{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:05:22Z","timestamp":1790737522099,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T00:00:00Z","timestamp":1510185600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["K23HD070774"],"award-info":[{"award-number":["K23HD070774"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 HD061265"],"award-info":[{"award-number":["R01 HD061265"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern AIDS Soc"],"published-print":{"date-parts":[[2017,11]]},"abstract":"Abstract<\/jats:title>Introduction<\/jats:title>Despite declining risk of vertical HIV<\/jats:styled-content> transmission, prophylactic cotrimoxazole (CTX<\/jats:styled-content>) remains widely used to reduce morbidity and mortality in the event of HIV<\/jats:styled-content> infection among exposed infants, with an inherent risk of conferring commensal antimicrobial resistance. Using data from a randomized, placebo\u2010controlled trial of infant CTX<\/jats:styled-content> prophylaxis, we sought to quantify emergence of antibiotic resistance.<\/jats:p><\/jats:sec>Methods<\/jats:title>HIV<\/jats:styled-content>\u2010exposed uninfected infants enrolled in the Botswana Mpepu study were randomized to prophylactic CTX<\/jats:styled-content> or placebo between 14 and 34\u00a0days of life and continued through 15\u00a0months. Stool samples were collected from a subset of participating infants at randomization, three, and six months, and stored at \u221270\u00b0C prior to culture. Specimens that grew Escherichia coli (E.\u00a0coli)<\/jats:italic> or Klebsiella<\/jats:italic> species (Klebsiella<\/jats:italic> spp.) underwent antibiotic susceptibility testing by Kirby Bauer method using CTX<\/jats:styled-content> (CTX<\/jats:styled-content> 1.25\/23.75\u00a0\u03bcg) and Amoxicillin (10\u00a0\u03bcg) in Mueller Hinton agar. Fisher's exact testing was used to compare prevalence of resistance by randomization arm (CTX<\/jats:styled-content>\/placebo).<\/jats:p><\/jats:sec>Results and Discussion<\/jats:title>A total of 381 stool samples from 220 infants were cultured: 118 at randomization, 151 at three months, and 112 at six\u2010months. E.\u00a0coli<\/jats:italic> was isolated from 206 specimens and Klebsiella<\/jats:italic> spp. from 138 specimens. Resistance to CTX<\/jats:styled-content> was common in both E.\u00a0coli<\/jats:italic> and Klebsiella<\/jats:italic> spp. at the randomization visit (52.2% and 37.7% respectively) and did not differ by study arm. E.\u00a0Coli<\/jats:italic> isolates from CTX<\/jats:styled-content> recipients at three and six months had 94.9% and 84.2% CTX<\/jats:styled-content> resistance, as compared with 51.4% and 57.5% CTX<\/jats:styled-content> resistance in isolates from placebo recipients (p<\/jats:italic>=0.01). Klebsiella<\/jats:italic> spp. isolates from CTX<\/jats:styled-content> recipients had 79.0% and 68.8% CTX<\/jats:styled-content> resistance at three and six months, as compared with 19.1% and 14.3% in isolates from placebo recipients (p<\/jats:italic><0.01).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>HIV<\/jats:styled-content>\u2010exposed infants randomized to CTX<\/jats:styled-content> prophylaxis had increased CTX<\/jats:styled-content>\u2010resistant commensal gastrointestinal bacteria compared with placebo recipients. Additional research is needed to determine the longer\u2010term clinical, microbiologic, and public health consequences of antimicrobial resistance selected by infant CTX<\/jats:styled-content> prophylaxis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25021","type":"journal-article","created":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T17:40:56Z","timestamp":1512150056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cotrimoxazole prophylaxis was associated with enteric commensal bacterial resistance among HIV\u2010exposed infants in a randomized controlled trial, Botswana"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4478-4471","authenticated-orcid":false,"given":"Kathleen M","family":"Powis","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital Departments of Medicine and Pediatrics Boston MA United States"},{"name":"Department of Immunology and Infectious Diseases Harvard T. H. Chan School of Public Health Boston MA United States"},{"name":"Botswana\u2010Harvard AIDS Institute Partnership Gaborone Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajini","family":"Souda","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Botswana Gaborone Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Lockman","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases Harvard T. H. Chan School of Public Health Boston MA United States"},{"name":"Botswana\u2010Harvard AIDS Institute Partnership Gaborone Botswana"},{"name":"Brigham and Women's Hospital Infectious Disease Division Boston MA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gbolahan","family":"Ajibola","sequence":"additional","affiliation":[{"name":"Botswana\u2010Harvard AIDS Institute Partnership Gaborone Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara","family":"Bennett","sequence":"additional","affiliation":[{"name":"Bennett Statistical Consulting, Inc. Ballston Lake NY United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Leidner","sequence":"additional","affiliation":[{"name":"Goodtables Data Consulting Norman OK United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Harvard T. H. Chan School of Public Health Boston MA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sikhulile","family":"Moyo","sequence":"additional","affiliation":[{"name":"Botswana\u2010Harvard AIDS Institute Partnership Gaborone Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"van Widenfelt","sequence":"additional","affiliation":[{"name":"Botswana\u2010Harvard AIDS Institute Partnership Gaborone Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruna B","family":"Jibril","sequence":"additional","affiliation":[{"name":"Ministry of Health Gaborone Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Makhema","sequence":"additional","affiliation":[{"name":"Botswana\u2010Harvard AIDS Institute Partnership Gaborone Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Essex","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases Harvard T. H. Chan School of Public Health Boston MA United States"},{"name":"Botswana\u2010Harvard AIDS Institute Partnership Gaborone Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger L","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases Harvard T. H. Chan School of Public Health Boston MA United States"},{"name":"Botswana\u2010Harvard AIDS Institute Partnership Gaborone Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,9]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"World Health Organization.Guidelines on co\u2010trimoxazole prophylaxis for HIV\u2010related infections among children adolescents and adults \u2010 recommendations for a public health approach.2006[cited 2016 October 21]. Available from:http:\/\/www.who.int\/hiv\/pub\/guidelines\/ctxguidelines.pdf?ua=1."},{"key":"e_1_2_10_3_1","unstructured":"World Health Organization UNICEF.Towards Universal Access: Scaling priority HIV\/AIDS interventions in the health sector.2008[cited 2016 October 21]. Available from:http:\/\/www.who.int\/hiv\/pub\/towards_universal_access_report_2008.pdf?ua=1."},{"key":"e_1_2_10_4_1","unstructured":"UNAIDS.Report on the Global HIV\/AIDS Epidemic.2008[cited 2016 October 23]. Available from:http:\/\/www.unaids.org\/sites\/default\/files\/media_asset\/jc1510_2008globalreport_en_0.pdf."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.11.100818"},{"key":"e_1_2_10_6_1","unstructured":"l.Children and AIDS \u2010 Third Stocktaking Report 2008.2008[cited 2016 October 23]. Available from:http:\/\/www.unicef.org\/publications\/files\/CATSR_EN_11202008.pdf."},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3280114ed7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17442-4"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0593-7"},{"key":"e_1_2_10_10_1","unstructured":"UNAIDS.Prevention Gap Report.2016. Available from:http:\/\/www.unaids.org\/sites\/default\/files\/media_asset\/2016-prevention-gap-report_en.pdf."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-013-0419-x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)07399-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.a257"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ309"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/tmi.12352"},{"key":"e_1_2_10_16_1","volume-title":"2016 Conference on Retroviruses and Opportunistic Infections","author":"Shapiro RL","year":"2016"},{"key":"e_1_2_10_17_1","volume-title":"Performance standards for antimicrobial susceptibility testing; twenty\u2010fifth informational supplement","author":"Clinical and Laboratory Standards Institute","year":"2015"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/320710"},{"issue":"3","key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"320","DOI":"10.4269\/ajtmh.2008.79.320","article-title":"Does cotrimoxazole prophylaxis for the prevention of HIV\u2010associated opportunistic infections select for resistant pathogens in Kenyan adults?","volume":"79","author":"Hamel MJ","year":"2008","journal-title":"Am J Trop Med Hyg"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-8-40"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17225-5"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid0801.010018"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.4103\/0974-777X.56255"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.4314\/ahs.v14i4.8"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.6.1479-1484.2000"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000354907"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad9378"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2974"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.qai.0000188122.15493.0a"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e31817109a4"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.inf.0000264527.69954.4c"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17140-7"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/519847"}],"container-title":["Journal of the International AIDS Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjia2.25021","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jia2.25021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T12:37:53Z","timestamp":1696163873000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jia2.25021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1002\/jia2.25021"],"URL":"https:\/\/doi.org\/10.1002\/jia2.25021","archive":["Portico"],"relation":{},"ISSN":["1758-2652","1758-2652"],"issn-type":[{"value":"1758-2652","type":"print"},{"value":"1758-2652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11]]},"assertion":[{"value":"2017-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-10-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e25021"}}