Lactobacillus reuteri vs Placebo in Children With Diarrhea
Lactobacillus reuteri vs Placebo in Children With Diarrhea
Of 96 patients enrolled, nine (11%) had started a probiotic/antibiotic treatment before admission, seven (8%) received exclusively or mainly intravenous fluids for rehydration, in three (2%) a bacterial origin was identified (two patients Campylobacter, and in 1 Salmonella spp.) and three (2%) refused to participate therefore, a total of 74 patients were enrolled into the study, 37 in the L. reuteri group and 37 in the control group. Five patients, two from the L. reuteri group and three from the control group, were withdrawn from the study (Figure 1) because of either one of the following reasons: parental noncompliance (three patients); protocol deviations (two patients). Sixty-nine children, mean age 23.5 months, completed the study (Figure 1).
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Figure 1.
Enrolment, assigned, intervention and follow-up.
Data are available in 64 children; in 10 children with prompt recovery, additional test would have not been justified on the basis of routine clinical care. Rotavirus antigen was identified in 43 patients (62%) and adenovirus in 10 (14%) while in 11 (24%) no aetiology was found. No significant differences regarding age, gender or duration of diarrhoea before intervention were found between the study groups. The clinical characteristics and severity of gastroenteritis did not differ between treatment group and control group.
The clinical characteristics of the treatment groups are presented in the Table 1. Both groups were similar in age, nutritional status, duration of diarrhoea before admission, stool output (first 4 h of the rehydration phase), percentage of dehydration and ethology. On admission most patients had mild dehydration. The serum sodium was between 130 and 144 mmol/L, with a mean of 138 mmol/L. The degree of dehydration in rotavirus-positive children was not significantly more severe than in negative patients.
No patient was lost in follow-up before stool consistency had normalised; no patient was excluded from the analysis.
The clinical outcome of the two treatment arms was similar for weight gain (190 ± 152 g), consumption of ORS solution (310.5 ± 215.3 mL/kg) correction of acidosis (base deficit -0.9 ± 1.5 mmol/L) and serum Na (138 ± 2 mmol/L).
Days 0–7 were calculated as 24-h periods after the initiation of treatment. L. reuteri significantly reduced the duration of watery diarrhoea as compared with placebo (2.1 ± 1.7 vs. 3.3 ± 2.1 days; P < 0.03) and the effect of L. reuteri was mostly seen in the second/third day of treatment (Figure 2). The intention-to-treat analysis shows that on the first day of treatment, watery diarrhoea persisted in 100% of those receiving placebo and in 87% of those receiving L. reuteri; on the second day of treatment watery diarrhoea persisted in 81% of the placebo and 55% of the L. reuteri recipients (P < 0.02). The frequency of watery diarrhoea per 24-h period was still significantly reduced on the third day of treatment in the L. reuteri recipients as compared with placebo recipients (73% vs. 46%; P < 0.03). Therefore, the number of children with a normalised stool consistency was significantly higher on day 2 and day 3 in the L. reuteri group. The per protocol analysis is reported in Table 2.
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Figure 2.
Percentage of patients with persisting watery diarrhoea in the groups receiving placebo (grey) and Lactobacillus reuteri (white).
The mean (±s.d.) frequencies of watery diarrhoea in placebo and L. reuteri groups at day 1, 2, 3 and 4 were 7.2 (2.4) vs. 6.9 (3.2), 6.3 (2.1) vs. 4.3 (1.7), 4.3 (2.3) vs. 2.1 (1.8) and 1.8 (1.3) vs. 1.5 (0.9) (P = N.S.; P < 0.02; P < 0.03; P = N.S. respectively).
Fewer patients receiving L. reuteri, compared with those receiving placebo, had vomiting, starting from the second day of treatment (35% vs. 55%; P = 0.16).
Side effects were not reported by the parents or physicians and none was excluded for low compliance. There was not a significant difference in hospital stay between the groups.
Results
Of 96 patients enrolled, nine (11%) had started a probiotic/antibiotic treatment before admission, seven (8%) received exclusively or mainly intravenous fluids for rehydration, in three (2%) a bacterial origin was identified (two patients Campylobacter, and in 1 Salmonella spp.) and three (2%) refused to participate therefore, a total of 74 patients were enrolled into the study, 37 in the L. reuteri group and 37 in the control group. Five patients, two from the L. reuteri group and three from the control group, were withdrawn from the study (Figure 1) because of either one of the following reasons: parental noncompliance (three patients); protocol deviations (two patients). Sixty-nine children, mean age 23.5 months, completed the study (Figure 1).
(Enlarge Image)
Figure 1.
Enrolment, assigned, intervention and follow-up.
Microbiologic Analyses
Data are available in 64 children; in 10 children with prompt recovery, additional test would have not been justified on the basis of routine clinical care. Rotavirus antigen was identified in 43 patients (62%) and adenovirus in 10 (14%) while in 11 (24%) no aetiology was found. No significant differences regarding age, gender or duration of diarrhoea before intervention were found between the study groups. The clinical characteristics and severity of gastroenteritis did not differ between treatment group and control group.
Baseline Characteristics
The clinical characteristics of the treatment groups are presented in the Table 1. Both groups were similar in age, nutritional status, duration of diarrhoea before admission, stool output (first 4 h of the rehydration phase), percentage of dehydration and ethology. On admission most patients had mild dehydration. The serum sodium was between 130 and 144 mmol/L, with a mean of 138 mmol/L. The degree of dehydration in rotavirus-positive children was not significantly more severe than in negative patients.
No patient was lost in follow-up before stool consistency had normalised; no patient was excluded from the analysis.
Outcomes
The clinical outcome of the two treatment arms was similar for weight gain (190 ± 152 g), consumption of ORS solution (310.5 ± 215.3 mL/kg) correction of acidosis (base deficit -0.9 ± 1.5 mmol/L) and serum Na (138 ± 2 mmol/L).
Days 0–7 were calculated as 24-h periods after the initiation of treatment. L. reuteri significantly reduced the duration of watery diarrhoea as compared with placebo (2.1 ± 1.7 vs. 3.3 ± 2.1 days; P < 0.03) and the effect of L. reuteri was mostly seen in the second/third day of treatment (Figure 2). The intention-to-treat analysis shows that on the first day of treatment, watery diarrhoea persisted in 100% of those receiving placebo and in 87% of those receiving L. reuteri; on the second day of treatment watery diarrhoea persisted in 81% of the placebo and 55% of the L. reuteri recipients (P < 0.02). The frequency of watery diarrhoea per 24-h period was still significantly reduced on the third day of treatment in the L. reuteri recipients as compared with placebo recipients (73% vs. 46%; P < 0.03). Therefore, the number of children with a normalised stool consistency was significantly higher on day 2 and day 3 in the L. reuteri group. The per protocol analysis is reported in Table 2.
(Enlarge Image)
Figure 2.
Percentage of patients with persisting watery diarrhoea in the groups receiving placebo (grey) and Lactobacillus reuteri (white).
The mean (±s.d.) frequencies of watery diarrhoea in placebo and L. reuteri groups at day 1, 2, 3 and 4 were 7.2 (2.4) vs. 6.9 (3.2), 6.3 (2.1) vs. 4.3 (1.7), 4.3 (2.3) vs. 2.1 (1.8) and 1.8 (1.3) vs. 1.5 (0.9) (P = N.S.; P < 0.02; P < 0.03; P = N.S. respectively).
Fewer patients receiving L. reuteri, compared with those receiving placebo, had vomiting, starting from the second day of treatment (35% vs. 55%; P = 0.16).
Side effects were not reported by the parents or physicians and none was excluded for low compliance. There was not a significant difference in hospital stay between the groups.
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