利奈唑胺治疗儿童重症结核性脑膜炎的疗效和安全性研究

目的 探讨利奈唑胺治疗儿童重症结核性脑膜炎的疗效和安全性,为儿童重症结核性脑膜炎的提供有效的药物方案。方法 回顾性分析2017年1月—2020年12月在广州市胸科医院儿科住院的诊断重症结核性脑膜炎40例患儿资料,按随机方法,将重症结核性脑膜炎患儿分为观察组20例和对照组20例,对照组采用常规抗结核治疗方案,观察组在常规抗结核治疗的基础上,加用利奈唑胺。分析比较两组患儿治疗前后格拉斯哥（GCS）评分、脑脊液指标（包括白细胞计数、葡萄糖、蛋白定量、氯化物）和体温恢复情况,同时记录不良反应发生情况。结果 两组治疗后GCS评分以及脑脊液各项指标水平均有改善,且治疗4周时,观察组GCS评分（13.35±1.96）分以及脑脊液白细胞计数（28.61±23.46）×10⁶/L、蛋白定量（466.33±158.35）mg/L明显低于对照组,观察组的葡萄糖（2.75±0.42）mmol/L、氯化物（144.94±31.89）mmol/L明显高于对照组,差异有统计学意义（P<0.05）。两组不良反应均在调整药物后好转,无严重不良反应发生。结论 利奈唑胺具有抗结核作用,在结核性脑膜炎早期加用利奈唑胺可以有效改善儿童重症结核性脑膜炎患者的GCS评分、脑脊液指标恢复情况,能显著改善儿童重症结核性脑膜炎的病情,同时不良反应发生率低。     

卫生技术评估在新型噁唑烷酮药物康替唑胺遴选评价中的应用

目的 通过卫生技术评估新型唑烷酮类抗菌药康替唑胺,为医院遴选、临床合理使用新型噁唑烷酮药物提供循证依据。方法 按照药品目录遴选评价管理指南评估细则对国产康替唑胺片进行量化评估,通过检索中国知网、万方、维普、PubMed、Metstr等中外文数据库及相关政府网站获得康替唑胺的适应证、药理作用、指南推荐情况、药品价格等信息,按照药学特性、有效性、安全性、经济性及其他属性量化评价,汇总得分并根据评分划分推荐级别。结果 综合评估结果显示,康替唑胺药学特性18.8分,有效性15分,安全性14.2分,经济性14分,其他属性10分,总得分72分,可推荐进入医疗机构用药目录。结论 康替唑胺作为新品种可以推荐进入医疗机构用药目录,对于临床上利奈唑胺无法治愈的耐甲氧西林金黄色葡萄球菌（MRSA）感染,康替唑胺片有望成为更加安全的抗菌药物选择。     

利奈唑胺治疗老年心功能不全革兰阳性球菌感染患者的临床分析

目的:总结分析利奈唑胺治疗革兰阳性球菌感染的老年心功能不全患者的临床疗效及安全性。方法:回顾分析4家医院2009年1月-2011年1月收治的使用利奈唑胺治疗的革兰阳性球菌感染的35例心功能不全老年患者的临床资料。结果:全部患者均检出革兰阳性菌株,25例感染部位为肺,10例为血液,利奈唑胺治疗后总有效率为82.9%,有效时间为3～10d,有24例直接使用利奈唑胺治疗,用药后清除21例(87.5%),11例为万古霉素无效或不能耐受后换用利奈唑胺治疗,用药后清除8例(72.7%),共6例出现不良反应,3例皮疹,2例血小板减少,1例腹泻,全部患者都能够耐受。结论:利奈唑胺治疗革兰阳性球菌感染的老年心功能不全患者疗效确切、安全,可一线应用于抗革兰阳性球菌感染治疗或万古霉素治疗无效时换用利奈唑胺。     

利奈唑胺对分枝杆菌体外抑菌作用的初步研究

目的 评价利奈唑胺对MTB和5种非结核分枝杆菌(NTM)的体外抑菌作用,探讨利奈唑胺与其他抗结核药物联合使用时的体外相互作用.方法 采用微孔板Alamar Blue法测定利奈唑胺对MTB临床株121株、NTM临床菌株30株及相应标准菌株的MIC,观察利奈唑胺与7种常用抗结核药物联合使用时,对H37Rv和8株MTB 临床分离株的MIC值的影响,通过计算分级抑菌浓度指数,观察利奈唑胺与其他抗结核药物联合使用时是否存在协同作用.结果 94.2%(114/121)的MTB临床分离株可被≤1 mg/L的利奈唑胺抑制生长,利奈唑胺对敏感和MDR菌株及其他形式的耐药菌株的MIC差异无统计学意义(X2=0.481,P＞0.05).若以＞1 mg/L作为耐药标准,则5种NTM菌株中仅堪萨斯分枝杆菌对利奈唑胺敏感,脓肿分枝杆菌和偶然分枝杆菌均对利奈唑胺全耐药,鸟分枝杆菌和胞内分枝杆菌对利奈唑胺部分敏感.利奈唑胺与7种抗结核药物在体外联合使用时未表现出相关性.结论 利奈唑胺有很好的抗MTB活性,且与细菌对其他药物是否耐药无关.利奈唑胺对堪萨斯分枝杆菌有很好的抗菌活性,与其他常用抗结核药物联合使用时未表现出相关性.

Abstract：

Objective To evaluate the mycobactericidal efficacy of linezolid to Mycobacterium tuberculosis bacilli and Non-tuberculous mycobacteria ( NTM ) in vitro, and to analyze the interaction between linezolid and other anti-TB drugs in vitro.Methods The minimum inhibition concentrations (MICs) of 121 Mycobacterium tuberculosis clinical isolates and 30 non tuberculousis Mycobacteria isolates and the corresponding standard strains to linezolid were tested by Microplate Alamar Blue assay (MABA).The interactions between linezolid and rifampicin, isoniazid, streptomycin, ethambutol, kanamycin, ofloxacin,and rifabutin were also tested in vitro by fractional inhibitory concentration index ( FICI ) method.Results 94.2% ( 114/121 ) of the Mycobacterium tuberculosis isolates were inhibited by linezolid at concentrations ≤1 mg/L.There was no statistical difference in the MIC values of sensitive strains, MDR strains, and drug resistant strains other than MDR ( x2 = 0.481, P ＞0.05 ).Only Mycobacterium kansasii was totally sensitive to linezolid among the 5 tested NTM strains.In vitro drug combination testing displayed overall non-association between linezolid and 7 other anti-TB drugs among 8 clinical isolates and H37 Ry.Conclusions Linezolid showed great mycobactericidal efficacy to Mycobacterium tuberculosis clinical isolates in vitro,regardless of the strains' drug resistant parameters.This study also showed non-association of the interactions between linezolid and 7 other anti-TB drugs in vitro.     

利奈唑胺耐药肠球菌感染危险因素及耐药机制分析

目的 分析医院获得性和社区获得性利奈唑胺耐药肠球菌(LRE)感染的危险因素及其主要耐药机制.方法 收集2018年9月—2020年12月分离的LRE菌株,根据LRE感染来源分为医院获得性和社区获得性,采用回顾性病例对照研究分别分析两种感染的危险因素.通过PCR和测序技术等方式检测菌株已知利奈唑胺耐药机制.结果 共检出38...     

Antibiotic-induced serotonin syndrome

Due to its broad spectrum of clinical presentations and to the large number of available serotonergic medications, serotonin syndrome (SS) remains an elusive diagnosis to many clinicians. SS results from the over-stimulation of serotonin receptors by a variety of mechanisms. New medications with the potential to cause SS are released regularly, and among them is the antibiotic linezolid. We present a case of SS in a 36-year-old woman that occurred after linezolid was added to a drug regimen that included lithium, venlafaxine, and imipramine.     

利奈唑胺和万古霉素治疗重症医学科院内耐甲氧西林金黄色葡萄球菌肺炎疗效及安全性研究

目的比较利奈唑胺与万古霉素对ICU患者耐甲氧西林金黄色葡萄球菌(MRSA)肺部感染的疗效及安全性。方法对2008年5月至2010年11月温州市中医院收治的72例肺部MRSA感染的患者,分别给予利奈唑胺(0.6 g/次,每日2次)和万古霉素(1.0 g/次,每日2次)治疗,观察并比较两种方法的临床疗效、细菌学疗效及不良反应。结果万古霉素与利奈唑胺治疗MRSA的治愈率分别为25.7%和18.9%,临床总有效率分别为65.7%和51.4%,细菌清除率分别为71.4%和48.6%,不良反应总发生率为8.5%和5.4%,两组间MRSA治愈率、总有效率和不良反应总发生率比较差异无统计学意义(P>0.05),细菌清除率比较差异有统计学意义(P<0.05)。结论对于ICU患者肺部MRSA感染,利奈唑胺与万古霉素敏感率均很高,总体疗效相似,且安全性及耐受性较好,利奈唑胺痰菌清除率略高于后者。     

Complete blindness after optic neuropathy induced by short-term linezolid treatment in a patient suffering from muscle dystrophy

We present a case of severe optic neuropathy following linezolid treatment, which led to complete irreversible blindness, in a patient with progressive muscular dystrophy, treated with linezolid for 16 days for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Interruption of antibiotic therapy did not lead to remission of ocular symptoms. Administration of linezolid may lead to severe neuropathy even in the case of short-term treatment.     

利奈唑胺相关血小板减少的危险因素分析

目的探讨利奈唑胺相关血小板减少的危险因素。方法收集2011年1月至2012年7月在复旦大学附属中山医院因感染应用利奈唑胺的162例住院患者的临床资料并进行回顾性分析,根据用药后是否出现血小板减少,将患者分为血小板减少组和血小板正常组。主要分析指标为患者性别、年龄、体重,应用利奈唑胺前血小板计数、血清肌酐清除率(Ccr)、白蛋白、血红蛋白、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,应用利奈唑胺的剂量、给药途径和持续时间,以及合并用药情况等。对影响血小板计数的相关变量分别进行t检验、Mann-Whitney U检验和Kruskal-Wallis H检验,对筛选出的危险因素进行逐步Logistic回归统计分析,计算比值比(OR)及95%置信区间(CI)。结果 162例患者中男113例,女49例,年龄19～96岁,平均年龄(57.2±16.1)岁;用药方法均为静脉滴注,600 mg/次,2次/d。应用利奈唑胺的时间为1～46 d,中位时间6 d。血小板正常组115例,血小板减少组47例。47例患者用药后出现血小板减少的中位时间为4.5 d,血小板计数平均为(53±29)×109/L,其中轻、中、重度分别为25、10、12例。逐步Logistic回归分析显示,用药前Ccr<50 ml/min的OR为6.75,95%CI为2.93～15.58,P=0.000;血小板计数<100×109/L的OR为4.54,95%CI为1.53～13.50,P=0.006;应用利奈唑胺时间>14 d的OR为4.00,95%CI为1.40～11.39,P=0.009;用药前AST>75 U/L的OR为2.73,95%CI为1.07～6.99,P=0.036。结论应用利奈唑胺前Ccr、血小板计数低于正常、AST高于正常和应用利奈唑胺时间>14 d可能为利奈唑胺相关血小板减少的危险因素。     

Linezolid alone and in combination with rifampicin prevents experimental vascular graft infection due to methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis

BACKGROUND: In this report we describe the in vivo antibacterial activity of linezolid in an experimental graft infection model in rats and compare it with teicoplanin. The objective of this study was also to determine the effects of the interaction of linezolid when it was combined with rifampicin and test this effect against strains of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. MATERIALS AND METHODS: Graft infections were established in the subcutaneous tissue of 130 Wistar rats by implantation of Dacron grafts followed by a topical inoculation with 2 x 10(7) CFU of clinical isolates of MRSA and MRSE. The study included a control group and six groups for each of the staphylococcal strains: an inoculated group that did not receive any antibiotic prophylaxis, two inoculated groups that received intraperitoneal prophylaxis with teicoplanin or linezolid alone, an inoculated group that received rifampicin-soaked grafts, and two inoculated groups that received a combination prophylaxis consisting of intraperitoneal teicoplanin or linezolid and rifampicin-soaked grafts. RESULTS: There was a reduction in the quantitative bacterial graft cultures in all prophylaxis groups when compared with inoculated control groups. There was not a statistically significant difference between linezolid and teicoplanin prophylaxis groups. The best results were obtained by a combination of rifampicin-soaked grafts with linezolid or teicoplanin. CONCLUSIONS: We found no evidence to suggest that linezolid differs from teicoplanin regarding effectiveness in the prevention of prosthetic vascular graft infection. Linezolid plus rifampicin and teicoplanin plus rifampicin are demonstrated to be valuable prophylactic regimens.