Farmacoriflessioni
I probiotici in gastroenterologia pediatrica: evidenze cliniche
PROBIOTICS IN PAEDIATRIC GASTROENTEROLOGY
MASSIMO FONTANA, LAURA MARTELLI
Unità Operativa di Pediatria, Ospedale dei Bambini “Vittore Buzzi”, Milano
Marzo 2004 - pagg. 175 -182
Abstract
Probiotics are dietary supplements made of live micro-organisms which improve the microbial
environment of the gut. Out of 16 randomized controlled trials (RCTs) 11 showed positive
results on the duration of the diarrhoea, although there are no data on important outcomes
such as duration of hospital stay, foecal output and dehydration. 5 RCTs have evaluated
the efficacy of probiotics in preventing diarrhoea in high risk patients, yielding conflicting
results. The efficacy on antibiotic-related diarrhoea due to C. difficile is well documented
but the effect is clinically modest. A large study on 1237 at risk newborn babies
showed a 50% reduction of necrotizing enterocolitis. Studies on probiotics in chronic inflammatory
diseases of the intestine have so far produced conflicting results.
Parole chiave
Suggerite dall'AI
Classificazione MeSH
Bibliografia
1. Fuller R. Probiotics in human medicine. Gut
1991;32:439-42.
2. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double- blind, placebo-controlled trials. J Pediatr Gastroenterol Nutr 2001;33:S17-S25.
3. Van Niel CW, Feudtner C, Garrison MM, Christakis DA. Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics 2002;109:678-684.
4. WHO. The rational use of drugs in the management of acute diarrea in children. Geneva, Switzerland: WHO, 1990.
5. Costa-Ribeiro H, Ribeiro TCM, Mattos AP, et al. Limitations of probiotic therapy in acute,stroenterol Nutr 2003;36:112-5.
6. Guandalini S, Pensabene L, Zikri MA, et al. Lactobacilluss GG administered in oral rehydratation solution to children with acute diarrea: a multicenter european trial. J Pediatr Gastroenterol Nutr 2000;30:54-60.
7. Rosenfeldt V, Michaelsen KF, Jakobsen M, et al. Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers. Pediatr Infect Dis J 2002;21:417-9.
8. Guarino A, Canani RB, Spagnuolo MI, Albano F, Di Benedetto L. Oral bacterial therapy reduces the duration of symptoms and of viral excretion in children with mild diarrhea. J Pediatr Gastroenterol Nutr 1997;25:516-9.
9. Simakachorn N, Pichaipat V, Rithipornpaisarn P, Kongkaew C, Tongpradit P, Varavithya W. Clinical evaluation of the addition of lyophilized, heat-killed Lactobacillus acidophilus LB to oral rehydration therapy in the treatment of acute diarrhea in children. J Pediatr Gastroenterol Nutr 2000:30:68-72.
10. Boulloche J, Mouterde O, Mallet E. Traitement des diarrhées aigues chez le nourrisson et le jeune enfant. Etude controlée de l’activité antidiarrhéique de L. acidophilus tués (souche LB) contre un placebo et un médicament de référence (lopéramide). Ann Pédiatr 1994;41:457-63.
11. Kaila M, Isolauri E, Saxelin M, et al. Viable versus inactivated Lactobacillus strain GG in acute Rotavirus diarrhoea. Arch Dis Child 1995;72:51-3.
12. Saavedra JM, Bauman NA, Oung I, et al. Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. Lancet 1994;344:1046-9.
13. Szajewska H, Kotowska M, Mrukowicz JZ, et al. Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants. J Pediatr 2001;138:361-5.
14. Mastretta E, Longo P, Laccisaglia A, et al. Effect of Lactobacillus GG and breast-feeding in the prevention of Rotavirus nosocomial infection. J Pediatr Gastroenterol Nutr 2002; 35:527-31.
15. Oberhelman RA, Gilman RH, Sheen P, et al. A placebo-controlled trial of Lactobacillus GG to prevent diarrhea in undernourished Peruvian children. J Pediatr 1999;134:15-20.
16. Hatakka K, Savilahti E, Ponka A, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centers: double blind, randomised trial. BMJ 2001;322:1-5.
17. Hilton E, Kolakowski P, Singer C, Smith M. Efficacy of Lactobacillus GG as a diarrhea preventive. J Travel Med 1997;4: 41-3.
18. Black FT, Anderson PL, Orskov J, Gaarslev K, Laulund S. Prophylactic efficacy of Lactobacilli on traveler’s diarrhea. Travel Med 1989;7:333-5.
19. D’Souza AL, Rajkumar C, Cooke J, Bulpitt CJ. Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ 2002; 324:1361-6.
20. Arvola T, Laiho K, Torkkeli S, et al. Prophylactic Lactobacillus GG reduces antibiotic- associated diarrhea in children with respiratory infections: a randomized study. Pediatrics 1999;104:e64.
21. Saavedra JM. Probiotics plus antibiotics: regulating our bacterial environment. J Pediatr 1999;135:535-7.
22. Elstner Cl, Lindsay AN, Book LS, et al. Lack of relationship of Clostridium difficile to antibiotic-associated diarrhea in children. Pediatr Infect Dis 1983;2:364-6.
23. Pochapin MB, Oltikar A, Pringe-Smith R, Schreiber C. A prospective randomized placebo- controlled trial of Lactobacillus GG in combination with standard antibiotics for the treatment of Clostridium difficile infection. Am J Gastroenterol 1998;93:1697.
24. Buts JP, Corthier G, Delmee M. Saccharomyces boulardii for Clostridium difficile-associated enteropathies in infants. J Pediatr Gastroenterol Nutr 1993;16:419-25.
25. Hoyos AB. Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Int J Infect Dis 1999;3:197- 202.
26. Dani C, Biadaioli R, Bertini G, Martelli E, Rubaltelli FF. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study. Biol Neonate 2002;82:103-8.
27. Prantera C, Scribano ML, Falasco G, Andreoli A, Luzi C. Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn’s Disease: a randomized controlled trial with Lactobacillus GG. Gut 2002; 51:405-9.
28. Gupta P, Andrew H, Kirschner BS, Guandalini S. Is Lactobacillus GG helpful in children with Crohn’s disease? Results of a preliminary, open-label study. J Pediatr Gastroenterol Nutr 2000;31:453-7.
29. Saint-Marc T, Blehaut H, Musial Ch, Touraine JL. Diarrhoen im zusammenhang mit AIDS (doppelblindstudie mit Saccharomyces boulardii). Sem Hopitaux, Paris 1995;71:735- 41.
30. Saint-Marc T, Rossello-Prats L, Touraine JL. Efficacité de Saccharomyces boulardii dans le traitement des diarrhées du SIDA. Ann Med Interne, Paris 1991;142:64-5.
31. Saxelin M, Chuang NH, Chassy B, et al. Lactobacilli and bacteremia in Southern Finland, 1989-1992. Clin Infect Dis 1996;22: 564-6.
32. Rautio M, Jousimies-Somer H, Kauma H, et al. Liver abscess due to a Lactobacillus rhamnosus strain indistinguishable from L. rhamnosus strain GG. Clin Infect Dis 1999; 28:1159-60.
33. Edmond MB, Ober JF, Weibaum DL, et al. Vancomycin-resistant Enterococcus faecium bacteremia: risk factors for infection. Clin Inf Dis 1995;20:1126-33.
34. Boyce JM, Opal SM, Chow JW, et al. Outbreak of multidrug-resistant Enterococcus faecium with transferable vanB class vancomycin resistance. J Clin Microbiol 1994; 32:1148-53.
35. Hamilton-Miller JMT, Shah S, Smith CT. “Probiotic” remedies are not what they seem. BMJ 1996;312:55-6.
36. Hamilton-Miller JM, Shah S, Winkler JT. Public health issues arising from microbiological and labelling quality of foods and supplements containing probiotic micro-organisms. Public Health Nutr 1999;2: 223-9.
37. Green DH, Wakeley PR, Page A, et al. Characterization of two Bacillus probiotics. Appl Environ Microbiol 1999;65:4288-91.
38. Marchand J, Vandenplas Y. Micro-organisms administered in the benefit of the host: myths and facts. Eur J Gastroenterol Hepatol 2000;12:1077-88.
2. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double- blind, placebo-controlled trials. J Pediatr Gastroenterol Nutr 2001;33:S17-S25.
3. Van Niel CW, Feudtner C, Garrison MM, Christakis DA. Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics 2002;109:678-684.
4. WHO. The rational use of drugs in the management of acute diarrea in children. Geneva, Switzerland: WHO, 1990.
5. Costa-Ribeiro H, Ribeiro TCM, Mattos AP, et al. Limitations of probiotic therapy in acute,stroenterol Nutr 2003;36:112-5.
6. Guandalini S, Pensabene L, Zikri MA, et al. Lactobacilluss GG administered in oral rehydratation solution to children with acute diarrea: a multicenter european trial. J Pediatr Gastroenterol Nutr 2000;30:54-60.
7. Rosenfeldt V, Michaelsen KF, Jakobsen M, et al. Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers. Pediatr Infect Dis J 2002;21:417-9.
8. Guarino A, Canani RB, Spagnuolo MI, Albano F, Di Benedetto L. Oral bacterial therapy reduces the duration of symptoms and of viral excretion in children with mild diarrhea. J Pediatr Gastroenterol Nutr 1997;25:516-9.
9. Simakachorn N, Pichaipat V, Rithipornpaisarn P, Kongkaew C, Tongpradit P, Varavithya W. Clinical evaluation of the addition of lyophilized, heat-killed Lactobacillus acidophilus LB to oral rehydration therapy in the treatment of acute diarrhea in children. J Pediatr Gastroenterol Nutr 2000:30:68-72.
10. Boulloche J, Mouterde O, Mallet E. Traitement des diarrhées aigues chez le nourrisson et le jeune enfant. Etude controlée de l’activité antidiarrhéique de L. acidophilus tués (souche LB) contre un placebo et un médicament de référence (lopéramide). Ann Pédiatr 1994;41:457-63.
11. Kaila M, Isolauri E, Saxelin M, et al. Viable versus inactivated Lactobacillus strain GG in acute Rotavirus diarrhoea. Arch Dis Child 1995;72:51-3.
12. Saavedra JM, Bauman NA, Oung I, et al. Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. Lancet 1994;344:1046-9.
13. Szajewska H, Kotowska M, Mrukowicz JZ, et al. Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants. J Pediatr 2001;138:361-5.
14. Mastretta E, Longo P, Laccisaglia A, et al. Effect of Lactobacillus GG and breast-feeding in the prevention of Rotavirus nosocomial infection. J Pediatr Gastroenterol Nutr 2002; 35:527-31.
15. Oberhelman RA, Gilman RH, Sheen P, et al. A placebo-controlled trial of Lactobacillus GG to prevent diarrhea in undernourished Peruvian children. J Pediatr 1999;134:15-20.
16. Hatakka K, Savilahti E, Ponka A, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centers: double blind, randomised trial. BMJ 2001;322:1-5.
17. Hilton E, Kolakowski P, Singer C, Smith M. Efficacy of Lactobacillus GG as a diarrhea preventive. J Travel Med 1997;4: 41-3.
18. Black FT, Anderson PL, Orskov J, Gaarslev K, Laulund S. Prophylactic efficacy of Lactobacilli on traveler’s diarrhea. Travel Med 1989;7:333-5.
19. D’Souza AL, Rajkumar C, Cooke J, Bulpitt CJ. Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ 2002; 324:1361-6.
20. Arvola T, Laiho K, Torkkeli S, et al. Prophylactic Lactobacillus GG reduces antibiotic- associated diarrhea in children with respiratory infections: a randomized study. Pediatrics 1999;104:e64.
21. Saavedra JM. Probiotics plus antibiotics: regulating our bacterial environment. J Pediatr 1999;135:535-7.
22. Elstner Cl, Lindsay AN, Book LS, et al. Lack of relationship of Clostridium difficile to antibiotic-associated diarrhea in children. Pediatr Infect Dis 1983;2:364-6.
23. Pochapin MB, Oltikar A, Pringe-Smith R, Schreiber C. A prospective randomized placebo- controlled trial of Lactobacillus GG in combination with standard antibiotics for the treatment of Clostridium difficile infection. Am J Gastroenterol 1998;93:1697.
24. Buts JP, Corthier G, Delmee M. Saccharomyces boulardii for Clostridium difficile-associated enteropathies in infants. J Pediatr Gastroenterol Nutr 1993;16:419-25.
25. Hoyos AB. Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Int J Infect Dis 1999;3:197- 202.
26. Dani C, Biadaioli R, Bertini G, Martelli E, Rubaltelli FF. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study. Biol Neonate 2002;82:103-8.
27. Prantera C, Scribano ML, Falasco G, Andreoli A, Luzi C. Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn’s Disease: a randomized controlled trial with Lactobacillus GG. Gut 2002; 51:405-9.
28. Gupta P, Andrew H, Kirschner BS, Guandalini S. Is Lactobacillus GG helpful in children with Crohn’s disease? Results of a preliminary, open-label study. J Pediatr Gastroenterol Nutr 2000;31:453-7.
29. Saint-Marc T, Blehaut H, Musial Ch, Touraine JL. Diarrhoen im zusammenhang mit AIDS (doppelblindstudie mit Saccharomyces boulardii). Sem Hopitaux, Paris 1995;71:735- 41.
30. Saint-Marc T, Rossello-Prats L, Touraine JL. Efficacité de Saccharomyces boulardii dans le traitement des diarrhées du SIDA. Ann Med Interne, Paris 1991;142:64-5.
31. Saxelin M, Chuang NH, Chassy B, et al. Lactobacilli and bacteremia in Southern Finland, 1989-1992. Clin Infect Dis 1996;22: 564-6.
32. Rautio M, Jousimies-Somer H, Kauma H, et al. Liver abscess due to a Lactobacillus rhamnosus strain indistinguishable from L. rhamnosus strain GG. Clin Infect Dis 1999; 28:1159-60.
33. Edmond MB, Ober JF, Weibaum DL, et al. Vancomycin-resistant Enterococcus faecium bacteremia: risk factors for infection. Clin Inf Dis 1995;20:1126-33.
34. Boyce JM, Opal SM, Chow JW, et al. Outbreak of multidrug-resistant Enterococcus faecium with transferable vanB class vancomycin resistance. J Clin Microbiol 1994; 32:1148-53.
35. Hamilton-Miller JMT, Shah S, Smith CT. “Probiotic” remedies are not what they seem. BMJ 1996;312:55-6.
36. Hamilton-Miller JM, Shah S, Winkler JT. Public health issues arising from microbiological and labelling quality of foods and supplements containing probiotic micro-organisms. Public Health Nutr 1999;2: 223-9.
37. Green DH, Wakeley PR, Page A, et al. Characterization of two Bacillus probiotics. Appl Environ Microbiol 1999;65:4288-91.
38. Marchand J, Vandenplas Y. Micro-organisms administered in the benefit of the host: myths and facts. Eur J Gastroenterol Hepatol 2000;12:1077-88.