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

<i<Cloistridioides difficile</i< (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...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Guido Granata [verfasserIn] Davide Mariotti [verfasserIn] Paolo Ascenzi [verfasserIn] Nicola Petrosillo [verfasserIn] Alessandra di Masi [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	TcdA TcdB toxin toxemia

Übergeordnetes Werk:	In: Antibiotics - MDPI AG, 2013, 10(2021), 9, p 1093
Übergeordnetes Werk:	volume:10 ; year:2021 ; number:9, p 1093

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/antibiotics10091093

Katalog-ID:	DOAJ005171687

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520			\|a <i<Cloistridioides difficile</i< (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%, <i<p</i< = 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.
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allfields	10.3390/antibiotics10091093 doi (DE-627)DOAJ005171687 (DE-599)DOAJ300627ca71594a80a23ee59af30f9eb9 DE-627 ger DE-627 rakwb eng RM1-950 Guido Granata verfasserin aut High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<Cloistridioides difficile</i< (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%, <i<p</i< = 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. <i<Clostridium difficile</i< <i<Clostridioides difficile</i< TcdA TcdB toxin toxemia Therapeutics. Pharmacology Davide Mariotti verfasserin aut Paolo Ascenzi verfasserin aut Nicola Petrosillo verfasserin aut Alessandra di Masi verfasserin aut In Antibiotics MDPI AG, 2013 10(2021), 9, p 1093 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:10 year:2021 number:9, p 1093 https://doi.org/10.3390/antibiotics10091093 kostenfrei https://doaj.org/article/300627ca71594a80a23ee59af30f9eb9 kostenfrei https://www.mdpi.com/2079-6382/10/9/1093 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 9, p 1093
spelling	10.3390/antibiotics10091093 doi (DE-627)DOAJ005171687 (DE-599)DOAJ300627ca71594a80a23ee59af30f9eb9 DE-627 ger DE-627 rakwb eng RM1-950 Guido Granata verfasserin aut High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<Cloistridioides difficile</i< (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%, <i<p</i< = 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. <i<Clostridium difficile</i< <i<Clostridioides difficile</i< TcdA TcdB toxin toxemia Therapeutics. Pharmacology Davide Mariotti verfasserin aut Paolo Ascenzi verfasserin aut Nicola Petrosillo verfasserin aut Alessandra di Masi verfasserin aut In Antibiotics MDPI AG, 2013 10(2021), 9, p 1093 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:10 year:2021 number:9, p 1093 https://doi.org/10.3390/antibiotics10091093 kostenfrei https://doaj.org/article/300627ca71594a80a23ee59af30f9eb9 kostenfrei https://www.mdpi.com/2079-6382/10/9/1093 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 9, p 1093
allfields_unstemmed	10.3390/antibiotics10091093 doi (DE-627)DOAJ005171687 (DE-599)DOAJ300627ca71594a80a23ee59af30f9eb9 DE-627 ger DE-627 rakwb eng RM1-950 Guido Granata verfasserin aut High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<Cloistridioides difficile</i< (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%, <i<p</i< = 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. <i<Clostridium difficile</i< <i<Clostridioides difficile</i< TcdA TcdB toxin toxemia Therapeutics. Pharmacology Davide Mariotti verfasserin aut Paolo Ascenzi verfasserin aut Nicola Petrosillo verfasserin aut Alessandra di Masi verfasserin aut In Antibiotics MDPI AG, 2013 10(2021), 9, p 1093 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:10 year:2021 number:9, p 1093 https://doi.org/10.3390/antibiotics10091093 kostenfrei https://doaj.org/article/300627ca71594a80a23ee59af30f9eb9 kostenfrei https://www.mdpi.com/2079-6382/10/9/1093 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 9, p 1093
allfieldsGer	10.3390/antibiotics10091093 doi (DE-627)DOAJ005171687 (DE-599)DOAJ300627ca71594a80a23ee59af30f9eb9 DE-627 ger DE-627 rakwb eng RM1-950 Guido Granata verfasserin aut High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<Cloistridioides difficile</i< (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%, <i<p</i< = 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. <i<Clostridium difficile</i< <i<Clostridioides difficile</i< TcdA TcdB toxin toxemia Therapeutics. Pharmacology Davide Mariotti verfasserin aut Paolo Ascenzi verfasserin aut Nicola Petrosillo verfasserin aut Alessandra di Masi verfasserin aut In Antibiotics MDPI AG, 2013 10(2021), 9, p 1093 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:10 year:2021 number:9, p 1093 https://doi.org/10.3390/antibiotics10091093 kostenfrei https://doaj.org/article/300627ca71594a80a23ee59af30f9eb9 kostenfrei https://www.mdpi.com/2079-6382/10/9/1093 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 9, p 1093
allfieldsSound	10.3390/antibiotics10091093 doi (DE-627)DOAJ005171687 (DE-599)DOAJ300627ca71594a80a23ee59af30f9eb9 DE-627 ger DE-627 rakwb eng RM1-950 Guido Granata verfasserin aut High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<Cloistridioides difficile</i< (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%, <i<p</i< = 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. <i<Clostridium difficile</i< <i<Clostridioides difficile</i< TcdA TcdB toxin toxemia Therapeutics. Pharmacology Davide Mariotti verfasserin aut Paolo Ascenzi verfasserin aut Nicola Petrosillo verfasserin aut Alessandra di Masi verfasserin aut In Antibiotics MDPI AG, 2013 10(2021), 9, p 1093 (DE-627)726120596 (DE-600)2681345-2 20796382 nnns volume:10 year:2021 number:9, p 1093 https://doi.org/10.3390/antibiotics10091093 kostenfrei https://doaj.org/article/300627ca71594a80a23ee59af30f9eb9 kostenfrei https://www.mdpi.com/2079-6382/10/9/1093 kostenfrei https://doaj.org/toc/2079-6382 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2021 9, p 1093
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callnumber-first	R - Medicine
author	Guido Granata
spellingShingle	Guido Granata misc RM1-950 misc <i<Clostridium difficile</i< misc <i<Clostridioides difficile</i< misc TcdA misc TcdB misc toxin misc toxemia misc Therapeutics. Pharmacology High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection
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topic_title	RM1-950 High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection <i<Clostridium difficile</i< <i<Clostridioides difficile</i< TcdA TcdB toxin toxemia
topic	misc RM1-950 misc <i<Clostridium difficile</i< misc <i<Clostridioides difficile</i< misc TcdA misc TcdB misc toxin misc toxemia misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc <i<Clostridium difficile</i< misc <i<Clostridioides difficile</i< misc TcdA misc TcdB misc toxin misc toxemia misc Therapeutics. Pharmacology
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title	High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection
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title_full	High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection
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title_sort	high serum levels of toxin a correlate with disease severity in patients with <i<clostridioides difficile</i< infection
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title_auth	High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection
abstract	<i<Cloistridioides difficile</i< (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%, <i<p</i< = 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.
abstractGer	<i<Cloistridioides difficile</i< (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%, <i<p</i< = 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.
abstract_unstemmed	<i<Cloistridioides difficile</i< (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%, <i<p</i< = 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.
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container_issue	9, p 1093
title_short	High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection
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High Serum Levels of Toxin A Correlate with Disease Severity in Patients with <i<Clostridioides difficile</i< Infection

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