Pharmacokinetics and penetration of linezolid into inflamed soft tissue in diabetic foot infections

Objective  Physiological changes and local and systemic inflammation may affect plasma and tissue pharmacokinetics of antimicrobial agents in diabetics. The aim of the study was to investigate the penetration of linezolid into inflamed areas of infected diabetic foot wounds and the pharmacokinetics in the risk population of diabetics. Methods  Pharmacokinetics and tissue penetration of linezolid into inflamed diabetic foot infection (DFI) tissue were determined at steady state in 15 patients with diabetes type 2 and DFI following administration of multiple oral doses of 600 mg given every 12 h. Second debridement was performed on days 4–6, 3 h after linezolid administration. Linezolid concentrations were determined in perinecrotic wound tissue of inflamed diabetic foot by high-performance liquid chromatography (HPLC). Results  A mean maximum plasma concentration (C_max) in plasma of 14.3 mg/L was attained at a median of 2.0 h [time to reach C_max (T_max) range 0.5–6.0 h). Area under the concentration time curve from zero to 12 h (AUC_0–12 h) with a mean of 114.1 mg∙h/L and C_min of 5.4 mg/L were achieved in patients with diabetes mellitus type 2. Penetration of linezolid into inflamed areas of DFI with tissue/plasma ratios of mean 101.7% [95% confidence interval (CI) 56; 148%] produced a mean concentration of 9.6 μg/g (95% CI 7.4; 11.8 μg/g) greater than those predicted to be effective against methicillin-resistant staphylococci [minimum concentration that inhibits 90% of organisms (MIC₉₀) of 4 mg/L]. Tissue/plasma ratios correlated positive with systemic inflammation. Conclusion  Plasma pharmacokinetics of linezolid in diabetics and adequate levels in inflamed areas of diabetic foot wound suggest that an oral dose of 600 mg bd of linezolid provides effective concentrations for treating methicillin-resistant Staphylococcus aureus (MRSA) in DFI. Presented in part at the 41th Annual Meeting of the European Association for Study of Diabetes, September 2005 in Athens, Greece, and at the 7th Annual Congress of the German Clinical Pharmacology, November 2005 in Dresden, Germany     

In vitro activity of new fluoroquinolones and linezolid against non-tuberculous mycobacteria

The objective of the study was to determine the activity of new fluoroquinolones and linezolid against 108 clinical isolates of different species of non-tuberculous mycobacteria isolated in Spain. Gatifloxacin and moxifloxacin were found to be more effective than levofloxacin. Mycobacterium kansasii was more susceptible to the fluoroquinolones tested than M. avium complex and M. fortuitum was more susceptible than M. chelonae. Linezolid was more active against M. kansasii than against M. avium complex. A better understanding of the relationship between the in vitro activity of these compounds and their usefulness in the treatment of these infections is needed. The new fluoroquinolones exhibit good activity against M. kansasii and M. fortuitum and linezolid is active against M. kansasii.     

利奈唑胺在大鼠血、脑组织和脑脊液中的药代动力学研究

目的 探讨利奈唑胺在大鼠血、脑组织和脑脊液中药代动力学特性,为临床治疗中枢神经系统感染提供参考.方法 78只清洁型SD大鼠,尾静脉单次注射利奈唑胺54 mg/kg后,采用高效液相色谱法测定大鼠不同时间点的血、脑组织和脑脊液中利奈唑胺的药物浓度,计算其药代动力学参数.结果 注射后0～19h,利奈唑胺在大鼠的血、脑组织和脑脊液的峰浓度（Cmax）分别为31.39、5.11、23.97 μg/ml;消除半衰期（t1/2）分别为2.67、2.42、1.99 h;药物浓度-时间曲线下面积（AUC 0～∞）分别为134.55、28.23、136.43 h·μg/ml,血脑屏障穿透率为76.36％.结论 利奈唑胺能很好地进入脑脊液达到有效的抑菌浓度,具有良好的药代动力学特征和组织穿透性.     

强化期利奈唑胺替代乙胺丁醇治疗药物敏感肺结核的临床效果观察

目的 探讨在抗结核标准治疗方案中使用利奈唑胺代替乙胺丁醇方案治疗药物敏感肺结核的效果.方法 将2018年1月—2020年7月在盘锦市传染病医院就诊的43例药物敏感肺结核患者随机分为对照组和利奈唑胺组.对照组给予标准抗结核方案治疗.利奈唑胺组使用利奈唑胺替代标准抗结核治疗方案中的乙胺丁醇进行治疗.比较两组的治疗效果、治疗...     

利奈唑胺、万古霉素对甲氧西林耐药的金黄色葡萄球菌的防耐药突变体选择浓度的研究

目的：比较利奈唑胺、万古霉素对耐甲氧西林金黄色葡萄球菌的防耐药突变选择能力;研究防耐药突变体选择浓度（MPC）和最低抑菌浓度（MIC）的相关性。方法：采用琼脂微量稀释法测定利奈唑胺、万古霉素对35株耐甲氧西林金黄色葡萄球菌（MRSA）临床分离菌株的MPC和MIC;采用线性回归法比较利奈唑胺、万古霉素对MRSA的MPC和MIC的相关性;结合人体药代动力学数据,预测利夺唑胺、万古霉素对MRSA的防耐药突变体选择能力。结果：利奈唑胺、万古霉素对35株MRSA的MPC90值（抑制90％的细菌发生细菌耐药的最低防耐药突变体选择浓度）分别为16.8μg／mL,选择指数（MPC90／MIC90）均为8。两药对MRSA的MPC和MIC的线性相关系数R^2分别为0．32和0．008。结合两药药代动力学参数,利奈唑胺药物浓度在整个给药间隔落在耐药突变选择窗理论（MSW）中,万古霉素药物浓度在大部分给药间隔落在MPC之上。结论：万古霉素对MRSA的防耐药选择能力强于利奈唑胺;MPC和MIC的相关性差。     

对1例骨折截肢术后老年患者使用利奈唑胺的药物监测

1例70a女性患者,因右股骨远端骨折合并双下肢动脉硬化闭塞症、高血压、类风湿性关节炎入院。入院后由于右足感染不能控制,行右大腿上段截肢术。术后合并血流感染和肺内感染,根据细菌培养结果,给予利奈唑胺600mg,q12h,ivgtt。3d后患者出现转氨酶ALT、AST分别升高至163IU·L-1、541IU·L-1,白细胞和血小板减少,遂将利奈唑胺剂量调整为400mg,q12h,ivgtt,后转氨酶恢复正常。停药后,白细胞和血小板恢复正常。     

静脉滴注利奈唑胺致白细胞及中性粒细胞减少1例

1例57a女性患者,既往患慢性肾功能衰竭,行持续不卧床腹膜透析治疗。因急性腹膜炎静脉滴注利奈唑胺0.6g,bid。用药2d后,出现白细胞及中性粒细胞减少,WBC2.43×109·L-1,N0。立即停药,给予粒细胞集落刺激因子100μg对症治疗。2d后复查血常规WBC9.10×109·L-1,N41.6%。之后换用其他抗菌药物,未出现白细胞及中性粒细胞减少。     

A consensus statement on empiric therapy for suspected gram-positive infections in surgical patients

BACKGROUND: Multidrug resistance among gram-positive pathogens in tertiary and other care centers is common. A systematic decision pathway to help select empiric antibiotic therapy for suspected gram-positive postsurgical infections is presented. DATA SOURCES: A Medline search with regard to empiric antibiotic therapy was performed and assessed by the 15-member expert panel. Two separate panel meetings were convened and followed by a writing, editorial, and review process. CONCLUSIONS: The main goal of empiric treatment in postsurgical patients with suspected gram-positive infections is to improve clinical status. Empiric therapy should be initiated at the earliest sign of infection in all critically ill patients. The choice of therapy should flow from beta-lactams to vancomycin to parenteral linezolid or quinupristin-dalfopristin. In patients likely to be discharged, oral linezolid is an option. Antibiotic resistance is an important issue, and in developing treatment algorithms for reduction of resistance, the utility of these new antibiotics may be extended and reduce morbidity and mortality.     

In vitro activity of moxifloxacin,levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosis

The in vitro activity of moxifloxacin, gatifloxacin, levofloxacin and linezolid was evaluated against 234 strains of Mycobacterium tuberculosis isolated in the Southeast of Spain. All drugs tested showed good activity, with an MIC₉₀ of less than 1 mg/l, and were active against isociacide and rifampicin resistant strains. Three strains were resistant to isoniazid and to the fluoroquinolones, which suggested the existence of mechanisms of resistance not yet described. These new compounds may prove to be therapeutic alternatives for treatment of multi-resistant tuberculosis and further studies should be done to demonstrate their true usefulness.     

Linezolid – ein neues Antibiotikum zur Behandlung von MRSA-Infektionen in der Unfallchirurgie? 2 Fallberichte

Problem: Infections with Methicillin-resistant Staphylococcus aureus are reported increasingly in intensive care unit and ward, that means not only a dangerous disease but also a considerable expenditure factor. Methods: In trauma surgery we could observe the Linezolid treatment of 2 patients with a MRSA infection. After treatment with Vancomycin and further evidence of MRSA the application of Linezolid was continued during 3 weeks accompanied by further microbiologic investigations. Results: In a 73 year old man with humerus shaft fracture the MRSA osteomyelitis was eradicated with Linezolid (600 mg/day per os over 3 weeks) after radical débridement and reosteosynthesis. The MRSA pneumonia in a 14 year old girl was treated successfully by Linezolid (600 mg/day i.v. over 3 weeks) and pneumotherapy. Follow up excluded further MRSA infection. Conclusions: Linezolid represents an efficient new reserve antibiotic. In case of pneumonia, severe skin and soft tissue infections good results can be expected. The treatment of osteomyelitis has been reported only in single cases.