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Predictive factors, outcomes, and molecular epidemiology of Clostridioides difficile diarrhea in Brazilian hospitals

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Abstract

Little is known about the role of lineage of strains of Clostridioides difficile (CD) on the clinical presentation of CD infection (CDI) in Latin America, especially regarding the treatment response. We conducted a multicenter, prospective study to investigate the predictive factors and treatment outcomes of CDI in hospitalized patients and to performed phenotypical and molecular characterization of CD strains. A total of 361 diarrheic patients at 5 hospitals from different regions of the country were enrolled. All stool samples were tested for glutamate dehydrogenase (GDH), toxins A and B, and toxin genes using a nucleic acid amplification test (NAAT). Specimens were cultured and susceptibility profile and whole-genome sequencing (WGS) were performed. CDI positivity was 15% (56/377). Predictive factors for CDI were prior use of meropenem (OR 4.09, 95% CI 2.097–7.095; p<0.001), mucus in stools (OR 3.29; 95% CI 1.406–7.722; p=0.006) and neutrophil left-shift with >20% of bands (OR 3.77; 95% IC 1.280–11.120; p=0.016). Overall mortality was 19%, with no deaths attributed to CDI. Oral metronidazole was used in 74% of cases, with 85% of cure and 14% of recurrence. A total of 35 CD isolates were recovered, all of them susceptible to metronidazole and vancomycin. The WGS revealed 17 different STs, six of which were novel. ST42 was the most common ST and hypervirulent strains were not found. Severe CDI were caused by ST42, ST5, ST8, ST48, ST33 and a novel ST667. The ermB gene was more frequently found in isolates of ST42 (p=0.004).

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Data Availability

The data supporting the findings of this study are available within the corresponding author.

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Acknowledgements

Special thanks to bioMérieux, for the donation of chromogenic culture medium, ChromID C. difficile agar® and Pfizer that supported this work.

Funding

Pfizer (grant 53233563) supported this work, as independent researcher.

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Authors and Affiliations

  1. Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, R. Pastor Samuel Munguba, 1290 - Rodolfo Teófilo, Fortaleza, Ceará, 60430-372, Brazil

    Evelyne Santana Girão, Daniely Viana Costa & Geovania Maciel

  2. Divisão de Moléstias Infecciosas, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

    Evelyne Santana Girão, Bruno de Melo Tavares, Lauro Vieira Perdigão Neto, Icaro Boszczowski, Thais Guimarães & Silvia Figueiredo Costa

  3. Hospital São José de Doenças Infecciosas, Fortaleza, Brazil

    Evelyne Santana Girão & Janete Romão

  4. LIM-49, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Sania Alves dos Santos, Gessica Lorena Gamarra, Camila Rizek, Roberta Cristina Martins, Lauro Vieira Perdigão Neto, Constancia Diogo, Tatiana D’ Annibale Orsi & Silvia Figueiredo Costa

  5. Hospital das Clínicas, Universidade Federal do Paraná, Curitiba, Brazil

    Hugo Manuel Paz Morales, Keite da Silva Nogueira & Adriane Ceshin Maestri

  6. Hospital Alemão Oswaldo Cruz, São Paulo, Brazil

    Icaro Boszczowski & Filipe Piastrelli

  7. Departamento de Morfologia, Universidade Federal do Ceará, Fortaleza, Brazil

    Cecilia Leite Costa & Gerly Anne de Castro Brito

Authors
  1. Evelyne Santana Girão
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  2. Bruno de Melo Tavares
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  3. Sania Alves dos Santos
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  4. Gessica Lorena Gamarra
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  6. Roberta Cristina Martins
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  7. Lauro Vieira Perdigão Neto
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  8. Constancia Diogo
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  9. Tatiana D’ Annibale Orsi
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  10. Hugo Manuel Paz Morales
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  17. Geovania Maciel
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  18. Janete Romão
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  19. Thais Guimarães
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  21. Silvia Figueiredo Costa
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by: Evelyne Santana Girão, Silvia Figueiredo Costa, Bruno de Melo Tavares, Sania Alves dos Santos, Gessica Lorena Gamarra, Camila Rizek, Roberta Cristina Martins, Lauro Vieira Perdigão Neto, Constancia Diogo, Tatiana D’ Annibale Orsi, Hugo Manuel Paz Morales, Keite da Silva Nogueira, Adriane Ceshin Maestri, Icaro Boszczowski, Filipe Piastrelli, Cecilia Leite Costa, Daniely Viana Costa, Geovania Maciel, Janete Romão. The first draft of the manuscript was written by: Evelyne Santana Girão. The final review was done by Silvia Figueiredo Costa. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Evelyne Santana Girão.

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Competing interests

All authors declare no competing interests.

Ethical approval

This protocol was approved by the ethical committee from all participating institutions: Hospital Universitário Walter Cantídio, from Federal University of Ceará, in Fortaleza, Ceara (N°2.217.633); Hospital São José de Doenças Infecciosas, in Fortaleza, Ceará (N°2.144.350); Hospital das Clínicas, from University of São Paulo, in São Paulo, São Paulo (N°2.025.392) and Hospital Alemão Oswaldo Cruz, in São Paulo, São Paulo (N°2.025.392); and Hospital das Clínicas, from Federal University of Paraná, in Curitiba, Paraná (N°2.480.851)

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Girão, E.S., de Melo Tavares, B., dos Santos, S.A. et al. Predictive factors, outcomes, and molecular epidemiology of Clostridioides difficile diarrhea in Brazilian hospitals. Eur J Clin Microbiol Infect Dis 40, 1821–1832 (2021). https://doi.org/10.1007/s10096-021-04189-3

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