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。     

利奈唑胺致慢性肾脏病患者转氨酶升高、血小板减少、乳酸酸中毒一例并文献复习

1例终末期肾脏病患者,使用利奈唑胺后出现转氨酶升高、血小板减少和乳酸酸中毒并发症,停药后病情得到缓解。本文通过对该病例资料进行分析,提示慢性肾脏病患者使用利奈唑胺时,需要密切监测患者临床症状及相关实验室检查。利奈唑胺在该人群中应用的安全性和耐受性需要临床进一步验证。     

利奈唑胺与万古霉素治疗医院获得性耐甲氧西林金黄色葡萄球菌肺炎的疗效比较

目的:比较利奈唑胺与万古霉素治疗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:将72例医院获得性MRSA肺炎患者随机均分为两组,利奈唑胺组患者静脉滴注利奈唑胺600 mg,q 12 h;万古霉素组患者静脉滴注万古霉素500 mg,q 8 h。两组患者疗程均为14 d。评价和比较两组患者的临床疗效、细菌学疗效及不良反应情况。结果:利奈唑胺组患者总有效率和细菌清除率显著高于万古霉素组,两组比较差异均有统计学意义(P<0.05),而不良反应发生率与万古霉素组比较差异无统计学意义(P>0.05)。结论:对于医院获得性MRSA肺炎的治疗利奈唑胺总体疗效优于万古霉素,而安全性相似。     

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.     

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.     

利奈唑胺对革兰阳性球菌的体外抗菌活性研究

目的检测利奈唑胺对临床分离的金黄色葡萄球菌、表皮葡萄球菌、溶血葡萄球菌、粪肠球菌、屎肠球菌等革兰阳性球菌的体外抗菌活性,为临床合理使用抗生素提供依据。方法采用VITEK-32全自动微生物分析仪和ATB自动微生物分析仪鉴定和药敏系统对临床分离的常见革兰阳性球菌267株进行鉴定和药敏试验．根据其药敏结果比较8种抗菌药物对葡萄球菌、肠球菌的抗菌活性。结果在临床分离的267株菌中金黄色葡萄球闺111株,MRSA74株（占66．7％）,凝同酶阴性葡萄球菌96株（表皮葡萄球菌57株、溶血葡萄球菌39株）,MRCNS有80株（占86．0％）,粪肠球菌45株、屎肠球菌13株。利奈唑胺对207株葡萄球菌、58株肠球菌体外抗菌活性分别为100％,93．1％,与万古霉素相当,明显高于其他常用的抗生素（如红霉素、头孢唑林、环丙沙星等）。其对金黄色葡萄球菌、凝固酶阴性葡萄球菌、肠球菌的MIC50和MIC90分别为1．1mg／L;1.1mg／L：2.4mg／L。结论耐甲氧西林葡萄球菌发生率高,多重耐药严重,利奈唑胺对葡萄球菌的抗菌活性与万古霉素相当．对肠球菌也有较强的抗菌活性。葡萄球菌、肠球菌对左氧氟沙星、四环素、红霉素均产生了不同程度的耐药性。     

万古霉素、利奈唑胺治疗MRSA 感染的成本效益分析

目的 比较和分析万古霉素与利奈唑胺在治疗自耐甲氧西林金黄色葡萄球菌（MRSA）感染方面的区别与联系,为临床合理用药提供理论依据。方法 采用回顾性分析,选取2014 年1 月-2016 年3 月西安医学院第一附属医院存在MRSA 感染并使用万古霉素或（和）利奈唑胺治疗的病例资料,比较患者使用万古霉素与利奈唑胺的疗效和药物经济学情况,评价其合理性。结果 在治疗MRSA 感染时,利奈唑胺对肾功能的影响低于万古霉素（P <0.05）;万古霉素组的疗程和住院天数分别为（7.04±0.45）d、（10.76±0.53）d,利奈唑胺组疗程和住院天数分别为（5.12±0.47）d、（8.06±0.58）d,两者疗程与住院天数差异有统计学意义（P <0.05）;药物利用指数（DUI）均<1。利奈唑胺有效率高于万古霉素（P <0.05）;利奈唑胺的成本效果比（C/E）低于万古霉素。结论 与万古霉素比较,在治疗MRSA 感染过程中。利奈唑胺对肾功能的影响小、成本效益更优、疗效及安全性更好。     

利奈唑胺体外诱导金黄色葡萄球菌耐药的实验研究

目的：体外诱导金黄色葡萄球菌对利奈唑胺耐药,研究分析其耐药后菌株变化。方法用利奈唑胺浓度2倍递增的方法对9株临床分离金黄色葡萄球菌（5株MSSA、4株MRSA）和质控菌株ATCC25923进行体外诱导;PCR扩增诱导前后金黄色葡萄球菌23S rRNA的V区基因并测序、Blast比对,分析突变与耐药性的关系;比较诱导前后金黄色葡萄球菌的适应性以及对抗菌药物的耐药性变化。结果10株实验菌株中有9株诱导出稳定的利奈唑胺耐药性,其中5株耐药菌发生了突变;利奈唑胺耐药后金黄色葡萄球菌生长速率减慢,对其他抗菌药物耐药性也发生改变。结论经利奈唑胺诱导后金黄色葡萄球菌可以获得稳定耐药性,但同时也产生了适应性代价,其耐药机制与23S rRNA的V区基因突变相关,并且可能有其他耐药机制的参与。