{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:00:40Z","timestamp":1788454840862,"version":"build-2803163510"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,4,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) \u226431 weeks from the Metronidazole Pharmacokinetics in Premature Infants (PTN_METRO, NCT01222585) study. First, we used linear correlation to compare 42 paired DBS and plasma metronidazole concentrations from 21 preterm infants [mean (SD): post natal age 28.0 (21.7) days, GA 26.3 (2.4) weeks]. Using the resulting predictive equation, we estimated plasma metronidazole concentrations (ePlasma) from 399 DBS collected from 122 preterm and term infants [mean (SD): post natal age 16.7 (15.8) days, GA 31.4 (5.1) weeks] from the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP, NCT01994993) trial. When evaluating the PTN_METRO model using ePlasma from the SCAMP trial, we found that the model generally predicted ePlasma well in preterm infants with GA \u226431 weeks. When including ePlasma from term and preterm infants with GA &gt;31 weeks, the model was optimized using a sigmoidal Emax maturation function of postmenstrual age on clearance and estimated the exponent of weight on volume of distribution. The optimized model supports existing dosing guidelines and adds new data to support a 6-hour dosing interval for infants with postmenstrual age &gt;40 weeks. Using an opportunistic DBS to externally validate and optimize a metronidazole population pharmacokinetic model was feasible and useful in this vulnerable population.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01533-23","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T13:06:59Z","timestamp":1712149619000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8009-8209","authenticated-orcid":false,"given":"Rachel L.","family":"Randell","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Duke University, Durham, North Carolina, USA"},{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Balevic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University, Durham, North Carolina, USA"},{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel G.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University, Durham, North Carolina, USA"},{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cohen-Wolkowiez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University, Durham, North Carolina, USA"},{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University, Durham, North Carolina, USA"},{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saranya","family":"Venkatachalam","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Bendel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Bliss","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Chaaban","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Chhabra","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Hackensack University Medical Center, Hackensack, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane E. 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