Novel 6-Month Treatment for Drug-Resistant Tuberculosis,United States

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.     

血必净注射液联合利奈唑胺治疗重症肺炎有效性及安全性的Meta分析

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...     

New antimicrobial agents for the treatment of Gram-positive bacterial infections.

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.     

Safety, efficacy and pharmacokinetics of linezolid for treatment of resistant Gram-positive infections in cancer patients with neutropenia.

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 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.     

Update on linezolid: the first oxazolidinone antibiotic

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.     

耐多药结核病治疗药物及潜在药物的结构和性质计算

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。     

Linezolid-induced optic neuropathy

Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB) presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic optic neuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment.     

Use of linezolid in children: an overview of recent advances

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.     

Linezolid in the treatment of vancomycin-resistant Enterococcus faecium in solid organ transplant recipients: report of a multicenter compassionate-use trial

Abstract: Vancomycin‐resistant Enterococcus faecium (VRE) is increasing in incidence in solid organ transplant recipients and has a high (up to 83%) associated mortality rate. Until recently, there have been no consistently effective antimicrobial therapies for VRE infection. Linezolid is a new antibiotic that belongs to the class of oxazolidinones approved by the FDA for the treatment of VRE infections, including those with bacteremia. Here, we report the experience with linezolid in an open‐label, compassionate‐use trial at 53 US centers for the treatment of documented VRE infections in patients with solid organ transplants. Eighty‐five patients with solid organ transplants and documented VRE infections were studied. Blood cultures were positive for VRE in 43 patients, while 42 patients had other, non‐rectal, sites of infection. Fifty‐three patients responded well to treatment, with clinical resolution of the infection (62.4% survival rate). Of these, 47 had documented negative cultures post therapy. The mean duration of therapy for cured patients was 23.5 days. Thirty‐two (37.6%) patients died, 28 due to sepsis and organ failure (32.9% failure rate), and 4 due to unrelated causes. Mortality rates for patients with bacteremia were comparable to mortality rates observed with patients who had positive cultures from other sites. Adverse reactions to linezolid included thrombocytopenia (4.7%), decreased leukocyte count (3.5%), and an increase in blood pressure (1.2%), none of which led to discontinuation of therapy. Linezolid appears to be a safe and effective treatment option for VRE, even in the presence of bacteremia, and may lead to decreased mortality in solid organ transplant recipients with VRE infection.     

利奈唑胺联合布地奈德治疗儿童肺炎的效果观察

目的 研究利奈唑胺联合布地奈德治疗儿童肺炎的临床疗效。方法 选择2016年1月-2019年1月安康市中心医院的90例肺炎患儿作为研究对象,采用抽签法随机将患儿分为对照组和观察组,每组各45例。对照组患儿雾化吸入布地奈德气雾剂,500 μg/d,2次/d。观察组在对照组的基础上静脉滴注利奈唑胺注射液,10 mg/kg,2次/d,连续给药10 d,当患儿的病情稳定后,改为口服利奈唑胺片,10 mg/kg。两组疗程均为3周。观察两组患儿的临床疗效、住院时间及症状消失时间,同时比较两组治疗前后的总免疫球蛋白（Ig）E（T-IgE）和嗜酸性粒细胞（EOS）水平。结果 治疗后,观察组的总有效率为95.55%,明显高于对照组的77.78%（P<0.05）。治疗后,观察组的住院时间和发热、肺部湿啰音、咳嗽消失时间明显短于对照组（P<0.05）。两组治疗后EOS水平均显著降低（P<0.05）,且观察组治疗后的EOS水平明显低于对照组（P<0.05）,TIgE无明显改变。结论 利奈唑胺联合布地奈德对儿童肺炎具有比较确切的治疗效果,能缩短住院时间及症状消失时间,减轻气道炎症性反应,具有一定的临床推广应用价值。