{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:53:14Z","timestamp":1785779594775,"version":"3.56.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Increasing antimicrobial resistance poses a serious challenge for the treatment of\n                    <jats:italic>Shigella<\/jats:italic>\n                    infections, and there is an urgent need for alternative antibacterial treatments. We conducted a clinical trial to investigate the efficacy of oral tebipenem pivoxil, compared to intravenous ceftriaxone, in Bangladeshi children with shigellosis. Using demographic data of 2249 Bangladeshi children with suspected shigellosis, population pharmacokinetic (PK) simulations were conducted to simulate tebipenem PK profiles in children with the proposed dosing regimen. Subsequently, the model predictions estimated each virtual participant's fraction of time over the 3\u2010day treatment period during which simulated free tebipenem plasma concentration was above the minimum inhibitory concentration (\n                    <jats:italic>f<\/jats:italic>\n                    T &gt; MIC). Variability associated with the prevalence of different\n                    <jats:italic>Shigella<\/jats:italic>\n                    species in Bangladeshi children and the MIC distributions were incorporated.\n                    <jats:italic>Shigella<\/jats:italic>\n                    treatment effect was assumed for participants that had\n                    <jats:italic>f<\/jats:italic>\n                    T &gt; MIC for at least 40% of the 3\u2010day treatment period (40%\n                    <jats:italic>f<\/jats:italic>\n                    T &gt; MIC). The probability of achieving 40%\n                    <jats:italic>f<\/jats:italic>\n                    T &gt; MIC was 86.4% for 4\u2009mg\/kg tebipenem pivoxil three times daily (TID) dosing and 92.4% with 3\u2009mg\/kg tebipenem pivoxil four times daily (QID) dosing. Lastly, the probability of tebipenem pivoxil being non\u2010inferior to ceftriaxone, in a clinical trial containing 66 participants per arm, was evaluated for two dosing regimens. Three levels of ceftriaxone resistance were simulated to examine how dynamic ceftriaxone resistance may impact the trial outcome. Our findings suggest that more frequent tebipenem pivoxil dosing may increase the chance of producing treatment effects, contribute valuable insights to inform dosing strategy selection, and demonstrate a workflow that can be adapted to other drugs and diseases.\n                  <\/jats:p>","DOI":"10.1111\/cts.70453","type":"journal-article","created":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T07:06:07Z","timestamp":1766819167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetic and Pharmacodynamic Prediction for Tebipenem Pivoxil Treatment of Pediatric Shigellosis"],"prefix":"10.1111","volume":"19","author":[{"given":"Cindy X.","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharika","family":"Nuzhat","sequence":"additional","affiliation":[{"name":"Clinical and Diagnostic Services International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Ridwan","family":"Islam","sequence":"additional","affiliation":[{"name":"Nutrition Research Division International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Jayedul","family":"Bashar","sequence":"additional","affiliation":[{"name":"Nutrition Research Division International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhasish","family":"Das","sequence":"additional","affiliation":[{"name":"Nutrition Research Division International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rukaeya","family":"Amin","sequence":"additional","affiliation":[{"name":"Nutrition Research Division International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firdausi","family":"Qadri","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhana","family":"Khanam","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilruba","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Clinical and Diagnostic Services International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia B.","family":"Pavlinac","sequence":"additional","affiliation":[{"name":"Department of Global Health University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammod Jobayer","family":"Chisti","sequence":"additional","affiliation":[{"name":"Clinical and Diagnostic Services International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"},{"name":"Nutrition Research Division International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahmeed","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Clinical and Diagnostic Services International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"},{"name":"Nutrition Research Division International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"},{"name":"Office of the Executive Director International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B)  Dhaka Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8290-2347","authenticated-orcid":false,"given":"Samuel L. 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