Secondary Logo

Journal Logo

Original Studies

Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers

ROSENFELDT, VIBEKE MD; MICHAELSEN, KIM FLEISCHER MD, DR MED SCI; JAKOBSEN, MOGENS DR MED SCI; LARSEN, CHARLOTTE NEXMANN PhD; MØLLER, PETER LANGE PhD; TVEDE, MICHAEL MD; WEYREHTER, HEIKE MD; VALERIUS, NIELS HENRIK MD, DR MED SCI AND; PÆRREGAARD, ANDERS MD, DR MED SCI

Author Information
The Pediatric Infectious Disease Journal: May 2002 - Volume 21 - Issue 5 - p 417-419
  • Free

Abstract

INTRODUCTION

Certain strains of lactobacilli, designated as “probiotics,”1 promote recovery of acute rotavirus infection in hospitalized children. 2–10 Few studies have examined the effect of probiotics in nonhospitalized patients. The strain Lactobacillus GG ATCC 53103 (L. GG) has been shown in a placebo-controlled trial to shorten the duration of diarrhea in patients with less severe disease treated in an outpatient setting. 11 In patients treated with lactobacilli, excretion of rotavirus was reduced. In a preventive study Lactobacillus casei (strain DN-114 001) reduced the severity of diarrhea in children attending day-care centers (DCC). 12 In a randomized trial long term administration of milk supplemented with L. GG to children in DCC seemed to reduce the severity of respiratory infections. 13 Children who received the probiotic milk had significantly fewer days of absence from day-care centers because of illness and a 19% relative reduction in antibiotic treatments for respiratory infections. 13 Among children treated with probiotics, a 17% relative reduction in the number of lower respiratory infections, otitis media and sinusitis was noted. The number of days with respiratory and gastrointestinal symptoms and the time without diarrhea were not reduced.

The purpose of this study was to examine the effect of a mixture of two probiotic Lactobacillus strains in patients from DCC presenting with acute diarrhea. A beneficial effect of these particular strains was found in children hospitalized with acute diarrhea. 14 In hospitalized children the probiotic therapy was most effective if initiated within the first 2.5 days after onset of diarrhea.

MATERIALS AND METHODS

The study was performed during a 6-month period, including the rotavirus season, from December, 1998, through May, 1999. Parents/guardians of children attending 19 local DCC were invited to participate in the study. The parents were instructed to bring their child to the clinic whenever their child had acute diarrhea (defined as 2 or more consecutive loose stools/24 h, with duration of no more than 7 days). In determining when consistency was “loose,” the patients served as their own controls, according to the evaluation of the parents. Exclusion criteria were underlying chronic disease and prescription of antibiotics during the study period. During the 6-month study period 50 children from local DCC applied to the clinic with acute diarrhea. Seven patients were subsequently excluded: three children from the treatment group and 2 from the control group were hospitalized because of excessive vomiting and moderate dehydration; one patient (placebo group) received antibiotics; and 1 (placebo group) was noncompliant to the protocol (insufficient registration).

Children were randomly allocated in a double blind placebo-controlled fashion to receive either the bacterial or the placebo preparation. The bacterial preparation, described in detail in previous studies, 14, 15 consisted of lyophilized L. rhamnosus 19070-2 and L. reuteri DSM 12246. A dose of 1010 colony-forming units of each strain was given twice daily for 5 days. Clinical and microbial methods applied in the study are described in the accompanying article. 14

Statistics

Statistical analysis was performed using SPSS for Windows Version 7.0. Student’s t test and Fisher’s exact test were applied. P < 0.05 was chosen as the level of significance.

Ethics

The study was approved by The Ethical Committee of the Municipality of Copenhagen and Frederiksberg Journal No. 02-140/98 and by the Danish Medical Agency Journal No. 5312-19. Informed consent from the parents of the enrolled patients was obtained.

RESULTS

Forty-three patients with a median age of 22 months (range, 9 to 44 months) completed the study. In 25 patients rotavirus antigen was identified in stool samples as the only pathogen, and in 2 patients rotavirus and a bacterial pathogen (Campylobacter jejuni and Clostridium difficile) were demonstrated. Overall rotavirus was found in 63% of patients with acute diarrhea. Bacterial pathogens (Salmonella typhimurium and C. jejuni) without viral coinfection were identified in 2 patients. The clinical characteristics of the study groups, including age, gender, etiology and severity of gastroenteritis, were comparable (Table 1).

Table 1
Table 1:
Clinical characteristics of patients who completed the study

The mean duration of diarrhea after initiation of treatment was 76 h in patients treated with probiotics and 116 h in the control group (P = 0.05) (Table 2). At the end of intervention (120 h after enrollment), 2 of 24 patients in the treatment group vs. 7 of 19 in the control group still reported loose stools (P = 0.03). In patients treated early after onset of diarrhea (before 60 h), a more pronounced effect of probiotics was found. The time to recovery after early treatment was 79 h vs. 139 h after placebo (P = 0.02).

Table 2
Table 2:
Effect of probiotics

Identification of test strains

In 20 of 24 patients (83%) treated with the bacterial preparation, stool samples were obtained on Day 6 for identification of the ingested strains. L. rhamnosus 19070-2 was identified in 9 patients and both strains were identified in 4 patients. In 7 patients neither of the selected strains was identified. Overall 1 or both strains were recovered from stool specimens in 65% of examined patients.

Side effects

No serious adverse effects were registered. One patient from the treatment group complained of constipation and did not pass stools beginning on Day 3 in the intervention period and for a further 10 days.

DISCUSSION

Children attending DCC are at increased risk of upper respiratory infections and acute diarrhea. In DCC settings viral gastroenteritis is often a mild disease, but a shortening of the diarrheal phase would be important to these young patients as well as their parents. In the current study the efficacy of a mixture of two Lactobacillus strains to ameliorate acute diarrhea in children attending DCC was demonstrated.

In a previous study the probiotic L. GG, administered within the first 48 h of illness, was found shorten the duration of diarrhea in young children, observed in outpatient settings. 11 The duration of diarrhea was 6.0 days in the control group vs. 3.2 days in patients treated with the probiotic (P < 0.01). In the current study the duration of diarrhea before intervention ranged from 5 to 168 h. The probiotic mixture was most effective when given early in the diarrheal phase. In patients treated early the duration of diarrhea was reduced by ∼45%, which is consistent with previous reports. 2, 11, 14

After probiotic administration the test strains were recovered from fecal samples of two-thirds of the examined patients. This does not necessarily reflect noncompliance among recovered children to continuing treatment for the whole study period. Results from fecal samples may underestimate the extent of probiotic interference. In colonic biopsies adherent probiotic strains have been shown to persist on the mucosa after disappearing from fecal samples. 16 After oral administration the strains selected for the current study (L. rhamnosus 19070-2 and/or L. reuteri DSM 12246) were identified in colonic biopsies in 10 of 11 volunteers ((V Rosenfeldt and A Pœregaard, unpublished data).

Our study confirms that bacteriotherapy with selected probiotics (L. rhamnosus 19070-2 and L. reuteri DSM 12246) can effectively ameliorate acute diarrhea in patients treated in outpatient settings. Probiotics seem most effective when administered early in the diarrheal phase.

We thank the staff in the day-care centers of the municipality of Hvidovre for their participation in the study; The Clinical Research Unit, H:S Hvidovre Hospital, for performing the computerized randomization lists and for statistical advice; nurse Susanne Buus for performing the telephone interviews and keeping up contact with the day-care centers; and Anette Gregersen and Birgit Jørgensen, Department of Clinical Microbiology, H:S Rigshospitalet, Copenhagen, for performing the microbiologic analyses.

REFERENCES

1. Fuller R. Probiotics in human medicine. Gut 1991:439–42.
2. Isolauri E, Juntunen M, Rautanen T, Silanaukee P, Koivula T. A human Lactobacillus strain (Lactobacillus GG) promotes recovery from acute diarrhea in children. Pediatrics 1991; 88: 90–7.
3. Kaila M, Isolauri E, Virtananen E, Laine S, Arvilommi H. Enhancement of the circulating antibody secreting cell response in human diarrhea by a human Lactobacillus strain. Pediatr Res 1992; 32: 141–4.
4. Isolauri E, Kaila M, Mykkanen H, Ling W, Salminen S. Oral bacteriotherapy for viral gastroenteritis. Dig Dis Sci 1994; 39: 2595–600.
5. Majamaa H, Isolauri E, Saxelin M, Vesikari T. Lactic acid bacteria in the treatment of acute rotavirus gastroenteritis. J Pediatr Gastroentol Nutr 1995; 20: 333–8.
6. Kaila M, Isolauri E, Arvilommi H, Vesikari T. Viable vs. inactivated Lactobacillus strain GG in acute rotavirus diarrhea. Arch Dis Child 1995; 72: 51–3.
7. Shornikova A, Isolauri E, Burkanova L, Lukovnikova S, Vesikari T. A trial in Karelian republic of oral rehydration and Lactobacillus GG for treatment of acute diarrhea. Acta Pediatr 1997; 86: 460–5.
8. Shorkinova AV, Casas I, Isolauri E, Mykkanen H, Vesikari T. Lactobacillus reuteri as a therapeutic agent in acute diarrhea in young children. J Pediatr Gastroenterol Nutr 1997; 24: 399–404.
9. Shorkinova AV, Casas I, Mykkanen H, Salo E, Vesikari T. Bacteriotherapy with Lactobacillus reuteri in rotavirus gastroenteritis. J Pediatr Infect Dis J 1997; 16: 1103–7.
10. Guandalini S, Pensabene L, Zikri M, et al. Lactobacillus GG administered in oral solution to children with acute diarrhoea: a multicenter study. J Pediatr Gastroenterol Nutr 2000; 30: 54–60.
11. Guarino A, Canari R, Spagnuolo M, Albano F, Benedetto L. Oral bacteriotherapy reduces the duration of symptoms and of viral excretion in children with mild diarrhea. J Pediatr Gastroenterol Nutr 1997; 25: 516–9.
12. Pedone CA, Bernabeu AO, Postaire ER, Bouley CF, Reinert P. The effect of supplementation with milk fermented by Lactobacillus casei (strain DN-114 001) on acute diarrhea in children attending day care centers. Int J Clin Pract 1999; 53: 179–84.
13. Hatakka K, Savilathi 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: 1327.
14. Rosenfeldt V, Michaelsen KM, Jakobsen M, et al. Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhea. Pediatr Infect Dis J 2002; 21: 411–16.
15. Nexmann Jacobsen C, Rosenfeldt V, et al. Screening of probiotic activities of 47 strains of Lactobacillus spp. by in vitro techniques and evaluation of the colonisation ability of five selected strains in humans. Appl Environ Microbiol 1999; 65: 4949–56.
16. Alander M, Satokari R, Korpela R, et al. Persistence of colonization of human colonic mucosa by a probiotic strain, Lactobacillus rhamnosus GG, after oral consumption Appl Environ Microbial 1999; 65: 351–4.
Keywords:

Probiotics; day-care centers; childhood diarrhea; Lactobacillus

© 2002 Lippincott Williams & Wilkins, Inc.