The use of antibiotics has saved millions of human lives, however consumption of antibiotics can select for antibiotic resistant organisms and may lead to changes in commensal microbiome. This study is designed to estimate the effect of antibiotic consumption on microbiome in a rural region of rural Burkina Faso. Changes in the intestinal and nasopharyngeal microbiome and resistome following a short course of antibiotics will be measured.
This study is designed to better understand the effect of a short course of antibiotics on changes in intestinal and nasopharyngeal microbiome on treated children and untreated household contacts. The investigators hypothesize that a short course of antibiotics will lead to decreased bacterial diversity shortly after completion of the antibiotic course, and higher probability of identification of bacterial resistance genes in rectal and nasopharyngeal samples. The investigators hypothesize that a 5-day course of antibiotics (azithromycin, amoxicillin, or co-trimoxazole) will lead to significantly decreased intestinal and nasopharyngeal bacterial diversity among children aged 6-59 months. Specific Aim 1. Determine the effect of treatment with antibiotics on microbiome diversity in children aged 6-59 months following a 5-day course of antibiotics. Specific Aim 1A. Determine the direct effect of a 5-day course of azithromycin, amoxicillin, or co-trimoxazole on intestinal and nasopharyngeal bacterial diversity in children aged 6-59 months compared to no treatment. Specific Aim 1B. Determine the indirect effect of antibiotic treatment of children in a household on intestinal and nasopharyngeal bacterial diversity in an untreated child aged 6-59 months. Specific Aim 1C. Assess the association between intestinal bacterial diversity and anthropometry in a population-based sample of children.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
252
Children in this arm will receive Azithromycin once a day.
Children in this arm will receive Amoxicillin twice a day.
Children in this arm will receive co-trimoxazole once a day.
UCSF Proctor Foundation
San Francisco, California, United States
Centre de Recherche en Santé de Nouna
Nouna, Burkina Faso
Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome
The primary outcome of the study was pre-specified as α-diversity (inverse Simpson's) at the genus level, expressed in effective number. Simpson's Alpha Diversity were obtained at Baseline and Post-treatment in this study. The minimum of Simpson's index of diversity is 0, there is no maximum. Higher Simpson's index of diversity means more diverse. There are no subscales.
Time frame: Baseline and Day 9
Simpson's Index of Diversity (Alpha Diversity) in Microbiome
Direct and indirect effect of antibiotics on alpha diversity from rectal samples
Time frame: Day 9
Weight-for-height Z-score
Nutritional status as determined by weight-for-height Z-score vs. Placebo household Weight-for-height Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Weight-for-height Z (WHZ) scores were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of \< -2 means moderately wasted (WHZ). A cutoff of \< -3 means wasted (WHZ).
Time frame: Day 35
Height-for-age Z-score
Nutritional status as determined by height-for-age Z-score Height-for-age Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Height-for-age Z (HAZ) score were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of \< -2 means moderately stunted (HAZ). A cutoff of \< -3 means severely stunted (HAZ).
Time frame: Day 35
Weight-for-age Z-score
Nutritional status as determined by weight-for-age Z-score vs. Placebo household Weight-for-age Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Weight-for-age Z-score (WAZ) scores were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of \< -2 means moderately underweight (WAZ). A cutoff of \< -3 means severely underweight (WAZ).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Children in this arm will receive Placebo once a day.
Time frame: Day 35
Mid-upper Arm Circumference
Nutritional status as determined by mid-upper arm circumference in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Mid-upper arm circumference (MUAC) in each antibiotic group compared with placebo 4 weeks after last antibiotic dose. MUAC is a measure to assess nutritional status. It is measured on a straight left arm, mid-way between the tip of the shoulder and the tip of the elbow. It identifies acute malnutrition and is commonly used in children 6-59 months of age as well as pregnant women. MUAC less than 115 mm indicates severe wasting or severe acute malnutrition (SAM). MUAC greater than or equal to 115 mm and less than 125 mm indicates moderate wasting or moderate acute malnutrition (MAM).
Time frame: Day 35
Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome
Shannon's Alpha Diversity at Baseline and Post-treatment. combines richness and diversity. Shannon's index of diversity (alpha diversity) measures both the number of species and the inequality between species abundances. A large value is given by the presence of many species with well balanced abundances.
Time frame: Baseline and Day 9 (Post- Treatment)
Shannon's Index of Diversity (Alpha Diversity) in Nasopharyngeal Microbiome
Direct and indirect effects of antibiotics on Shannon's index of bacterial diversity
Time frame: Day 9
L1-norm Distance on Bacterial Reads (Intestinal)
L1-norm distance on bacterial reads (intestinal) - L1 norm is equivalent to Shannon's diversity. Shannon's Alpha Diversity combines richness and diversity. Shannon's index of diversity (alpha diversity) measures both the number of species and the inequality between species abundances. A large value is given by the presence of many species with well balanced abundances.
Time frame: Baseline and Day 9 (Post- Treatment)
L1-norm Distance on Bacterial Reads (Nasopharyngeal)
L1-norm distance on bacterial reads (nasopharyngeal)
Time frame: Day 9
L2-norm Distance on Bacterial Reads (Intestinal)
L2-norm distance on bacterial reads (intestinal) - L2 norm is equivalent to Simpson's diversity. Simpson's Alpha Diversity were obtained at Baseline and Post-treatment in this study. The minimum of Simpson's index of diversity is 0, there is no maximum. Higher Simpson's index of diversity means more diverse. There are no subscales.
Time frame: Baseline and Day 9 (Post- Treatment)
L2-norm Distance on Bacterial Reads (Nasopharyngeal)
L2-norm distance on bacterial reads (nasopharyngeal)
Time frame: Day 9
Number of Participants With Macrolide Resistance Genes
Prevalence of macrolide resistance genes measured using DNA-seq from rectal swabs.
Time frame: 2 years
Alpha Diversity in the Intestinal Microbiome
Alpha diversity in the intestinal microbiome using DNA-seq from rectal swabs
Time frame: 2 years