Антибиотикоассоциированная диарея (ААД) встречается примерно у 11% детей, получающих антибиотики (АБ). Она может быть связана с Clostridium difficile, реже – с другими условно-патогенными микробами, в большинстве случаев этиология ААД остается неясной. С C. difficile связаны наиболее тяжелые формы ААД, в частности псевдомембранозный колит. Факторы риска развития ААД – повторные курсы АБ, особенно цефалоспоринов III поколения и амоксициллина клавуланата, а также повторные госпитализации и хронические заболевания кишечника: болезнь Гиршпрунга, муковисцидоз, болезнь Крона, язвенный колит. Клинически ААД может проявляться простой диареей, колитом и псевдомембранозным колитом, который имеет высокий риск осложнений. Несмотря на более высокую частоту выявления C. difficile у детей первых месяцев жизни, симптомы обычно отсутствуют или слабо выражены. Риск манифестной формы выше в возрасте от 6 мес до 2 лет. Лечение ААД требует отмены причинного АБ и назначения пробиотиков с доказанной эффективностью, среди которых наиболее предпочтителен Энтерол®. Тяжелые формы C. difficile-ассоциированной диареи требуют также назначения специфических АБ: метронидазола, ванкомицина, при упорном течении – рифаксимина. Профилактика ААД состоит в строгом выборе АБ в соответствии с показаниями и параллельном назначении Энтерола.
Antibiotic-associated diarrhea (AAD) occurs in approximately 11% of children receiving antibiotics (AB). It may be associated with Clostridium difficile, at least – with other opportunistic pathogens, in most cases, the etiology of the AMA remains unclear. With C. difficile associated most severe forms of the AMA, in particular pseudomembranous colitis. Risk factors for AMA – AB repeat courses, especially cephalosporins III generation and amoxicillin clavulanate, as well as re-hospitalization and chronic bowel disease: Hirschsprung's disease, cystic fibrosis, Crohn's disease, ulcerative colitis. Clinically AMA may surface with simple diarrhea, colitis and pseudomembranous colitis, which has a high risk of complications. Despite the higher incidence of C. difficile detection in children during the first months of life, symptoms are usually absent or mild. The risk of symptomatic forms above the age of 6 months to 2 years. AMA Treatment requires the removal of the causative AB and destination of probiotics with proven efficacy, the most preferred Enterol. Severe forms of C. difficile-associated diarrhea also require the appointment of specific AB: metronidazole, vancomycin, with persistent course – rifaximin. AMA Prevention is simple and consists in choosing AB in accordance with the indications and parallel assignment Enterol.
1. Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992; 15: 573–81.
2. Beaugerie L, Flahault A, Barbut F et al. Antibiotic-associated diarrhea and Clostridium difficile in the community. Aliment Pharmacol Ther 2003; 17: 905–12.
3. Bouhnik Y. Microflora and diarrhoea: antibiotic-associated diarrhoea. In: Rambaut JC, Buts JP, eds. Gut Microflora. Paris: John Libbey Eurotex, 2006; p. 181–97.
4. Wistrom J, Norrby SR, Myhre EB et al. Frequency of antibiotic-associated diarrhoea in 2,462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother 2001; 47: 43–50.
5. McFarland LV, Brandmarker SA, Guandalini S. Pediatric Clostridium difficile: a phantom menace or clinical reality? J Pediatr Gasroenterol Nutr 2000; 31: 220–31.
6. Delmee M, Verellen G, Avesani V et al. Clostridium difficile in neonates: serogrouping and epidemiology. Eur J Pediatr 1988; 147: 36–40.
7. Larson HE, Barclay FE, Honour P et al. Epidemiology of Clostridium difficile in infants. J Infect Dis 1982; 146: 727–33.
8. Ferroni A, Merckx J, Ancelle T et al. Nosocomial outbreak of Clostridium difficile diarrhea in a pediatric service. Eur J Clin Microbiol Infect Dis 1997; 16: 928–33.
9. Buts JP. The clinical significance of Clostridium difficile infections in infants and children. In: Rambaud JC, LaMont JT. Updates of Clostridium difficile. Paris: Springer-Verlag, 1996; p. 29–36.
10. Benoit R, Danquechin DE, Loulergue J et al. Diarroea post-antibiotique: role de Klebsiella oxytoca. Gasroenterol Clin Biol 1992; 16: 860–4.
11. Lamont J. Recent advances in the structures and function of Clostridium difficile toxins. In: Rambaud JC, LaMont JT. Updates of Clostridium difficile. Paris: Springer-Verlag, 1996; p. 72–86.
12. Price AB. Pseudomembranous colitis. In: Wright R, ed. Recent advances in gastroenterology. London: WB Saunders, 2005; p. 15–172.
13. Mylonakis E, Ryan ET, Calderwood SB. Clostridium difficile-associatied diarrhea: a review. Arch Intern Med 2000; 161 (525): 5–33.
14. Cooperstock M. Clostridium difficile in infants and children. In: Rambaud JC, Ducluzeau R, eds. Clostridium difficile-associated intestinal diseases. Paris: Springer-Verlag, 1990; p. 81–94.
15. Harris PR, Figueroa-Colon R. Rectal prolapse in children associated with Clostridium difficile infection. Ped Infect Dis J 1995; 14: 78–80.
16. Garlani MJ, Murray JC, Morad AB et al. Chronic osteomyelitis caused by Clostridium difficile in an adolescent with sickle cell disease. Ped Infect Dis J 1996; 15: 1054–6.
17. Thomas DFM, Fernie DS, Bayston R et al. Clostridial toxins in neonatal necrotising enterocolitis. Arch Dis Child 1984; 59: 270–83.
18. Cetina-Sauri G, Sierra Basto G. Therapeutic evaluation of Saccharomyces boulardii in children with acute diarrhea. Annales de Pediatrie 1994; 41 (6): 397–400.
19. Castaneda C, Garcia E, Santa Cruz M et al. Effects of Saccharomyces boulardii in children with chronic diarrhea, especially cases due to giardiasis. Revista Mexicana de Puericultura y Pediatria 1995; 2: 12.
20. Castagliuolo I, LaMont JT, Nikulasson ST et al. Saccharomyces boulardii protease inhibits Clostridium difficile toxin A effects in the rat ileum. Infect Immun 1996; 12: 5225–32.
21. Gedek BR. Adherence of E. coli serogroup O-157 and the Salmonella typhimurium mutant DT 104 to the surface of Saccharomyces boulardii. Mycoses 1999; 42 (4): 261–4.
22. Cherucka D, Dahan S, Mograbi B et al. Saccharomyces boulardii preserves the barrier function and modulates the signal transduction pathway induced in enteropathogenic Escherichia coli-infected T84 cells. Infect Immun 2000; 68: 5998–6004.
23. Dahan S, Dalmasso G, Imbert V et al. Saccharomyces boulardii interferes with enterohemorrhagic Escherichia coli-induced signaling pathways in T84 cells. Infect Immun 2003; 72 (2): 766–73.
24. Buts JP, Bernasconi P, van Craymest MP et al. Response of human and rat small intestinal mucosa to oral administration of Saccharomyces boulardii. Pediatr Res 1986; 20: 192–6.
25. Sougiolzis S. Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-kB-mediated IL-8 gene expression. Biochem Biophys Res Commun 2006; 2: 23.
26. Girard-Pipau F, Pompei A, Schneider S et al. Intestinal microflora, short chain and cellular fatty acids, influence of a probiotic Saccharomyces boulardii. Microb Ecolog Health Dis 2002; 14: 220–7.
27. Buts JP, Corthier G, Delmee M. Saccharomyces boulardii for Clostridium difficile-associated entheropathies in infants. J Pediatr Gastroenterol Nutr 1993; 16: 419–25.
28. Costalos C, Skouteri V, Gounaris A et al. Enteral feeding of premature infants with Saccharomyces boulardii. Early Hum Dev 2003; 11: 89–96.
________________________________________________
1. Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992; 15: 573–81.
2. Beaugerie L, Flahault A, Barbut F et al. Antibiotic-associated diarrhea and Clostridium difficile in the community. Aliment Pharmacol Ther 2003; 17: 905–12.
3. Bouhnik Y. Microflora and diarrhoea: antibiotic-associated diarrhoea. In: Rambaut JC, Buts JP, eds. Gut Microflora. Paris: John Libbey Eurotex, 2006; p. 181–97.
4. Wistrom J, Norrby SR, Myhre EB et al. Frequency of antibiotic-associated diarrhoea in 2,462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother 2001; 47: 43–50.
5. McFarland LV, Brandmarker SA, Guandalini S. Pediatric Clostridium difficile: a phantom menace or clinical reality? J Pediatr Gasroenterol Nutr 2000; 31: 220–31.
6. Delmee M, Verellen G, Avesani V et al. Clostridium difficile in neonates: serogrouping and epidemiology. Eur J Pediatr 1988; 147: 36–40.
7. Larson HE, Barclay FE, Honour P et al. Epidemiology of Clostridium difficile in infants. J Infect Dis 1982; 146: 727–33.
8. Ferroni A, Merckx J, Ancelle T et al. Nosocomial outbreak of Clostridium difficile diarrhea in a pediatric service. Eur J Clin Microbiol Infect Dis 1997; 16: 928–33.
9. Buts JP. The clinical significance of Clostridium difficile infections in infants and children. In: Rambaud JC, LaMont JT. Updates of Clostridium difficile. Paris: Springer-Verlag, 1996; p. 29–36.
10. Benoit R, Danquechin DE, Loulergue J et al. Diarroea post-antibiotique: role de Klebsiella oxytoca. Gasroenterol Clin Biol 1992; 16: 860–4.
11. Lamont J. Recent advances in the structures and function of Clostridium difficile toxins. In: Rambaud JC, LaMont JT. Updates of Clostridium difficile. Paris: Springer-Verlag, 1996; p. 72–86.
12. Price AB. Pseudomembranous colitis. In: Wright R, ed. Recent advances in gastroenterology. London: WB Saunders, 2005; p. 15–172.
13. Mylonakis E, Ryan ET, Calderwood SB. Clostridium difficile-associatied diarrhea: a review. Arch Intern Med 2000; 161 (525): 5–33.
14. Cooperstock M. Clostridium difficile in infants and children. In: Rambaud JC, Ducluzeau R, eds. Clostridium difficile-associated intestinal diseases. Paris: Springer-Verlag, 1990; p. 81–94.
15. Harris PR, Figueroa-Colon R. Rectal prolapse in children associated with Clostridium difficile infection. Ped Infect Dis J 1995; 14: 78–80.
16. Garlani MJ, Murray JC, Morad AB et al. Chronic osteomyelitis caused by Clostridium difficile in an adolescent with sickle cell disease. Ped Infect Dis J 1996; 15: 1054–6.
17. Thomas DFM, Fernie DS, Bayston R et al. Clostridial toxins in neonatal necrotising enterocolitis. Arch Dis Child 1984; 59: 270–83.
18. Cetina-Sauri G, Sierra Basto G. Therapeutic evaluation of Saccharomyces boulardii in children with acute diarrhea. Annales de Pediatrie 1994; 41 (6): 397–400.
19. Castaneda C, Garcia E, Santa Cruz M et al. Effects of Saccharomyces boulardii in children with chronic diarrhea, especially cases due to giardiasis. Revista Mexicana de Puericultura y Pediatria 1995; 2: 12.
20. Castagliuolo I, LaMont JT, Nikulasson ST et al. Saccharomyces boulardii protease inhibits Clostridium difficile toxin A effects in the rat ileum. Infect Immun 1996; 12: 5225–32.
21. Gedek BR. Adherence of E. coli serogroup O-157 and the Salmonella typhimurium mutant DT 104 to the surface of Saccharomyces boulardii. Mycoses 1999; 42 (4): 261–4.
22. Cherucka D, Dahan S, Mograbi B et al. Saccharomyces boulardii preserves the barrier function and modulates the signal transduction pathway induced in enteropathogenic Escherichia coli-infected T84 cells. Infect Immun 2000; 68: 5998–6004.
23. Dahan S, Dalmasso G, Imbert V et al. Saccharomyces boulardii interferes with enterohemorrhagic Escherichia coli-induced signaling pathways in T84 cells. Infect Immun 2003; 72 (2): 766–73.
24. Buts JP, Bernasconi P, van Craymest MP et al. Response of human and rat small intestinal mucosa to oral administration of Saccharomyces boulardii. Pediatr Res 1986; 20: 192–6.
25. Sougiolzis S. Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-kB-mediated IL-8 gene expression. Biochem Biophys Res Commun 2006; 2: 23.
26. Girard-Pipau F, Pompei A, Schneider S et al. Intestinal microflora, short chain and cellular fatty acids, influence of a probiotic Saccharomyces boulardii. Microb Ecolog Health Dis 2002; 14: 220–7.
27. Buts JP, Corthier G, Delmee M. Saccharomyces boulardii for Clostridium difficile-associated entheropathies in infants. J Pediatr Gastroenterol Nutr 1993; 16: 419–25.
28. Costalos C, Skouteri V, Gounaris A et al. Enteral feeding of premature infants with Saccharomyces boulardii. Early Hum Dev 2003; 11: 89–96.
Авторы
Е.А.Корниенко*
ГБОУ ВПО Санкт-Петербургский государственный педиатрический медицинский университет Минздрава России. 194100, Россия, Санкт-Петербург, Литовская ул., д. 2
*elenkornienk@yandex.ru
________________________________________________
E.A.Kornienko*
Saint Petersburg State Pediatric Medical University of the Ministry of Health of the Russian Federation. 194100, Russian Federation, Saint Petersburg, Litovskaja ul., d. 2
*elenkornienk@yandex.ru