利奈唑胺治疗广泛耐药肺结核病的效果观察及不良反应的处置

广泛耐药结核病（extensively drug resistant tuberculosis,XDR-TB）指结核病患者感染的结核分枝杆菌体外被证实除对异烟肼、利福平耐药外,还对任何氟喹诺酮类药物产生耐药,以及3种二线抗结核注射药物（卷曲霉素、卡那霉素和阿米卡星）中的至少1种耐药[1]。XDR-TB是最为严重的一种耐药结核病,由于缺乏有效的药物,其临床治疗效果极差,死亡率高且死亡发生的速度快,     

利奈唑胺血清药物浓度监测在耐药结核病患者中的应用

利奈唑胺是一种新型的?唑烷酮类抗生素,是治疗耐药结核病的关键药物,该药治疗窗口狭窄,虽然疗效明显,但是临床应用不良反应的发生率高,如何安全有效地应用该药治疗耐药结核病一直困扰临床医生。治疗药物监测（therapeuticdrugmonitoring,TDM）通过监测患者血液中的药物浓度,可为药物剂量调整提供依据,使药物达到有效治疗浓度的同时最大程度地降低不良反应发生。目前国内外均有报道利用TDM研究利奈唑胺在耐药结核病患者中的最佳使用剂量和疗程,探讨利奈唑胺的谷浓度、峰浓度与不良反应发生率之间的关系,特别是对老年人、儿童、肝肾功能不全的患者临床安全使用利奈唑胺个体化治疗进行系列的探索研究。本文对利奈唑胺不良反应的发生机制、利奈唑胺的使用剂量及安全性、利奈唑胺药物浓度的影响因素、TDM的方式和应用等进行综述,为更加安全有效地应用利奈唑胺治疗耐药结核病提供参考。     

利奈唑胺治疗老年重症肺炎的疗效和安全性评价

目的 对比观察利奈唑胺治疗老年重症耐甲氧西林金黄色葡萄球菌( MRSA)的有效性及安全性.方法回顾性分析我院2009年1月至2010年12月收治的老年重症MRSA肺炎患者50例,分为利奈唑胺治疗组和万古霉素治疗组,比较两组患者的临床治疗总有效率、细菌清除率及不良反应发生率等指标.结果 利奈唑胺组与万古霉素组临床总有效率分别为75.0％、46.2％,差异有统计学意义(P＜0.05);细菌清除率分别为70.8％、53.8％,差异无统计学意义(P＞0.05);不良反应发生率分别为16.7％、46.2％,差异有统计学意义(P＜0.05).结论 利奈唑胺组治疗老年重症MRSA肺炎临床疗效优于万古霉素组,对老年重症MRSA肺炎患者安全、有效.     

利奈唑胺联合方案治疗耐多药结核病效果及不良反应研究

目的探讨含利奈唑胺联合方案治疗对耐多药结核病患者痰菌阴转率、病灶吸收情况、空洞变化情况及不良反应的影响。方法收集2012年1月—2017年12月于我院治疗的60例耐多药结核病患者临床资料,根据治疗方案将患者分为对照组与研究组。对照组治疗方案为左氧氟沙星、阿米卡星、吡嗪酰胺、丙硫异烟胺及对氨基水杨酸。研究组治疗方案为在对照组治疗方案基础上给予利奈唑胺治疗。比较2组患者痰菌阴转率、病灶吸收情况、空洞变化情况及不良反应。结果治疗6个月,研究组痰菌阴转率与病灶吸收有效率均大于对照组(P均<0.05),空洞变化有效率及不良反应发生率与对照组无显著差异(P均> 0.05)。结论含利奈唑胺联合方案治疗可提高耐多药结核病患者痰菌阴转率和病灶吸收有效率,但易发生血小板减少,贫血等不良反应,须定期进行血常规检查。空洞变化有效率及不良反应与对照组相同。     

利奈唑胺不良反应文献分析

目的探讨利奈唑胺不良反应发生的一般规律及特点,为临床医师、临床药师合理用药提供科学依据。方法检索2000～2012年中国知网《CHKD期刊全文数据库》和《万方数据知识服务平台》内收录的50例利奈唑胺不良反应患者的文献资料并进行统计分析。结果利奈唑胺所致不良反应常在用药第1周（46.43%）、第2周（30.36%）发生;50例患者中70岁以上高龄患者占66%;不良反应多为对血液系统的影响（86%）,主要表现为血小板减少（76%）,64.10%血小板减少患者血小板低至50×109/L以下,最低值4×109/L,其他表现为全血细胞减少、贫血、粒细胞减少、白细胞减少,再次为血乳酸水平升高、血压升高等。结论临床医师、药师应重视利奈唑胺所致的严重不良反应,注意加强用药监护,确保用药安全、有效。     

利奈唑胺治疗老年肺部感染的临床疗效分析

目前耐甲氧西林金黄色葡萄球菌(MRSA)检出率有逐年升高的趋势,其对β-内酰胺类、氟喹诺酮类等多种抗生素大多耐药,临床多首选万古霉素,但近年来又出现了对万古霉素中介或耐药的金葡菌,对革兰阳性菌感染的治疗提出了新的挑战[1].利奈唑胺作为第一个应用于临床的新型恶唑烷酮类抗菌药,其在体内外对各类革兰阳性球菌具有高度抗菌活性,且由于其作用靶点和作用方式的独特,故其在临床应用上越来越受到关注.本文对在我院住院治疗的老年肺部感染患者应用利奈唑胺的疗效及其安全性进行总结分析.     

利奈唑胺治疗腹腔感染1例报告

1 病历资料 患者男,39岁,因"反复发作上腹痛6年,加重5 d"于2007-11-29入院.患者自述2001-2007年"胆囊炎"和"急性胰腺炎"多次发作,均经内科治疗后好转.5 d前因劳累及饮酒后再发腹痛,在外院查血尿淀粉酶增高,经内科治疗不能缓解,逐渐出现腹压增高、血压下降、少尿症状,遂在外院急诊行"胰腺松解术,胃、空肠、胆囊造瘘术".     

含贝达喹啉及利奈唑胺方案治疗耐多药结核病24周疗效及安全性观察

目的 评价含贝达喹啉联合利奈唑胺方案治疗耐多药结核病(multidrug-resistant tuberculosis,MDR-TB)的早期疗效及安全性.方法 纳入2018年3月至2020年10月成都市公共卫生临床医疗中心门诊及住院部确诊为MDR-TB的患者68例,所有患者均给予贝达喹啉联合利奈唑胺的方案抗痨,动态监测...     

利奈唑胺治疗难治性胆道感染1例报告

1 病历资料 患者男,83岁,因"头晕、恶心、呕吐半个月,加重伴发热半天"于2008-03-17入院.半个月前无明显诱因出现恶心、头昏、呕吐胃内容物.口服药物治疗效果不佳(药物不详),半天前症状突然加重并伴有发热达39℃.到我院急诊,查白细胞16.8×109/L(中性粒细胞0.13),血红蛋白145 g/L,血小板计数109×109/L.     

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.     

Systematic review and meta-analysis of the efficacy and safety of therapy with linezolid containing regimens in the treatment of multidrug-resistant and extensively drug-resistant tuberculosis

Background

Linezolid containing regimens have been proposed as potentially valuable alternatives for the treatment of patients with multidrug-resistant tuberculosis (MDR-TB) or extensively drug-resistant TB (XDR-TB).

Methods

A systematic review and meta-analysis was conducted to assess the efficacy, safety and tolerability of linezolid for drug-resistant TB (DR-TB) treatment. We searched the Cochrane Controlled Trial Registry, PubMed, Embase, Science Citation Index Expanded (SCI) and China National Knowledge Infrastructure (CNKI), database up to May 2014 to identify studies providing data of the use of linezolid for the treatment of DR-TB.

Results

The search yielded 15 studies (367 patients) including one randomized controlled trial (RCT), covering 239 patients who could be evaluated for effectiveness; 83% [95% confidence interval (CI), 75-90%; I²=62.8%] had a favorable outcome, defined as either cure or treatment completion. The pooled rate of culture conversion was 89% (95% CI, 83-95%; I²=49.6%). Between the group receiving daily linezolid doses of ≤600 or >600 mg, the mortality was considerably lower in patients treated with less than 600 mg/day (P value <0.001). Of 367 patients for whom data on safety was available, peripheral neuropathy (31%, 95% CI, 19-42%; I²=81.7%) and anemia (25%, 95% CI, 15-34%; I²=76.6%) were the main adverse effects. Patients receiving less than 600 mg/day were more likely to experience nervous system adverse events (P value <0.01).

Conclusions

The available evidence suggests that linezolid could be considered as a promising option as treatment of MDR/XDR TB. Randomized trials are warranted to define the dose and frequency of administration.     

Efficacy and safety of linezolid in liver transplant patients

S. Radunz, B. Juntermanns, G.M. Kaiser, J. Treckmann, Z. Mathe, A. Paul, F.H. Saner. Efficacy and safety of linezolid in liver transplant patients
Transpl Infect Dis 2011: 13: 353–358. All rights reserved Abstract: Bacterial infections are the main cause of death within the first year after liver transplantation, and the increased incidence of multidrug‐resistant gram‐positive pathogens has created a major challenge in the treatment of these patients. Linezolid, the first US Food & Drug Administration‐approved oxazolidinone, offers a valuable novel treatment option for serious gram‐positive infections. Linezolid is relatively non‐toxic but prolonged treatment with linezolid was associated with thrombocytopenia. Here we report on the experience of linezolid treatment in adult liver transplant patients, who are at an increased risk for thrombocytopenia because of hypersplenism. From November 2003 until December 2009, we evaluated the clinical course of 46 liver transplant patients (27 male/19 female) in our surgical intensive care unit. For proven or probable gram‐positive infection, all patients received linezolid 600 mg intravenously every 12 h. On clinical improvement, treatment was changed to oral linezolid 600 mg twice daily. Treatment duration was 11 ± 7 days. Treatment indications were pneumonia (n=8), blood stream infection (n=30), and surgical site/abdominal infection (n=3). Clinical cure was achieved in 43 out of 46 patients. During the course of treatment, no cases of severe thrombocytopenia occurred and a statistically significant platelet count increase was seen from day 1 (110 ± 73/nL) to day 7 (165 ± 116/nL) and day 14 (180 ± 140/nL). We did not observe any further adverse events, especially no severe neurological complications (e.g., serotonin syndrome) or signs of lactate acidosis. Two patients died from uncontrolled vancomycin‐resistant Enterococcus faecium sepsis with septic shock and one due to uncontrolled methicillin‐resistant Staphylococcus aureus pneumonia. These deaths were considered to be unrelated to linezolid treatment, and linezolid was regarded as the optimal treatment choice in these patients. A subgroup analysis of patients treated for >14 days revealed no statistically significant differences when compared with patients on shorter treatment. In particular, no cases of thrombocytopenia occurred during longer treatment. In conclusion, linezolid is a safe and effective treatment for adult liver transplant patients with gram‐positive infections.     

阿奇霉素对儿童重症肺炎急性期疗效及消化道反应的观察

目的探究阿奇霉素治疗儿童重症肺炎支原体肺炎急性期的临床疗效与不良反应,旨在进一步提高儿童重症肺炎支原体肺炎的治疗。方法选取我院2013年2月至2015年2月收治的重症肺炎支原体肺炎患儿共98例,按照入院时间顺序随机分为对照组与观察组,两组患儿均接受重症肺炎对症处理与护理。对照组接受红霉素静脉滴注,观察组接受阿奇霉素治疗。比较两组患儿重症肺炎支原体肺炎临床症状与体征消失时间及消化道等不良反应发生率。结果观察组患儿重症肺炎治疗痊愈率为64.0%,明显高于对照组痊愈率43.8%,P0.05。观察组重症肺炎支原体肺炎症状、体征包括憋喘、发热、咳嗽、肺部湿啰音消失时间均短于对照组,P0.05。观察组患儿治疗过程中出现的不良反应包括恶心、呕吐、腹痛、腹泻及皮疹,不良反应发生率为10.0%,明显低于对照组不良反应发生率33.3%,P0.05。结论阿奇霉素对儿童重症肺炎支原体肺炎急性期有较好的治疗效果,缩短了重症肺炎相关症状与体征持续的时间,且不良反应发生率低,适合临床推广使用。     

Successful treatment of methicillin-resistant Staphylococcus aureus pulmonary infection with linezolid in a patient with cystic fibrosis

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of pulmonary infection in patients with cystic fibrosis (CF). Because these organisms are frequently multidrug-resistant, most patients require intravenous therapy with vancomycin. We report on the first case of successful treatment of a pulmonary exacerbation due to MRSA in a CF patient with a new antimicrobial, linezolid. We demonstrated equivalence of intravenous and oral dosing in this patient, suggesting that oral linezolid may be an excellent alternative to intravenous vancomycin for CF patients infected with MRSA.     

利奈唑胺谷浓度在利福平耐药结核病患者中的监测与应用

目的?探讨利奈唑胺谷浓度在利福平耐药结核病患者中的有效参考浓度范围,并分析利奈唑胺谷浓度的影响因素及利奈唑胺不良反应发生的影响因素,为其在利福平耐药结核病患者个体化治疗中的应用提供理论依据。方法?选取我院使用利奈唑胺治疗耐药肺结核的94例次患者的血液样本,使用全自动二维液相色谱法测定利奈唑胺谷浓度,构建多元线性回归模型分析利奈唑胺谷浓度的影响因素。应用多元Logistic回归模型探讨药物不良反应发生的影响因素。对利奈唑胺谷浓度进行描述性统计,结合疗效及不良反应发生情况初步确定利奈唑胺谷浓度的有效参考范围。结果?患者血利奈唑胺谷浓度在0.12～6.62 mg/L之间,平均血药谷浓度值为1.24 mg/L。用药剂量及体质量指数是影响利奈唑胺谷浓度的重要因素（P=0.000,P=0.033）,得到下列回归方程：Y（谷浓度）= -0.029+5.058X1（用药剂量）-0.079X2（BMI）（R2=0.467）。谷浓度和肌酐清除率与药物不良反应的发生有关联,即每增加1个单位的谷浓度,不良反应的发生风险增加为之前的6.519倍,每增加1个单位肌酐清除率,不良反应的发生风险降低为之前0.957倍。结论?结合疗效相关性及不良反应发生情况,建议利奈唑胺治疗耐药结核的血药谷浓度的推荐参考范围在0.25～2.00 mg/L之间。可通过建立的多元线性回归方程预测利奈唑胺谷浓度,指导利奈唑胺个体化治疗。