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We summarize clinical and pharmacokinetic\/pharmacodynamic (PK\/PD) data that compare dosing strategies for SSTIs. Additionally, we conduct population PK target attainment simulations for varying doses of cephalexin and cefadroxil for\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    and Group A\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    . Although some clinical data support lower doses in mild SSTIs, higher doses optimize PK\/PD parameters in moderate\u2013severe SSTIs, especially due to\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    . Further prospective clinical and PK\/PD studies, especially in obese adults, would be beneficial.\n                  <\/jats:p>","DOI":"10.1002\/phar.70179","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T06:09:55Z","timestamp":1781158195000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Getting It Right the Second Time: How Can we Optimize First\u2010Generation Cephalosporin Dosing for Skin and Soft Tissue Infections in the 21st Century?"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4566-1905","authenticated-orcid":false,"given":"Jonathan H.","family":"Ryder","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3068-3732","authenticated-orcid":false,"given":"Shawnalyn W.","family":"Sunagawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science University of Nebraska Medical Center  Omaha Nebraska USA"},{"name":"Antiviral Pharmacology Laboratory, College of Pharmacy University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-5434","authenticated-orcid":false,"given":"Nathaniel J.","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice Midwestern University  Downers Grove Illinois USA"},{"name":"Pharmacometrics Center of Excellence Midwestern University  Downers Grove Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9928-4546","authenticated-orcid":false,"given":"Trevor C.","family":"Van Schooneveld","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0018-7963","authenticated-orcid":false,"given":"Jeremy E.","family":"Tigh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Good Samaritan Regional Medical Center  Corvallis Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0935-6455","authenticated-orcid":false,"given":"Sean N.","family":"Avedissian","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science University of Nebraska Medical Center  Omaha Nebraska USA"},{"name":"Antiviral Pharmacology Laboratory, College of Pharmacy University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6302-9471","authenticated-orcid":false,"given":"Nicolas","family":"Cortes\u2010Penfield","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2016.05.064"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/2150131915583659"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw463"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02626\u201015"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0149\u20102918(01)80109\u20100"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz977"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofv181"},{"key":"e_1_2_15_9_1","unstructured":"FDA \u201cKeflex (Cephalexin Capsules USP) 2023\u201d https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/050405s110lbl.pdf."},{"key":"e_1_2_15_10_1","unstructured":"FDA \u201cDuricef (Cefadroxil Monohydrate USP)\u201d https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2002\/50512s44lbl.pdf."},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu444"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.5653"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007997209111143"},{"issue":"9","key":"e_1_2_15_14_1","first-page":"559","article-title":"The Efficacy of Twice Daily Cephalexin","volume":"2","author":"Browning A. 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