623. Dynamic nature of the gut resistome among infants in Singapore
Session: Poster Abstract Session: Microbiome and Beyond
Thursday, October 4, 2018
Room: S Poster Hall
Background:

The gut microbiome harbours antibiotic resistance genes (ARGs), known as the resistome, that has the potential to spread and contribute to the global crisis of antibacterial resistance. Little is known about the genomic traits of the infant resistome, especially in areas with high endemic antibacterial resistance.

Methods:

We analyzed ARGs among a subset of infants from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort. The subset included 75 mostly term, healthy Singaporean infants born from Nov 2009 to May 2011. Stool samples collected at week 3 (W3), months 3 (M3), 6 (M6) and 12 (M12) were analyzed using shotgun metagenomics. Sequencing reads were assembled into contigs using MEGAHIT. ARGs were identified using ResFinder 2.1. Demographic, perinatal factors, pre- and postnatal antibiotic exposure were collected.

Results:

188 stool samples from 75 infants were studied. Of the 169 ARGs detected, the 4 commonest ARGs were blaZ, fosA, tet(M) and mef(A), conferring resistance to β-lactams, fosfomycin, tetracyclines, and macrolides respectively. The number of ARGs per infant increased over time (median: W3=18.0, M12=22.0, p<0.05).

At W3, 118 ARGs were detected among 28 infants. The most prevalent ARGs were fos(A) and blaZ (both 96.4%) at W3. Among the 22 infants who had samples at W3 and M12, only 6 of 118 ARGs detected at W3 were also present at M12. These were mef(A), msr(D), tet(W), erm(B), tet(M) and fosA, conferring macrolide and tetracycline resistance. Their prevalence among at M12 was 100%, 93.3%, 90.9%, 84.6%, 68.8% and 52.4% respectively.

ARGs were not associated with gender, race, delivery mode, peripartum or postnatal antibiotics in infancy. Of note, longitudinal analysis showed that only the cfxA gene, which confers β-lactam resistance, was more prevalent in infants whose mothers received antibiotics in pregnancy than those whos mothers did not (adjusted p<0.05).

Conclusion:

In regions with high endemic antimicrobial resistance such as Singapore, the infant gut harbours a diversity of ARGs as early as 3 weeks of age. Few ARGs persisted through infancy, implying the dynamic nature of the infant resistome. The lack of association of ARGs with most clinical variables evaluated here suggests that other unrecognized factors may contribute to the plasticity of ARGs in the infant gut resistome.

Amanda Zain, MMed1, Gaik Chin Yap, MSc2, Rikky W. Purbojati, MSc3, Daniela Isabel Moses, PhD3, Lynette P.C. Shek, FRCPCH1, Anne Goh, MMed4, Hugo P. S. Van Bever, PhD1, Oon Hoe Teoh, MMed4, Jian Yi Soh, MMed1, Biju Thomas, MD3, Mahesh Babu Ramamurthy, MD1, Daniel Y. T. Goh, MMed1, Christophe Lay, PhD5, Evelyn Loo Xiu Ling, PhD6, Shu-E Soh, PhD7, Fabian Yap, MMed4, Kok Hian Tan, MRCOG4, Yap-Seng Chong, PhD7, Keith M. Godfrey, PhD8, Peter D. Gluckman, MD6, Stephan Schuster, PhD3, Ritu Banerjee, MD, PhD9 and Bee Wah Lee, MBBS1, (1)Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore, (2)Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, (3)Singapore Center On Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, Singapore, (4)Department of Paediatrics Allergy and Respiratory, KK Children’s and Women’s Hospital, Singapore, Singapore, (5)Department of Paediatrics, Yong Loo Lin School of Medicine, Singapore, Singapore, (6)Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research Singapore, Singapore, Singapore, (7)Department of Obstetrics & Gynaecology, National University of Singapore, Singapore, Singapore, (8)MRC Lifecourse Epidemiology Unit and NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, (9)Division of Pediatric Infectious Diseases, Vanderbilt University, Nashville, TN

Disclosures:

A. Zain, None

G. C. Yap, None

R. W. Purbojati, None

D. I. Moses, None

L. P. C. Shek, None

A. Goh, None

H. P. S. Van Bever, None

O. H. Teoh, None

J. Y. Soh, None

B. Thomas, None

M. B. Ramamurthy, None

D. Y. T. Goh, None

C. Lay, None

E. Loo Xiu Ling, None

S. E. Soh, None

F. Yap, None

K. H. Tan, None

Y. S. Chong, None

K. M. Godfrey, None

P. D. Gluckman, None

S. Schuster, None

R. Banerjee, Accelerate Diagnostics, Biomerieux, BioFire: Grant Investigator , Research grant and Research support .

B. W. Lee, None

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