Antibiotic-associated Diarrhea
Conditions
Brief summary
Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. One of the most common indications for probiotic treatment is the prevention of antibiotic-associated diarrhea (AAD). Unfortunately, many probiotic products used for AAD are not supported by rigorous independent research, and often results in non-evidence-based usage. The overarching objective is to move research forward for the most well-studied Bifidobacterium strain. The primary aim is to test the efficacy of high dose, BB-12-supplemented yogurt in preventing AAD, compared to yogurt without BB-12, in children receiving antibiotics. Other aims are to further assess the safety of yogurt supplemented with BB-12, and to carry out longitudinal community structure and gene expression analysis of fecal microbiota to evaluate the impact of high dose BB-12 in a pediatric population receiving antibiotics. The microbiota includes hundreds of species, and its disruption is hypothesized to be an important factor in the development of AAD.
Interventions
BIOLOGICALBifidobacterium animalis subsp. lactis BB-12
Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt
OTHERControl
Yogurt without Bifidobacterium animalis subsp. lactis BB-12
Sponsors
Penn State University
University of Maryland, Baltimore
Georgetown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
1. Child is between ages of 3-12 years 2. Caregiver has the ability to read, speak and write English or Spanish 3. Household has refrigerator for proper storage of drink 4. Household has telephone access 5. Enrollment must take place within 24 hours of starting antibiotics 6. Child was outpatient treated 7. Child was prescribed treatment with a penicillin or cephalosporin class antibiotic regimen for 7-10 days for a respiratory infection; The following is a list (non-exhaustive) of inclusive antibiotics: 1. Amoxicillin 2. Augmentin (amoxicillin/clavulanate) 3. Ancef (cefazolin) 4. Cefadroxil 5. Cephalexin 6. Cephradine 7. Duricef (cefadroxil) 8. Keflex (cephalexin) 9. Kefzol (cefazolin) 10. Velosef (cephradine) 11. Ceclor (cefaclor) 12. Cefotan 13. Cefoxitin 14. Ceftin (cefuroxime) 15. Cefzil (cefprozil) 16. Lorabid (loracarbef) 17. Mefoxin (Cefoxitin) 18. Zinacef (cefuroxime) 19. Omnicef (cefdinir) 20. Suprax (cefixime) 21. Dicloxacillin 22. Pen-Vee K (penicillin)
Exclusion criteria
1. Developmental delays 2. Any chronic condition, such as diabetes or asthma, that requires medication 3. Prematurity, or born prior to 37 weeks gestation/of pregnancy 4. Congenital anomalies 5. Failure to thrive 6. Allergy to strawberry 7. Active diarrhea (diarrhea is defined in this study as three or more loose stools per day for two consecutive days) 8. Any other medicines used except anti-pyretic medicines (pro re nata concomitant medications are allowed) 9. Parental belief of lactose intolerance 10. History of heart disease, including valvulopathies or cardiac surgery, any implantable device or prosthetic 11. History of gastrointestinal surgery or disease 12. Milk-protein allergy 13. Allergy to any component of the product or the yogurt vehicle 14. Allergy or a hypersensitivity to the antibiotic prescribed by her/his provider 15. Allergy to any of the following medications: 1. Tetracycline 2. Erythromycin 3. Trimethoprim 4. Ciprofloxacin 16. blood oxygen saturation is less than 90% (if enrollment/baseline visit is completed in person and if the participant was prescribed antibiotics during a telemedicine visit)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Diarrhea | 14 days | Diarrhea is clinically defined as three or more loose stools per day for two consecutive days. This will be a dichotomous (yes or no) outcome of diarrhea. |
| Adverse Events | Days 0-180 | Number of reported adverse events over the duration of the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pediatric Quality-of-life Score | 7 days | The PedsQL Measurement Measurement Model for the Pediatric Quality-of-Life Inventory. Based on the PedsQL form filled out by participants, the scores were translated using the PedsQL form guidelines: 0=100, 1=75, 2=50,3=25,4=0. The raw scores of participants were averaged after translation. The lowest possible score is 0 and the highest possible score is 100. A higher score indicates a healthier lifestyle. |
| Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | 14 days | This will be a dichotomous (yes or no) outcome of loose stools, constipation, fever, flatulence, lack of appetite, pain, rash, vomiting, cough, earache, nasal congestion, runny nose, sore throat. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BB-12 Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt
Bifidobacterium animalis subsp. lactis BB-12: Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt | 125 |
| Control Yogurt without Bifidobacterium animalis subsp. lactis BB-12
Control: Yogurt without Bifidobacterium animalis subsp. lactis BB-12 | 130 |
| Total | 255 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Withdrawal by Subject | 14 | 7 |
Baseline characteristics
| Characteristic | Control | Total | BB-12 |
|---|---|---|---|
| Age, Continuous | 6.44 years STANDARD_DEVIATION 2.87 | 6.70 years STANDARD_DEVIATION 2.8 | 6.97 years STANDARD_DEVIATION 2.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 58 Participants | 116 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 68 Participants | 129 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 10 Participants | 6 Participants |
| Health Insurance Status No | 4 participants | 14 participants | 10 participants |
| Health Insurance Status Unknown | 3 participants | 8 participants | 5 participants |
| Health Insurance Status Yes | 123 participants | 233 participants | 110 participants |
| Marital Status of Accompanying Guardian Divorced | 2 Participants | 6 Participants | 4 Participants |
| Marital Status of Accompanying Guardian Living with a Partner | 6 Participants | 19 Participants | 13 Participants |
| Marital Status of Accompanying Guardian Married | 92 Participants | 174 Participants | 82 Participants |
| Marital Status of Accompanying Guardian Not reported/Unknown | 12 Participants | 20 Participants | 8 Participants |
| Marital Status of Accompanying Guardian Separated | 5 Participants | 7 Participants | 2 Participants |
| Marital Status of Accompanying Guardian Single | 12 Participants | 28 Participants | 16 Participants |
| Marital Status of Accompanying Guardian Widowed | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 17 Participants | 36 Participants | 19 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 23 Participants | 46 Participants | 23 Participants |
| Race (NIH/OMB) White | 82 Participants | 159 Participants | 77 Participants |
| Region of Enrollment United States | 130 participants | 255 participants | 125 participants |
| Sex: Female, Male Female | 64 Participants | 117 Participants | 53 Participants |
| Sex: Female, Male Male | 62 Participants | 127 Participants | 65 Participants |
| Smoking in the Household No | 125 Participants | 237 Participants | 112 Participants |
| Smoking in the Household Unknown | 3 Participants | 9 Participants | 6 Participants |
| Smoking in the Household Yes | 2 Participants | 9 Participants | 7 Participants |
| total annual income of all the family members living in the household before taxes $100,001 - $150,000 | 15 Participants | 32 Participants | 17 Participants |
| total annual income of all the family members living in the household before taxes < $15,000 | 6 Participants | 13 Participants | 7 Participants |
| total annual income of all the family members living in the household before taxes $150,001 - $200,000 | 15 Participants | 25 Participants | 10 Participants |
| total annual income of all the family members living in the household before taxes $15,000 - $30,000 | 8 Participants | 26 Participants | 18 Participants |
| total annual income of all the family members living in the household before taxes > $200,000 | 29 Participants | 58 Participants | 29 Participants |
| total annual income of all the family members living in the household before taxes $30,001 - $50,000 | 8 Participants | 18 Participants | 10 Participants |
| total annual income of all the family members living in the household before taxes $50,001 - $75,000 | 7 Participants | 12 Participants | 5 Participants |
| total annual income of all the family members living in the household before taxes $75,001 - $100,000 | 5 Participants | 9 Participants | 4 Participants |
| total annual income of all the family members living in the household before taxes Prefer not to answer/Unknown | 37 Participants | 62 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 125 | 0 / 130 |
| other Total, other adverse events | 64 / 125 | 69 / 130 |
| serious Total, serious adverse events | 0 / 125 | 0 / 130 |
Outcome results
Primary
Adverse Events
Number of reported adverse events over the duration of the study
Time frame: Days 0-180
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BB-12 | Adverse Events | 144 AE events |
| Control | Adverse Events | 148 AE events |
Primary
Number of Participants Experiencing Diarrhea
Diarrhea is clinically defined as three or more loose stools per day for two consecutive days. This will be a dichotomous (yes or no) outcome of diarrhea.
Time frame: 14 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BB-12 | Number of Participants Experiencing Diarrhea | Yes | 3 Participants |
| BB-12 | Number of Participants Experiencing Diarrhea | No | 122 Participants |
| Control | Number of Participants Experiencing Diarrhea | Yes | 2 Participants |
| Control | Number of Participants Experiencing Diarrhea | No | 128 Participants |
Secondary
Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea.
This will be a dichotomous (yes or no) outcome of loose stools, constipation, fever, flatulence, lack of appetite, pain, rash, vomiting, cough, earache, nasal congestion, runny nose, sore throat.
Time frame: 14 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Loose stools | 25 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Constipation | 15 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Fever | 11 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Flatulence | 6 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Lack of Appetite | 8 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Pain | 16 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Rash | 4 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Vomiting | 8 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Cough | 13 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Earache | 6 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Nasal Congestion | 14 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Runny nose | 10 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Sore throat | 5 Events |
| BB-12 | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Diarrhea | 3 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Nasal Congestion | 12 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Loose stools | 19 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Vomiting | 2 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Constipation | 21 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Sore throat | 13 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Fever | 14 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Cough | 17 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Flatulence | 4 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Runny nose | 9 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Lack of Appetite | 10 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Earache | 1 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Pain | 14 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Diarrhea | 2 Events |
| Control | Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea. | Rash | 10 Events |
Secondary
Pediatric Quality-of-life Score
The PedsQL Measurement Measurement Model for the Pediatric Quality-of-Life Inventory. Based on the PedsQL form filled out by participants, the scores were translated using the PedsQL form guidelines: 0=100, 1=75, 2=50,3=25,4=0. The raw scores of participants were averaged after translation. The lowest possible score is 0 and the highest possible score is 100. A higher score indicates a healthier lifestyle.
Time frame: 7 days
Population: Some participants did not fill out the PEDSQL Day 7 form.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BB-12 | Pediatric Quality-of-life Score | 85 score on a scale | Standard Deviation 19 |
| Control | Pediatric Quality-of-life Score | 91 score on a scale | Standard Deviation 10 |