{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T01:23:39Z","timestamp":1793669019990,"version":"4.5.1"},"reference-count":73,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"694","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,5,3]]},"abstract":"<jats:p>Bacterial bloodstream infections (BSIs) resulting in late-onset sepsis affect up to half of extremely preterm infants and have substantial morbidity and mortality. Bacterial species associated with BSIs in neonatal intensive care units (NICUs) commonly colonize the preterm infant gut microbiome. Accordingly, we hypothesized that the gut microbiome is a reservoir of BSI-causing pathogenic strains that increase in abundance before BSI onset. We analyzed 550 previously published fecal metagenomes from 115 hospitalized neonates and found that recent ampicillin, gentamicin, or vancomycin exposure was associated with increased abundance of Enterobacteriaceae and Enterococcaceae in infant guts. We then performed shotgun metagenomic sequencing on 462 longitudinal fecal samples from 19 preterm infants (cases) with BSI and 37 non-BSI controls, along with whole-genome sequencing of the BSI isolates. Infants with BSI caused by Enterobacteriaceae were more likely than infants with BSI caused by other organisms to have had ampicillin, gentamicin, or vancomycin exposure in the 10 days before BSI. Relative to controls, gut microbiomes of cases had increased relative abundance of the BSI-causing species and clustered by Bray-Curtis dissimilarity according to BSI pathogen. We demonstrated that 11 of 19 (58%) of gut microbiomes before BSI, and 15 of 19 (79%) of gut microbiomes at any time, harbored the BSI isolate with fewer than 20 genomic substitutions. Last, BSI strains from the Enterobacteriaceae and Enterococcaceae families were detected in multiple infants, indicating BSI-strain transmission. Our findings support future studies to evaluate BSI risk prediction strategies based on gut microbiome abundance in hospitalized preterm infants.<\/jats:p>","DOI":"10.1126\/scitranslmed.adg5562","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T17:58:34Z","timestamp":1683136714000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":93,"title":["Gut pathogen colonization precedes bloodstream infection in the neonatal intensive care unit"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1568-7733","authenticated-orcid":true,"given":"Drew J.","family":"Schwartz","sequence":"first","affiliation":[{"name":"Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Center for Women\u2019s Infectious Disease Research, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Pediatrics, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitan","family":"Shalon","sequence":"additional","affiliation":[{"name":"Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1646-7460","authenticated-orcid":true,"given":"Kate","family":"Wardenburg","sequence":"additional","affiliation":[{"name":"Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2558-6637","authenticated-orcid":true,"given":"Anna","family":"DeVeaux","sequence":"additional","affiliation":[{"name":"Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan A.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Hall-Moore","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. Malick","family":"Ndao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1682-1607","authenticated-orcid":true,"given":"Janice E.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Louisville School of Medicine, Norton Children\u2019s Hospital, Louisville, KY 40202, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Radmacher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Louisville School of Medicine, Norton Children\u2019s Hospital, Louisville, KY 40202, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Escobedo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Oklahoma, Oklahoma City, OK 73117, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1137-840X","authenticated-orcid":true,"given":"Carey-Ann D.","family":"Burnham","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2103-2496","authenticated-orcid":true,"given":"Barbara B.","family":"Warner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4078-7517","authenticated-orcid":true,"given":"Phillip I.","family":"Tarr","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0455-8370","authenticated-orcid":true,"given":"Gautam","family":"Dantas","sequence":"additional","affiliation":[{"name":"Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Pediatrics, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St.\u00a0Louis, MO 63110, USA."},{"name":"Department of Biomedical Engineering, Washington University in St.\u00a0Louis, St.\u00a0Louis, MO 63130, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60820-4"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2014-306213"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2013.09.011"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2012.11.089"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(18)30063-8"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-3782(12)70019-1"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01191"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-2860"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.110.2.285"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000001570"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2006.01.002"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1159\/000497781"},{"key":"e_1_3_3_15_2","first-page":"675","article-title":"Risk factors and outcomes of late-onset bacterial sepsis in preterm neonates born at < 32 weeks\u2019 gestation","volume":"32","author":"Shah J.","year":"2015","unstructured":"J.\u00a0Shah, A. L.\u00a0Jefferies, E. W.\u00a0Yoon, S. K.\u00a0Lee, P. S.\u00a0Shah; Canadian Neonatal Network, Risk factors and outcomes of late-onset bacterial sepsis in preterm neonates born at < 32 weeks\u2019 gestation. Am.\u00a0J.\u00a0Perinatol. 32, 675\u2013682 (2015).","journal-title":"Am.\u00a0J.\u00a0Perinatol."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.746111"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2020.03.034"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-200211000-00010"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/2049-2618-2-1"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0493-5"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.24"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03241-8"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu084"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0617-x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0130604"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-021-01025-4"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-00797-0"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.213256.116"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00731-19"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.03.007"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0321-5"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0202-8"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-3409"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy882"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052876"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409497111"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00081-7"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0550-2"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-3423"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2018.1481042"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-0179"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009442"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2020.4719"},{"key":"e_1_3_3_44_2","unstructured":"R.\u00a0A.\u00a0A. Moehring Elizabeth Dodds Developing patient safety outcome measures and measurement tools for antibiotic stewardship programs metric guide (2017)."},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00670-13"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02018-w"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28048-7"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000002558"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2021.1940792"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0626-9"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.3390\/bios10050050"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0626-z"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/3509676"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06393-w"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3181e7884f"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2016.06.001"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65088"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx373"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017288"},{"key":"e_1_3_3_61_2","unstructured":"B. Bushnell BBMap: A fast accurate splice-aware aligner. Lawrence Berkeley National Laboratory. LBNL Report no. LBNL-7065E; retrieved from https:\/\/escholarship.org\/uc\/item\/1h3515gn (2014)."},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.2012.0021"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0997-x"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.186072.114"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt086"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1237-9"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004557"},{"key":"e_1_3_3_68_2","first-page":"D517","article-title":"CARD 2020: Antibiotic resistome surveillance with the comprehensive antibiotic resistance database","volume":"48","author":"Alcock B. P.","year":"2019","unstructured":"B. P.\u00a0Alcock, A. R.\u00a0Raphenya, T.\u00a0T.\u00a0Y.\u00a0Lau, K. K.\u00a0Tsang, M.\u00a0Bouchard, A.\u00a0Edalatmand, W.\u00a0Huynh, A.\u00a0L.\u00a0V.\u00a0Nguyen, A. A.\u00a0Cheng, S.\u00a0Liu, S. Y.\u00a0Min, A.\u00a0Miroshnichenko, H.-K.\u00a0Tran, R. E.\u00a0Werfalli, J. A.\u00a0Nasir, M.\u00a0Oloni, D. J.\u00a0Speicher, A.\u00a0Florescu, B.\u00a0Singh, M.\u00a0Faltyn, A.\u00a0Hernandez-Koutoucheva, A. N.\u00a0Sharma, E.\u00a0Bordeleau, A. C.\u00a0Pawlowski, H. L.\u00a0Zubyk, D.\u00a0Dooley, E.\u00a0Griffiths, F.\u00a0Maguire, G. L.\u00a0Winsor, R. G.\u00a0Beiko, F.\u00a0S.\u00a0L.\u00a0Brinkman, W.\u00a0W.\u00a0L.\u00a0Hsiao, G. V.\u00a0Domselaar, A. G.\u00a0McArthur, CARD 2020: Antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res. 48, D517\u2013D525 (2019).","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_3_69_2","unstructured":"Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing (Clinical and Laboratory Standards Institute 2016)."},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa345"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030126"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-021-00893-z"}],"updated-by":[{"DOI":"10.1126\/scitranslmed.adp7701","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000}}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adg5562","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T17:58:21Z","timestamp":1714586301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adg5562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,3]]},"references-count":73,"journal-issue":{"issue":"694","published-print":{"date-parts":[[2023,5,3]]}},"alternative-id":["10.1126\/scitranslmed.adg5562"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adg5562","relation":{"correction":[{"id-type":"doi","id":"10.1126\/scitranslmed.adp7701","asserted-by":"object"}]},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,3]]},"assertion":[{"value":"2023-01-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadg5562"}}