Vancomycin exposure from active calcium sulfate bone filler
Détails
ID Serval
serval:BIB_CDC4660C6308
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Institution
Titre
Vancomycin exposure from active calcium sulfate bone filler
Titre de la conférence
80. Jahrestagung der Schweizerischen Gesellschaft für Allgemeine Innere Medizin
Adresse
Basel, Schweiz, 23-25. Mai 2012
ISBN
1424-4985
ISSN-L
1424-4977
Statut éditorial
Publié
Date de publication
2012
Volume
19
Série
Swiss Medical Forum = Forum Médical Suisse
Pages
112S
Langue
anglais
Résumé
Objective: Bone cements and substitutes are commonly used in surgery to deliver antibiotics locally. The objective of this study was to assess the systemic absorption and disposition of vancomycin in patients treated with active calcium sulfate bone filler and to predict systemic concentrations under various conditions.
Method: 277 blood samples were taken from 42 patients receiving vancomycin in bone cement during surgery. Blood samples were collected from 3h to 10 days after implantation. Vancomycin was measured by immunoenzymatic assay. Population pharmacokinetic (PK) analysis was performed using NONMEM to assess average estimates and variability of PK parameters. Based on the final model, simulations with various doses and renal function levels were performed.
Results: The patients were 64 ± 20 years old, their body weight was 81 ± 22 kg and Cockcroft-Gault creatinine clearance (CLcr) 98 ± 55 mL/min. Vancomycin doses ranged from 200 mg to 6000 mg and implantation sites were hip (n=16), tibia (10) or others (16). Concentration profiles remained low and consistent with absorption rate-limited first-order release, while showing prominent variability. Mean clearance (CL) was 3.87 L/h (CV 35%), absorption rate constant (ka) 0.004 h-1 (66%) and volume of distribution (V) 9.5 L. Simulations with up to 8000 mg vancomycin implant showed systemic concentrations exceeding 20 mg/L for 3.5 days in 43% of the patients with CLcr 15 mL/min, whereas 7% of the patients with normal renal function had a concentration above 20 mg/L for 1.1 days. Subtherapeutic concentrations (0.4-4 mg/L) were predicted during a median of 22 days in patients with normal renal function and 4000 mg vancomycin implant, with limited influence of dose or renal function.
Conclusion: Vancomycin-laden calcium sulfate implant does not raise toxicity concern. Selection of resistant bacteria, such as Enterococcus and Staphylococcus species, might however be a concern, as simulations show persistent subtherapeutic systemic concentrations during 3 to 4 weeks in these patients.
Method: 277 blood samples were taken from 42 patients receiving vancomycin in bone cement during surgery. Blood samples were collected from 3h to 10 days after implantation. Vancomycin was measured by immunoenzymatic assay. Population pharmacokinetic (PK) analysis was performed using NONMEM to assess average estimates and variability of PK parameters. Based on the final model, simulations with various doses and renal function levels were performed.
Results: The patients were 64 ± 20 years old, their body weight was 81 ± 22 kg and Cockcroft-Gault creatinine clearance (CLcr) 98 ± 55 mL/min. Vancomycin doses ranged from 200 mg to 6000 mg and implantation sites were hip (n=16), tibia (10) or others (16). Concentration profiles remained low and consistent with absorption rate-limited first-order release, while showing prominent variability. Mean clearance (CL) was 3.87 L/h (CV 35%), absorption rate constant (ka) 0.004 h-1 (66%) and volume of distribution (V) 9.5 L. Simulations with up to 8000 mg vancomycin implant showed systemic concentrations exceeding 20 mg/L for 3.5 days in 43% of the patients with CLcr 15 mL/min, whereas 7% of the patients with normal renal function had a concentration above 20 mg/L for 1.1 days. Subtherapeutic concentrations (0.4-4 mg/L) were predicted during a median of 22 days in patients with normal renal function and 4000 mg vancomycin implant, with limited influence of dose or renal function.
Conclusion: Vancomycin-laden calcium sulfate implant does not raise toxicity concern. Selection of resistant bacteria, such as Enterococcus and Staphylococcus species, might however be a concern, as simulations show persistent subtherapeutic systemic concentrations during 3 to 4 weeks in these patients.
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Création de la notice
17/02/2014 13:20
Dernière modification de la notice
20/08/2019 15:48
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