Sequence-Based Identification of Metronidazole-Resistant Clostridioides difficile Isolates
Emerging infectious diseases, vol. 28, pp. 2308–2311
Abstract
C lostridioides difficile is a major cause of antibiotic- associated colitis (1).Antimicrobial drug-resistant infections are a global economic and healthcare burden (2).Resistance is generally low to commonly prescribed antimicrobial drugs used for primary C. difficile infections.However, high rates of metronidazole resistance have been observed for C. difficile isolates carrying the 7-kb plasmid pCD-METRO, in particular for isolates belonging to PCR ribotype (RT) 010 and RT020 (clade 1) and the epidemic strain RT027 (clade 2) (3) (Figure , panel A).This plasmid has been reported in C. difficile isolates from countries in Europe. The StudySince the discovery of pCD-METRO, we have implemented PCR that uses primers oBH-1 (5′-CCTCGTAGAATCCGGTGCAA-3′) and oBH-2 (5′-TATTTCCTTGCCGCTGAGGT-3′) for national sentinel surveillance and diagnostics of C. difficile infections in the Netherlands.The primers are specific for open reading frame (ORF) 6 of pCD-METRO (Figure , panel A).Since 2019, we have tested 3,257 isolates and identified 8 (0.25%) additional pCD-METRO-positive isolates; this percentage is consistent with previous findings (3).We have a total of 27 human and animal C. difficile isolates in our collection that are pCD-METRO-positive.Most of the isolates (22/27, 81%) belong to nontoxigenic PCR RT010, including isolate 1143 from Brazil.Isolate 1143 is one of 8 canine isolates that showed phenotypic resistance to metronidazole (MIC = 32 mg/L) by Etest on Brucella blood agar (BBA); the Etest was performed at the Universidade Federal do Rio de Janeiro in Brazil.The isolate from Brazil confirmed that pCD-METRO is present in C. difficile not only in Europe but also in South America.The 1143 isolate was not characterized further because it belonged to PCR RT010, in which pCD-METRO is most frequently observed.The high number of C. difficile RT010 isolates carrying pCD-METRO might be related to genomic background of the isolates (4) or sampling bias; a higher prevalence of metronidazole resistance has been observed among RT010 strains (3,5).Low-frequency horizontal gene transfer is more likely to occur after prolonged co-colonization of nontoxigenic C. difficile and pCD-METRO donor bacteria, and acquisition of the plasmid might occur from a source after metronidazole exposure.For example, dogs carry nontoxigenic C. difficile frequently and are often treated with metronidazole (6).The presence of pCD-METRO in toxigenic isolates might also be underestimated; antimicrobial susceptibility testing is not routinely performed, and plasmid carriage is not assessed, even when metronidazole treatment fails.
Authors 8
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Leiden University · Universidade Federal do Rio de Janeiro · Brigham and Women's Hospital · European Bioinformatics Institute · Harvard University · Leiden University Medical Center · Wellcome Sanger Institute · National Institute for Public Health and the Environment
Affiliation as printed
Centre for Microbial Cell Biology , Leiden , the Netherlands
(L. Bry);
Brigham & Women's Hospital, Boston, Massachusetts, USA
Centre for Microbial Cell Biology, Leiden, the Netherlands (W.K. Smits); Leiden University Medical Center, Leiden, the Netherlands
Harvard Medical School, Boston (L. Bry); European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (E.O. Ferreira
Wellcome Sanger Institute, Hinxton (G.A
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Leiden University · Universidade Federal do Rio de Janeiro · Brigham and Women's Hospital · European Bioinformatics Institute · Harvard University · Leiden University Medical Center · Wellcome Sanger Institute · National Institute for Public Health and the Environment
Affiliation as printed
Centre for Microbial Cell Biology , Leiden , the Netherlands
(L. Bry);
Brigham & Women's Hospital, Boston, Massachusetts, USA
Centre for Microbial Cell Biology, Leiden, the Netherlands (W.K. Smits); Leiden University Medical Center, Leiden, the Netherlands
Harvard Medical School, Boston (L. Bry); European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (E.O. Ferreira
Wellcome Sanger Institute, Hinxton (G.A
-
Leiden University · Universidade Federal do Rio de Janeiro · Brigham and Women's Hospital · European Bioinformatics Institute · Harvard University · Leiden University Medical Center · Wellcome Sanger Institute · National Institute for Public Health and the Environment
Affiliation as printed
Centre for Microbial Cell Biology , Leiden , the Netherlands
(L. Bry);
Brigham & Women's Hospital, Boston, Massachusetts, USA
Centre for Microbial Cell Biology, Leiden, the Netherlands (W.K. Smits); Leiden University Medical Center, Leiden, the Netherlands
Harvard Medical School, Boston (L. Bry); European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (E.O. Ferreira
Wellcome Sanger Institute, Hinxton (G.A
-
Leiden University · Universidade Federal do Rio de Janeiro · Brigham and Women's Hospital · European Bioinformatics Institute · Harvard University · Leiden University Medical Center · Wellcome Sanger Institute · National Institute for Public Health and the Environment
Affiliation as printed
Centre for Microbial Cell Biology , Leiden , the Netherlands
(L. Bry);
Brigham & Women's Hospital, Boston, Massachusetts, USA
Centre for Microbial Cell Biology, Leiden, the Netherlands (W.K. Smits); Leiden University Medical Center, Leiden, the Netherlands
Harvard Medical School, Boston (L. Bry); European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (E.O. Ferreira
Wellcome Sanger Institute, Hinxton (G.A
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Grace A. Blackwell Aachen
Leiden University · Universidade Federal do Rio de Janeiro · Brigham and Women's Hospital · European Bioinformatics Institute · Harvard University · Leiden University Medical Center · Wellcome Sanger Institute · National Institute for Public Health and the Environment
Affiliation as printed
(L. Bry);
Brigham & Women's Hospital, Boston, Massachusetts, USA
Centre for Microbial Cell Biology, Leiden, the Netherlands (W.K. Smits); Leiden University Medical Center, Leiden, the Netherlands
Harvard Medical School, Boston (L. Bry); European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (E.O. Ferreira
Wellcome Sanger Institute, Hinxton (G.A
-
Leiden University · Universidade Federal do Rio de Janeiro · Brigham and Women's Hospital · European Bioinformatics Institute · Harvard University · Leiden University Medical Center · Wellcome Sanger Institute · National Institute for Public Health and the Environment
Affiliation as printed
Centre for Microbial Cell Biology , Leiden , the Netherlands
(L. Bry);
Brigham & Women's Hospital, Boston, Massachusetts, USA
Centre for Microbial Cell Biology, Leiden, the Netherlands (W.K. Smits); Leiden University Medical Center, Leiden, the Netherlands
Harvard Medical School, Boston (L. Bry); European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (E.O. Ferreira
Wellcome Sanger Institute, Hinxton (G.A
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Eliane de Oliveira Ferreira Aachen
Leiden University · Universidade Federal do Rio de Janeiro · Brigham and Women's Hospital · European Bioinformatics Institute · Harvard University · Leiden University Medical Center · Wellcome Sanger Institute · National Institute for Public Health and the Environment
Affiliation as printed
(L. Bry);
Brigham & Women's Hospital, Boston, Massachusetts, USA
Centre for Microbial Cell Biology, Leiden, the Netherlands (W.K. Smits); Leiden University Medical Center, Leiden, the Netherlands
Harvard Medical School, Boston (L. Bry); European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (E.O. Ferreira
Wellcome Sanger Institute, Hinxton (G.A
-
Leiden University · Universidade Federal do Rio de Janeiro · Brigham and Women's Hospital · European Bioinformatics Institute · Harvard University · Leiden University Medical Center · Wellcome Sanger Institute · National Institute for Public Health and the Environment
Affiliation as printed
Centre for Microbial Cell Biology , Leiden , the Netherlands
(L. Bry);
Brigham & Women's Hospital, Boston, Massachusetts, USA
Centre for Microbial Cell Biology, Leiden, the Netherlands (W.K. Smits); Leiden University Medical Center, Leiden, the Netherlands
Harvard Medical School, Boston (L. Bry); European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (E.O. Ferreira
Wellcome Sanger Institute, Hinxton (G.A
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