Respiratory Tract Infections
Conditions
Keywords
Probiotic, Cultured dairy drink, Health, 10 day antibiotic, Otherwise healthy
Brief summary
The purpose of this study is to determine the effectiveness of commercially available kefir on preventing antibiotic-associated diarrhea compared to placebo in children ages 1-5.
Detailed description
Diarrhea is a common and costly disease of children in the United States. Children less than 5 years of age experience 20-35 million episodes of diarrhea per year. These episodes lead to 2-3.5 million physician visits (which account for 10% of all visits), more than 200,000 hospitalizations (13% of hospital admissions in children less than 5 years), and 325-425 deaths annually. In 1991, the outpatient costs of treating diarrhea for children under age 3 were calculated at 0.6-1 billion dollars per year. Acute diarrhea in young children is almost always caused by infections or antibiotics. The rate of diarrhea associated with antibiotic usage is 20-35%, with children 3-36 months receiving on average 2-3 antibiotic prescriptions per year. Studies have shown that diarrhea due to either antibiotics or infections is caused by disturbances of the microflora of the gastrointestinal tract. The current treatment for diarrhea in young children is oral rehydration, which is used to treat dehydration but plays no role in prevention. Probiotics are live microorganisms which, when administered in sufficient amounts, may improve health. Probiotics have the potential to treat and prevent diarrhea by improving the intestinal flora when disturbed by events such as antibiotics. Important to their use is that they are of human origin, survive passage through the gut, and are safe in very large dosages. Studies have examined the potential health benefits of probiotics in the prevention and treatment of both antibiotic and infectious diarrhea. The probiotics have generally been given as supplements or pills. In placebo controlled randomized studies using these techniques, probiotics have generally been shown to decrease antibiotic associated diarrhea by 15-25% over placebo. Other studies have enrolled children with acute diarrhea, generally from rotavirus, and found a 30-50% cure rate in the probiotic group over placebo. Kefir, available in the United States, is a milk product derived by the action of ten probiotics. A daily dose of 10\^6-10\^9 colony forming units of probiotics has been studied and recommended for health benefits.
Interventions
OTHERKefir
The intervention was Kefir,a drink that is commercially available in the United States. The following probiotics are present in the Kefir: Lactococcus lactis, Lactococcus plantarum, Lactococcus rhamnosus, Lactococcus casei, Lactococcus lactis subspecies diacetylactis, Leuconostoc cremoris, Bifidobacterium longum, Bifidobacterium breve, Lactobacillus acidophilus, and 1 yeast, Saccharomyces florentinus. Parents were asked to ensure that their enrolled child consumed at least half of the bottle (150mL) everyday.
OTHERPlacebo
The intervention was Kefir, a drink that is commercially available in the United States. The following probiotics are present in active Kefir: Lactococcus lactis, Lactococcus plantarum, Lactococcus rhamnosus, Lactococcus casei, Lactococcus lactis subspecies diacetylactis, Leuconostoc cremoris, Bifidobacterium longum, Bifidobacterium breve, Lactobacillus acidophilus, and 1 yeast, Saccharomyces florentinus. The placebo group was heat-treated to kill all cultures. Parents were asked to ensure that their enrolled child consumed at least half of the bottle (150 mL)everyday.
Sponsors
Lifeway Foods, Inc.
Georgetown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 5 Years
Healthy volunteers
Yes
Inclusion criteria
* Ability to speak and write English * Aged 1-5 years * Male or female * Diagnosed with an upper respiratory infection and placed on a penicillin class antibiotic regimen for 10 days
Exclusion criteria
* Developmental delays * Chronic conditions, such as diabetes or asthma, that require medication * Prematurity, birth weight \<2500 grams * Allergy to kefir and/or milk * Active diarrhea * Congenital anomalies * Failure to thrive * Parental belief of lactose intolerance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Participants With Diarrhea by Parental Report | 14 days | The primary outcome was the incidence of participants receiving antibiotics with diarrhea during the 14-day follow-up period, as determined by parental report. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | 14 days | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools. Outcomes assessed by parental report via daily diary and phone follow-ups with study research assistants on days 0, 5, 10, and 15. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 150mL per day, administered orally for 10 consecutive days. Placebo was heat-treated to kill all cultures. | 64 |
| Kefir 150mL per day, administered orally for 10 consecutive days. Active kefir contained probiotics Lactococcus lactis, Lactococcus plantarum, Lactococcus rhamnosus, Lactococcus casei, Lactococcus lactis subspecies diacetylactis, Leuconostoc cremoris, Bifidobacterium longum, Bifidobacterium breve, Lactobacillus acidophilus, and 1 yeast, Saccharomyces florentinus. | 61 |
| Total | 125 |
Baseline characteristics
| Characteristic | Placebo | Kefir | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 64 Participants | 61 Participants | 125 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 64 participants | 61 participants | 125 participants |
| Sex: Female, Male Female | 33 Participants | 28 Participants | 61 Participants |
| Sex: Female, Male Male | 31 Participants | 33 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 64 | 1 / 61 |
| serious Total, serious adverse events | 0 / 64 | 0 / 61 |
Outcome results
Primary
Incidence of Participants With Diarrhea by Parental Report
The primary outcome was the incidence of participants receiving antibiotics with diarrhea during the 14-day follow-up period, as determined by parental report.
Time frame: 14 days
Population: Prior estimates of the sample size showed that 62 per group would have 80% power for detecting a difference of 20% in the rates of diarrhea. This was based on the placebo group having a 10% (which is consistent with published literature) rate of diarrhea. Analysis performed used the intention to treat and no imputation was required.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Kefir | Incidence of Participants With Diarrhea by Parental Report | 18.0 Percentage of participants |
| Placebo | Incidence of Participants With Diarrhea by Parental Report | 21.9 Percentage of participants |
Comparison: Reply: The null hypothesis was the rates of diarrhea for Kefir vs. Placebo are not different. Post power calculation was not performed because the difference observed (21.9% vs. 18%) was less than a difference that which would be considered clinically important.p-value: >0.0595% CI: [0.54, 1.43]Chi-squared
Secondary
Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools
Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools. Outcomes assessed by parental report via daily diary and phone follow-ups with study research assistants on days 0, 5, 10, and 15.
Time frame: 14 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Kefir | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | constipation | 19.7 Percentage of participants |
| Kefir | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | earaches | 23.0 Percentage of participants |
| Kefir | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | stomach pain | 8.2 Percentage of participants |
| Kefir | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | fever | 45.9 Percentage of participants |
| Kefir | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | irritability | 19.7 Percentage of participants |
| Kefir | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | runny nose | 77.0 Percentage of participants |
| Kefir | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | lethargy | 16.4 Percentage of participants |
| Kefir | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | vomiting | 16.4 Percentage of participants |
| Kefir | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | loose stools | 29.5 Percentage of participants |
| Kefir | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | cough | 68.9 Percentage of participants |
| Placebo | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | loose stools | 32.8 Percentage of participants |
| Placebo | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | vomiting | 10.9 Percentage of participants |
| Placebo | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | stomach pain | 14.1 Percentage of participants |
| Placebo | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | constipation | 17.2 Percentage of participants |
| Placebo | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | runny nose | 82.8 Percentage of participants |
| Placebo | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | cough | 53.1 Percentage of participants |
| Placebo | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | earaches | 17.2 Percentage of participants |
| Placebo | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | irritability | 18.8 Percentage of participants |
| Placebo | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | lethargy | 21.9 Percentage of participants |
| Placebo | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | fever | 39.1 Percentage of participants |