Fariborz Mansour-Ghanaei, Afshin Shafaghi, Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
Najaf Dehbashi, Department of Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran
Kamyar Yazdanparast, Department of Microbiology, Shiraz University of Medical Sciences, Shiraz, Iran
Correspondence to: Professor Fariborz Mansour-Ghanaei, Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Sardar-e-jangle Ave, Razi Hospital, Rasht 41448-95655, Iran.  ghanaei@gums.ac.ir
Telephone: +98-131-5535116    Fax: +98-131-2232514
Received: 2003-04-12    Accepted: 2003-05-24

Abstract
AIM: To compare the efficacy of antibiotics therapy alone with antibiotics and saccharomyces boulardii in treatment of acute amebiasis.

METHODS: In a double blind, random clinical trial on patients with acute intestinal amoebiasis, 57 adult patients with acute amoebiasis, diagnosed with clinical manifestations (acute mucous bloody diarrhea) and amebic trophozoites engulfing RBCs found in stool were enrolled in the study. Regimen 1 included metronidazole (750 mg Tid) and iodoquinol (630 mg Tid) for 10 days. Regimen 2 contained capsules of lyophilized saccharomyces boulardii (250 mg Tid) orally in addition to regimen 1. Patients were re-examined at two and four weeks after the treatment, and stool examination was performed at the end of week 4. Student’s t-test, c² and McNemar’s tests were used for statistical analysis.

RESULTS: Three patients refused to participate. The other 54 patients were randomized to receive either regimen 1 or regimen 2 (Groups 1 and 2 respectively, each with 27 patients). The two groups were similar regarding their age, sex and clinical manifestations. In Group 1, diarrhea lasted 48.0±18.5 hours and in Group 2, 12.0±3.7 hours (P<0.0001). In Group 1, the durations of fever and abdominal pain were 24.0±8.8 and 24.0±7.3 hours and in Group 2 they were 12.0±5.3 and 12.0±3.2 hours, respectively (P<0.001). Duration of headache was similar in both groups. At week 4, amebic cysts were detected in 5 cases (18.5 %) of Group 1 but in none of the Group 2 (P<0.02).

CONCLUSION: Adding saccharomyces boulardii to antibiotics in the treatment of acute amebiasis seems to decrease the duration of clinical symptoms and cyst passage.

Mansour-Ghanaei F, Dehbashi N, Yazdanparast K, Shafaghi A. Efficacy of saccharomyces boulardii with antibiotics in acute amoebiasis. World J Gastroenterol  2003; 9(8): 1832-1833
http://www.wjgnet.com/1007-9327/9/1832.asp

INTRODUCTION
Intestinal amoebiasis is caused by the protozoan entamoeba histolytica. This organism feeds on the intestinal contents without any invasion to human tissue. It occasionally invades the intestinal wall and causes dysentery. It may also spread from the bowel to the liver and other organs and cause abscess in these organs. In addition, it may persist as cysts in the intestine and the patients become long-term cyst carriers, most of whom remain asymptomatic^[1,2].
     In most cases, the organism is avirulent but it may become virulent under different circumstances like immune suppression, malnutrition and alterations in intestinal flora^[3,4].
     Entamoeba histolytica is common all over the world but is more virulent in areas with low hygienic standards and in tropical and subtropical regions^[1].
     A luminal amebicide achieving high concentrations in the intestine like iodoquinol, paromomycin or diloxanide furoate is usually used to treat cysts. Tissue amebicides with high concentrations in the blood like the nitroimidazoles (especially metronidazole) are the cornerstone of treatment of invasive amoebiasis^[5].
     Saccharomyces boulardii is saprophytic, thermophylic yeast, which is found growing applications in the prevention and treatment of human septic enteritis^[6,7]. The optimal temperature for this yeast to grow is 37 °C. The gastric juice has no effect on it and it grows all along the gastrointestinal tract. It is used clinically as an oral lyophilized preparation^[8]. No significant side effects have been reported with its consumption^[9-11].
      We assessed the effects of adding saccharomyces boulardii to the standard treatment for invasive amoebiasis.
      To compare the routine treatment by means of metronidazole and iodoquinol with metronidazole, iodoquinol and saccharomyces boulardii in the treatment of acute amoebiasis, we performed this study on 57 patients at Shahid Beheshti Educational and Therapeutic Center in Shiraz during one-year period from March 21, 1995 to March 21, 1996.

MATERIALS AND METHODS
Patients with acute amebic dysentery who consented to participate were enrolled. The diagnosis was made according to compatible clinical presentations (acute mucous bloody diarrhea, fever and abdominal pain) and presence of amoeba trophozoite engulfing RBCs in diarrheal stool. Pregnant females, those on maintenance of hemodialysis, steroids or chemotherapy were excluded. The patients were then randomized to receive either metronidazole 750 mg and iodoquinol 650 mg thrice a day for 10 days (Group 1) or the same medication plus lyophilized saccharomyces boulardii (Ultra-levure, Bio codex, Montrougo, France) 250 mg orally thrice a day (Group 2).
     The patients were followed up at two and four weeks. At each visit in addition to recording patients symptoms and possible adverse effects, pill count was performed. At the end of week 4, another stool examination (fresh spread and floatation) was done. Student’s t-test, Chi-square and McNemar’s tests were used for statistical analysis.

RESULTS
57 consenting patients were randomized (29 in Group 1 and 28 in Group 2). Two patients from Group 1 and one from Group 2 were excluded because of non-compliance. There were 12 (44.4 %) females in Group 1 and 10 (37 %) females in Group 2. Mean age was 29.3 years in Group 1 and 30.8 years in Group 2. Table 1 shows frequency of clinical findings in both groups. The two groups were comparable regarding their clinical presentations, too.

Table 1  Clinical manifestations in two therapeutic groups

N.S=Not significant.

     As shown in Table 2, adding saccharomyces boulardii to the usual treatment of acute amebic dysentery decreased the mean duration of diarrhea to almost 25 % (P<0.0001) and the duration of abdominal pain and fever to almost half (P<0.001). Headache lasted almost equally in the two groups.

Table 2  Time of recovery from main clinical findings

N.S=not significant.

     Amebic cysts were found in stool specimens of 5 patients (18.5 %) in group 1 and none in group 2 at week 4 (P<0.02, Table 3).

Table 3  Amebic cyst carriers in the fourth week after the treatment

DISCUSSION
Saccharomyces boulardii is a saprophytic yeast which is recommended for the prevention and treatment of septic enteritis^[6,7] especially diarrhea caused by clostridium difficile^[8,12,13]. It can also reduce the incidence of traveler’s diarrhea^[12] and prevent the occurrence of diarrhea in acutely ill patients fed by nasogastric tube^{[14, 15]}. Other diseases in which saccharomyces boulardii has been achieved some success include antibiotic associated colitis^{[11, 16]} and Crohn’s disease^[9]. Considering its inhibitory activity on enteropathogens and its anti-diarrheal characteristics, it has also been used in children with diarrhea^[17]. Saccharomyces boulardii has been shown to have trophical effects on the small intestine in healthy human volunteers^[18].
    The exact mechanism by which this yeast prevents or improves diarrhea is still unclear. Saccharomyces boulardii may cause its trophic effect on the small intestine by releasing spermine and spermidine^[6]. This yeast can hinder the cholera toxin excretion in the jejunum of mice.
    Our data showed that co-administration of lyophilized saccharomyces boulardii with conventional treatment for acute amebic colitis significantly decreased the duration of symptoms and chances of cyst carriers after 4 weeks. This may be due to its potential to restore the beneficial normal flora of the gut, although the precise mechanism of the action remains to be elucidated. Considering the lack of any reported adverse reactions to this product, if our results are reproduced by other investigators, then lyophilized saccharomyces boulardii would be a very useful addition to the treatment of acute amebic dysentery.

ACKNOWLEDGMENT
We would like to thank Dr. Amirhossein Bagherzadeh, the member of Gastrointestinal & Liver Diseases Research Center, Guilan University of Medical Sciences, for his help in preparing and reviewing this manuscript.

REFERENCES
1    Nanda R, Baveja U, Anand BS. Entamoeba Histolytica cyst passers: clinical features and outcome in untreated 
      subjects. Lancet 1984; 2:301-303
2    Lai SW, Lin HC, Lin CC. Clinical analysis of a dysentery outbreak in Taichung, Taiwan .Chung Hua Min Kuo Hsiao Erh Ko 
      I Hsueh Hui Tsa Chih 2000; 41: 18-21
3    Lewis EA, Antia AU. Amoebic colitis. Trop Med Hyg 1969; 112:633-638
4    Neal RA. Pathogenesis of amoebiasis. Gut  1971; 12: 482-486
5    Reed SL. Amebiasis and infection with free- living amebas. In: Braunwald E, eds. Harrison’s principles of 
      internal medicine. New york: McGraw-Hill 2001: 1199-1203
6    Buts JP, De-Keyser N, De-Raedemaeker L. Saccharomyces boulardii enhances rat intestinal enzyme expression 
      by endoluminal release of polyamines. Pediatr Res  1994; 36: 522-527
7    Muller J, Remus N, Harms KH. Mycoserological study of the treatment of paediatric cystic fibrosis patients 
      with saccharomyces boulardii. Mycoses  1995; 38:119-123
8    Corthier G, Dubos F, Ducluzeau R. Prevention of C difficile induced mortality in gnotobiotic mice by 
      Saccharomyces  boulardii.Can J Microbiol 1986; 32: 894-896
9    Plein K, Hotz J. Therapeutic effects of saccharomyces boulardii on mild residual symptoms in a stable phase of 
      Crohn’s disease with special respect to chronic diarrhea- a pilot study. Z Gastroenterol 1993; 31: 129-134
10  Kollaritsch H, Holst H, Grobara P, Wiedermann G. Prevention of traveler’s diarrhea with saccharomyces boulardii. 
      Results of a placebo controlled double - blind study. Fortschr Med 1993; 111: 152-156
11  McFarland LV, Surawicz CM, Greenberg RN. A randomized placebo - controlled trial of saccharomyces boulardii 
      in combination with standard antibiotics for clostridium difficile disease.JAMA 1994; 271: 1913-1918
12  Pothoulakis C, Kelly CP, Joshi MA. Saccharomyces boulardii in inhibits clostridium difficile toxin A binding and 
      enterotoxicity in rat ileum. Gastroenterology 1993; 104: 1108-1115
13  Castagliuolo I, LaMont JT, Nikulasson ST, Pothoulakis C. Saccharomyces boulardii protease inhibits clostridium 
      difficile toxin A effects in rat ileum. Infect Immun 1996; 64: 5225-5232
14  Bleichner G, Blehaut H, Mentec H, Moyse D. Saccharomyces boulardii prevents diarrhea in critically ill tube-fed patients. 
      A multicenter randomized double- blind placebo - controlled trial. Intensive Care Med 1997; 23: 517-523
15  Surawicz CM, Elmer GW, Speelman P. Prevention of antibiotic-associated diarrhea by saccharomyces boulardii: 
      A prospective study. Gastroenterology 1989; 96: 981-988
16  McFarland LV, Surawicz CM, Greenberg RN, Elmer GW. Prevention of ?- Lactam - associated diarrhea by 
      saccharomyces boulardii compared with placebo. Am J Gastroenterol 1995; 90: 439-448
17  Saavedra J. Probiotics and infectious diarrhea. Am J Gastroenterol 2000; 95: S16-S18
18  Jahn HU, Ullrich R, Schneider T, Liehr RM, Schieferdecker HL, Holst H, Zeitz M. Immunological and trophical effects 
      of saccharomyces boulardii on the small intestine in healthy human volunteers. Digestion 1996; 57: 95-104

   Edited by Xu XQ  

Reviews	Add
more>>