重症肺炎患者利奈唑胺经验治疗临床观察

目的观察利奈唑胺经验治疗重症肺炎患者的临床疗效及安全性,达到合理使用利奈唑胺经验治疗重症肺炎的目的。方法收集2010年6月-2012年12月医院呼吸内科重症肺炎应用利奈唑胺初始经验治疗的52例住院患者临床资料,根据患者年龄、初始应用时间、联合用药、肺CT特征、治疗48h后病原学结果,观察各组间疗效及不良反应发生率,并进行差异性比较和原因分析。结果 52例重症肺炎患者利奈唑胺经验治疗后,总有效率82.69%、治愈率38.46%、病死率17.31%;血小板减少、凝血酶原时间延长、部分凝血活酶时间延长发生率,分别为19.23%、19.23%、10.15%,血尿发生率为7.69%,随着肝损伤程度加重,不良反应发生率越高。结论采用利奈唑胺经验治疗重症肺炎患者可提高其治愈率、降低病死率、血小板减少等不良反应发生可能与肝功能的基础状态有关。     

Severe linezolid-induced lactic acidosis in a child with acute lymphoblastic leukemia: A case report

Linezolid is an antibiotic increasingly used for treatment of resistant Gram-positive infections, which blocks bacterial proteosythesis through direct inhibition of mitochondrial ribosomes. The most common adverse effects of linezolid include gastrointestinal symtoms, peripheral neuropathy, bone marrow depression and lactic acidosis.Here we present a rare case of a 9-year-old female, a survivor of acute lymphoblastic leukemia (ALL) and a hematopoietic stem cell transplant (HSCT), who developed life-threatening lactic acidosis with vomiting, impaired consciousness and Kussmaul breathing after 51 days of intravenous linezolid administration due to mycobacterial infection. She fully recovered after drug discontinuation and normalization of the plasma levels.We conclude that plasma lactate concentrations should be monitored closely during any linezolid treatment, particularly in patients with hepatic or renal dysfunction.     

万古霉素与利奈唑胺治疗老年人MRSA肺炎的疗效与安全性分析

目的：比较利奈唑胺与万古霉素治疗老年人医院获得性耐甲氧西林金黄色葡萄球菌（MRSA）肺炎的疗效和安全性。方法57例老年医院获得性MRSA肺炎患者随机分成利奈唑胺组（29例）与万古霉素组（28例）,疗程结束后比较两组临床有效率、细菌学清除率及不良反应情况。结果利奈唑胺组临床有效率75.9%,万古霉素组67.9%,两组差异无统计学意义（P＞0.05）。利奈唑胺组血小板减少发生率20.7%,用药前后的差异有统计学意义（P＜0.05）;万古霉素组肾功能损害发生率14.2%。结论利奈唑胺治疗老年人医院获得性肺炎临床疗效与万古霉素相仿,但其不良反应相对轻微。     

利奈唑胺治疗慢性肾功能衰竭伴重症肺部感染二例

病例1 患者女,67岁,因＂反复气喘4年,加重3周＂于2008年10月24日入院.患者2004年无明显诱因出现反复气喘,当时步行上3楼感气短,夜间可平卧,伴心悸、乏力,经治疗后好转,平时未规则服用药物.     

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.     

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.     

Synthesis and antibacterial evaluation of oxazolidin-2-ones structurally related to linezolid

Compounds structurally related to the known antimicrobial drug linezolid were selected in order to evaluate the influence of electron-withdrawing properties and altered geometric features as a result of the N-substituent modification. After a preliminary study of molecular modeling, cinnamoyl-, pyridin- and pyrimidinoxazolidin-2-ones were synthesized. None of the new compounds showed antibacterial activity.     

Linezolid, Critical Characteristics

Summary In spite of a constantly expanding information base with the oxazolidinones generally and linezolid specifically, we have elected here to focus on the key characteristics of linezolid. Linezolid is the first member of a new class of antimicrobial agents, the oxazolidinones, to be tested in humans in Phase I, Phase II and Phase III clinical trials. The oxazolidinones have a novel mechanism of action in that they inhibit initiation complex formation in bacterial protein synthesis and, consistent with a novel mechanism of action, they do not exhibit cross-resistance with existing antibacterial agents. Importantly, resistance development as measured in the laboratory occurs very slowly, there is no evidence of rapid resistance development. The spectrum of oxazolidinone activity is principally gram-positive and in vitro studies demonstrate that linezolid is equivalent to vancomycin in vitro. Linezolid is orally as well as intravenously active and orally administered linezolid is as efficacious in mouse models of bacterial disease as is subcutanously administered vancomycin against appropriate pathogens. The exceptional oral behavior of linezolid in mouse models is readily explained by the observation that oral linezolid is 100% bioavailable and that administration of 400- and 600-mg doses of linezolid in humans results in blood level curves which predict that linezolid will be very well suited for bid dosing. Additionally, the blood level concentrations are in significant and very comfortable excess of the MIC₉₀ concentrations for the important gram-positive pathogens for the bulk of the dosing interval.     

Linezolid Treatment for Osteomyelitis due to Staphylococcus Epidermidis with Reduced Vancomycin Susceptibility

Limited therapeutic options are available for vancomycin intermediate-resistant Staphylococcus Epidermidis (VISE) infections and no optimum therapy has been established. We report a case of VISE skull osteomyelitis that was successfully treated with linezolid. The patient was a 53-year-old man who presented with headache, nausea and dysphasia. Brain computerized tomography (CT) demonstrated a subdural hematoma in the left hemisphere. Craniotomy and hematoma evacuation was performed and he showed good recovery despite a scalp wound infection caused by methicillin-resistant Staphylococcus aureus (MRSA). The organism isolated from the scalp wound was sensitive to vancomycin. The patient was treated with intravenous vancomycin for 44 days. However, he showed a high fever, persistent positive methicillin-resistant Staphylococcus Epidermidis (MRSE) blood cultures, and a deteriorating clinical status. He underwent infected skull bone flap removal and linezolid treatment for 35 days. During one year of follow up, he has not had any further episodes of osteomyelitis or fever. Linezolid has shown to be effective agent to eradiate osteomyelitis caused by VISE.