河北省五市结核分枝杆菌耐药情况及耐多药菌株对利奈唑胺的敏感性

目的了解河北省结核分枝杆菌耐药情况,以及耐多药结核分枝杆菌对利奈唑胺的敏感性,指导临床治疗耐多药结核病。方法收集河北省五市六所医院2016年1—12月974例结核病患者分离菌株及患者临床信息,检测结核分枝杆菌对抗结核药物异烟肼(INH)、利福平(RFP)、链霉素(SM)、乙胺丁醇(EMB)、氧氟沙星(OFX)、卡那霉素(KM)的敏感性,采用分层随机法选取100株耐多药结核分枝杆菌,检测其对利奈唑胺的敏感性。结果结核病初治患者的耐药率和耐多药率分别为26.6%(200/753)和13.5%(102/753),复治患者的耐药率和耐多药率分别为59.7%(132/221)和53.4(118/221),复治患者耐药率和耐多药率均高于初治患者(χ~2值分别为83.7、93.5,均P0.01)。一线抗结核药物INH、RFP、SM和EMB的耐药率分别为25.8%、23.7%、16.7%和7.1%;二线抗结核药物OFX和KM的耐药率为4.7%(37/782)和4.0%(31/782);耐多药结核分枝杆菌对利奈唑胺的敏感率为80.8%(59/73)。结论结核病复治患者耐药率和耐多药率高于初治患者,利奈唑胺体外对耐多药结核分枝杆菌具有良好的抗菌活性。     

Linezolid compared with vancomycin for the prevention of methicillin-resistant Staphylococcus aureus or Staphylococcus epidermidis vascular graft infection in rats: A randomized, controlled, experimental study

Background: Graft infections are severe complications of vascular surgery that may result in amputation or mortality. Staphylococci are the most frequent cause of vascular graft infections.Objective: In this study we assessed the prophylactic efficacy of linezolid in comparison with vancomycin in preventing prosthetic vascular graft infection due to methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE).Methods: This randomized, controlled, experimental study using healthy adult (aged >5 months) male Wistar rats was conducted in the research laboratory of the Pamukkale University, Denizli, Turkey. The study consisted of an uncontaminated control group and 3 groups for both staphylococcal strains: a contaminated group that did not receive any antibiotic prophylaxis; a contaminated group that received preoperative intraperitoneal (IP) prophylaxis with vancomycin; and a contaminated group that received preoperative IP prophylaxis with linezolid. All rats received a vascular Dacron graft placed inside a subcutaneous pocket created on the right side of the median line. Sterile saline solution (1 mL), to which MRSA or MRSE at a concentration of 2 × 10⁷ colony-forming units per milliliter had been added, was inoculated onto the graft surface using a tuberculin syringe to fill the pocket. The grafts were explanted 7 days after implantation and assessed by quantitative culture.Results: Seventy rats (mean [SD]weight, 323.7 [17.9]g; mean [SD]age, 5.98 [0.64] months) were evenly divided between the 7 groups. Statistical analysis of the quantitative graft culture suggested that both vancomycin and linezolid were effective in significantly inhibiting bacterial growth when compared with the untreated contaminated groups (all, P < 0.001). However, a statistically significant difference was not observed between the bacteria count in the vancomycin and linezolid prophylaxis groups. When a comparison was made between the bacterial growth in the contaminated control groups, MRSA had significantly greater affinity to the Dacron prostheses than MRSE (all, P < 0.001).Conclusion: Our study found that linezolid was as effective as vancomycin in suppressing colony counts in MRSA- or MRSE-infected vascular Dacron grafts in rats.     

基于随机对照试验的儿童利奈唑胺抗感染治疗有效性和安全性的Meta 分析

目的:评价利奈唑胺在儿科感染患者中应用的有效性和安全性。方法:检索Pumed、EMBase、the Cochrane Library、中国知网(CNKI)、万方数据库和中国生物医学文献数据库(CBM),检索时限均从建库至2017年7月。纳入利奈唑胺治疗儿科感染患者的相关随机对照试验(RCT),应用RevMan 5.3 软件进行Meta 分析。结果:共纳入2篇RCT文献,包括815例患儿。对照组为万古霉素等其他抗革兰阳性菌有效的阳性对照药物。有效性研究显示,试验组临床有效性[OR= 1.39,95% CI(0.98,1.98),P=0.07]和微生物有效性[OR=1.12,95%CI(0.61,2.03),P=0.72]与对照组比较差异无统计学意义(P>0.05);亚组分析显示,利奈唑胺治疗耐甲氧西林金黄色葡萄球菌(MRSA)[OR=1.20,95%CI(0.18,7.92),P=0.85]和甲氧西林敏感金黄色葡萄球菌(MSSA)[OR =1.05,95%CI(0.48,2.30), P=0.90]疗效与对照组比较差异无统计学意义( P>0.05)。安全性研究显示,试验组与对照组腹泻[RR=0.86,95%CI(0.51,1.45),P=0.58]、恶心[RR=1.31, 95%CI(0.54,3.18),P=0.55]、呕吐[RR=0.56,95%CI(0.25,1.22),P =0.14]和中性粒细胞减少[RR =1.34,95%CI(0.73,2.49),P=0.35]发生率比较差异无统计学意义(P>0.05)。结论:基于目前的RCT 研究,利奈唑胺治疗儿科患者感染性疾病的有效性较好,但与其他抗菌药物的有效性和安全性比较无显著优势,有待更大规模的临床试验进一步深入研究。     

Risk factors associated with high linezolid trough plasma concentrations

Aim: The major concern of linezolid is the adverse events. High linezolid trough serum concentration (C_min) has been associated with toxicity. The aim of this study was to analyze factors associated with high C_min.

Methods: Main clinical characteristics of 104 patients treated with 600 mg/12 hours of linezolid were retrospectively reviewed. Samples were obtained just before the next dose after at least three doses and within the first 8 days of treatment. High C_min was considered when it was >8 mg/L. Univariate and multivariate analysis were performed.

Results: 34.6% patients had a C_min >8 mg/L, and they were older and had more frequently an estimated glomerular filtration by MDRD <40 mL/min. There were more patients co-treated with rifampin in the group with low C_min. The only factor independently associated with C_min >8 was the renal function. Patients with an eGF < 40 mL/min had significantly higher C_min than those with eGF > 80 mL/min (OR: 4.273) and there was a trend towards a high C_min in patients with eGF between 40-80 mL/min (OR: 2.109).

Conclusions: High C_min were frequent, especially in patients with MDRD <40 mL/min. Therapeutic drug monitoring could be useful to avoid toxicity in patients with renal dysfunction.     

利奈唑胺和糖肽类抗生素对复杂性皮肤及软组织感染治疗效果的荟萃分析

目的 对现已发表的利奈唑胺和糖肽类抗生素治疗革兰阳性球菌复杂性皮肤及软组织感染的文献进行综合分析,评价利奈唑胺的疗效及安全性是否优于糖肽类抗生素.方法 计算机检索Medline数据库、Embase数据库、Ovid数据库、Cochrane 图书馆及中文生物医学期刊数据库等网络资源,并查阅所有纳入的参考文献,进行荟萃分析....     

Comparative activity of linezolid against staphylococci and enterococci isolated in Italy

The activity of linezolid, a new oxazolidinone, was tested against 862 Gram-positive cocci isolated in Italy and compared with the activities of 12 antibiotics. Overall, MIC₉₀s for linezolid (2–4 mg/L) indicated an in vitro activity comparable to that of vancomycin in methicillin-resistant Staphylococcus aureus (4 mg/L), S. epidermidis (2 mg/L) and methicillin-susceptible strains. Enterococcus faecalis strains were susceptible to linezolid (MIC₉₀ 2–4 mg/L), glycopeptides and β -lactams. In E. faecium , only glycopeptides (MIC₉₀ 2 mg/L) and linezolid (MIC₉₀ 2 mg/L) were active. Linezolid was the only drug active against two strains of Enterococcus showing a VanA phenotype. Owing to its antibacterial profile, linezolid represents a promising drug for the treatment of Gram-positive infections.     

利奈唑胺滴眼液在兔眼角膜内的药动学

目的探讨利奈唑胺滴眼液单次滴兔眼后在角膜中的药动学特征。方法 40只新西兰大白兔,局部滴入利奈唑胺滴眼液50μL,采用高效液相色谱法测定兔眼角膜中利奈唑胺的药物浓度,用DAS 2.1.1软件计算药动学参数。结果给药后0～120 h,利奈唑胺在兔眼角膜中的最高浓度为(58.62±15.48)μg.g 1,消除半衰期t1/2为(38.09±11.59)h,药时曲线下面积AUC0 t为(2 459.02±508.95)μg.h.g 1,AUC0∞为(2 834.13±578.96)μg.h.g 1。结论利奈唑胺滴眼液单次滴兔眼后在角膜中具有良好的药代动力学特征和组织通透性。     

监测利奈唑胺对临床分离的耐甲氧西林金黄色葡萄球菌的体外抗菌活性

目的 了解临床分离的耐甲氧西林金黄色葡萄球菌(MRSA)对利奈唑胺的敏感性及对其他抗菌药物的耐药情况,为临床合理选用抗菌药物提供依据.方法 收集本院2008年6月至2011年6月期间住院患者各类临床送检标本,进行细菌学培养鉴定,按湖北地区监测网统一方案进行药物敏感性试验,依据CLSI2009年版标准判读结果,用WHONET 5.4软件进行统计数据分析.结果 2008年6月至2011年6月期间共分离出金黄色葡萄球菌297株,其中MRSA 116株.分离出MRSA的标本以痰标本为主,其次为分泌物和血液.MRSA对利奈唑胺、万古霉素、替考拉林敏感率为100%;对复方新诺明、氯霉素敏感率大于80%;对青霉素、苯唑西林100%耐药;对其他药物敏感性较低.结论 MRSA对大部分抗菌药物仍维持较高的耐药率,利奈唑胺与万古霉素、替考拉林一样是为数不多,仍然对MRSA表现较强抗菌活性的药物之一.     

MRSA对万古霉素、替考拉宁和利奈唑胺体外诱导耐药性比较

[目的]通过比较万古霉素、替考拉宁和利奈唑胺体外诱导耐甲氧西林金葡菌(methicillin-resistant Staphylococcus aureus,MRSA)前后的最低抑菌浓度(minimal inhibitory concentration,MIC)变化,探讨此3种抗菌药物在诱导耐药性上有无差别。[方法]琼脂二倍稀释法检测9株MRSA分别对万古霉素、替考拉宁、利奈唑胺的MIC,筛选出2株对3种药物均敏感的MRSA,用上述3种药物分别诱导2株MRSA25代,最后检测诱导后的MRSA菌株对3种药物的MIC,应用统计学软件进行数据分析。[结果]经万古霉素、替考拉宁、利奈唑胺分别诱导25代后的MRSA菌株与各自诱导前比较,万古霉素和利奈唑胺的MIC升高2倍,替考拉宁的MIC升高2.67倍,但各组间MIC变化无差别,均未见耐药株产生;各组对照组的MRSA菌株经无药平皿传代,各药对其MIC无变化。[结论]3种抗菌药物在诱导MRSA耐药上无差别。     

Clinical pharmacology of linezolid: an oxazolidinone antimicrobial agent

The oxazolidinones are a new class of antibiotics whose mechanism of action is the inhibition of bacterial protein synthesis by binding to the 50S ribosomal subunit. Linezolid is the first member of this class of antibiotics to be approved by the US FDA and other regulatory bodies for the treatment of infections caused by antibiotic-resistant Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus, glycopeptide-intermediate S. aureus and vancomycin-resistant Enterococcus, in adults and children.