new CDI infection is also important as treatment regimes can vary, it can be difficult to achieve this in practice.…”

Section: Resultsmentioning

confidence: 99%

“…Patients in hospital (either with initial or recurrent infection) are subject to closer monitoring, which primarily involves referencing stool charts, recording bowel movements, testing for white blood cell counts, assessing inflammatory marker, and, in more complex 10.3389/fmed.2022.1033417 cases, CT imaging (Int2, 5, 7). This is to check for compilations such as severe dehydration, acute kidney injury, fever, ileus, and toxic megacolon (23) and side effects of medication.…”

Section: Patient Monitoring and Follow-upmentioning

confidence: 99%

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

et al. 2023

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IntroductionArriving 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.MethodsWe 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 discussionWe 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.

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Identification of ADS024, a newly characterized strain of Bacillus velezensis with direct Clostridiodes difficile killing and toxin degradation bio-activities

O’Donnell

Hegarty

Healy

et al. 2022

Sci Rep

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Clostridioides difficile infection (CDI) remains a significant health threat worldwide. C. difficile is an opportunistic, toxigenic pathogen that takes advantage of a disrupted gut microbiome to grow and produce signs and symptoms ranging from diarrhea to pseudomembranous colitis. Antibiotics used to treat C. difficile infection are usually broad spectrum and can further disrupt the commensal gut microbiota, leaving patients susceptible to recurrent C. difficile infection. There is a growing need for therapeutic options that can continue to inhibit the outgrowth of C. difficile after antibiotic treatment is completed. Treatments that degrade C. difficile toxins while having minimal collateral impact on gut bacteria are also needed to prevent recurrence. Therapeutic bacteria capable of producing a range of antimicrobial compounds, proteases, and other bioactive metabolites represent a potentially powerful tool for preventing CDI recurrence following resolution of symptoms. Here, we describe the identification and initial characterization of ADS024 (formerly ART24), a novel therapeutic bacterium that can kill C. difficile in vitro with limited impact on other commensal bacteria. In addition to directly killing C. difficile, ADS024 also produces proteases capable of degrading C. difficile toxins, the drivers of symptoms associated with most cases of CDI. ADS024 is in clinical development for the prevention of CDI recurrence as a single-strain live biotherapeutic product, and this initial data set supports further studies aimed at evaluating ADS024 in future human clinical trials.

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Microbiota restoration for recurrent Clostridioides difficile: Getting one step closer every day!

Abstract: Khanna S (Mayo Clinic, Rochester, MN, USA). Microbiota restoration for recurrent Clostridioides difficile: Getting one step closer every day! (Review).

Cited by 15 publications

References 76 publications

Gut Microbiota and Clostridium difficile: What We Know and the New Frontiers

Gut Microbiota and Clostridium difficile: What We Know and the New Frontiers

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

Identification of ADS024, a newly characterized strain of Bacillus velezensis with direct Clostridiodes difficile killing and toxin degradation bio-activities

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