{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T01:49:51Z","timestamp":1781056191820,"version":"3.54.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T00:00:00Z","timestamp":1665100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Anti-staphylococcal penicillins (ASPs) are among the most commonly prescribed antibiotics in children and are associated with a risk of drug-induced liver injury (DILI). Despite the frequent use of ASPs in children, there is no consensus on whether liver function tests (LFTs) should be routinely monitored during treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To review the literature on the frequency of ASP-related DILI in children to determine the incidence, risk factors and outcomes of hepatotoxicity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>PubMed, MEDLINE and Embase were searched in January 2022 for original studies of children who received cloxacillin, dicloxacillin, flucloxacillin, methicillin, nafcillin or oxacillin that included \u226510 children aged up to 18 years, and presented data on the incidence of DILI in children exposed to ASPs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Overall, two studies of oral flucloxacillin, two of intravenous (IV) methicillin, three of IV nafcillin and four of IV oxacillin were included. The mean onset of DILI ranged between 7.0 and 19.0\u2005days following commencement of antibiotic treatment and all episodes resolved between 14.2 and 16.0\u2005days after drug discontinuation, with no specific treatment required. This review found that the incidence of DILI in children was 1 in 50\u200a000 for oral flucloxacillin and ranged from 1 in 3 to 13 for IV oxacillin, methicillin and nafcillin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This review found that routine LFT monitoring is not required in children receiving low dose oral flucloxacillin in a primary care setting, although pharmacovigilance is critical. For IV preparations, the existing data support routine LFT monitoring in those receiving treatment for at least 7\u2005days.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac325","type":"journal-article","created":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T06:07:52Z","timestamp":1665122872000},"page":"3221-3230","source":"Crossref","is-referenced-by-count":7,"title":["Frequency of drug-induced liver injury in children receiving anti-staphylococcal penicillins"],"prefix":"10.1093","volume":"77","author":[{"given":"Kailey","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Paediatrics, The University of Melbourne , Parkville , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Coombs","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit and Pharmacy Department, The Royal Children\u2019s Hospital , Melbourne, Parkville , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Gwee","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The University of Melbourne , Parkville , Australia"},{"name":"Infectious Diseases Unit and Pharmacy Department, The Royal Children\u2019s Hospital , Melbourne, Parkville , Australia"},{"name":"Infectious Diseases Research Group, Murdoch Children\u2019s Research Institute , Parkville , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,7]]},"reference":[{"key":"2022112816493813600_dkac325-B1","doi-asserted-by":"crossref","first-page":"e217-222","DOI":"10.3399\/bjgp14X677842","article-title":"Oral penicillin prescribing for children in the UK: a comparison with BNF for Children age-band recommendations","volume":"64","author":"Saxena","year":"2014","journal-title":"Br J Gen Pract"},{"key":"2022112816493813600_dkac325-B2","doi-asserted-by":"crossref","first-page":"657","DOI":"10.5694\/mja13.00154","article-title":"Australia-wide point prevalence survey of the use and appropriateness of antimicrobial prescribing for children in hospital","volume":"201","author":"Osowicki","year":"2014","journal-title":"Med J Aust"},{"key":"2022112816493813600_dkac325-B3","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S1089-3261(03)00032-1","article-title":"Drug-induced cholestasis","volume":"7","author":"Levy","year":"2003","journal-title":"Clin Liver Dis"},{"key":"2022112816493813600_dkac325-B4","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1001\/jama.1965.03080080064024","article-title":"Cholestatic hepatitis following the administration of sodium oxacillin","volume":"191","author":"Pas","year":"1965","journal-title":"JAMA"},{"key":"2022112816493813600_dkac325-B5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1365-2125.2004.02133.x","article-title":"Acute and clinically relevant drug-induced liver injury: a population based case-control study","volume":"58","author":"de Abajo","year":"2004","journal-title":"Br J Clin Pharmacol"},{"key":"2022112816493813600_dkac325-B6","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.1128\/AAC.03122-15","article-title":"Adverse events lead to drug discontinuation more commonly among patients who receive nafcillin than among those who receive oxacillin","volume":"60","author":"Viehman","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"key":"2022112816493813600_dkac325-B7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12876-016-0550-0","article-title":"The incidence, presentation, outcomes, risk of mortality and economic data of drug-induced liver injury from a national database in Thailand: a population-base study","volume":"16","author":"Sobhonslidsuk","year":"2016","journal-title":"BMC Gastroenterol"},{"key":"2022112816493813600_dkac325-B8","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1179\/1973947813Y.0000000090","article-title":"Antibiotic induced liver injury: what about children?","volume":"25","author":"Serranti","year":"2013","journal-title":"J Chemother"},{"key":"2022112816493813600_dkac325-B9","first-page":"816","article-title":"HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin","volume":"2009","author":"Daly","journal-title":"Nat Genet"},{"key":"2022112816493813600_dkac325-B10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1590\/1806-9282.66.1.12","article-title":"Flucloxacillin-induced hepatotoxicity - association with HLA-B*5701","volume":"66","author":"Teixeira","year":"2020","journal-title":"Rev Assoc Med Bras"},{"key":"2022112816493813600_dkac325-B11","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/0168-8278(92)90029-O","article-title":"Liver damage from flucloxacillin, cloxacillin and dicloxacillin","volume":"15","author":"Olsson","year":"1992","journal-title":"J. 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