High Serum Levels of Toxin A Correlate with Disease Severity in Patients with Clostridioides difficile Infection

Granata, Guido; Mariotti, Davide; Ascenzi, Paolo; Petrosillo, Nicola; Masi, Alessandra di

doi:10.3390/antibiotics10091093

Cited by 6 publications

(4 citation statements)

References 32 publications

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“…They also observed toxemia in 33 out of 35 patients studied, indicating a high prevalence of toxins in the bloodstream. This suggests a potential association between elevated serum TcdA levels and the development of severe complications in CDI cases [183].…”

Section: Toxemia and Extraintestinal Damage Caused By Tcda And Tcdbmentioning

confidence: 93%

Exploring the Toxin-Mediated Mechanisms in Clostridioides difficile Infection

Pourliotopoulou,

Karampatakis,

Kachrimanidou

2024

Microorganisms

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Clostridioides difficile infection (CDI) is the leading cause of nosocomial antibiotic-associated diarrhea, and colitis, with increasing incidence and healthcare costs. Its pathogenesis is primarily driven by toxins produced by the bacterium C. difficile, Toxin A (TcdA) and Toxin B (TcdB). Certain strains produce an additional toxin, the C. difficile transferase (CDT), which further enhances the virulence and pathogenicity of C. difficile. These toxins disrupt colonic epithelial barrier integrity, and induce inflammation and cellular damage, leading to CDI symptoms. Significant progress has been made in the past decade in elucidating the molecular mechanisms of TcdA, TcdB, and CDT, which provide insights into the management of CDI and the future development of novel treatment strategies based on anti-toxin therapies. While antibiotics are common treatments, high recurrence rates necessitate alternative therapies. Bezlotoxumab, targeting TcdB, is the only available anti-toxin, yet limitations persist, prompting ongoing research. This review highlights the current knowledge of the structure and mechanism of action of C. difficile toxins and their role in disease. By comprehensively describing the toxin-mediated mechanisms, this review provides insights for the future development of novel treatment strategies and the management of CDI.

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Section: Toxemia and Extraintestinal Damage Caused By Tcda And Tcdbmentioning

confidence: 93%

Exploring the Toxin-Mediated Mechanisms in Clostridioides difficile Infection

Pourliotopoulou,

Karampatakis,

Kachrimanidou

2024

Microorganisms

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“…Toxigenic strains may produce both toxin A and toxin B (causing the majority of CDIs), TcdB alone (A−B+strains), or TcdA alone (A+B−strains) [ 58 , 59 , 60 , 61 ]. Recent research proves the positive correlation between high serum levels of toxin A and the severity of CDI [ 62 ]. Toxemia could explain systemic clinical manifestations in severe cases of CDI [ 63 , 64 ].…”

Section: Pathogenic Mechanismsmentioning

confidence: 99%

The Current Knowledge on Clostridioides difficile Infection in Patients with Inflammatory Bowel Diseases

et al. 2022

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Clostridioides difficile (C. difficile) represents a major health burden with substantial economic and clinical impact. Patients with inflammatory bowel diseases (IBD) were identified as a risk category for Clostridioides difficile infection (CDI). In addition to traditional risk factors for C. difficile acquisition, IBD-specific risk factors such as immunosuppression, severity and extension of the inflammatory disease were identified. C. difficile virulence factors, represented by both toxins A and B, induce the damage of the intestinal mucosa and vascular changes, and promote the inflammatory host response. Given the potential life-threatening complications, early diagnostic and therapeutic interventions are required. The screening for CDI is recommended in IBD exacerbations, and the diagnostic algorithm consists of clinical evaluation, enzyme immunoassays (EIAs) or nucleic acid amplification tests (NAATs). An increased length of hospitalization, increased colectomy rate and mortality are the consequences of concurrent CDI in IBD patients. Selection of CD strains of higher virulence, antibiotic resistance, and the increasing rate of recurrent infections make the management of CDI in IBD more challenging. An individualized therapeutic approach is recommended to control CDI as well as IBD flare. Novel therapeutic strategies have been developed in recent years in order to manage severe, refractory or recurrent CDI. In this article, we aim to review the current evidence in the field of CDI in patients with underlying IBD, pointing to pathogenic mechanisms, risk factors for infection, diagnostic steps, clinical impact and outcomes, and specific management.

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“…Regarding CDI pathogenesis, the work by Di Masi et al presented a novel semiquantitative diagnostic method to measure the serum levels of CD toxins, i.e., toxin A and toxin B [12]. By the use of this new assay, the authors report the detection of toxemia in 33 out of the 35 CDI cases included in the study.…”

mentioning

confidence: 99%

“…By the use of this new assay, the authors report the detection of toxemia in 33 out of the 35 CDI cases included in the study. The relationship between toxin A serum levels and CDI severity was also assessed, reporting that, at the time of CDI diagnosis, the proportion of severe CDI cases with a toxin A serum level >60 pg/µL was higher than in mild CDI cases (29.4% versus 66.6%, p = 0.04) [12]. Of interest, this study showed that toxemia is much more frequent than expected in CDI patients, and that high serum levels of toxin A correlate with CDI severity [12].…”

mentioning

confidence: 99%