A series of three cases of severe Clostridium difficile infection in Australia associated with a binary toxin producing Glade 2 ribotype 251 strain

Michael C. Wehrhahn, Caitlin Keighley, Jelica Kurtovic, Daniel R. Knight, Stacey Hong, Melanie L. Hutton, Dena Lyras, Qinning Wang, Rupert Leong, Tom Borody, Michael Edye, Thomas V. Riley

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Abstract

Three patients with severe Clostridium difficile infection (CDI) caused by an unusual strain of C. difficile, PCR ribotype (RT) 251, were identified in New South Wales, Australia. All cases presented with severe diarrhoea, two had multiple recurrences and one died following a colectomy. C difficile RT251 strains were isolated by toxigenic culture. Genetic characterisation was performed using techniques including toxin gene profiling, PCR ribotyping, whole genome sequencing (WGS), in-silico multi-locus-sequence-typing (MLST) and core-genome single nucleotide variant (SNV) analyses. Antimicrobial susceptibility was determined using an agar incorporation method. In vitro toxin production was confirmed by Vero cell cytotoxicity assay and pathogenicity was assessed in a murine model of CDI. All RT251 isolates contained toxin A (tcdA), toxin B (tcdB) and binary toxin (cdtA and cdtB) genes. Core-genome analyses revealed the RT251 strains were clonal, with 0-5 SNVs between isolates. WGS and MLST clustered RT251 in the same evolutionary Glade (Glade 2) as RT027. Despite comparatively lower levels of in vitro toxin production, in the murine model RT251 infection resembled RT027 infection. Mice showed marked weight loss, severe disease within 48 h post-infection and death. All isolates were susceptible to metronidazole and vancomycin. Our observations suggest C difficile RT251 causes severe disease and emphasise the importance of ongoing surveillance for new and emerging strains of C. difficile with enhanced virulence. (C) 2018 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)117-123
Number of pages7
JournalAnaerobe
Volume55
DOIs
Publication statusPublished - Feb 2019

Cite this

Wehrhahn, Michael C. ; Keighley, Caitlin ; Kurtovic, Jelica ; Knight, Daniel R. ; Hong, Stacey ; Hutton, Melanie L. ; Lyras, Dena ; Wang, Qinning ; Leong, Rupert ; Borody, Tom ; Edye, Michael ; Riley, Thomas V. / A series of three cases of severe Clostridium difficile infection in Australia associated with a binary toxin producing Glade 2 ribotype 251 strain. In: Anaerobe. 2019 ; Vol. 55. pp. 117-123.
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abstract = "Three patients with severe Clostridium difficile infection (CDI) caused by an unusual strain of C. difficile, PCR ribotype (RT) 251, were identified in New South Wales, Australia. All cases presented with severe diarrhoea, two had multiple recurrences and one died following a colectomy. C difficile RT251 strains were isolated by toxigenic culture. Genetic characterisation was performed using techniques including toxin gene profiling, PCR ribotyping, whole genome sequencing (WGS), in-silico multi-locus-sequence-typing (MLST) and core-genome single nucleotide variant (SNV) analyses. Antimicrobial susceptibility was determined using an agar incorporation method. In vitro toxin production was confirmed by Vero cell cytotoxicity assay and pathogenicity was assessed in a murine model of CDI. All RT251 isolates contained toxin A (tcdA), toxin B (tcdB) and binary toxin (cdtA and cdtB) genes. Core-genome analyses revealed the RT251 strains were clonal, with 0-5 SNVs between isolates. WGS and MLST clustered RT251 in the same evolutionary Glade (Glade 2) as RT027. Despite comparatively lower levels of in vitro toxin production, in the murine model RT251 infection resembled RT027 infection. Mice showed marked weight loss, severe disease within 48 h post-infection and death. All isolates were susceptible to metronidazole and vancomycin. Our observations suggest C difficile RT251 causes severe disease and emphasise the importance of ongoing surveillance for new and emerging strains of C. difficile with enhanced virulence. (C) 2018 Elsevier Ltd. All rights reserved.",
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A series of three cases of severe Clostridium difficile infection in Australia associated with a binary toxin producing Glade 2 ribotype 251 strain. / Wehrhahn, Michael C.; Keighley, Caitlin; Kurtovic, Jelica; Knight, Daniel R.; Hong, Stacey; Hutton, Melanie L.; Lyras, Dena; Wang, Qinning; Leong, Rupert; Borody, Tom; Edye, Michael; Riley, Thomas V.

In: Anaerobe, Vol. 55, 02.2019, p. 117-123.

Research output: Contribution to journalArticle

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AU - Hutton, Melanie L.

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AB - Three patients with severe Clostridium difficile infection (CDI) caused by an unusual strain of C. difficile, PCR ribotype (RT) 251, were identified in New South Wales, Australia. All cases presented with severe diarrhoea, two had multiple recurrences and one died following a colectomy. C difficile RT251 strains were isolated by toxigenic culture. Genetic characterisation was performed using techniques including toxin gene profiling, PCR ribotyping, whole genome sequencing (WGS), in-silico multi-locus-sequence-typing (MLST) and core-genome single nucleotide variant (SNV) analyses. Antimicrobial susceptibility was determined using an agar incorporation method. In vitro toxin production was confirmed by Vero cell cytotoxicity assay and pathogenicity was assessed in a murine model of CDI. All RT251 isolates contained toxin A (tcdA), toxin B (tcdB) and binary toxin (cdtA and cdtB) genes. Core-genome analyses revealed the RT251 strains were clonal, with 0-5 SNVs between isolates. WGS and MLST clustered RT251 in the same evolutionary Glade (Glade 2) as RT027. Despite comparatively lower levels of in vitro toxin production, in the murine model RT251 infection resembled RT027 infection. Mice showed marked weight loss, severe disease within 48 h post-infection and death. All isolates were susceptible to metronidazole and vancomycin. Our observations suggest C difficile RT251 causes severe disease and emphasise the importance of ongoing surveillance for new and emerging strains of C. difficile with enhanced virulence. (C) 2018 Elsevier Ltd. All rights reserved.

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KW - Ribotype 251

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KW - Fatal infection

KW - LABORATORY-BASED SURVEILLANCE

KW - DISEASE

KW - DIVERSITY

KW - EMERGENCE

KW - HEALTH

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