万古霉素治疗革兰阳性球菌血流感染患者的血药浓度监测

目的了解本院革兰阳性球菌血流感染患者万古霉素的临床应用及血清谷浓度的监测。方法采用荧光偏振免疫偏振法测定万古霉素血清谷浓度,并结合住院患者的临床资料(基础疾病、病原学结果、万古霉素血清谷浓度、疗效、肾功能情况等),对血流感染革兰阳性球菌并应用万古霉素的25例患者进行回顾性分析。结果血流感染耐甲氧西林金黄色葡萄球菌(MRSA)11例(44.0%),屎肠球菌14例(56.0%);临床治愈率32.0%。25例患者共进行万古霉素血清谷浓度测定38例次,血清谷浓度范围2.99~39.1μg/mL,均值(14.96±7.83)μg/mL,其中达到靶浓度15~20μg/mL者8例(21.0%)。临床治愈组与临床无效组万古霉素血清谷浓度分别为(14.69±7.20)、(15.13±8.53)μg/mL(P=0.85)。肾毒性发生6例(24.0%),APACHEⅡ评分均值17分,均为临床无效组。11例MRSA血流感染中,1例万古霉素最低抑菌浓度(MIC)值为2 mg/L,其余万古霉素MIC值均为1 mg/L;临床治愈组万古霉素曲线下面积(AUC)与MIC浓度比值(AUC/MIC)为209±114。结论按照指南的标准,25例血流感染患者万古霉素血清谷浓度达标率低,需加强对这一类患者血清谷浓度的监测力度,并随时调整用药,给出个体化的用药方案。     

头孢硫脒在治疗革兰阳性菌烧伤感染中的作用

目的 探讨应用头孢硫脒在防治革兰阳性菌烧伤感染中的作用。方法 140例烧伤感染患者随机分成两组。试验组76例，应用头孢硫脒治疗；对照组64例，给予头孢呋辛治疗。疗程7-14d，并进行细菌敏感性试验。结果 头孢硫脒组有效率95％，头孢呋辛组有效率44％，两组总有效率有显著差异（P〈0．01）。烧伤感染革兰阳性菌的主要致病菌对头孢硫脒的敏感性较高。体外药敏试验显示头孢硫脒对细菌的清除率为87．17％。结论 临床研究证实头孢硫脒对治疗烧伤革兰阳性菌疗效良好。可作为治疗烧伤革兰阳性菌感染的一线应用抗生素。     

湖北地区革兰氏阳性球菌耐药现状与变迁

湖北地区自1996年开始细菌耐药性监测，革兰氏阳性球菌分离率逐年升高，近年二、三级医院均达40％，以凝固酶阴性葡萄球菌居首位。MRSA5年上升14％，医院问差异明显；VRE分离率为2％～3％，以VanB型为主；PISP PRSP分离率为41．6％，其中儿童为65％。SMZ/TMP与氯霉素对金黄色葡萄球菌的耐药率似呈下降趋势，而庆大霉素、环丙沙星、四环素、红霉素、克林霉素的耐药率显著上升。二级医院MRSA平均为8．6％。     

头孢硫脒对老年人呼吸道革兰氏阳性细菌感染疗法观察

目的探讨头孢硫脒对老年人呼吸道革兰氏阳性细菌感染的临床疗效,细菌阴转率及安全性.方法选择住院呼吸道革兰氏阳性细菌感染并且年龄≥60岁的老年病人共14例,用头孢硫脒进行治疗,每天4g,分2次给药,静脉滴注,疗程5～16(9.4士3.1)d,不同时使用其它抗生素.结果总有效率及治疗后细菌阴转率均达到86%,而且,用药期间除1例患者出现皮肤瘙痒外,未发现其它不良反应,亦无肝肾功能方面的损害.结论头孢硫脒用于治疗老年人呼吸道革兰氏阳性细菌感染疗效确切,不良反应少,是一种安全、有效的药物.     

Pharmacological strategies to decrease transfusion requirements in patients undergoing surgery

Surgical procedures are inevitably associated with bleeding. The amount of blood loss may vary widely between different surgical procedures and depends on surgical as well as non-surgical factors. Whereas adequate surgical haemostasis may suffice in most patients, pro-haemostatic pharmacological agents may be of additional benefit in patients with (diffuse) surgical bleeding or in patients with a specific underlying haemostatic defect. In general, surgical haemostasis and pharmacological therapies can be complementary in controlling blood loss. The use of pharmacological therapies to reduce blood loss and blood transfusions in surgery has historically been restricted to a few drugs. Antifibrinolytic agents (aprotinin, tranexamic acid and aminocaproic acid) have the best evidence supporting their use, especially in cardiac surgery, liver transplantation and some orthopaedic surgical procedures. Meta-analyses of randomised, controlled trials in cardiac patients have suggested a slight benefit of aprotinin, compared with the other antifibrinolytics. Desmopressin is the treatment of choice in patients with mild haemophilia A and von Willebrand disease. It has also been shown to be effective in patients undergoing cardiac surgery who received aspirin up to the time of operation. However, overall evidence does not support a beneficial effect of desmopressin in patients without pre-existing coagulopathy undergoing elective surgical procedures. Topical agents, such as fibrin sealants have been successfully used in a variety of surgical procedures. However, only very few controlled clinical trials have been performed and scientific evidence supporting their use is still limited. Novel drugs, like recombinant factor VIIa (eptacog alfa), are currently under clinical investigation. Recombinant factor VIIa has been introduced for the treatment of haemophilia patients with inhibitors, either in surgical or non-surgical situations. Preliminary data indicate that it may also be effective in surgical patients without pre-existing coagulation abnormalities. More clinical trials are warranted before definitive conclusions can be drawn about the safety and the exact role of this new drug in surgical patients. Only adequately powered and properly designed randomised, clinical trials will allow us to define the most effective and the safest pharmacological therapies for reducing blood loss and transfusion requirements in surgical patients. Future trials should also consider cost-effectiveness because of considerable differences in the costs of the available pro-haemostatic pharmacological agents.     

Mohnarin 2008年度报告:华北地区革兰阳性菌临床感染特征及结果分析

目的 调查华北地区细菌感染患者革兰阳性菌的耐药状况.方法 在统一方案和统一标准前提下,收集包括北京、天津、河北、内蒙古和山两5个地区临床分离革兰阳性菌药物敏感性结果,用WHONET 5.4软件进行数据分析.结果 自2008年1月至2008年12月共收集革兰阳性菌11630株,包括葡萄球菌属7551株,肠球菌2933株,链球菌867株,其它革兰阳性菌289株.耐甲氧西林金黄色葡萄球菌(MRSA)和凝固酶阴性耐甲氧西林葡萄球菌(MRCNS)的比例分别为62.8%和81.5%.肺炎链球菌对青霉素的不敏感率为38.8%.粪肠球菌和屎肠球菌万古霉素耐药率分别为2.6%和6.4%.结论 革兰阳性菌耐药呈现明显上升趋势,临床应采取积极措施,合理用药,以减少耐药发生.     

肿瘤医院感染患者革兰阳性菌分布与耐药性及经验性抗MRSA的研究

目的:调查肿瘤医院感染患者革兰阳性菌的分布与耐药性,为临床经验性初始治疗医院获得性肺炎提供依据.方法:回顾性收集2018年中山大学肿瘤防治中心所有感染患者的病原菌并进行药敏试验,分析革兰阳性菌分布与耐药性,并计算抗药性金黄色葡萄球菌(MRSA)的比例.结果:在2712病原菌分离株中,革兰阳性菌占26.3％,最常见的是凝...     

我院ICU下呼吸道感染革兰阳性菌分离情况及耐药性分析

目的:探讨我院ICU下呼吸道感染中常见的革兰阳性细菌分离情况及耐药性,以指导临床用药.方法:采用回顾性分析方法,收集我院ICU下呼吸道感染临床送检的痰培养的资料,包括细菌鉴定及药敏试验.细菌鉴定采用法国梅里埃公司VITEK-32全自动微生物分析系统鉴定;药敏试验方法,采用K-B(Kirby-Bauer)法,严格按照CLSI标准判定敏感菌株.结果:共分离到病原菌504株,革兰阳性菌145株,占分离菌的28.8%,以金黄色葡萄球菌为主,占革兰阳性菌的63.4%;革兰阴性菌286株,占分离菌的56.7%;真菌73株,占分离菌的14.5%.药敏结果提示,革兰阳性菌对青霉素的耐药率达100%,对万古霉素、替考拉宁的敏感率达100%.结论:革兰阳性细菌是ICU下呼吸道感染的主要病原微生物之一,其耐药现象严重;万古霉素、替考拉宁是治疗耐药的革兰阳性菌感染的有效药物.     

Cation substitution in cationic phosphonolipids: a new concept to improve transfection activity and decrease cellular toxicity

Cationic lipids have been shown to be an interesting alternative to viral vector-mediated gene delivery into in vitro and in vivo model applications. Prior studies have demonstrated that even minor structural modifications of the lipid hydrophobic domain or of the lipid polar domain result in significant changes in gene delivery efficiency. Previously, we developed a novel class of cationic lipids called cationic phosphonolipids and described the ability of these vectors to transfer DNA into different cell lines and in vivo. Up until now, in all new cationic lipids, nitrogen atoms have always carried the cationic or polycationic charge. Recently we have developed a new series of cationic phosphonolipids characterized by a cationic charge carried by a phosphorus or arsenic atom. In a second step, we have also examined the effects of the linker length between the cation and the hydrophobic domain as regards transfection activity. Transfection activities of this library of new cationic phosphonolipids were studied in vitro in different cell lines (HeLa, CFT1, K562) and in vivo using a luciferase reporter gene. A luminescent assay was carried out to assess luciferase expression. We demonstrated that cation substitution on the polar domain of cationic phosphonolipids (N --> P or As) results in significant increase in transfection activity for both in vitro and in vivo assays and decrease of cellular toxicity.     

Liposomes for systematic delivery of vancomycin hydrochloride to decrease nephrotoxicity: Characterization and evaluation

Vancomycin hydrochloride （VANH）, the first glycopeptide antibiotic, is a water-soluble drug for the treatment of acute osteomyelitis. Liposomal formulations of VANH have already been manipulated and characterized, which was a mean of increasing their therapeutic index, reducing their toxicity and altering drug biodistribution. One of the challenges for preparing VANH-Lips is their low encapsulation efficiency (EE). In the present study, we aim to improve the liposomal formulation of VANH for higher EE, longer systemic circulation, reduced nephrotoxicity and enhanced antimicrobial activities. Vancomycin hydrochloride-loaded liposomes (VANH-Lips) were formulated by the method of modified reverse phase evaporation. Based on the optimization of formulation with orthogonal experimental design, the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78 ± 2.56% and 188.4 ± 2.77 nm. In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation. After intravenous injection to mice, the mean residence time (MRT) of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution (VANH-Sol) group. Furthermore, the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection. In conclusion, VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.     

万古霉素类药物在血培养呈阳性败血症儿童中的应用分析

目的：调研上海交通大学医学院附属新华医院2005-2006年万古霉素类药物在血培养呈阳性败血症患儿中的应用情况，发现儿科用药潜在的问题，从而优化用药。方法：回顾性调查分析本院2005—2006年使用万古霉素类药物治疗血培养呈阳性的败血症患儿的病史记录。就用药方案、微生物学检查和药品不良反应等信息判断万古霉素类药物的应用是否合理。结果：调研符合要求的病史115份中，53．0％的患儿用药基本合理，30．0％的患儿用药时间不规范。含万古霉素类药物的治疗方案以一联或两联抗菌药物为主。病史记录显示共发生6例药品不良反应。结论：万古霉素在血培养呈阳性败血症患儿的使用应得到进一步规范管理。     

The many roles of chemokine receptors in neurodegenerative disorders: emerging new therapeutical strategies

Chemokines and chemokine receptors, primarily found to play a role in leukocyte migration to the inflammatory sites or to second lymphoid organs, have recently been found expressed on the resident cells of the central nervous system (CNS). These proteins are important for the development of the CNS and are involved in normal brain functions such as synaptic transmission. Increasing lines of evidence have implicated an involvement for chemokines and their receptors in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), human immunodeficiency virus-associated dementia (HAD), multiple sclerosis (MS), and stroke. Specific inhibition of the biological activities of chemokine receptors could gain therapeutic benefit for these neurodegenerative disorders. In recent years, non-peptide antagonists of chemokine receptors have been disclosed and tested in relevant pharmacological models and some of these inhibitors have entered clinical trials. The aim of this review is to outline the recent progress regarding the role of chemokines and their receptors in neurodegenerative diseases and the advancements in the development of chemokine receptor inhibitors as potential therapeutic approaches for these neurodegenerative diseases.     

利奈唑胺和万古霉素对重症监护治疗病房革兰阳性球菌感染患者治疗效果的Meta分析

目的:比较、评价利奈唑胺和万古霉素治疗重症监护治疗病房(intensive care unit,ICU)革兰阳性球菌感染患者的疗效及安全性。方法:采用Meta分析的方法,用计算机检索Pub Med、Cochrane Library、CNKI和万方数据库,评价筛选文献,纳入利奈唑胺和万古霉素的随机对照试验(RCT),并采用Rev Man 5.2进行Meta分析。结果:6个随机对照试验,共纳入革兰阳性球菌感染的ICU患者444名,其中利奈唑胺组218名,万古霉素组226名。Meta分析显示,临床治疗有效率,利奈唑胺优于万古霉素[OR=3.07,95%CI(1.76,5.34),P<0.01],细菌清除率上,利奈唑胺高于万古霉素[OR=3.83,95%CI(1.81,8.12),P=0.000 5];微生物学治愈率和不良反应发生率,利奈唑胺与万古霉素两组间差异均无统计学意义。结论:在治疗ICU重症患者革兰氏阳性球菌感染中,利奈唑胺在临床有效率和细菌清除率方面,明显优于万古霉素,而在微生物学治愈率和不良反应发生率上利奈唑胺则和万古霉素相当,但仍需要更大样本量、更加严格设计的随机对照试验进一步验证。     

急性白血病患者革兰阳性菌血流感染的病原学及临床特征分析

目的 分析急性白血病(acute leukemia, AL)患者合并革兰阳性菌血流感染(bloodstream infection, BSI)的病原学分布、耐药情况及临床特征,为临床诊疗及预后评估提供理论依据。方法 收集2010年1月—2018年12月湖南省3家大型医院血液科1012例AL合并血流感染患者的临床资料,对其中261例革兰阳性菌感染患者的病原学及临床特征进行分析。结果 AL合并血流感染的患者中25.8%为革兰阳性菌感染,主要致病菌有凝固酶阴性葡萄球菌(137株,52.5%)、链球菌(51株,19.5%)、金黄色葡萄球菌(38株,14.6%)。绝大多数革兰阳性菌对苯唑西林、青霉素G、红霉素耐药率较高,而对糖肽类抗菌药物(万古霉素、替考拉宁)及利奈唑胺的敏感率达90%以上。感染性休克、启动敏感抗菌药物治疗时间＞48h是AL患者并革兰阳性菌血流感染30d内死亡的独立危险因素(P＜0.05)。结论     

急性白血病患者革兰阳性菌血流感染的病原学及临床特征分析

目的分析急性白血病(acute leukemia, AL)患者合并革兰阳性菌血流感染(bloodstream infection, BSI)的病原学分布、耐药情况及临床特征,为临床诊疗及预后评估提供理论依据。方法收集2010年1月—2018年12月湖南省3家大型医院血液科1012例AL合并血流感染患者的临床资料,对其中261例革兰阳性菌感染患者的病原学及临床特征进行分析。结果 AL合并血流感染的患者中25.8%为革兰阳性菌感染,主要致病菌有凝固酶阴性葡萄球菌(137株,52.5%)、链球菌(51株,19.5%)、金黄色葡萄球菌(38株,14.6%)。绝大多数革兰阳性菌对苯唑西林、青霉素G、红霉素耐药率较高,而对糖肽类抗菌药物(万古霉素、替考拉宁)及利奈唑胺的敏感率达90%以上。感染性休克、启动敏感抗菌药物治疗时间>48h是AL患者并革兰阳性菌血流感染30d内死亡的独立危险因素(P<0.05)。结论 AL患者革兰阳性菌血流感染耐药情况严峻,临床上对考虑合并革兰阳性菌血流感染的AL患者应及早应用糖肽类抗菌药物及利奈唑胺或替加环素,并根据药敏结果及疗效调整用药。     

Treatment of Helicobacter Pylori infection: optimization strategies in a high resistance era

Introduction: Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders and in the prevention of gastric cancer. Due to increasing antimicrobial resistance, performance of standard triple therapies has now declined to unacceptably low levels.

Areas covered: In this article: i) we critically revise optimization tools aiming to improve the outcome of standard treatments; ii) we provide updated evidence on the efficacy and rationale for the use of several non-bismuth quadruple regimens in clinical practice, recommended as preferred empirical therapies in areas of high clarithromycin resistance.

Expert opinion: Prolonged (14-day) treatment duration may boost the efficacy of standard triple therapy by approximately 5%. Use of a high-dose PPI and/or new-generation PPIs, rabeprazole and esomeprazole, might improve eradication rates, particularly in regions where the CYP2C19 rapid metabolizer phenotype is prevalent. Adjunctive probiotics may be considered to improve treatment tolerability, though more data are required to better define their role in H. pylori eradication. Among non-bismuth quadruple regimens, both concomitant and sequential therapies are appropriate options for high-resistance settings; however, concomitant therapy appears to be less impaired by dual clarithromycin/metronidazole resistance. Hybrid therapy is a promising new alternative which seems not to be inferior to concomitant therapy.     

老年患者大剂量使用万古霉素血药浓度监测结果及肾毒性分析

目的: 了解老年患者大剂量使用万古霉素的血药浓度情况以及对肾功能的影响。方法: 51例老年感染患者给予万古霉素1 g静滴q12h,对万古霉素血清谷浓度以及治疗前后相关肾功能指标进行统计分析。结果: 采用万古霉素1 g静脉滴注q12h的给药剂量,56.9%老年患者血药谷浓度超过20 mg·L^-1,并且治疗前后血肌酐值有统计学差异(P<0.05);无论患者肾功能是否正常,给予万古霉素1 g 12h治疗前后内生肌酐清除率有有统计学差异(P<0.05)。结论: 老年患者用万古霉素抗感染治疗时,经验性给予1 g q12h的剂量,初步观察到血药谷浓度很可能会超过参考范围,并会引起肾功能的损害,但本研究样本量小,仍需大样本的进一步研究论证。     

Treatments for astrocytic tumors in children: current and emerging strategies

Strategies for the treatment of childhood cancer have changed considerably during the last 50 years and have led to dramatic improvements in long-term survival. Despite these accomplishments, CNS tumors remain the leading cause of death in pediatric oncology. Astrocytic tumors form the most common histologic group among childhood brain tumors. They are a heterogeneous group that from a practical therapeutic point of view can be subdivided into low-grade astrocytomas (LGA), optic pathway gliomas (OPG), high-grade astrocytomas (HGA), and brainstem gliomas (BSG). This article focuses on the practical application of treatments that lead to long-term survival, improved quality of life, and reduced long-term complications. Improvement in therapy has led to better outcomes for patients with LGA and OPG. Careful follow-up without any treatment is indicated for a small percentage of patients diagnosed with LGA with an indolent course including children with neurofibromatosis type 1 (NF1). Surgery is the main recommended treatment for children with resectable LGA. Radiation therapy is generally recommended for children with progressive LGA, or after failure of chemotherapy, accomplishing tumor control at 10 years in over 60% of patients. Cytotoxic chemotherapy is usually reserved for children who have had treatment failure with surgery and radiation therapy. It is also offered for children who are too young to be treated with radiation or to defer or avoid radiotherapy. Carboplatin and vincristine achieve 5% complete and 28% partial responses but the use of vincristine is criticized due to poor penetration of the CNS. A regimen of tioguanine, procarbazine, mitolactol, lomustine, and vincristine is frequently administered as an alternative to carboplatin and vincristine in LGA. The introduction of temozolomide has allowed better responses, including a 24% complete response rate compared with 0-5% complete response rates with the previous regimens. OPG are usually histologically LGA, and are treated with similar chemotherapy regimens. OPG is the most common type of brain tumor associated with NF1. Tumor growth in some of these patients is slow with no treatment recommended for an extended period of time. The prognosis for children with the remaining types of astrocytomas remains poor. Surgical resection is typically the first step in the treatment of HGA followed in older children by radiation therapy. The data regarding chemotherapy are mixed. Combination chemotherapy before or after radiation, including cisplatin, carmustine, cyclophosphamide, and vincristine or carboplatin, ifosfamide, cyclophosphamide, and etoposide has provided disappointing results. Clinical trials with temozolomide and agents directed against single targets have not shown substantially better results, but it is hoped that currently conducted studies will provide better outcomes. Diffuse intrinsic BSG are among the most difficult-to-treat brain tumors. Surgical treatment is not recommended for diffuse intrinsic BSG and standard radiation therapy is typically given in children aged >3 years. None of the numerous chemotherapy regimens, including temozolomide, has provided a significant response rate or an improvement in survival. It is expected that newer agents affecting multiple targets such as AEE-788 and antineoplastons, and combinations of single-targeted agents with chemotherapy will provide better results. Careful evaluation of histology, location of the tumor, patient age, and consideration of treatment-related morbidity play an important part in selecting between clinical observation, surgery, radiation, chemotherapy, or investigational agents. The goals of treatment for astrocytic tumors should extend well beyond objective responses and increased survival. Improvement of quality of life is an equally important objective of treatment. Radiation therapy and chemotherapy result in serious late toxicities.     

Neurotherapeutics in multiple sclerosis: novel agents and emerging treatment strategies

New insights into the complex immunopathogenesis of multiple sclerosis have led to a proliferation of promising new therapeutic strategies. While the current armamentarium of immunomodulatory medications has demonstrated beneficial effects on the disease, more effective and tolerable therapies are needed. Several novel therapeutic strategies under investigation include oral therapies, monoclonal antibodies, symptomatic treatments, insights into neuroprotection and repair as well as combination regimens. New therapies may prove more efficacious and tolerable than the available arsenal of treatments; however, decisions regarding first-line therapies will expectedly become more complicated, with greater influence if risk-to-benefit ratios in light of premature safety data. Biomarker profiles may help elucidate disease subtypes as well as therapeutic response in an effort to individualize treatment choice. This review will highlight recent promising therapeutic strategies under investigation in the field of MS.