{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T08:44:05Z","timestamp":1769762645102,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community\u2010acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for <jats:italic>Streptococcus pneumoniae<\/jats:italic>, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using NONMEM v7.3, Monte Carlo simulations (<jats:italic>N<\/jats:italic>\u00a0=\u00a010,000) were conducted for AMOX 15\u2009mg\/kg\/dose PO every 8\u2009h (standard\u2010dose), AMOX 45\u2009mg\/kg\/dose PO every 12\u00a0h (high\u2010dose), and PENG 62,500\u2009units\/kg\/day IV every 6\u2009h using six virtual subjects with ages spanning 3\u2009months to 15\u2009years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%<jats:italic>f<\/jats:italic>T&gt;MIC) across the population of pneumococci for 30%\u201350% of the dosing interval.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2\u00a0mg\/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5\u00a0mg\/L) breakpoints. As compared to CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% <jats:italic>f<\/jats:italic>T&gt;MIC in the serum at the susceptible MICs, standard\u2010dose AMOX achieved &gt;4% PTA (CLSI) and &gt;86% PTA (EUCAST); high\u2010dose AMOX achieved &gt;73% PTA (CLSI) and &gt;99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard\u2010dose AMOX, high\u2010dose AMOX, and PENG achieved &gt;71%, &gt;93%, and 100% PTA, respectively, in the serum at 30%\u201350% <jats:italic>f<\/jats:italic>T&gt;MIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High\u2010dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2756","type":"journal-article","created":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T08:44:00Z","timestamp":1672044240000},"page":"606-614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Amoxicillin and penicillin G dosing in pediatric community\u2010acquired pneumococcal pneumonia in the era of conjugate pneumococcal vaccines"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0514-0294","authenticated-orcid":false,"given":"Dustin","family":"Huynh","sequence":"first","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of California at San Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norint","family":"Tung","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of California at San Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quang","family":"Dam","sequence":"additional","affiliation":[{"name":"Miller Children's and Women's Hospital of Long Beach  Long Beach California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tri","family":"Tran","sequence":"additional","affiliation":[{"name":"School of Medicine University of California Riverside  Riverside California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina G.","family":"Hulten","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Infectious Diseases Baylor College of Medicine  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4281-1824","authenticated-orcid":false,"given":"Christopher J.","family":"Harrison","sequence":"additional","affiliation":[{"name":"School of Medicine University of Missouri\u2010Kansas City  Kansas City Missouri USA"},{"name":"Children's Mercy Hospital  Kansas City Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheldon L.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Infectious Diseases Baylor College of Medicine  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of California at San Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler H.","family":"Do","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of California at San Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amartya","family":"Setty","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of California at San Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Le","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of California at San Diego  San Diego California USA"},{"name":"Miller Children's and Women's Hospital of Long Beach  Long Beach California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir625"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1405870"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.06.057"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix115"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw067"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/514622"},{"key":"e_1_2_8_8_1","unstructured":"Clinical Growth Charts 2017.https:\/\/www.cdc.gov\/growthcharts\/clinical_charts.htm"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-009-1389-1"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccc.2010.11.004"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00608225"},{"key":"e_1_2_8_12_1","unstructured":"Pediatric & Neonatal Lexi\u2010Drugs Online. 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