Alimentary tract and pancreas

Alimentarni trakt i pankreas

ARCH GASTROENTEROHEPATOL 2001; 20 ( No 3 – 4 ):

Evaluation of the efficacy of Saccharomyces boulardii in children with acute diarrhoea

Ispitivanje efikasnosti Sacharomyces boulardii u dece sa akutnom dijarejom

( accepted September 10th, 2001 )

Nafiye Urganci, Tugçin Polat, Metin Uysalol, Feyzullah Çetinkaya

Clinic of Pediatrics, Sisli Etfal Hospital, Istanbul, Turkey

Address correspondence to: Dr Nafiye Urganci

Dereboyu cad, Cudi Efendi sok.

Pinyal apt. No:3/6

Ortaköy-Istanbul/ Turkey

e-mail: nafiyeurgancı@mynet.

****************** *****************

Saccharomyces boulardii, children, acute darrhoea. Gastroenteroloska

sekcija SLD-

01712, 2001.

SUMMARY

A double-blind placebo-controlled study was designed to evaluate the efficacy and tolerability of the yeast Saccharomyces boulardii as an antidiarrheal agent in 100 infant and small children with acute diarhoreal illness. Evaluation of the results showed reduction in the number of stools and an improvement in their consistency in Saccharomyces boulardii group. After 48h and 96h children treated with Saccharomyces boulardii scored better than controls. It is concluded that in Saccharomyces boulardii group significantly more children recovered and normalised stolls than controls without adverse reactions. This yeast can be used as an adjunct to oral rehydration in treating acute diarrhea in infants.

Key words: Saccharomyces boulardii, efficacy, acute diarrhea, treatment.

SAZETAK

Ova dvostruko-slepa i placebo-kontrolisana studija je planirana da bi se odredila delotvornost i podosljivost primene kvasnice Saccharomyces boulardii u grupi od 100 odojadi i male dece sa akutnim prolivom. Procena uspesnosti lecenja je nacinjena na osnovu smanjenja broja stolica i normalizacije njihove konzistencije. Posle 48h i 96h od pocetka primene, Saccharomyces boulardii grupa dece je bila znacajnije bolje u pogledu broja i konzistencije stolica. Zakljuceno je da je primena Saccharomyces boulardi korisna u dece sa ajutnom dijarejom i da ona nema nezeljenih dejstava.

Kljucne reci: Saccharomyces boulardii, efikasnost, akutna dijareja, lecenje.

INTRODUCTION

In more than 90% of cases, non-haemorrhagic acute diarrhoea is self-limiting disease not lasting more than one week. Its management consists of preventing dehydration by administration of oral rehydration solutions, adequate nutrition, and restriction of antimicrobials use excepot in specific cases (1,2,3).

The use of yeasts in the treatment of acute diarrhea is encouraging due to their anti-diarrhoeal activity and safety (4-6). The use of Saccharomyces boulardii (Saccharomyces cerevisiae Hansen CBS 5926) ( SB ) alongside oral rehydration represents a new therapy for acute diarrhoea (7-12).

Saccharomyces boulardii(SB) is a non-toxic, and non-transmissible yeast strain which specific mechanisim of action encompassing bioregulatory effect on the intestinal flora and the disaccharidase enzymes (7). Saccharomyces boulardii has functional properties similar to those of the normal intestinal flora with natural resistance to antibacterial agents except antimycotics (11) Clinical trials and experimental studies demonstrated that oral treatment with a lyophilized preparation of SB has beneficial effects in preventing the occurrence of complications linked to changes in the normal gut flora such as intestinal bacterial overgrowth ( 6-13).

MATERIAL AND METHOD

From june 2000 until 20 May 2001, 100 consecutive paediatric cases ( age range: 2- 29 months; mean 10.8 months+/-0,9 months) with acute, non-bacterial diarrhoea who were able to receive oral medication enrolled this study. Stool micropscopy, stool culture, Rota virus detection, whole blood count, and serum C-reactive protein level were carried out in all patients. All children have been suffering from diarrhoea lasting more than 48 hours. They had no concominant illnesses and were not receiving any medication including antimicrobials, antidiarrheals or other drugs which may influence intestinal motility. No children with severe serum electrolyte changes and dehydration were included in this study. Patients who exhibited during the study deterioration of their diarrhoeal illness or any concominant disease thus required other drugs were excluded from the study.

Children were divided into 2 groups. First group received 250 mg SB every 24 hour diluted into 5 ml of cold liquid. Second group received 250 mg placebo (glucose) diluted into 5 ml of cold liquid every 24hour. All patients were given World Health Organisation oral reehydration solution and normal food for their ages.

After 48h and 96h stool frequency and its consistency were recoreded. The criterion of treatment efficacy was an absence of liquid stools and progressive reduction of stool frequency.

Statistical analysis was carried out using the Chi-square test and Student’s t-test for two independent samples.

RESULTS

One hundred patients completed the study. Group 1 (50 patients) represented 24 boys and 26 girls ( mean of age 11.5 ± 7.1 months ), group 2 (50 patients); 22 boys and 28 girls ( mean age of 10.1 ± 5.1 months). There were no significant differences between the two groups (p>0.05).

Statically significant differences were found regarding number of stools after 48h (p<0,01) and 96h (p<0,05) in SB treatment group. Table1. Figure 1.

Percentage of cases cured after 48h (p<0,01) and 96h (p<0,05) were statically higher in SB group of children. Table2. Figure2.

DISCUSSION

It is well recognised that antimicrobial use in acute diarrhoea may ocassionally have adverse effects discrupting the intestinal ecosystem and prolonging disease duration which is normally short and self-limiting (14). The use of antimicrobials in diarrhoea is therefore restricted and has very specific indications (15).

Saccharomyces boulardii is a termophilic, nontoxic yeast presently used in many countries in acute GI infections and antibiotic-induced GI disturbances (16). It is well tolerated, and possibly inducing significant reduction of duration of diarrhoea and its complications (8,10,12). Its efficacy is attributed to an inhibitory effect on the growth of pathogenic strains, complement activation, acceleration of the migration of polymorphonuclear cells and monocytes etc (16,17). In addition Saccharomyces boulardii increases secretion of IgA and polymeric immunoglobulin receptor was found in intestinal fluid and mucosa in rats treated with SB. These changes may explain the beneficial effects of the yeast therapy in certain intestinal disorders (16,18). Torres and Manzano recognised indepedentlly good response in more than 90% of adults and adolescents from the 3rd day of SB therapy (14,19). Chapoy reported 80% efficacy of SB treatment in his controlled paediatric study while Sanchez fiugures were lower 60%; however, the patients in the last study had already received various treatment modalities (7,20). Cetina-Sauri confirmed favourable effects of SB therapy in acute diarrhoea which was visible surprisingly after 24h of SB treatment commence (21).

In the present study we found remarcable reduction of stool frequency in the active treatment group vs placebo and higher percentage of cases cured starting from 48h. We were able to continue normal milk feeding in the majority of infants and toddlers treated with SB due to the fact the SB specifically increases intestinal lactase and sucrase activity (22). Lactose intolerance was recorded in 8% of SB treated cases and in 26% of cases in placebo group.

In conclusion, we confirmed that in infant and small children with acute diarrhoea treatment with SB achieves signifant reduction in the duration of diarrhoea and number of stool even in the early period of SB preparation use. In the light of these results and the previously established safety, Saccharomyces boulardii preparation might be recommended for routine unse in children with acute diarrhoea parallely with oral rehydration solution.

REFERENCES:

Mota Hernandez F. Abuso de antimicrobianos y otros conceptos erroneos en el tratamiento de diarreas en ninos. Bol Med Hosp Infant Mex 1987; 44: 577-579.

Khattab AK. Oral rehydration therapy. Pediatrics 1987; 1: 31-40.

Anonimo. El uso de los medicamontos en el manejo de la diarrea aguda en menores de 5 anos., WHO/CDC/CMT 1986: 1.

Brunnel M; Patte F. Proprietes vitaminiques B d’une levure du genre Saccharomyces, prescrite lors de la prophylaxie et du traitement des accidents dus aux antibiotiques. La clinique 1972; 67: 1987-2004

Frugiers S, psatte F. Antagonisme in vitro entre L’ultralevure et differents germes bacteriens. Med Paris 1975; 45: 3-8.

Massot J, Deconclois M, Astoin J. Protection par Saccharomyces boulardii de la diarrhee a Escherichia coli du sourceau. Ann Phar 1982; 40: 445-449.

Chapoy, P.Traitement des diarrhees aigues infantiles: essai controle de Saccharomyces boullardi. Ann Ped 1985; 36: 561-563.

Buts J.P, Corthier G, Delmee M. Saccharomyces boulardii for Clostridium difficile-associated enteropathies. J Pediatr Gastroenterol Nutr 1993; 16: 419-425.

Cetina-Sauri, Busto GS. Evaluacion terapeutica de Saccharomyces boulardii en ninos con diarrea aguda.Tribuna Medica 1989; 56: 111-115.

Mc Farland LV, Surawicz CM, Greenberg RN et al. A randomized placebo controlled trail of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994; 24: 1913-1918.

Collard A. Des levures et des hommes : fermentation, medicaments et biotechnologies.These de doctorat en pharmacie. Montpellier 1984; 34-23

Surawicz CM, Elmer GW, Speelman P, McFarland LV, Chinn J, Van Belle G. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: A prospective study. Gastroenterology 1989; 96: 981-988.

Massot J, Sanchez O, Couchy R, Astoin J, Parodi L. Bacterio-pharmacological activity of Saccharomyces Boulardii in clindamycin induced colitis in the hamster. Drug Res 1984; 34: 794-797.

Manzano TF, Carbajal RA, Garza AC et al. Saccharomyces cerevisae Hansen CBS 5926 en diarreas agudas.Comp Inv Clin Lat Am Mex. 1986; 6: 29-33.

Kumate J. Antibioticos y quimioterapicos.2a.Ed.Mexico, Ed Francisco Mendez Cervantes; 1981, 94-96.

Buts J.P, Bernasconi P, Vaerman JP, Dive C. Stimulation of Secretory IgA and Secretory Component of Immunoglobulins in Small Intestine of Rats Treated with Saccharomyces Boulardii. Dig Dis Sci 1990: 35: 251-256.

Du Luzzio NP. Immunopharmacology of glucan, a broad spectrum enhancer of host defense mechanisms trends. Pharmacol Sci 1983; 4: 344-347.

Buts J.P, De Keyser N, De Raedemacker L. Saccharomyces boulardii enhances rat intestinal enzyme expression by endoluminal release of polyamines. Pediatr Res 1994; 4 : 522-527.

19.Torrez P. Emprigo de um levedu Saccharomyces no tratamiento de diarreas agudas. A Folha Medica (Brasil) 1982: 84; 131-134.

20.Sanchez MT, Hernandez AM, Paz MG. Saccharomyces cerevisae Hansen CBS 5926 en pacientes pediatricos multitratados diarrea aguda.Comp Univ Clin Lat Am Mex 1986; 6: 51-54.

21.Cetina-Sauri, G., Busto, G.S.Therapeutic evaluation of Saccharomyces

Boulardii in children with acute diarrhea. Ann Ped 1994; 6:

397-400

22.Buts J.P, Bernasconi P, Van Craynes MP, Maldague P, De Meyer R.

Response of human and rat small intestinal mucosa to oral dministration

of S. Boulardii. Pediatr Res 1986; 20: 192-196.

Table1: Number of stools and days of treatment


	Group1 (S. boulardii)	Group2 (Placebo)
DAY	Mean SD	Mean SD	P value
Initial 2 4	7.78 1.86 3.78 0.71 2.70 0.67	7.32 1.92 4.24 0.99 3.12 0.93	p>0,05 p<0,01 p<0,05

Table2:Number and percentage of cases cured in 48 hours and 96 hours

Group1

(S. boulardii)

Group2

(Placebo)

Effectiveness

No of %

Cases

No of %

Cases

P value

In 48 hours

In 96 hours

22 44

42 84

8 16

32 64

X2=8.04 p<0,01

X2=4.21 p<0,05

Figure1: Number of stools and days of treatment.

Figure2: Percentage of cases cured in 48 and 96 h. Preceeding the beginning of the treatment.