Impact of Key Components of Intensified Ceftaroline Dosing on Pharmacokinetic/Pharmacodynamic Target Attainment
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| Titel: | Impact of Key Components of Intensified Ceftaroline Dosing on Pharmacokinetic/Pharmacodynamic Target Attainment |
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| Autoren: | Iris K. Minichmayr, Sebastian G. Wicha, Peter Matzneller, Charlotte Kloft, Markus Zeitlinger |
| Quelle: | Clin Pharmacokinet |
| Verlagsinformationen: | Springer Science and Business Media LLC, 2023. |
| Publikationsjahr: | 2023 |
| Schlagwörter: | Staphylococcus aureus [MeSH], Anti-Bacterial Agents [MeSH], Humans [MeSH], Cephalosporins/pharmacology [MeSH], Ceftaroline [MeSH], Original Research Article, Microbial Sensitivity Tests [MeSH], Staphylococcus aureus, Ceftaroline, Pharmacokinetic/Pharmacodynamic Target Attainment, Humans, Microbial Sensitivity Tests, Ceftaroline Dosing, Evaluation, 3. Good health, Anti-Bacterial Agents, Cephalosporins |
| Beschreibung: | Ceftaroline fosamil is a β-lactam antibiotic approved as a 600 mg twice daily dose (≤1 h infusion, 'standard dosing') or a 600 mg thrice daily dose (2 h infusion) to treat complicated skin and soft tissue infections caused by Staphylococcus aureus (minimum inhibitory concentration [MIC] 2-4 mg/L). We sought to systematically evaluate the relative impact of the three key components of the intensified dosing regimen (i.e. shortened dosing interval, prolonged infusion duration and increased total daily dose [TDD]) on the pharmacokinetic/pharmacodynamic (PK/PD) target attainment given different grades of bacterial susceptibility.A population PK model was developed using data from 12 healthy volunteers (EudraCT-2012-005134-11) receiving standard or intensified dosing. PK/PD target attainment (ƒT>MIC = 35% and 100%) after 24 h was compared following systematically varied combinations of the (1) dosing interval (every 12 h [q12h]→ every 8 h [q8h]); (2) infusion duration (1 h→2 h); and (3) individual and total daily dose (400→900 mg, i.e. TDD 1200→1800 mg), as well as for varying susceptibility of S. aureus (MIC 0.032-8 mg/L).A two-compartment model with linear elimination adequately described ceftaroline concentrations (n = 274). The relevance of the dosing components dosing interval/infusion duration/TDD for ƒT>MIC systematically changed with pathogen susceptibility. For susceptible pathogens with MIC ≤1 mg/L, shortened dosing intervals appeared as the main driver of the improved target attainment associated with the intensified dosing regimen, followed by increased TDD and infusion duration. For less susceptible pathogens, the advantage of q8h dosing and 2 h infusions declined, and increased TDD improved ƒT>MIC the most.The analysis calls to mind consideration of dose increases when prolonging the infusion duration in the case of low bacterial susceptibility. |
| Publikationsart: | Article Other literature type |
| Sprache: | English |
| ISSN: | 1179-1926 0312-5963 |
| DOI: | 10.1007/s40262-023-01325-4 |
| DOI: | 10.17169/refubium-41840 |
| Zugangs-URL: | https://pubmed.ncbi.nlm.nih.gov/38007714 https://repository.publisso.de/resource/frl:6491154 https://refubium.fu-berlin.de/handle/fub188/42115 https://doi.org/10.17169/refubium-41840 https://doi.org/10.1007/s40262-023-01325-4 |
| Rights: | CC BY NC CC BY URL: http://creativecommons.org/licenses/by-nc/4.0/Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (http://creativecommons.org/licenses/by-nc/4.0/) . |
| Dokumentencode: | edsair.doi.dedup.....73aab8436619db8c8fbb03442292802e |
| Datenbank: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | Ceftaroline fosamil is a β-lactam antibiotic approved as a 600 mg twice daily dose (≤1 h infusion, 'standard dosing') or a 600 mg thrice daily dose (2 h infusion) to treat complicated skin and soft tissue infections caused by Staphylococcus aureus (minimum inhibitory concentration [MIC] 2-4 mg/L). We sought to systematically evaluate the relative impact of the three key components of the intensified dosing regimen (i.e. shortened dosing interval, prolonged infusion duration and increased total daily dose [TDD]) on the pharmacokinetic/pharmacodynamic (PK/PD) target attainment given different grades of bacterial susceptibility.A population PK model was developed using data from 12 healthy volunteers (EudraCT-2012-005134-11) receiving standard or intensified dosing. PK/PD target attainment (ƒT>MIC = 35% and 100%) after 24 h was compared following systematically varied combinations of the (1) dosing interval (every 12 h [q12h]→ every 8 h [q8h]); (2) infusion duration (1 h→2 h); and (3) individual and total daily dose (400→900 mg, i.e. TDD 1200→1800 mg), as well as for varying susceptibility of S. aureus (MIC 0.032-8 mg/L).A two-compartment model with linear elimination adequately described ceftaroline concentrations (n = 274). The relevance of the dosing components dosing interval/infusion duration/TDD for ƒT>MIC systematically changed with pathogen susceptibility. For susceptible pathogens with MIC ≤1 mg/L, shortened dosing intervals appeared as the main driver of the improved target attainment associated with the intensified dosing regimen, followed by increased TDD and infusion duration. For less susceptible pathogens, the advantage of q8h dosing and 2 h infusions declined, and increased TDD improved ƒT>MIC the most.The analysis calls to mind consideration of dose increases when prolonging the infusion duration in the case of low bacterial susceptibility. |
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| ISSN: | 11791926 03125963 |
| DOI: | 10.1007/s40262-023-01325-4 |