Table 6.
Antibiotic resistance genes (ARG) encoding Classes of ARG | 7 days (n = 60 fecal samples) | 28 days (n = 64 fecal samples) | 4 months (n = 60 fecal samples) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
PEP | NPVP | FTC | P | FDR Q | PEP | NPVP | FTC | P | FDR Q | PEP | NPVP | FTC | P | FDR Q | |
(n = 20) | (n = 30) | (n = 10) | (n = 24) | (n = 31) | (n = 9) | (n = 24) | (n = 29) | (n = 7) | |||||||
Class A Beta lactamase | 0.61 | 4.2* | 0.00* | 0.001 | 0.020 | 0.00 | 0.00 | 0.00 | 0.080 | 0.586 | 1.43 | 1.0 | 0.00 | 0.443 | 1.327 |
Class C Beta lactamase | 0.00 | 0.00 | 0.20 | 0.126 | 0.229 | 0.98 | 0.22 | 0.00 | 0.492 | 0.812 | 9.1 | 12.7 | 9.5 | 0.605 | 1.134 |
Aminoglycoside acetyltransferase | 0.00 | 0.00 | 0.00 | 0.202 | 0.311 | – | – | – | – | – | – | – | – | – | – |
Aminoglycoside phosphotransferase | 0.00 | 0.00 | 0.00 | 0.590 | 0.653 | 0.00 | 0.16 | 0.00 | 0.114 | 0.497 | – | – | – | – | – |
Aminoglycoside nucleotidyltransferase | 0.00 | 0.00 | 0.00 | 0.765 | 0.765 | 0.00 | 0.00 | 0.00 | 0.296 | 0.426 | 0.00 | 0.00 | 0.00 | 0.584 | 0.814 |
Tetracycline efflux | 0.00 | 0.00* | 0.00 | 0.015 | 0.050 | 0.00 | 0.00 | 0.00 | 0.173 | 0.423 | 0.00 | 0.00 | 0.00 | 0.174 | 1.949 |
Tetracycline ribosomal protection | 0.00 | 0.26 | 4.4* | 0.047 | 0.118 | 0.52 | 3.7 | 1.77 | 0.397 | 0.615 | 6.4 | 23.4 | 23.4 | 0.407 | 1.041 |
Quinolone resistance† | 9.0 | 21.6 | 5.3 | 0.062 | 0.138 | 9.81 | 7.6 | 0.77 | 0.133 | 0.470 | 9.2 | 9.4 | 7.1 | 0.501 | 1.186 |
Macrolide/MLS resistance | 0.00 | 0.00 | 0.00 | 0.757 | 0.797 | – | – | – | – | – | – | – | – | – | – |
ABC efflux pump† | 0.13 | 1.15 | 0.25 | 0.206 | 0.294 | 1.06 | 1.35 | 0.06* | 0.013 | 0.414 | 0.70 | 0.96 | 0.83 | 0.766 | 0.887 |
RND antibiotic efflux | 5.2 | 41.9* | 38.4 | 0.034 | 0.097 | 37.7 | 53.7 | 4.1 | 0.170 | 0.683 | 94.0 | 116.7 | 90.3 | 0.674 | 0.936 |
MFS antibiotic efflux | 1.16 | 113.3 | 29.0 | 0.339 | 0.342 | 85.8 | 119.1 | 16.0 | 0.056 | 0.489 | 105.2 | 119.5 | 84.7 | 0.614 | 0.839 |
Multidrug efflux pump activity | 0.00 | 24.6 | 1.92 | 0.337 | 0.449 | 20.9 | 21.7 | 4.9 | 0.346 | 0.478 | 10.0 | 14.0 | 8.1 | 0.616 | 1.552 |
Multidrug resistance efflux pump | 0.00 | 0.00 | 0.00 | 0.668 | 0.742 | 0.00 | 0.00 | 0.00 | 0.603 | 0.678 | 0.18 | 0.00 | 0.60 | 0.496 | 0.819 |
Gene modulating antibiotic efflux | 5.6 | 41.0** | 0.76 | 0.012 | 0.060 | 14.7 | 20.1 | 0.34 | 0.163 | 0.376 | 19.7 | 27.7 | 27.5 | 0.645 | 0.871 |
SMR antibiotic efflux | – | 1.2 | – | – | – | 0.00 | 0.00 | 0.00 | 0.914 | 0.932 | – | – | – | – | – |
Chloramphenicol acetyltransferase | 0.00 | 0.00 | 0.00 | 0.071 | 0.142 | – | – | – | – | – | – | – | – | – | – |
Antibiotic target† | 0.48 | 0.00 | 0.00** | 0.013 | 0.052 | 0.00 | 0.00 | 0.00 | 0.266 | 0.396 | 0.00 | 0.00 | 0.00 | 0.720 | 0.768 |
Gene modulating resistance | 53.5 | 8.1** | 39.2 | 0.003 | 0.030 | 37.6 | 27.8 | 44.6 | 0.419 | 0.419 | 37.5 | 45.8 | 46.2 | 0.678 | 1.286 |
rRNA methyltransferase† | 0.00 | 10.6 | 10.6 | 0.128 | 0.213 | 6.0 | 8.8 | 1.72 | 0.008 | 0.464 | 4.1 | 5.4 | 4.4 | 0.665 | 0.887 |
Other ARG† | 5.3 | 16.7** | 2.02 | 0.011 | 0.073 | 7.3 | 8.4 | 0.26 | 0.132 | 0.413 | 7.2 | 10.5 | 6.3 | 0.613 |
Numbers are presented as median total reads normalized by the total number of reads in each fecal sample.
Antibiotic resistance genes analyzed using ShortBRED.
PEP, probiotic extremely preterm infants; NPVP, non-probiotic very preterm infants; FTC, full-term control; FDR, false discovery rate.
Comparisons between all three treatment groups by nonparametric Kruskal–Wallis test.
Post-hoc comparisons by non-parametric Mann–Whitney U-test (vs. PEP) (**P < 0.01, *P < 0.05).
Comparison between different time points by generalized linear model with a Poisson family (†P < 0.05).
Genes modulating antibiotic efflux: norA, baeR, marA, phoQ, ramA, soxR. Genes modulating resistance: WblE, WhiB. Other ARG: bacA.
Bold indicates significant differences in median abundance of antibiotic resistance genes between the three groups (P- and Q-value).