Population pharmacokinetics of continuous-infusion ceftazidime in febrile neutropenic children undergoing HSCT: implications for target attainment for empirical treatment against Pseudomonas aeruginosa
| العنوان: | Population pharmacokinetics of continuous-infusion ceftazidime in febrile neutropenic children undergoing HSCT: implications for target attainment for empirical treatment against Pseudomonas aeruginosa |
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| المؤلفون: | Giulia Schillani, Piergiorgio Cojutti, Natalia Maximova, Federico Pea, William W. Hope |
| المساهمون: | Cojutti, Pier Giorgio, Maximova, Natalia, Schillani, Giulia, Hope, William, Pea, Federico |
| المصدر: | JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY |
| بيانات النشر: | Oxford University Press (OUP), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Ceftazidime, Kidney Function Tests, Gastroenterology, 0302 clinical medicine, Pharmacology (medical), Infusions, Intravenou, 030212 general & internal medicine, Child, Infusions, Intravenous, Original Research, Body surface area, education.field_of_study, medicine.diagnostic_test, Microbial Sensitivity Test, Hematopoietic Stem Cell Transplantation, Anti-Bacterial Agents, surgical procedures, operative, Treatment Outcome, Infectious Diseases, Pseudomonas aeruginosa, Female, Drug Monitoring, Monte Carlo Method, Human, medicine.drug, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Population, Microbial Sensitivity Tests, Neutropenia, Pseudomonas Infection, 03 medical and health sciences, Pharmacokinetics, Internal medicine, Anti-Bacterial Agent, medicine, Humans, Pseudomonas Infections, education, Febrile Neutropenia, Pharmacology, Kidney Function Test, business.industry, medicine.disease, Therapeutic drug monitoring, Pharmacodynamics, business, Febrile neutropenia |
| الوصف: | OBJECTIVES: To conduct a population pharmacokinetic analysis of continuous-infusion ceftazidime in a retrospective cohort of paediatric HSCT patients who were empirically treated for febrile neutropenia (FN) and who underwent therapeutic drug monitoring of ceftazidime steady-state plasma concentrations (C(ss)) for optimization of drug exposure. METHODS: A non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations were performed to calculate the PTA of the pharmacodynamic determinant of efficacy (C(ss)/MIC ≥4) against Pseudomonas aeruginosa with continuous-infusion ceftazidime dosages of 1–6 g daily. The C(ss) safety threshold was arbitrarily placed at 100 mg/L and advisable dosages were used. RESULTS: A total of 46 patients with 70 ceftazidime C(ss) values were included. Estimated glomerular filtration rate (eGFR) and body surface area were the covariates associated with drug clearance. At the EUCAST clinical breakpoint of 8 mg/L, simulations showed that continuous-infusion ceftazidime dosages of 4–6 g daily attained optimal PTAs (>90%) across most of 16 different clinical scenarios based on four classes of eGFR (50–145, 145.1–200, 200.1–286 and 286.1–422 mL/min/1.73 m(2)) and body surface area (0.30–0.64, 0.65–0.88, 0.89–1.34 and 1.35–1.84 m(2)). In patients with body surface area 0.30–0.64 m(2) and eGFR ≤200 mL/min/1.73 m(2) the advisable dose of 3 g daily allowed only suboptimal PTAs (87%. CONCLUSIONS: Continuous-infusion ceftazidime dosages ranging from 3 to 6 g daily according to different classes of eGFR and body surface area may allow optimized empirical treatment of P. aeruginosa infections in paediatric HSCT patients with FN. |
| وصف الملف: | application/pdf; ELETTRONICO |
| تدمد: | 1460-2091 0305-7453 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07e2fdb313ce89578c4c6fabee9cd4b9 https://doi.org/10.1093/jac/dkz065 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....07e2fdb313ce89578c4c6fabee9cd4b9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602091 03057453 |
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