{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:01:56Z","timestamp":1791298916161,"version":"4.1.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"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":[[2012,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Gentamicin is commonly used in the management of neonatal infections. Development of adaptive resistance is typical for aminoglycosides and reduces the antibacterial effect. There is, however, a lack of understanding of how this phenomenon influences the effect of different dosing schedules. The aim was to develop a pharmacokinetic-pharmacodynamic (PKPD) model that describes the time course of the bactericidal activity of gentamicin and its adaptive resistance and to investigate different dosing schedules in preterm and term newborn infants based on the developed model.\n            <jats:italic>In vitro<\/jats:italic>\n            time-kill curve experiments were conducted on a strain of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            (MIC of 2 mg\/liter). The gentamicin exposure was either constant (0.125 to 16 mg\/liter) or dynamic (simulated concentration-time profiles in a kinetic system with peak concentrations of 2.0, 3.9, 7.8, and 16 mg\/liter given as single doses or as repeated doses every 6, 12, or 24 h). Semimechanistic PKPD models were fitted to the bacterial counts in the NONMEM (nonlinear mixed effects modeling) program. A model with compartments for growing and resting bacteria, with a function allowing the maximal bacterial killing of gentamicin to reduce with exposure, characterized both the fast bactericidal effect and the adaptive resistance. Despite a lower peak concentration, preterm neonates were predicted to have a higher bacterial killing effect than term neonates for the same per-kg dose because of gentamicin's longer half-life. The model supported an extended dosing interval of gentamicin in preterm neonates, and for all neonates, dosing intervals of 36 to 48 h were as effective as a 24-h dosing interval for the same total dose.\n          <\/jats:p>","DOI":"10.1128\/aac.00694-11","type":"journal-article","created":{"date-parts":[[2011,10,29]],"date-time":"2011-10-29T03:20:13Z","timestamp":1319858413000},"page":"179-188","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":85,"title":["Pharmacokinetic-Pharmacodynamic Model for Gentamicin and Its Adaptive Resistance with Predictions of Dosing Schedules in Newborn Infants"],"prefix":"10.1128","volume":"56","author":[{"given":"Ami F.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"},{"name":"Institute for Medical Research, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet I.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"},{"name":"Hospital Pharmacy, University Hospital, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Cars","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena E.","family":"Friberg","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ejps.2006.05.014","article-title":"Application of a combined effect compartment and binding model for gastric acid inhibition of AR-HO47108: a potassium competitive acid blocker, and its active metabolite AR-HO47116 in the dog","volume":"29","author":"Abelo A","year":"2006","unstructured":"AbeloA AnderssonM HolmbergAA KarlssonMO. 2006. Application of a combined effect compartment and binding model for gastric acid inhibition of AR-HO47108: a potassium competitive acid blocker, and its active metabolite AR-HO47116 in the dog. Eur. J. Pharm. Sci. 29:91\u2013101.","journal-title":"Eur. J. Pharm. Sci"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-008-9094-4"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"713","DOI":"10.2165\/00003495-200161060-00001","article-title":"Aminoglycoside adaptive resistance: importance for effective dosage regimens","volume":"61","author":"Barclay ML","year":"2001","unstructured":"BarclayML BeggEJ. 2001. Aminoglycoside adaptive resistance: importance for effective dosage regimens. 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