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High Serum Levels of Toxin A Correlate with Disease Severity in Patients with Clostridioides difficile Infection
Cloistridioides difficile (CD) represents a major public healthcare-associated infection causing significant morbidity and mortality. The pathogenic effects of CD are mainly caused by the release of two exotoxins into the intestine: toxin A (TcdA) and toxin B (TcdB). CD infection (CDI) can also caus...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470527/ https://www.ncbi.nlm.nih.gov/pubmed/34572675 http://dx.doi.org/10.3390/antibiotics10091093 |
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author | Granata, Guido Mariotti, Davide Ascenzi, Paolo Petrosillo, Nicola di Masi, Alessandra |
author_facet | Granata, Guido Mariotti, Davide Ascenzi, Paolo Petrosillo, Nicola di Masi, Alessandra |
author_sort | Granata, Guido |
collection | PubMed |
description | Cloistridioides difficile (CD) represents a major public healthcare-associated infection causing significant morbidity and mortality. The pathogenic effects of CD are mainly caused by the release of two exotoxins into the intestine: toxin A (TcdA) and toxin B (TcdB). CD infection (CDI) can also cause toxemia, explaining the systemic complications of life-threatening cases. Currently, there is a lack of sensitive assays to detect exotoxins circulating in the blood. Here, we report a new semi-quantitative diagnostic method to measure CD toxins serum levels. The dot-blot assay was modified to separately detect TcdA and TcdB in human serum with a limit of detection at the pg/mL levels. TcdA and TcdB concentrations in the plasma of 35 CDI patients were measured at the time of CDI diagnosis and at the fourth and tenth day after CDI diagnosis and initiation of anti-CDI treatment. TcdA and TcdB levels were compared to those determined in nine healthy blood donors. Toxemia was detected in the plasma of 33 out of the 35 CDI cases. We also assessed the relationship between TcdA serum levels and CDI severity, reporting that at the time of CDI diagnosis the proportion of severe CDI cases with a TcdA serum level > 60 pg/µL was higher than in mild CDI cases (29.4% versus 66.6%, p = 0.04). In conclusion, data reported here demonstrate for the first time that toxemia is much more frequent than expected in CDI patients, and specifically that high serum levels of TcdA correlate with disease severity in patients with CDI. |
format | Online Article Text |
id | pubmed-8470527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84705272021-09-27 High Serum Levels of Toxin A Correlate with Disease Severity in Patients with Clostridioides difficile Infection Granata, Guido Mariotti, Davide Ascenzi, Paolo Petrosillo, Nicola di Masi, Alessandra Antibiotics (Basel) Article Cloistridioides difficile (CD) represents a major public healthcare-associated infection causing significant morbidity and mortality. The pathogenic effects of CD are mainly caused by the release of two exotoxins into the intestine: toxin A (TcdA) and toxin B (TcdB). CD infection (CDI) can also cause toxemia, explaining the systemic complications of life-threatening cases. Currently, there is a lack of sensitive assays to detect exotoxins circulating in the blood. Here, we report a new semi-quantitative diagnostic method to measure CD toxins serum levels. The dot-blot assay was modified to separately detect TcdA and TcdB in human serum with a limit of detection at the pg/mL levels. TcdA and TcdB concentrations in the plasma of 35 CDI patients were measured at the time of CDI diagnosis and at the fourth and tenth day after CDI diagnosis and initiation of anti-CDI treatment. TcdA and TcdB levels were compared to those determined in nine healthy blood donors. Toxemia was detected in the plasma of 33 out of the 35 CDI cases. We also assessed the relationship between TcdA serum levels and CDI severity, reporting that at the time of CDI diagnosis the proportion of severe CDI cases with a TcdA serum level > 60 pg/µL was higher than in mild CDI cases (29.4% versus 66.6%, p = 0.04). In conclusion, data reported here demonstrate for the first time that toxemia is much more frequent than expected in CDI patients, and specifically that high serum levels of TcdA correlate with disease severity in patients with CDI. MDPI 2021-09-10 /pmc/articles/PMC8470527/ /pubmed/34572675 http://dx.doi.org/10.3390/antibiotics10091093 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Granata, Guido Mariotti, Davide Ascenzi, Paolo Petrosillo, Nicola di Masi, Alessandra High Serum Levels of Toxin A Correlate with Disease Severity in Patients with Clostridioides difficile Infection |
title | High Serum Levels of Toxin A Correlate with Disease Severity in Patients with Clostridioides difficile Infection |
title_full | High Serum Levels of Toxin A Correlate with Disease Severity in Patients with Clostridioides difficile Infection |
title_fullStr | High Serum Levels of Toxin A Correlate with Disease Severity in Patients with Clostridioides difficile Infection |
title_full_unstemmed | High Serum Levels of Toxin A Correlate with Disease Severity in Patients with Clostridioides difficile Infection |
title_short | High Serum Levels of Toxin A Correlate with Disease Severity in Patients with Clostridioides difficile Infection |
title_sort | high serum levels of toxin a correlate with disease severity in patients with clostridioides difficile infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470527/ https://www.ncbi.nlm.nih.gov/pubmed/34572675 http://dx.doi.org/10.3390/antibiotics10091093 |
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