medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2021-32-10-15medalphabet-2333Research ArticleЭПИДЕМИОЛОГИЯ И ГИГИЕНАEPIDEMIOLOGY AND HYGIENEClostridium perfringens – антибиотико-ассоциированные и спорадические диареи у детей: возрастные, анамнестические и клинико-лабораторные характеристикиClostridium perfringens – antibiotic-associated and sporadic diarrhea in children: age, anamnestic and clinical and laboratory featureshttps://orcid.org/0000-0002-8939-2973КветнаяА. С.KvetnayaA. S.

Кветная Ася Степановна, д. м. н., проф., в. н. с. научно-исследовательского отдела медицинской микробиологии и молекулярной микробиологии

Санкт-Петербург

Kvetnaya Asya S., DM Sci (habil.), professor, leading researcher at Research Dept of Medical Microbiology and Molecular Microbiology

Saint Petersburg

asya41@mail.ruhttps://orcid.org/0000-0001-8071-3243ЖелезоваЛ. И.ZhelezovaL. I.

Железова Людмила Ильинична, к. м. н., с. н. с. научно-исследовательского отдела медицинской микробиологии и молекулярной микробиологии

Санкт-Петербург

Zhelezova Lyudmila I., PhD Med, senior researcher at Research Dept of Medical Microbiology and Molecular Microbiology

Saint Petersburg

ФГБУ «Детский научно-клинический центр инфекционных болезней Федерального медико-биологического агентства»РоссияPediatric Research and Clinical Centre for Infectious DiseasesRussian Federation202116122021032Эпидемиология, гигиена, инфекционные болезни (2)1015Copyright © Кветная А.С., Железова Л.И., 20212021Кветная А.С., Железова Л.И.Kvetnaya A.S., Zhelezova L.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/2333

В статье представлены результаты собственных исследований по проблеме двух клинических форм диареи у детей (спорадической и антибиотико-ассоциированной диареи – ААД), не связанных с пищей, обусловленных энтеропродуцирующими штаммами Clostridium perfringens (C. perfringens – Ср). В рамках разработанного алгоритма в ФГБУ «ДНКЦИБ ФМБА России» (Санкт-Петербург) проведен анализ результатов комплексного клинико-лабораторного обследования детей в возрасте от 2 месяцев до 18 лет с диареей (ОКИ, n = 406 детей) в 2019–2021 годах. Материалом для исследования служили пробы кала, копрофильтраты и штаммы микроорганизмов, определяющих микробиоценоз кишечника, в том числе энтеротоксигенные штаммы C. perfringens. Основную группу составили дети с диареей (n = 38 из 406; 9,35 ± 1,8 %), у которых при поступлении в копрофильтратах обнаруживали энтеротоксин C. perfringens в ИФА и из проб кишечного содержимого выделялись культуры энтеротоксигенных штаммов C. perfringens. В первую группу вошли дети (n = 30 из 406; 7,4 ± 1,8 %) с антибиотико-ассоциированной диареей, во вторую – дети (n = 8 из 406, 1,9 ± 1,9 % детей) со спорадической диареей. В структуре энтеротоксигенных C. perfringens – ассоциированных ААД (n = 38) составила 78,9 %, спорадическая – 21,1 %. Достоверно чаще ААД регистрировалась у детей в возрасте до 1 года, спорадическая – у всех детей старше 8 лет (р < 0,05). У всех больных ААД и у всех детей со спорадической диареей тяжесть течения и выраженность диарейного синдрома напрямую зависели от колонизационной активности (КОЕ/г) энтеротоксигенных C. perfringens (r = 0,78). Заболевание у больных ААД и спорадической диареей протекало преимущественно с синдромами гастроэнтерита, энтероколита и гемоколита. Случаи спорадической диареи отличались тяжелым и длительным характером течения, развитием глубоких декомпенсированных нарушений микробиоты толстой кишки, ассоциированных с высокой колонизационной активностью как энтеротоксигенных штаммов C. perfringens (КОЕ / г = 106–7), так и условно патогенных микроорганизмов Klebsiella spp., Staphylococcus aureus и Candida albicans (КОЕ / г = 106–7), (р < 0,05). Полученные результаты определяют тактику дифференциальной диагностики и лечения ААД и спорадических диарей, вызванных энтеропродуцирующими штаммами C. perfringens.

The article presents the data of the research on the problem of two clinical forms of enteroproducing Clostridium perfringens (C. perfringens) – associated infection in the children who are not connected with food – antibiotic-associated and sporadic forms. Within the period of 2019–2021 a retrospective analysis of the results of complex clinical and laboratory study of children aged from 2 months to 18 years with diarrhea (acute intestinal infection, n = 406 children) was carried out within the framework of the algorithm developed by Pediatric Research and Clinical Center for Infectious Diseases (Russia, Saint Petersburg). The material for the study included stool tests, coprofiltrates and strains of the microorganisms determinating microbiocoenosis of the intestines including enterotoxigenic strains of C. perfringens. The main group included children with diarrhea (n = 38 of 406 children with diarrhea) who at admission presented C. perfringens enterotoxin in coprofiltrates found by immune-enzyme analysis and there were identified the cultures of enterotoxigenic strains of C. perfringens by tests of intestinal contents. The first group included children (n = 30 of 406 children; 7 %) with antibiotic-associated diarrhea (AAD). The second group included children (n = 8 of 406 children; 2 %) with sporadic diarrhea. An overwhelming majority of patients with ААD (n = 20; 92.3 %) of the first 8 (100 %) years of life presented intensity of diarrhea syndrome in direct dependence on colonization activity of enterotoxigenic C perfringens (colony-forming units/g feces) (r = 0.78). The disease proceeded mainly with the syndromes of gastroenteritis, enterocolitis and hemorrhagic colitis. There was noted a reliable high frequency of severe forms of both ААD, and sporadic diarrhea (р < 0.05) caused by enterotoxigenic strains of C perfringens in children of the first year of life. Deep decompensated disorders of large intestine microbiota associated with Klebsiella spp., Staphylococcus aureus and Candida albicans, were characterized by severity and prolonged character of the course (р < 0.05). The received results determine the tactics of differential diagnosis and treatment of AAD and sporadic diarrhea caused by enteroproducing strains of C. perfringens.

детиC. perfringensэнтеротоксинмикробиотаААД и спорадическая диареяchildrenC. perfringensenterotoxinmicrobiotaААD and sporadic diarrheaReferencesМазанкова Л. В.,Чеботарева Т. А., Горбунов С. Б. и др. Дифференцированный подход к этиологической диагностике острой диареи у детей в эпидсезон клинические случаи. Журнал Фарматека, 2020. Т. 27. № 9. С. 103–107.Mazankova L. V., Chebotareva T. A., Gorbunov S. B. et al. Differentiated approach to the etiological diagnosis of acute diarrhea in children during the epidemiological season of clinical cases. Pharmateca Journal, 2020. T. 27. No. 9. P. 103–107.Успенский Ю. П., Фоминых Ю. А. Антибиотик-ассоциированная диарея: актуальность проблемы, профилактика и терапия. Архивъ внутренней медицины. № 2 (10). 2013. С. 46–53.Uspensky Yu.P., Fominykh Yu. A. Antibiotic-associated diarrhea: relevance of the problem, prevention and therapy. Archives of Internal Medicine. No. 2 (10). 2013. S. 46–53.Kiu R., Hall LJ. An update on the human and animal enteric pathogen Clostridium perfringens. Emerg Microb Infect. 2018; 7(1): 141.Kiu R., Hall LJ. An update on the human and animal enteric pathogen Clostridium perfringens. Emerg Microb Infect. 2018; 7(1): 141.Alam S., Muchatag M. Antibiotic associated diarrhea in children. Indian Pеdiatr. 2009. Vol. 46, No. 6. Р. 491–496.Alam S., Muchatag M. Antibiotic associated diarrhea in children. Indian Pеdiatr. 2009. Vol. 46, No. 6. Р. 491–496.Hobbs B. C., Smith M. T., Oakley C. L., Warrack G. H., Cruickshank J. C. Clostridium welchii food poisoning. J. Hyg. 1953; 51: 75–101. DOI: 10.1017/S 0022172400015515.[PMC free article] [PubMed] [CrossRet] [Google Scholar].Hobbs B. C., Smith M. T., Oakley C. L., Warrack G. H., Cruickshank J. C. Clostridium welchii food poisoning. J. Hyg. 1953; 51: 75–101. DOI: 10.1017/S 0022172400015515.[PMC free article] [PubMed] [CrossRet] [Google Scholar].McClane B.A.; Uzal F. A.; Miyakawa M. F.; Lyerly D.; Wilkins T. D. The enterotoxic clostridia. In The Prokan/otes, 3rd ed.; Dworkin M., Falkow S., Rosenburg E., Schleifer H., Stackebrandt E., Eds.; Springer NY Press.: New York, NY, USA, 2006; pp. 688–752.McClane B.A.; Uzal F. A.; Miyakawa M. F.; Lyerly D.; Wilkins T. D. The enterotoxic clostridia. In The Prokan/otes, 3rd ed.; Dworkin M., Falkow S., Rosenburg E., Schleifer H., Stackebrandt E., Eds.; Springer NY Press.: New York, NY, USA, 2006; pp. 688–752.Freedman J. C., A. Shrestha. Clostridium perfringens Enterotoxin: Action, Genetics, and Translational Application. Future Microbiol. 2016, 8, 73.Freedman J. C., A. Shrestha. Clostridium perfringens Enterotoxin: Action, Genetics, and Translational Application. Future Microbiol. 2016, 8, 73.Rood J. I. et al. Expansion of the Clostridium perfringens toxin-based typing scheme. Anaerobe (2018) 10.1016/j.anaerobe.2018.04.011.Rood J. I. et al. Expansion of the Clostridium perfringens toxin-based typing scheme. Anaerobe (2018) 10.1016/j.anaerobe.2018.04.011.Gilbert R. J. Cholesterol dependent cytolysins. Adv. Exp. Med. Biol. 2010; 677: 56–66. https://doi.org/10.1007/978–1–4419–63277–5.Gilbert R. J. Cholesterol dependent cytolysins. Adv. Exp. Med. Biol. 2010; 677: 56–66. https://doi.org/10.1007/978–1–4419–63277–5.Llanco LA., Nakano V., Avila-Campos M. J. Sialidase production and genetic diversity in Clostridium perfringens type A isolated from chicken with necrotic enteritis in Brazil. Curr. Microbiol. 2015; 70 (3): 330–7. https://doi.org/10.1007/s00284–014–0722–5.Llanco LA., Nakano V., Avila-Campos M. J. Sialidase production and genetic diversity in Clostridium perfringens type A isolated from chicken with necrotic enteritis in Brazil. Curr. Microbiol. 2015; 70 (3): 330–7. https://doi.org/10.1007/s00284–014–0722–5.Kiu R., Caim S., Alexander S., Pachori P., Hall L. J. Probing genomic aspects of the multihost pathogen Clostridium perfringens reveals significant pangenome diversity, and a diverse array of virulence factors. Front. Microbiol. 2017; 8; 2485. https://doi.org/10.3389/fmicb.2017.0248.Kiu R., Caim S., Alexander S., Pachori P., Hall L. J. Probing genomic aspects of the multihost pathogen Clostridium perfringens reveals significant pangenome diversity, and a diverse array of virulence factors. Front. Microbiol. 2017; 8; 2485. https://doi.org/10.3389/fmicb.2017.0248.Li J., McClane B. A. NanI sialidase can support the growth and survival of Clostridium perfringens strain F4969 using sialyated host macromolecules (Mucin) or Caco‑2 cells. Infect. Immun. 2018; 86 (2): e00547–17. https://doi.org/10.1128/iai.00547-17.Li J., McClane B. A. NanI sialidase can support the growth and survival of Clostridium perfringens strain F4969 using sialyated host macromolecules (Mucin) or Caco‑2 cells. Infect. Immun. 2018; 86 (2): e00547–17. https://doi.org/10.1128/iai.00547-17.Yan X., Porter C. J., Hardy S. P., Steer D., Smith A. I., Quinsey N. S., et al. Structural and functional analysis of the pore-forming toxin NetB from Clostridium perfringens. mBio. 2013; 4(1): e00019–13. https://doi.org/10.1128/mbio.00019-13.Yan X., Porter C. J., Hardy S. P., Steer D., Smith A. I., Quinsey N. S., et al. Structural and functional analysis of the pore-forming toxin NetB from Clostridium perfringens. mBio. 2013; 4(1): e00019–13. https://doi.org/10.1128/mbio.00019-13.Wisniewski J. A., Rood J. I. The Tcp conjugation system of Clostridium perfringens. Plasmid. 2017; 91: 28–36. https://doi.org/10.1016/j.plasmid.2017.03.001.Wisniewski J. A., Rood J. I. The Tcp conjugation system of Clostridium perfringens. Plasmid. 2017; 91: 28–36. https://doi.org/10.1016/j.plasmid.2017.03.001.Li J., Adams B., Bannam T., Mijmoto K. Et al. Toxin plasmids of Clostridium perfringens. Microbiol Mol Biol Rev. 2013 Jun; 77 (2): 208–233. DOI: 10.1128/MMBR. 00062–12.Li J., Adams B., Bannam T., Mijmoto K. Et al. Toxin plasmids of Clostridium perfringens. Microbiol Mol Biol Rev. 2013 Jun; 77 (2): 208–233. DOI: 10.1128/MMBR. 00062–12.Kiu R., Brown J., Bedwell H., Leclaire1 C. et al. Genomic analysis on broiler-associated Clostridium perfringens strains and exploratory caecal microbiome investigation reveals key factors linked to poultry necrotic enteritis. Animal Microbiome (2019) 1: 12. https://doi.org/10.1186/s42523-019-0015-1.Kiu R., Brown J., Bedwell H., Leclaire1 C. et al. Genomic analysis on broiler-associated Clostridium perfringens strains and exploratory caecal microbiome investigation reveals key factors linked to poultry necrotic enteritis. Animal Microbiome (2019) 1: 12. https://doi.org/10.1186/s42523-019-0015-1.Centers for Disease Control and prevention. Fatal foodbome Clostridium perfringens illness at a state psychiatric hospital – Louisiana, 2010. MMWR Morb Mortal Wkly Rep. 2012; 61 (32): 605–8.Centers for Disease Control and prevention. Fatal foodbome Clostridium perfringens illness at a state psychiatric hospital – Louisiana, 2010. MMWR Morb Mortal Wkly Rep. 2012; 61 (32): 605–8.Li J., Freedman J. C., Evans D. R., McClane B. A. CodY promotes sporulation and enterotoxin production by Clostridium perfringens type A strain SM101. Infect. Immun. 2017; 85 (3): e00855–16. https://doi.org/10.1128/iai.00855-16.Li J., Freedman J. C., Evans D. R., McClane B. A. CodY promotes sporulation and enterotoxin production by Clostridium perfringens type A strain SM101. Infect. Immun. 2017; 85 (3): e00855–16. https://doi.org/10.1128/iai.00855-16.Gibert M., Jolivet-Reynaud C., Popoff M. R. Beta2 toxin, a novel toxin produced by Clostridium perfringens. Gene. 1997; 203 (1): 65–73. https://doi.org/10.1016/s03781119(97)00493-9.Gibert M., Jolivet-Reynaud C., Popoff M. R. Beta2 toxin, a novel toxin produced by Clostridium perfringens. Gene. 1997; 203 (1): 65–73. https://doi.org/10.1016/s03781119(97)00493-9.Llanco LA., Nakano V., Avila-Campos M. J. Sialidase production and genetic diversity in Clostridium perfringens type A isolated from chicken with necrotic enteritis in Brazil. Curr. Microbiol. 2015; 70 (3): 330–7. https://doi.org/10.1007/s00284-0140722-5.Llanco LA., Nakano V., Avila-Campos M. J. Sialidase production and genetic diversity in Clostridium perfringens type A isolated from chicken with necrotic enteritis in Brazil. Curr. Microbiol. 2015; 70 (3): 330–7. https://doi.org/10.1007/s00284-0140722-5.Li J., McClane B. A. NanI sialidase can support the growth and survival of Clostridium perfringens strain F4969 using sialyated host macromolecules (Mucin) or Caco‑2 cells. Infect. Immun. 2018; 86(2): e00547–17. https://doi.org/10.1128/iai.00547-17.Li J., McClane B. A. NanI sialidase can support the growth and survival of Clostridium perfringens strain F4969 using sialyated host macromolecules (Mucin) or Caco‑2 cells. Infect. Immun. 2018; 86(2): e00547–17. https://doi.org/10.1128/iai.00547-17.

The authors declare that there are no conflicts of interest present.