强化期利奈唑胺替代乙胺丁醇治疗药物敏感肺结核的临床效果观察

目的 探讨在抗结核标准治疗方案中使用利奈唑胺代替乙胺丁醇方案治疗药物敏感肺结核的效果.方法 将2018年1月—2020年7月在盘锦市传染病医院就诊的43例药物敏感肺结核患者随机分为对照组和利奈唑胺组.对照组给予标准抗结核方案治疗.利奈唑胺组使用利奈唑胺替代标准抗结核治疗方案中的乙胺丁醇进行治疗.比较两组的治疗效果、治疗...     

Severe Pulmonary Disease Caused by Mycolicibacter kumamotonensis

Severe Mycolicibacter kumamotonensis-pulmonary disease was diagnosed in a 68-year-old immunocompetent woman in Greece; the disease was initially treated as tuberculosis. The patient responded favorably to a new treatment regimen of azithromycin, amikacin, moxifloxacin, and linezolid. Complete symptom resolution and radiologic improvement resulted.     

利奈唑胺治疗恶性肿瘤患者中性粒细胞减少并发革兰阳性菌感染的疗效观察

目的 评价利奈唑胺治疗中性粒细胞减少患者并发革兰阳性菌感染的临床疗效与安全性.方法 选择62例中性粒细胞减少并发革兰阳性菌感染的恶性肿瘤患者,给予所有患者静脉滴注利奈唑胺600 mg、1次/12 h,根据治疗情况连续使用7～21 d;观察治疗疗效以及患者的不良反应.结果 在使用利奈唑胺治疗后,患者临床治愈43例,有效12例,进步2例,无效5例,总有效率为88.71％,药物不良反应总发生率为11.29％.结论 利奈唑胺治疗恶性肿瘤患者中性粒细胞减少并发革兰阳性菌感染临床疗效确切,不良反应少.     

血必净联合利奈唑胺治疗老年重症肺炎的效果及对患者血清炎性因子水平的影响

目的 探讨血必净联合利奈唑胺治疗老年重症肺炎(SP)的效果及对患者血清炎性因子水平的影响.方法 选取2020年4月至2021年5月我院收治的66例老年SP患者,随机分为实验组和对照组各33例.对照组采用利奈唑胺治疗,实验组采用血必净联合利奈唑胺治疗,比较两组的临床疗效及治疗前后的血清炎性因子[C-反应蛋白(CRP)、肿...     

Linezolid Versus Vancomycin in the Empiric Treatment of Nosocomial Pneumonia: A Cost-Utility Analysis Incorporating Results from the ZEPHyR Trial

ObjectiveTo examine the cost-effectiveness of vancomycin versus linezolid in the empiric treatment of nosocomial pneumonias incorporating results from a recent prospective, double-blind, multicenter, controlled trial in adults with suspected methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia.MethodsA decision-analytic model examining the cost-effectiveness of linezolid versus vancomycin for the empiric treatment of nosocomial pneumonia was created. Publicly available cost, efficacy, and utility data populated relevant model variables. A probabilistic sensitivity analysis varied parameters in 10,000 Monte-Carlo simulations, and univariate sensitivity analyses assessed the impact of model uncertainties and the robustness of our conclusions.ResultsResults indicated that the cost per quality-adjusted life-year (QALY) increased 6% ($22,594 vs. $23,860) by using linezolid versus vancomycin for nosocomial pneumonia. The incremental cost per QALY gained by using linezolid over vancomycin was $6,089, and the incremental cost per life saved was $68,615 with the use of linezolid. Vancomycin dominated linezolid in the subset of patients with documented MRSA. The incremental cost per QALY gained using linezolid if no mortality benefit exists between agents or a 60-day time horizon was analyzed was $19,608,688 and $443,662, respectively.ConclusionsLinezolid may be a cost-effective alternative to vancomycin in the empiric treatment of patients with suspected MRSA nosocomial pneumonia; however, results of our model were highly variable on a number of important variables and assumptions including mortality differences and time frame analyzed.     

利奈唑胺在高龄老年患者中的临床应用

目的 调查利奈唑胺在高龄老年患者中的应用.方法 通过回顾性分析,了解利奈唑胺治疗老年病房中革兰阳性菌感染患者的疗效和不良反应.结果 53例共70例次应用利奈唑胺治疗的患者,其中,利奈唑胺注射液组15例次,临床有效率为60.0%,细菌清除率为80.0%;利奈唑胺片剂组51例次,临床有效率为60.8%,细菌清除率为60.5%,4例患者为序贯应用片剂和注射液,3例患者临床有效,细菌清除;不良反应主要表现为血小板降低,利奈唑胺片剂组和注射液组血小板降低的发生率分别为35.2%和46.7%(P<0.05).结论 利奈唑胺治疗高龄老年患者革兰阳性菌感染,疗效较好,片剂组比注射液组引起血小板降低的不良反应小.     

2例利奈唑胺中介粪肠球菌血流感染的毒力及耐药机制

目的对血流感染患者临床分离的利奈唑胺中介粪肠球菌的毒力因子及耐药机制进行初步研究。方法从2例血流感染患者血标本中分离2株利奈唑胺中介粪肠球菌,分析患者治疗经过,2株分离菌编号为A、B,测定其对利奈唑胺和万古霉素的最低抑菌浓度(MIC),采用聚合酶链反应(PCR)扩增毒力基因(esp、asa1、gelE、ace、agg、efaA、cylA、hyl)和利奈唑胺耐药相关基因,包括23SrRNA V区基因、cfr、cfr(B)及optrA基因片段,其中23SrRNA V区基因扩增产物送测序并分析有无突变位点。结果 2例患者培养出利奈唑胺中介粪肠球菌后均使用利奈唑胺治疗控制了临床症状。菌株A、B对万古霉素、替考拉宁、氨苄西林、呋喃妥因敏感,对利奈唑胺中介(MIC均为4μg/mL),对万古霉素敏感(MIC分别为1μg/mL和4μg/mL)。2株菌均含有多种毒力因子,菌株A仅cylA、hyl为阴性,菌株B仅hyl、esp为阴性,其余毒力基因均为阳性。菌株A的23SrRNA V区存在G2621T突变,菌株B未发现突变位点。菌株A和B耐药基因cfr、cfr(B)、optrA均为阴性。结论此研究中血流感染患者分离的利奈唑胺中介粪肠球菌对万古霉素和氨苄西林敏感,虽治疗结果提示利奈唑胺仍有效,但临床中选用利奈唑胺治疗需谨慎。靶位突变是该类药物重要的耐药机制,临床中治疗该类药物不敏感粪肠球菌感染需足够重视,其治疗策略仍需进一步探讨。     

利奈唑胺和万古霉素治疗化脓性脊柱炎的疗效、安全与经济性比较

目的 比较万古霉素与利奈唑胺治疗化脓性脊柱炎的有效性、安全性和经济性。 方法 回顾性分析某三级医院2019年1月—2022年12月骨科收治的使用万古霉素或利奈唑胺治疗的化脓性脊柱炎患者120例病历资料。其中使用万古霉素者71例(万古霉素组), 使用利奈唑胺者49例(利奈唑胺组), 收集两组患者的炎性指标、不良反应、抗菌药物治疗时间及抗菌药物总费用的资料, 比较两组患者治疗的有效性、安全性及经济性。 结果 万古霉素组和利奈唑胺组两组患者治疗后白细胞计数(WBC)、C反应蛋白(CRP)、疼痛视觉模拟量表(VAS)评分、Oswestry功能障碍指数(ODI)均低于治疗前, 差异均具有统计学意义(均P＜0.05);两组患者治疗后的上述指标比较, 差异无统计学意义(均P＞0.05);抗菌药物治疗时间和不良反应发生率比较, 差异均无统计学意义(均P＞0.05);而利奈唑胺组患者抗菌药物总费用低于万古霉素组, 差异有统计学意义(P＜0.05)。 结论 利奈唑胺治疗化脓性脊柱炎的有效性、安全性与万古霉素相当, 经济性优于万古霉素。     

利奈唑胺治疗老年患者革兰阳性球菌感染的疗效及安全性

目的探讨利奈唑胺治疗老年患者革兰阳性（G+）球菌感染的疗效及安全性。方法收集某院2013年1月-2014年12月所有住院患者中年龄＞60岁、因G+球菌感染使用利奈唑胺治疗10 d以上患者的病历资料,分析利奈唑胺的疗效,并比较利奈唑胺治疗前及用药后14 d实验室指标,分析其可能的不良反应。结果共纳入70例老年患者,感染部位以下呼吸道为主（占62.86%）,病原菌以金黄色葡萄球菌为主（占42.86%,其中MRSA19株）。80%以上的患者年龄＞70岁、住院时间＞30 d、入住重症监护病房（ICU）,70%以上患者有深静脉置管及留置导尿管。使用利奈唑胺治疗14 d后患者的血小板（PLT）计数为（132.00±45.00）×109/L,低于治疗前的（156.00±78.00）×109/L,差异有统计学意义（P=0.009）;总的治疗有效率为81.43%（57/70）,不良反应发生率为17.14%（12/70）。结论应用利奈唑胺治疗老年患者G+球菌感染疗效较好,可作为临床医生经验性抗感染选用药物之一,但在治疗过程中应加强对患者PLT计数的监测。     

替考拉宁与利奈唑胺治疗MRSA感染的临床比较

目的 评价替考拉宁与利奈唑胺随机对照治疗重症监护室MRSA感染患者的疗效和安全性.方法 对68例MRSA重症感染患者进行随机对照开放试验,分为替考拉宁组35例,剂量400mg/次,1次/12 h,3个剂量后,1次/d;利奈唑胺组33例,剂量600mg/次,1次/12 h,均为静脉滴注,疗程14～18 d;比较两组病例的疗效、细菌清除率、用药前后的肝肾功能改变.结果 替考拉宁与利奈唑胺治疗重症MRSA感染的临床有效率为88.6％和90.9％,细菌清除率为86.8％、88.2％,两组结果差异无统计学意义;患者治疗后14 d APACHEⅡ评分分别为(10.17±3.32)、(13.66±5.98)分,替考拉宁组优于利奈唑胺组,差异有统计学意义(P＜0.05);不良反应发生率分别为11.4％和18.2％,替考拉宁组的不良反应发生率小于利奈唑胺组,差异有统计学意义(P＜0.05).结论 替考拉宁和利奈唑胺在治疗MRSA所致重症感染均有良好疗效,替考拉宁的用药安全性更高.     

The ZEPHyR study: A randomized comparison of linezolid and vancomycin for MRSA pneumonia

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) accounts for 10–40% of hospital-acquired pneumonia, and even more in intensive care units. The current guidelines for the treatment of MRSA nosocomial pneumonia include vancomycin and linezolid. The authors of 2 prospective randomized trials comparing vancomycin and linezolid in nosocomial pneumonia had concluded to the non-inferiority of linezolid. A slight superiority of linezolid was observed in the MRSA pneumonia subgroup, in terms of clinical success and survival, but no definite conclusion could be drawn.MethodsA prospective randomized study was made to compare a fixed linezolid dose to dose-optimized vancomycin for the treatment of bacteriologically proven MRSA nosocomial pneumonia (ZEPHyR Study).ResultsAmong the 165 patients treated by linezolid (57.6%) in the PP population, 95 were clinically cured at the end of the study, compared to 81 of the 174 patients treated by vancomycin (46.6%) (IC 95% of the difference 0.5%–21.6%, P = 0.042). Nephrotoxicity in the mITT population reached 8.4% in the linezolid group compared to 18.2% in the vancomycin group.ConclusionLNZ was superior to vancomycin for the treatment of MRSA nosocomial pneumonia.     

利奈唑胺联用对耐甲氧西林金黄色葡萄球菌体外抗菌活性的研究

目的 探讨利奈唑胺与3种常用抗菌药物(利福平、左氧氟沙星、庆大霉素)分别联用对临床分离的MRSA的体外抗菌活性,为临床有效地治疗MRSA感染提供理论依据.方法 常规方法培养分离细菌,获得纯培养后用VITEK全自动微生物分析仪鉴定金黄色葡萄球菌,再根据CLSI(2006年)标准,微量肉汤法进行最低抑菌浓度(MIC值)的测定及药敏试验,并计算分级抑菌浓度(FIC)指数.结果 利奈唑胺、左氧氟沙星、利福平、庆大霉素对30株MRSA的MIC50分别为0.5～4、16～256、8～256、128～1024 μg/ml,MIC90分别为4、256、256、1024μg/ml;利奈唑胺与左氧氟沙星联用MIC90降为2μg/ml,利奈唑胺与利福平联用MIC90降为1μg/ml,利奈唑胺与庆大霉素联用MIC90降为2 ug/ml.结论 利奈唑胺对MRSA有较高敏感性,利奈唑胺与利福平联合应用以协同作用为主,利奈唑胺与左氧氟沙星、庆大霉素联合应用以协同和相加作用为主,二者均无拮抗作用.     

利奈唑胺治疗神经外科术后颅内感染疗效分析

目的评价利奈唑胺治疗神经外科术后颅内感染的临床疗效及安全性,为术后颅内感染的治疗提供参考。方法通过病历查询系统收集2011年1月-2012年12月北京天坛医院51例术后颅内感染后使用利奈唑胺治疗的患者病历资料,根据利奈唑胺治疗前后患者症状、体温、脑脊液细菌培养结果及脑脊液白细胞数、蛋白质、葡萄糖变化等指标,参照颅内感染的判定标准,评价患者使用利奈唑胺治疗颅内感染的有效性及安全性。结果51例神经外科术后发生颅内感染的患者在使用利奈唑胺治疗后,感染痊愈30例,显效12例,进步5例,无效4例,总有效率92.16%。有效的47例患者中,利奈唑胺的平均治疗时间为12.5 d（2～27 d）。其中11例脑脊液培养出革兰阳性菌者经利奈唑胺治疗后,脑脊液细菌培养均转为阴性。 结论利奈唑胺可有效控制万古霉素等治疗无效的葡萄球菌属、肠球菌属等革兰阳性菌引起的术后颅内感染。     

利奈唑胺治疗新生儿耐药革兰氏阳性球菌败血症临床分析

目的 观察分析利奈唑胺治疗新生儿耐药革兰氏阳性球菌败血症的临床疗效和安全性。 方法 回顾分析本院新生儿科收治的30例耐药革兰氏阳性球菌败血症的临床特征、细菌学结果以及应用利奈唑胺治疗的临床疗效和安全性。 结果 30例血培养共检出耐甲氧西林凝固酶阴性葡萄球菌 (methicillin resistant coagulase negative staphylococci,MRCNS)22株,屎肠球菌5株,耐甲氧西林金黄色葡萄球菌(methicillin-resistant staphylococcus aureus,MRSA)3株,药敏结果对青霉素、红霉素、氨苄西林、头孢唑啉等均耐药,对利奈唑胺敏感。MRCNS中表皮葡萄球菌12株、溶血葡萄球菌6株、人葡萄球菌2株,科氏葡萄球菌2株。治愈22例( 73.3%) ,显效5例(16.7%) ,进步自动出院2例(6.7%), 无效1例(3.3%) ,总有效率90%,血培养转阴率96.7%。治疗过程中5例(16.7%)发生不良反应,2例贫血,2例腹泻( 1例合并粒细胞减少),1例呕吐,不良反应均较轻微,不影响用药,未见血小板减少,肝肾功能损害,皮疹及听神经病变等不良反应。 结论 利奈唑胺治疗新生儿耐药革兰氏阳性球菌败血症疗效显著、安全性好。     

Synthesis and in vitro antibacterial activities of novel oxazolidinones

Design and synthesis of novel piperazinylaryloxazolidinones possessing heteroaryl groups are described and their in vitro antibacterial activities have been evaluated by MIC assay. Compounds (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrofuran-2-yl)-acryloyl]-piperazin-1-yl]-phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (6o), (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrothien-2-yl)-acryloyl]-piperazin-1-yl]-phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (6p) and N-oxide of (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrofuran-2-yl)-acryloyl]-piperazin-1-yl]-phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (9) showed superior antibacterial activities than linezolid and also active against the linezolid resistant Staphylococcus aureus strains.     

The first clinical experiences in Hungary with a new effective antibiotic (linezolid) effective against Gram-positive infections

INTRODUCTION: The occurrence of gram-positive infections caused by multiresistant organisms has increased significantly in general, particularly among the surgical patients, and only a few effective antibiotics are available. A new and effective, synthetic antibiotic, against gram-positives is the oxazolidinon group, that electively inhibits bacterial protein synthesis in the early phase. Linezolid, the first member of this group to be used in clinical practice is the linezolid was studied. AIMS: The purpose of this study was to evaluate the effectiveness and safety of linezolid in the gram-positive infections of surgical patients. METHODS: A 3rd phase, clinical trial was conducted at the Semmelweis University Ist Surgical Department in the period of 1999-2001. Twenty-one patients with gram-positive infections were enrolled to this study. The mean of age was 57 years. Patients were selected for linezolid treatment in whom the conventional anti-gram-positive antibiotic therapy caused difficulties. RESULTS: Sixteen patients out of 21 recovered, one patient was cured clinically, but not microbiologically, and one case showed microbiological cure with clinical failure. In one case the methicillin resistant Staphylococcus aureus carriership was cured. Two cases had a fatal outcome. The causes of death were mediastinitis plus pneumonia in one case, and diffuse peritonitis with renal insufficiency in the other. Withdrawal from the study occurred in one case, due to drug intolerance. CONCLUSIONS: The linezolid administration proved to be safe and effective even in those cases, in which either hypacusis or decreased renal function persisted, or oral intake was advantagous. Contraindication of linezolid therapy did not occur. Few side effects were observed. If the infection was polymicrobial, the linezolid could be combined with other antibiotics. Further investigations are mandatory to evaluate the role of linezolid in the treatment of methicillin resistant Staphylococcus aureus carriership.     

金黄色葡萄球菌的耐药性分析及流行病学分型

目的 研究金黄色葡萄球菌(SAU)的耐药性及流行病学分型特点.方法 应用Microscan Walkaway96全自动细菌鉴定仪进行菌种鉴定及抗菌药物敏感性试验;应用脉冲凝胶电泳将随机选取的部分MRSA进行分子流行病学分型.结果 共分离497株金黄色葡萄球菌,未发现万占霉素及利奈唑胺耐药及中介的菌株,SAU对磺胺甲噁唑/甲氧苄啶及氯霉素耐药率相对较低,分别为12.6％、5.9％ ;40株MRSA脉冲凝胶电泳分型共有6个分型,其中A型及其亚型最多,占47.5％,B型占20.0％,其余4个分型占32,5％.结论 万古霉素及利奈唑胺是对MRSA最为敏感的药物,医院MRSA分子流行病学分型以脉冲凝胶电泳分型A型及B型为主.     

Limited Capability for Testing Mycobacterium tuberculosis for Susceptibility to New Drugs

We surveyed availability of phenotypic drug susceptibility testing for drug-resistant Mycobacterium tuberculosis in Europe. Of 27 laboratories, 17 tested for linezolid, 11 for clofazimine, 9 for bedaquiline, and 6 for delamanid during 2019. Our findings indicate that testing capacity for newer and repurposed tuberculosis drugs exists, but its availability is limited.     

河北省五市结核分枝杆菌耐药情况及耐多药菌株对利奈唑胺的敏感性

目的了解河北省结核分枝杆菌耐药情况,以及耐多药结核分枝杆菌对利奈唑胺的敏感性,指导临床治疗耐多药结核病。方法收集河北省五市六所医院2016年1—12月974例结核病患者分离菌株及患者临床信息,检测结核分枝杆菌对抗结核药物异烟肼(INH)、利福平(RFP)、链霉素(SM)、乙胺丁醇(EMB)、氧氟沙星(OFX)、卡那霉素(KM)的敏感性,采用分层随机法选取100株耐多药结核分枝杆菌,检测其对利奈唑胺的敏感性。结果结核病初治患者的耐药率和耐多药率分别为26.6%(200/753)和13.5%(102/753),复治患者的耐药率和耐多药率分别为59.7%(132/221)和53.4(118/221),复治患者耐药率和耐多药率均高于初治患者(χ~2值分别为83.7、93.5,均P0.01)。一线抗结核药物INH、RFP、SM和EMB的耐药率分别为25.8%、23.7%、16.7%和7.1%;二线抗结核药物OFX和KM的耐药率为4.7%(37/782)和4.0%(31/782);耐多药结核分枝杆菌对利奈唑胺的敏感率为80.8%(59/73)。结论结核病复治患者耐药率和耐多药率高于初治患者,利奈唑胺体外对耐多药结核分枝杆菌具有良好的抗菌活性。