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Bone, subcutaneous tissue and plasma pharmacokinetics of cefuroxime in total knee replacement patients - a randomized controlled trial comparing continuous and short-term infusion.
APMIS ( IF 2.8 ) Pub Date : 2019-10-14 , DOI: 10.1111/apm.12996
Mikkel Tøttrup 1, 2, 3 , Kjeld Søballe 2, 4 , Bo M Bibby 5 , Tore F Hardlei 6 , Peter Hansen 1 , Kurt Fuursted 7 , Hanne Birke-Sørensen 2 , Mats Bue 1, 2
Affiliation  

Cefuroxime is widely used as antibiotic prophylaxis for orthopaedic procedures. We evaluated bone, subcutaneous tissue (SCT) and plasma pharmacokinetics of cefuroxime in male patients undergoing total knee replacement (TKR) after both traditional short-term infusion (STI) and continuous infusion (CI). Eighteen male patients undergoing TKR were randomly assigned to STI or CI of 1.5 g of cefuroxime. Measurements were obtained in plasma, SCT, cancellous and cortical bone every 30 min for 8 h following surgery. For sampling in solid tissues, microdialysis was applied. Population pharmacokinetic modelling was performed in order to estimate pharmacokinetic parameters, and to assess the probability of attaining cefuroxime concentrations above clinically relevant minimal inhibitory concentrations (MICs) for 65% and 90% of the 8 h dosing interval. Low SCT and cortical bone penetration were found in both the STI and the CI group, but the findings were only significant in the STI group. Irrespective of MIC, tissue and target, CI leads to improved probability of attaining relevant pharmacokinetic targets compared with STI. For the Staphylococcus aureus MIC breakpoint (4 μg/mL), STI leads to inadequate probability of target attainment. CI of 1.5 g of cefuroxime leads to improved probability of attaining relevant pharmacokinetic targets in male TKR patients compared with traditional STI. These findings suggest that application of CI may improve antibiotic prophylaxis for male TKR patients.

中文翻译:

头孢呋辛在全膝关节置换患者中的骨,皮下组织和血浆药代动力学-比较连续和短期输注的随机对照试验。

头孢呋辛被广泛用作骨科手术的抗生素预防措施。我们评估了传统短期输注(STI)和连续输注(CI)后接受全膝关节置换(TKR)的男性患者中头孢呋辛的骨,皮下组织(SCT)和血浆药代动力学。将18名接受TKR的男性患者随机分配至1.5 g头孢呋辛的STI或CI。术后8 h每30分钟对血浆,SCT,松质骨和皮质骨进行测量。为了在实体组织中取样,应用了微透析。进行群体药代动力学建模是为了评估药代动力学参数,并评估在8小时给药间隔的65%和90%时达到头孢呋辛浓度高于临床相关最小抑制浓度(MIC)的可能性。在STI和CI组中均发现SCT和皮质骨渗透率低,但仅在STI组中发现。与STI相比,无论MIC,组织和靶标如何,CI均可提高获得相关药代动力学靶标的可能性。对于金黄色葡萄球菌的MIC断裂点(4μg/ mL),STI导致靶标达成的可能性不足。与传统的STI相比,CI含量为1.5 g的头孢呋辛引起男性TKR患者达到相关药代动力学指标的可能性更高。这些发现表明,CI的使用可以改善男性TKR患者的抗生素预防。与STI相比,CI可提高达到相关药代动力学指标的可能性。对于金黄色葡萄球菌的MIC断裂点(4μg/ mL),STI导致靶标达成的可能性不足。与传统的STI相比,CI含量为1.5 g的头孢呋辛引起男性TKR患者达到相关药代动力学指标的可能性更高。这些发现表明,CI的使用可以改善男性TKR患者的抗生素预防。与STI相比,CI可提高达到相关药代动力学指标的可能性。对于金黄色葡萄球菌的MIC断裂点(4μg/ mL),STI导致靶标达成的可能性不足。与传统的STI相比,CI含量为1.5 g的头孢呋辛引起男性TKR患者达到相关药代动力学指标的可能性更高。这些发现表明,CI的使用可以改善男性TKR患者的抗生素预防。
更新日期:2019-11-01
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