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This document serves as a companion to the CDC Healthcare Infection Control Practices Advisory Committee (HICPAC) Guideline for Prevention of Infections in Neonatal Intensive Care Unit Patients. Central line-associated bloodstream infections (CLABSIs) are among the most frequent invasive infections among infants in the NICU and contribute to substantial morbidity and mortality. Infants who survive CLABSIs have prolonged hospitalization resulting in increased healthcare costs and suffer greater comorbidities including worse neurodevelopmental and growth outcomes. A bundled approach to central line care practices in the NICU has reduced CLABSI rates, but challenges remain. This document was authored by pediatric infectious diseases specialists, neonatologists, advanced practice nurse practitioners, infection preventionists, members of the HICPAC guideline-writing panel, and members of the SHEA Pediatric Leadership Council. For the selected topic areas, the authors provide practical approaches in question-and-answer format, with answers based on consensus expert opinion within the context of the literature search conducted for the companion HICPAC document and supplemented by other published information retrieved by the authors. Two documents in the series precede this one: \u201cPractical approaches to<jats:italic>Clostridioides difficile<\/jats:italic>prevention\u201d published in August 2018 and \u201cPractical approaches to<jats:italic>Staphylococcus aureus<\/jats:italic>prevention,\u201d published in September 2020.<\/jats:p>","DOI":"10.1017\/ice.2022.53","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T02:11:27Z","timestamp":1646359887000},"page":"550-564","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":42,"title":["SHEA Neonatal Intensive Care Unit (NICU) White Paper Series: Practical approaches for the prevention of central-line\u2013associated bloodstream infections"],"prefix":"10.1017","volume":"44","author":[{"given":"Martha","family":"Muller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina A.","family":"Bryant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Espinosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Quach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R.","family":"Rindels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan L.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M.","family":"Zangwill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo J.","family":"S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"S0899823X22000538_ref14","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2020-321174"},{"key":"S0899823X22000538_ref58","doi-asserted-by":"publisher","DOI":"10.1097\/01.PCC.0000288711.46009.58"},{"key":"S0899823X22000538_ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.04.045"},{"key":"S0899823X22000538_ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2012.05.030"},{"key":"S0899823X22000538_ref72","doi-asserted-by":"publisher","DOI":"10.1177\/1060028015569881"},{"key":"S0899823X22000538_ref12","doi-asserted-by":"publisher","DOI":"10.1017\/ice.2020.51"},{"key":"S0899823X22000538_ref82","doi-asserted-by":"publisher","DOI":"10.1097\/PTS.0000000000000246"},{"key":"S0899823X22000538_ref3","doi-asserted-by":"publisher","DOI":"10.1111\/apa.12764"},{"key":"S0899823X22000538_ref85","doi-asserted-by":"publisher","DOI":"10.1097\/NAN.0b013e3181f8586b"},{"key":"S0899823X22000538_ref51","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy584"},{"key":"S0899823X22000538_ref50","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2021-322844"},{"key":"S0899823X22000538_ref37","doi-asserted-by":"publisher","DOI":"10.1017\/ice.2020.467"},{"key":"S0899823X22000538_ref88","doi-asserted-by":"publisher","DOI":"10.1097\/ANC.0b013e318278b907"},{"key":"S0899823X22000538_ref25","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780190697174.001.0001"},{"key":"S0899823X22000538_ref44","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2013.175"},{"key":"S0899823X22000538_ref46","doi-asserted-by":"publisher","DOI":"10.1086\/657632"},{"key":"S0899823X22000538_ref86","doi-asserted-by":"publisher","DOI":"10.1097\/NAN.0000000000000328"},{"key":"S0899823X22000538_ref89","unstructured":"89. 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