{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T17:18:39Z","timestamp":1778260719675,"version":"3.51.4"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Australian Tropical Medical Commercialisation programme","award":["ATMC50298"],"award-info":[{"award-number":["ATMC50298"]}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["GNT1175509"],"award-info":[{"award-number":["GNT1175509"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["GNT119"],"award-info":[{"award-number":["GNT119"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["GNT1197177"],"award-info":[{"award-number":["GNT1197177"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Benzathine penicillin G (BPG) is the cornerstone of secondary prophylaxis to prevent Streptococcus pyogenes infections, which precede acute rheumatic fever (ARF). The paucity of pharmacokinetic (PK) data from children and adolescents from populations at the highest risk of ARF and rheumatic heart disease (RHD) poses a challenge for determining the optimal dosing and frequency of injections and undermines efforts to develop improved regimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a 6\u2005month longitudinal PK study of young people receiving BPG for secondary prophylaxis. Throat and skin swabs were collected for microbiological culture along with dried blood spot (DBS) samples for penicillin concentrations. DBSs were assayed using LC-MS\/MS. Penicillin concentration datasets were analysed using non-linear mixed-effects modelling and simulations performed using published BMI-for-age and weight-for-age data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Nineteen participants provided 75 throat swabs, 3 skin swabs and 216 penicillin samples. Throat cultures grew group C and G Streptococcus. Despite no participant maintaining penicillin concentration &amp;gt;20\u2005ng\/mL between doses, there were no S. pyogenes throat infections and no ARF. The median (range) observed durations &amp;gt;20\u2005ng\/mL for the low- and high-BMI groups were 14.5 (11.0\u201324.25) and 15.0 (7.5\u201318.25) days, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Few patients at highest risk of ARF\/RHD receiving BPG for secondary prophylaxis maintain penicillin concentrations above the target of 20\u2005ng\/mL beyond 2\u2005weeks during each monthly dosing interval. These PK data suggest that some high-risk individuals may get inadequate protection from every 4\u2005week dosing. Future research should explore this gap in knowledge and PK differences between different populations to inform future dosing schedules.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac231","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T10:55:35Z","timestamp":1657709735000},"page":"2679-2682","source":"Crossref","is-referenced-by-count":9,"title":["Population pharmacokinetic study of benzathine penicillin G administration in Indigenous children and young adults with rheumatic heart disease in the Northern Territory, Australia"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3121-4397","authenticated-orcid":false,"given":"Joseph","family":"Kado","sequence":"first","affiliation":[{"name":"Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia , Perth, WA , Australia"},{"name":"Medical School, University of Western Australia , Perth, WA , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8276-6784","authenticated-orcid":false,"given":"Sam","family":"Salman","sequence":"additional","affiliation":[{"name":"Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia , Perth, WA , Australia"},{"name":"Medical School, University of Western Australia , Perth, WA , Australia"},{"name":"Clinical Pharmacology and Toxicology Unit, PathWest , Perth, WA , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6448-4559","authenticated-orcid":false,"given":"Robert","family":"Hand","sequence":"additional","affiliation":[{"name":"Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia , Perth, WA , Australia"},{"name":"Department of Infectious Diseases, Royal Perth Hospital , Perth, WA , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Danila Dilba Health Service , Darwin, NT , Australia"},{"name":"National Centre for Epidemiology and Population Health, Australia National University , Canberra, ACT , Australia"},{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University , Darwin, NT , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Ralph","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University , Darwin, NT , Australia"},{"name":"Department of Infectious Diseases, Royal Darwin Hospital , Darwin, NT , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asha C","family":"Bowen","sequence":"additional","affiliation":[{"name":"Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia , Perth, WA , Australia"},{"name":"Medical School, University of Western Australia , Perth, WA , Australia"},{"name":"Department of Infectious Diseases, Perth Children\u2019s Hospital , Perth, WA , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhu","family":"Page-Sharp","sequence":"additional","affiliation":[{"name":"Curtin Medical School, Curtin University , Bentley, WA , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin T","family":"Batty","sequence":"additional","affiliation":[{"name":"Curtin Medical School, Curtin University , Bentley, WA , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Dolman","sequence":"additional","affiliation":[{"name":"Medical School, University of Western Australia , Perth, WA , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua R","family":"Francis","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University , Darwin, NT , Australia"},{"name":"Department of Infectious Diseases, Royal Darwin Hospital , Darwin, NT , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-9792","authenticated-orcid":false,"given":"Jonathan","family":"Carapetis","sequence":"additional","affiliation":[{"name":"Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia , Perth, WA , Australia"},{"name":"Medical School, University of Western Australia , Perth, WA , Australia"},{"name":"Curtin Medical School, Curtin University , Bentley, WA , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4334-5351","authenticated-orcid":false,"given":"Laurens","family":"Manning","sequence":"additional","affiliation":[{"name":"Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia , Perth, WA , Australia"},{"name":"Medical School, University of Western Australia , Perth, WA , Australia"},{"name":"Department of Infectious Diseases, Fiona Stanley Hospital , Perth, WA , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"2022093019445841200_dkac231-B1","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll 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