Carleigh Duke,Suzanne L Parker,Betty B Zam,Fabian Chiong,Cherian Sajiv,Basant Pawar,Aadith Ashok,Brynley P Cooper,Steven Y C Tong,Sonja Janson,Steven C Wallis,Jason A Roberts,Danny Tsai
{"title":"需要间歇性高通量血液透析的住院感染患者体内非结合型头孢唑啉的群体药代动力学:每周三次的透析后给药方案能否提供最佳治疗?","authors":"Carleigh Duke,Suzanne L Parker,Betty B Zam,Fabian Chiong,Cherian Sajiv,Basant Pawar,Aadith Ashok,Brynley P Cooper,Steven Y C Tong,Sonja Janson,Steven C Wallis,Jason A Roberts,Danny Tsai","doi":"10.1093/jac/dkae318","DOIUrl":null,"url":null,"abstract":"OBJECTIVES\r\nTo describe the population pharmacokinetics of cefazolin in infected hospitalized patients requiring intermittent haemodialysis (IHD).\r\n\r\nMETHODS\r\nThis prospective population pharmacokinetic study was conducted in IHD patients prescribed cefazolin 2 g three times weekly. Plasma samples were collected at prespecified timepoints and assayed for total and unbound concentrations using validated LC. Pharmacokinetic modelling and dosing simulations were performed using Pmetrics®. PTA in plasma suitable for MSSA (unbound trough concentrations of ≥2 mg/L for the final 24 h of a 72 h interval) were simulated for different dosing regimens. A PTA of ≥95% was deemed acceptable.\r\n\r\nRESULTS\r\nA total of 260 cefazolin concentrations (130 total, 130 unbound) were collected from 16 patients (14 female) with a median age of 51 years. The median (IQR) pre-dialysis unbound cefazolin concentration for a 3 day dose interval trough was 17.7 (13.5-31.4) mg/L. The median (IQR) unbound fraction was 0.38 (0.32-0.46). The lowest pre-dialysis unbound concentration was 9.1 mg/L. A two-compartment model with a complex protein-binding component adequately described the data. The mean unbound cefazolin CL during IHD was 16.4 ± 4.26 L/h, compared with 0.40 ± 0.19 L/h when dialysis was off. Duration of time on haemodialysis (TOH) was the only covariate supported in the final model. The 2 g three-times-weekly regimen was associated with a PTA of 99.7% on dosing simulations to maintain unbound concentrations of ≥2 mg/L with TOH of 6 months. The 1 g three-times-weekly post-dialysis was associated with a PTA of 95.4%.\r\n\r\nCONCLUSIONS\r\nA 2 g three-times-weekly post-dialysis cefazolin regimen is supported for MSSA infections.","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"7 1","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Population pharmacokinetics of unbound cefazolin in infected hospitalized patients requiring intermittent high-flux haemodialysis: can a three-times-weekly post-dialysis dosing regimen provide optimal treatment?\",\"authors\":\"Carleigh Duke,Suzanne L Parker,Betty B Zam,Fabian Chiong,Cherian Sajiv,Basant Pawar,Aadith Ashok,Brynley P Cooper,Steven Y C Tong,Sonja Janson,Steven C Wallis,Jason A Roberts,Danny Tsai\",\"doi\":\"10.1093/jac/dkae318\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"OBJECTIVES\\r\\nTo describe the population pharmacokinetics of cefazolin in infected hospitalized patients requiring intermittent haemodialysis (IHD).\\r\\n\\r\\nMETHODS\\r\\nThis prospective population pharmacokinetic study was conducted in IHD patients prescribed cefazolin 2 g three times weekly. Plasma samples were collected at prespecified timepoints and assayed for total and unbound concentrations using validated LC. Pharmacokinetic modelling and dosing simulations were performed using Pmetrics®. PTA in plasma suitable for MSSA (unbound trough concentrations of ≥2 mg/L for the final 24 h of a 72 h interval) were simulated for different dosing regimens. A PTA of ≥95% was deemed acceptable.\\r\\n\\r\\nRESULTS\\r\\nA total of 260 cefazolin concentrations (130 total, 130 unbound) were collected from 16 patients (14 female) with a median age of 51 years. The median (IQR) pre-dialysis unbound cefazolin concentration for a 3 day dose interval trough was 17.7 (13.5-31.4) mg/L. The median (IQR) unbound fraction was 0.38 (0.32-0.46). The lowest pre-dialysis unbound concentration was 9.1 mg/L. A two-compartment model with a complex protein-binding component adequately described the data. The mean unbound cefazolin CL during IHD was 16.4 ± 4.26 L/h, compared with 0.40 ± 0.19 L/h when dialysis was off. Duration of time on haemodialysis (TOH) was the only covariate supported in the final model. The 2 g three-times-weekly regimen was associated with a PTA of 99.7% on dosing simulations to maintain unbound concentrations of ≥2 mg/L with TOH of 6 months. The 1 g three-times-weekly post-dialysis was associated with a PTA of 95.4%.\\r\\n\\r\\nCONCLUSIONS\\r\\nA 2 g three-times-weekly post-dialysis cefazolin regimen is supported for MSSA infections.\",\"PeriodicalId\":14969,\"journal\":{\"name\":\"Journal of Antimicrobial Chemotherapy\",\"volume\":\"7 1\",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Antimicrobial Chemotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/jac/dkae318\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Antimicrobial Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jac/dkae318","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Population pharmacokinetics of unbound cefazolin in infected hospitalized patients requiring intermittent high-flux haemodialysis: can a three-times-weekly post-dialysis dosing regimen provide optimal treatment?
OBJECTIVES
To describe the population pharmacokinetics of cefazolin in infected hospitalized patients requiring intermittent haemodialysis (IHD).
METHODS
This prospective population pharmacokinetic study was conducted in IHD patients prescribed cefazolin 2 g three times weekly. Plasma samples were collected at prespecified timepoints and assayed for total and unbound concentrations using validated LC. Pharmacokinetic modelling and dosing simulations were performed using Pmetrics®. PTA in plasma suitable for MSSA (unbound trough concentrations of ≥2 mg/L for the final 24 h of a 72 h interval) were simulated for different dosing regimens. A PTA of ≥95% was deemed acceptable.
RESULTS
A total of 260 cefazolin concentrations (130 total, 130 unbound) were collected from 16 patients (14 female) with a median age of 51 years. The median (IQR) pre-dialysis unbound cefazolin concentration for a 3 day dose interval trough was 17.7 (13.5-31.4) mg/L. The median (IQR) unbound fraction was 0.38 (0.32-0.46). The lowest pre-dialysis unbound concentration was 9.1 mg/L. A two-compartment model with a complex protein-binding component adequately described the data. The mean unbound cefazolin CL during IHD was 16.4 ± 4.26 L/h, compared with 0.40 ± 0.19 L/h when dialysis was off. Duration of time on haemodialysis (TOH) was the only covariate supported in the final model. The 2 g three-times-weekly regimen was associated with a PTA of 99.7% on dosing simulations to maintain unbound concentrations of ≥2 mg/L with TOH of 6 months. The 1 g three-times-weekly post-dialysis was associated with a PTA of 95.4%.
CONCLUSIONS
A 2 g three-times-weekly post-dialysis cefazolin regimen is supported for MSSA infections.
期刊介绍:
The Journal publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents. The Journal publishes primarily in human medicine, and articles in veterinary medicine likely to have an impact on global health.