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. 2021 Mar 2;13(1):1870402. doi: 10.1080/19490976.2020.1870402

Table 4.

Associations between antibiotic use and changes in taxonomic composition of the microbiome in children up to 12 years

Study
Author, year, type of study, country, duration.
Antibiotic
(days of treatment where given)
Time from exposure to analysis Actinobacteria
(includes genus Bifidobacteria)
Bacteroidetes Firmicutes
(gram positive)
Proteobacteria
(gram negative)
Bai et al.32
Cross-Sectional
China
1–12 years
Cephalosporin, Penicillin
10 days
1–4 weeks No change in Actinobacteria F/B ratio decreased by approx. 1/3(p < .05) *
(increase in Bacteroidetes)
F/B ratio decreased by approx. 1/3 (p < .05) *
(decrease in Firmicutes)
No change
Bokulich et al.33
Cohort
USA
0–2 years
Cephalosporin
Beta lactams
Macrolides
Quinolones
Nitrofurantoin
3–139 days No change in Bifidobacteria Increased (p < .05) * Clostridiales decreased from 3–9 months of age* Increased (p < .05) *
Brunser et al.34
Cohort
Chile
0–2 years
Amoxicillin
7 days
1–3 weeks No change in Bifidobacteria No change n/a E. coli increased vs baseline
(Log 4.77 ± 0.96 vs Log 5.10 ± 1.39
p = .015)
Fouhy et al.36
Cohort
Ireland
Neonates
Ampicillin; gentamicin
2–9 days
4 weeks Lower levels of Bifidobacteria at 4 weeks vs control
(5% vs 25%; p = .013);
no difference at 8 weeks
No change Lower levels of Lactobacillus at 4 weeks vs control
(1% vs 4%; p < .009);
no difference at 8 weeks
Higher proportions of Proteobacteria (44% vs 23%; p < .005) and Enterobacteriaceae
(50% vs 32%; p = .006)
at 8 weeks vs control
Korpela et al.37
Retrospective cohort
Finland
2–7 years
Macrolides (M)
Penicillins (P)
<6 months Exposure in previous 6 months
M: Bifidobacterium (0.23-fold decrease p < .004)
P: Bifidobacterium: no change
Exposure in previous 6 months
M: Bacteroides increased (2.04-fold change p < .004)
P: Bacteroides: no change
Exposure in previous 6 months
M: Lactobacillus decreased (0.12-fold change p < .004), Clostridium increased (2.68-fold change p < .004)
P: Lactobacillus decreased (0.11-fold change p < .004), Clostridium: no change
M: Proteobacteria increased (1.96-fold change p < .02) with exposure in previous 6 months
P: no change
Mangin et al.38
Cohort
Chile
6–59 months
Amoxicillin
7 days
0 days Total Bifidobacterium concentrations not significantly altered but
complete disappearance of Bifidobacterium adolescentis species (0% vs 36.4% (p < .001)
n/a n/a n/a
Parker et al.40
RCT
India
6–11 months
Azithromycin
3 days
12 days No change in Actinobacteria or Bifidobacterium No change No change Proteobacteria reduced (relative abundance mean % ± SD: 15.889 ±13.207 (placebo) vs 10.200± 15.401 (azithromycin), FDR p < .001)
E.coli reduced (relative abundance mean % ± SD:12.087± 12.457 (placebo) vs 7.309 ±13.258 (azithromycin), FDR p < .013)
Penders et al.41
Cross sectional Netherlands
1 month
Amoxicillin** < 1 month Bifidobacteria median count placebo log10 CFU/g feces 10.70 vs amoxicillin log CFU/g feces 10.29 (p < .01) Bacteroides fragilis median count placebo log10 CFU/g feces 9.31 vs amoxicillin log10 CFU/g 6.39 (P < .01) No change (lactobacilli) No change in Clostridium difficile and E.Coli
Wei et al.29
RCT
Denmark
1–3 years
Azithromycin
3 days
14 days 50 x reduction (fold change) in genus Bifidobacterium at 14 days (p adjusted < 0.011 (FDR p < .05) n/a n/a n/a
Yassour et al.42
Cohort
Finland
2–36 months
Amoxicillin
Cefalexin
Clarithromycin Amoxicillin and clavulanic acid Trimethoprim and sulfadiazine
Azithromycin Cefaclor
Penicillin G Netilmicin
< 1 month n/a n/a Decrease in abundance of species from clostridium clusters and 14XIVa IV (T regulatory immune cells) at aged 3 (median abundance ~9% vs ~15% control) b (p = .037) n/a

Key: †Confidence intervals or Standard Deviation not available. # Approximate value taken from bar chart. No confidence intervals or SD available. *no raw data. ** authors state that the antibiotics taken were ‘mainly amoxicillin’. b raw data not given; approximate values taken from graph.

Abbreviations: CFU/g = Colony forming unit/gram; F/B ratio = Firmicutes/Bacteroidetes ratio. FDR – false discovery rate correction. M = macrolides . P = penicillins. n/a = Data not available.