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1.
Connie A. Haley Patricia Macias Supriya Jasuja Betsy A. Jones Marie-Claire Rowlinson Roshni Jaimon Pennelyn Onderko Elaine Darnall Maria E. Gomez Charles Peloquin David Ashkin Neela D. Goswami 《Emerging infectious diseases》2021,27(1):332
The US Food and Drug Administration approved a 6-month regimen of pretomanid, bedaquiline, and linezolid for extensively drug-resistant or multidrug-intolerant tuberculosis after a trial in South Africa demonstrated 90% effectiveness 6 months posttreatment. We report on a patient who completed the regimen using a lower linezolid dose. 相似文献
2.
目的 评价血必净注射液联合利奈唑胺治疗重症肺炎的有效性与安全性。方法 检索中国知网(CNKI)、万方数据库(Wanfang)、维普数据库(VIP)、中国生物医学文献数据库(CBM)、Cochrane Library、PubMed、Web of Science和Embase数据库,检索时限为各数据库建库至2022年6月,收集血必净注射液联合利奈唑胺治疗重症肺炎的随机对照试验,采用Review Manager 5.4.1对纳入文献进行质量评价、数据整合分析和偏倚风险评估;Stata14.0进行敏感性分析。结果 共纳入12项随机对照试验,涉及949例患者,观察组478例,对照组471例。Meta分析结果显示,观察组的临床总有效率[RR=1.24, 95%CI (1.18, 1.31), P<0.000 01]、细菌清除率[RR=1.38, 95%CI (1.22, 1.55), P<0.000 01]显著高于对照组。观察组的血常规恢复正常时间[MD=-1.38, 95%CI (-1.55,-1.20), P<0.000 01]、体温恢复正常时间[MD=-1.68, 95%C... 相似文献
3.
Since the 1970s, resistance to antimicrobial agents has become an escalating problem. In the last 25 years, treatment of infections caused by Gram-positive bacteria has been more problematical than ever, with infections being caused by multidrug-resistant organisms, particularly methicillin-resistant staphylococci, penicillin- and erythromycin-resistant pneumococci, and vancomycin-resistant enterococci. There is a continuing effort in the pharmaceutical industry to develop new antimicrobial agents for the treatment of resistant infections. Linezolid, quinupristin-dalfopristin, daptomycin, tigecyline, new glycopeptides and ceftobiprole are the main agents recently introduced or under clinical development. This review summarises their major properties, the results of recent studies with these agents, and future treatment possibilities. 相似文献
4.
P F Smith M C Birmingham G A Noskin A K Meagher A Forrest C R Rayner J J Schentag 《Annals of oncology》2003,14(5):795-801
BACKGROUND: Linezolid is a recently approved oxazalidinone with extended activity against Gram-positive bacteria. We evaluated the results of linezolid therapy in neutropenic cancer patients with Gram-positive bacterial infections from a compassionate-use program. PATIENTS AND METHODS: This was a prospective, multicenter, open-label, non-comparative, non-randomized compassionate-use treatment program in patients with serious Gram-positive infections. To qualify for enrollment patients were required to have an infection resistant to available antimicrobial agents, or in whom available agents had failed or to which they were intolerant. Patients with absolute neutrophil counts (ANC) <500 cells/mm(3) or <1000 cells/mm(3) and expected to decrease to <500 cells/mm(3), and who received linezolid 600 mg twice daily were included. Plasma samples for population pharmacokinetic analysis were collected. Clinical and microbiological assessments of outcomes were made at the end of therapy and at short-term follow-up. RESULTS: Of the patients in the compassionate-use trial, 103 were neutropenic. The mean [standard deviation (SD)] age was 50.1 (17.5) years, 47% were female, and 47.6% had a baseline ANC =100 cells/mm(3). The mean (SD) duration of linezolid therapy was 14.6 (11.4) days. The most common site of infection was the bloodstream (90.3%), and the most commonly identified pathogen was vancomycin-resistant Enterococcus faecium (83%). A total of 83 (80.5%) and 52 (50.4%) patients were evaluable for clinical and microbiological outcomes at the end of therapy, respectively. Clinical and microbiological cure rates in the evaluable patients were 79% and 86%, respectively. Linezolid was well-tolerated in this patient population, with an overall adverse event rate of 17.5%; 5% of patients required discontinuation of the drug due to side-effects. The pharmacokinetics of linezolid in patients with neutropenia did not differ from the overall compassionate-use population. CONCLUSIONS: Linezolid was safe and effective in treating resistant Gram-positive infections in neutropenic cancer patients. Comparative clinical trials to evaluate further the effectiveness and safety of linezolid in this patient population are warranted. 相似文献
5.
目的探讨利奈唑胺滴眼液单次滴兔眼后在房水中的浓度及其药代动力学特征。方法 54只新西兰家兔,局部滴入利奈唑胺滴眼液50 ml,采用高效液相色谱法测定兔眼房水中利奈唑胺的药物浓度,计算其药代动力学参数。结果给药后0~120 h,利奈唑胺在兔眼房水中的达峰浓度为(84.92±67.04)μg/ml,消除半衰期t1/2为(43.28±38.11)h,药时曲线下面积AUC0~t为(1 747.44±871.36)μg.h.ml-1,AUC0~∞为(2 335.25±1 102.42)μg.h.ml-1。空白房水不干扰利奈唑胺的含量测定。结论利奈唑胺滴眼液单次滴兔眼后在房水中具有良好的药动学特征和组织通透性。 相似文献
6.
目的探讨应用利奈唑胺患者的肾功能对该药所致血小板减少的影响,为肾功能不全患者安全使用利奈唑胺提供依据。方法收集2008年1月至2011年5月因革兰阳性菌致肺部感染在空军总医院住院、单独或联合应用利奈唑胺治疗的肾功能不全、肾功能正常患者的临床资料进行回顾性分析,主要观察指标为用药前后血小板计数和血清肌酐、尿素氮水平。为排除联合用药的影响,按照年龄、住院时间匹配原则,选择同期因感染住院且肾功能正常、未使用利奈唑胺但使用利奈唑胺联合疗法中的另外1种抗菌药物的患者,作为单独应用该种抗菌药物的对照。结果应用利奈唑胺患者共43例,其中肾功能不全患者(肾功能不全组,22例)男15例,女7例,年龄38~93(74.8±14.2)岁,16例联用利奈唑胺和其他抗菌药物,包括替考拉宁(1例)、美罗培南(4例)、万古霉素(1例)、甲硝唑(1例)、亚胺培南西司他丁钠(6例)和头孢哌酮舒巴坦(3例);肾功能正常患者(肾功能正常组,21例)男17例、女4例,年龄38~90(73.8±13.7)岁。替考拉宁、美罗培南、万古霉素、甲硝唑、亚胺培南西司他丁钠和头孢哌酮舒巴坦组各22例。应用利奈唑胺的时间:肾功能不全组为1~13(5.4±3.6)d,肾功能正常组为2~13(5.9±3.0)d。肾功能不全组应用利奈唑胺前后血小板计数分别为(207±94)×109/L和(131±97)×109/L,差异有统计学意义(P<0.01)。肾功能正常组患者应用利奈唑胺前后小板计数分别为(208±89)×109/L和(181±94)×109/L,差异无统计学意义(P>0.05)。肾功能不全组与肾功能正常组血小板减少发生率分别为59.1%(13/22)与28.6%(6/21),差异有统计学意义(P<0.05)。2组出现血小板减少的患者均无出血症状,停药3~10(5.7±3.3)d后均逐渐恢复至基线水平。肾功能不全组中联用甲硝唑、万古霉素、替考拉宁者各1例,均出现血小板减少;联用美罗培南者4例,3例出现血小板减少;联用头孢哌酮舒巴坦者3例,2例出现血小板减少;联用亚胺培南西司他汀钠者6例,3例出现血小板减少。而替考拉宁、美罗培南、万古霉素、甲硝唑、亚胺培南西司他丁钠和头孢哌酮舒巴坦组患者用药前后血小板计数差异均无统计学意义(均P>0.05),仅有头孢哌酮舒巴坦组的1例患者出现血小板减少(轻度)。肾功能不全组患者联用利奈唑胺和上述6种抗菌药物之一时血小板减少发生率与单独使用其中1种抗菌药物的各组患者比较,差异均有统计学意义(均P<0.05)。结论患者肾功能对利奈唑胺所致血小板减少发生率有一定影响。肾功能不全患者应用利奈唑胺期间应定期监测血小板计数,一旦出现血小板减少应立即停药。 相似文献
7.
Yousra Kherabi Mathilde Frchet-Jachym Christophe Rioux Yazdan Yazdanpanah Frdric Mchaï Valrie Pourcher Jrme Robert Lorenzo Guglielmetti for the MDR-TB Management Group 《Emerging infectious diseases》2022,28(9):1796
Definitions of resistance in multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant tuberculosis (XDR TB) have been updated. Pre–XDR TB, defined as MDR TB with additional resistance to fluoroquinolones, and XDR TB, with additional resistance to bedaquiline or linezolid, are frequently associated with treatment failure and toxicity. We retrospectively determined the effects of pre-XDR/XDR TB resistance on outcomes and safety of MDR TB treatment in France. The study included 298 patients treated for MDR TB at 3 reference centers during 2006–2019. Of those, 205 (68.8%) cases were fluoroquinolone-susceptible MDR TB and 93 (31.2%) were pre-XDR/XDR TB. Compared with fluoroquinolone-susceptible MDR TB, pre-XDR/XDR TB was associated with more cavitary lung lesions and bilateral disease and required longer treatment. Overall, 202 patients (67.8%) had favorable treatment outcomes, with no significant difference between pre-XDR/XDR TB (67.7%) and fluoroquinolone-susceptible MDR TB (67.8%; p = 0.99). Pre-XDR/XDR TB was not associated with higher risk for serious adverse events. 相似文献
8.
《Expert opinion on pharmacotherapy》2013,14(13):2315-2326
Linezolid is the first of an entirely new class of antibiotics, the oxazolidinones, in decades. It has a spectrum of activity against virtually all important Gram-positive pathogens. The unique mechanism of action of linezolid makes cross-resistance with other antimicrobial agents unlikely. Linezolid has both intravenous and oral formulations and the latter is 100% bioavailable. Since its first approval and marketing in March 2000 in the US, linezolid has gained approval for use in many other countries for the treatment of community-acquired and nosocomial pneumonia, complicated and uncomplicated skin and soft-tissue infections, and infections caused by methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, including cases with concurrent bacteraemia. Several earlier comprehensive reviews summarised the chemistry, mechanism of action, pharmacokinetics, clinical efficacy and safety profile of linezolid. The present review provides an update on the latest data regarding the antimicrobial activity of linezolid versus other commonly used agents, the clinical and health-economic outcomes of linezolid versus vancomycin and teicoplanin, and safety issues. 相似文献
9.
目的:比较分析耐多药结核病(MDR-TB)临床治疗药物和潜在药物结构与性质差异,为开发新药提供参考。方法:运用密度泛函理论M06-2X/6-311+G(2d,p)方法,对噁唑烷酮类MDR-TB治疗药物利奈唑胺(Lin),临床试验药物舒特唑胺(Sut)、德帕唑胺(Del)、TBI-223(223)及新近合成化合物19c的药效构象、几何和电子结构、红外(IR)、紫外-可见(UV-Vis)、电子圆二色(ECD)谱进行计算比较,并借助概念密度泛函理论进行分子全局反应指数分析,使用药物代谢动力学平台开展成药性和ADME/Tox评估。结果:计算显示19c增加一个手性中心明显减少了药效构象,在不同溶剂环境中,五种化合物药效结构几何参数值相近,计算值与晶体参数吻合较好。极性环境使Del极性改变最大。计算红外光谱特征与实验吻合。Lin计算的紫外最大吸收波数与实验完全一致,Del紫外吸收光谱以HOMO电子向LUMO跃迁为主,其他均以HOMO向LUMO+2跃迁为主,都具有双峰曲线。Sut计算ECD峰与实验相吻合。19c、Sut和Lin静电势分布主要集中在噁唑烷酮端,而Del和223则另一端呈电势负性。五种化合物反应指数彼此数值接近。类药性评价显示Del分布系数与其他差别大,整体彼此相近。动力学参数五种化合物比较一致,但临床用药Lin的参数更优。结论:新化合物19c较MDR-TB临床治疗药物及临床试验药物具有优势,存在进一步开发的价值。 相似文献
10.
《Expert review of anti-infective therapy》2013,11(6):947-952
Linezolid is the first member of a new generation of antibiotics, the synthetic oxazolidinones, to become available, with a broad spectrum of in vitro activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and vancomycin-resistant E. faecium. Linezolid is showing great promise currently for the treatment of multiresistant Gram-positive bacterial infections, especially complicated skin infections, catheter-induced bacteremia or nosocomial pneumonia both in the community and in a hospital setting, in children and in adults. Although most recent reports are favorable and anticipatory of a more extensive use of linezolid in appropriately selected pediatric population groups in the near future, following treatment failure of conventional antimicrobial agents, more clinical trials are, however, required to investigate the safety profile and tolerability of this new antibiotic in the pediatric population. 相似文献