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基于替考拉宁的抗菌疗法治疗金黄色葡萄球菌骨与关节感染:耐受性、疗效及皮下给药经验

Teicoplanin-based antimicrobial therapy in Staphylococcus aureus bone and joint infection: tolerance, efficacy and experience with subcutaneous administration.

作者信息

Peeters Olivier, Ferry Tristan, Ader Florence, Boibieux André, Braun Evelyne, Bouaziz Anissa, Karsenty Judith, Forestier Emmanuel, Laurent Frédéric, Lustig Sébastien, Chidiac Christian, Valour Florent

机构信息

Regional Referral Center for Bone and Joint Infection, Hospices Civils de Lyon, Lyon, France.

Infectious Disease Department, Hospices Civils de Lyon, Groupement Hospitalier Nord, 103 Grande Rue de la Croix-Rousse, 69004, Lyon, France.

出版信息

BMC Infect Dis. 2016 Nov 3;16(1):622. doi: 10.1186/s12879-016-1955-7.

Abstract

BACKGROUND

Staphylococci represent the first etiologic agents of bone and joint infection (BJI), leading glycopeptides use, especially in case of methicillin-resistance or betalactam intolerance. Teicoplanin may represent an alternative to vancomycin because of its acceptable bone penetration and possible subcutaneous administration.

METHODS

Adults receiving teicoplanin for S. aureus BJI were included in a retrospective cohort study investigating intravenous or subcutaneous teicoplanin safety and pharmacokinetics.

RESULTS

Sixty-five S. aureus BJIs (orthopedic device-related infections, 69 %; methicillin-resistance, 17 %) were treated by teicoplanin at the initial dose of 5.7 mg/kg/day (IQR, 4.7-6.5) after a loading dose of 5 injections 12 h apart. The first trough teicoplanin level (C) reached the therapeutic target (15 mg/L) in 26 % of patients, only. An overdose (C >25 mg/L) was observed in 16 % patients, 50 % of which had chronic renal failure (p = 0.049). Seven adverse events occurred in 6 patients (10 %); no predictive factor could be highlighted. After a 91-week follow-up (IQR, 51-183), 27 treatment failures were observed (42 %), associated with diabetes (OR, 5.1; p = 0.057), systemic inflammatory disease (OR, 5.6; p = 0.043), and abscess (OR, 4.1; p < 10). A normal CRP-value at 1 month was protective (OR, 0.2; p = 0.029). Subcutaneous administration (n = 14) showed no difference in pharmacokinetics and tolerance compared to the intravenous route.

CONCLUSIONS

Teicoplanin constitutes a well-tolerated therapeutic alternative in S. aureus BJI, with a possible subcutaneous administration in outpatients. The loading dose might be increase to 9-12 mg/kg to quickly reach the therapeutic target, but tolerance of such higher doses remains to be evaluated, especially if using the subcutaneous route.

摘要

背景

葡萄球菌是骨与关节感染(BJI)的首要病原体,导致糖肽类药物的使用,尤其是在耐甲氧西林或不耐β-内酰胺的情况下。替考拉宁因其可接受的骨穿透性和可能的皮下给药方式,可能成为万古霉素的替代药物。

方法

接受替考拉宁治疗金黄色葡萄球菌BJI的成年人纳入一项回顾性队列研究,调查静脉或皮下注射替考拉宁的安全性和药代动力学。

结果

65例金黄色葡萄球菌BJI(骨科器械相关感染占69%;耐甲氧西林占17%),在间隔12小时注射5次负荷剂量后,初始剂量为5.7mg/kg/天(四分位数间距,4.7 - 6.5)的替考拉宁进行治疗。仅26%的患者首次替考拉宁谷浓度(C)达到治疗目标(15mg/L)。16%的患者出现药物过量(C>25mg/L),其中50%患有慢性肾衰竭(p = 0.049)。6例患者(10%)发生7起不良事件;未发现预测因素。经过91周的随访(四分位数间距,51 - 183),观察到27例治疗失败(42%),与糖尿病(比值比,5.1;p = 0.057)、全身性炎症疾病(比值比,5.6;p = 0.043)和脓肿(比值比,4.1;p<0.10)相关。1个月时CRP值正常具有保护作用(比值比,0.2;p = 0.029)。与静脉途径相比,皮下给药(n = 14)在药代动力学和耐受性方面无差异。

结论

替考拉宁是金黄色葡萄球菌BJI中耐受性良好的治疗选择,门诊患者可能可行皮下给药。负荷剂量可增至9 - 12mg/kg以快速达到治疗目标,但如此高剂量的耐受性仍有待评估,尤其是采用皮下途径时。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57bb/5093939/a31e6ef21981/12879_2016_1955_Fig1_HTML.jpg

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