26例氨曲南不良反应报告文献分析

<正>氨曲南(Aztreonam)是单环β-内酰胺类抗生素,通过抑制细菌细胞壁的合成而起杀菌作用,主要用于治疗革兰阴性需氧菌引起的感染。由于氨曲南不用皮试,且与青霉素之间无交叉过敏反应,不诱导细菌产生β-内酰胺酶,同时对细菌产生的大多数β-内酰胺酶高度稳定,在临床上得到了广泛     

氨曲南的不良反应分析

氨曲南是单环β-内酰胺类抗生素,对大多数需氧-革兰阴性杆菌具有较好作用,它在我国使用有10余年,广泛用于各种严重感染.本文对1994-2009年中国期刊全文数据库中文献报道的氨曲南的不良反应进行整理,收集氨曲南导致ADR 13例,以过敏反应最为常见,偶见中枢神经系统反应及造血系统损害.     

抗生素氨曲南市场概述

通用名称：氨曲南（Aztreonam）／噻肟单酰胺菌素,商品名称：君刻单;分子式：C13H17N508S2;剂型、规格：注射用氨曲南：0．5g、lg/瓶（效价）。氨曲南是第一个用于临床的单环β-内酰胺抗生素,具有疗效确切,抗菌谱广,体内分布广,对β-内酰胺酶稳定的特点。     

双纸片增效试验筛查金属β-内酰胺酶

目的：建立简便的双纸片增效试验,筛查产金属β-内酰胺酶的铜绿假单胞菌.方法：3组不同底物的双纸片增效试验检测金属β-内酰胺酶,比较其结果.结果：75株耐亚胺培南的铜绿假单胞菌分别应用亚胺培南、头孢他啶、氨曲南和其EDTA复合纸片检出金属β-内酰胺酶阳性株分别为13,11,10株,阳性率分别为17.3%,14.7%和13.3%;联合应用3组底物,检出阳性株18株,阳性率为24.0%.结论：双纸片增效试验可作为金属β-内酰胺酶的初筛试验.     

耐头孢他啶大肠埃希氏菌产β-内酰胺酶的特性研究

目的:研究耐头孢他啶大肠埃希氏菌产β-内酰胺酶的特性。方法:采用K-B纸片扩散法和等电聚焦对2株耐药大肠埃希氏菌产β-内酰胺酶类型进行初步判断;采用碱裂解法提取质粒并进行PCR扩增测序;β-内酰胺酶经饱和硫酸铵反抽提及SephadexG-75凝胶过滤和DE-52阴离子交换层析法纯化;以SDS-PAGE法测定其分子量及紫外分光光度法测定其酶动力学参数。结果:2株菌产生一种等电点为8.7的超广谱β-内酰胺酶(CTX-M-1V),分子量为29kDa,能水解头孢噻肟和氨曲南,不能水解亚胺培南,对舒巴坦(IC50=94nmol/L)和他唑巴坦(IC50=5nmol/L)敏感。结论:CTX-M-1V为对抑制剂敏感的CTX-M型超广谱-内酰胺酶。     

干预前后氨曲南的临床应用及安全性评价

目的 通过分析干预前后氨曲南的使用情况,为临床合理用药提供依据。方法 采用回顾性调查方法,对2012年和2013年第2季度笔者所在医院氨曲南的使用情况和不良反应进行分析。结果 干预前有无适应证选药、用法用量错误及联合用药不合理等现象,干预后氨曲南使用基本合理,不良反应发生率为0.67%。结论 氨曲南临床应用干预效果明显,干预后氨曲南应用不合理情况明显降低。     

不同工艺制备注射用氨曲南的稳定性研究

目的探讨注射用氨曲南以不同工艺制备的稳定性。方法以冷冻干燥法和直接混合法制备了注射用氨曲南;考察光、热对其稳定性的影响。结果注射用氨曲南冷冻干燥品对热不稳定,有关物质明显增加,对光不稳定,外观变黄。注射用氨曲南的直接混合粉末受光、热的影响较小。结论冷冻干燥法制备得无定形粉末,稳定性次于β晶形的氨曲南与精氨酸直接混合所得的注射用氨曲南;水分偏高大大降低样品的热稳定性,故水分的限度要严格控制。     

氨曲南治疗慢性肾功能不全患者肺部及尿路感染疗效

目的探讨使用氨曲南治疗慢性肾功能不全患者肺部感染和尿路感染临床疗效。方法68例患者用氨曲南2.0g,加入氯化钠注射液100mL中,静脉滴注,每12h1次,疗程7～14d。检测血常规、尿常规、肝功能、肾功能,并作细菌学检查和药物敏感性测定。结果68例患者治疗后痊愈39例,显效17例,进步9例,无效3例,临床总有效率82.35%（56/68）;耐药率为14.76%;肾功能指标治疗前后无变化;不良反应仅2例。结论氨曲南作为结构独特的单环类β-内酰胺类抗生素,对肾脏毒副作用轻,用于慢性肾功能不全的抗菌治疗,具有疗效显著、不良反应少和使用方便等优点,值得临床应用。     

氨曲南不良反应的临床特点分析

探讨氨曲南不良反应的特点及其相关因素,为临床合理用药提参考.检索氨曲南不良反应的文献报道(2000年1月～2010年12月国内医药学期刊),进行统计分析.氨曲南不良反应的临床表现多样,以过敏性反应为主,占70.83%.临床医务工作者应重视氨曲南不良反应的监测,做到合理用药,确保用药安全.     

氨曲南的药理作用及临床应用

氨曲南(Aztreonam)是第一个新型合成单环β-内酰胺抗生素,对革兰氏阴性菌有很强的抗菌活性,对各种β-内酰胺酶稳定,肌注吸收完全迅速,形成较高血及组织药浓度。临床应用证实,对各种由多种抗药性需氧革兰氏阴性菌引起的危及生命的严重感染有效并且安全。本文综述了氨曲南的抗菌活性、药物动力学、临床应用以及使用剂量、给药途径和不良反应。     

Polysorbate 80 coated poly (ɛ-caprolactone)-poly (ethylene glycol)-poly (ɛ-caprolactone) micelles for paclitaxel delivery

Physicochemical properties of two anhydrates (α-form and β-form) and three hydrates (hemihydrate, monohydrate and sesquihydrate) of sitafloxacin (STFX), a novel fluoroquinolone antibiotic, were investigated and correlated with the crystal structure of each crystalline form. STFX sesquihydrate showed larger weight change between 1% and 95% relative humidities (RHs) than other crystalline forms. In the crystal of sesquihydrate, STFX molecules form a channel structure where water molecules exist. Contrary to sesquihydrate, water molecules in a monohydrate are located in well-defined and isolated crystallographic sites. The β-form exhibited the worst photostability than any other forms under the irradiation of a D65 lamp. The intramolecular hydrogen bonding in the β-form caused a red shift on the solid-state UV spectrum by prolonging the conjugation system of the quinolone ring, resulting in greater absorption of photoenergy and consequent degradation. Solubility is also affected by the crystalline structure. Standard free energy of the formation of STFX molecule in each crystalline form and/or lattice energy binding STFX molecules to retain the crystal structure might cause a difference in solubility.     

铜绿假单胞菌感染耐药性及与β内酰胺酶的关系

目的研究本地区老年患者铜绿假单胞菌感染的分布特点及其耐药状况以及与产β-内酰胺酶的关系。方法采用K-B法测定亚胺培南等11种抗菌药物对182株铜绿假单胞菌及38株产β-内酰胺酶的铜绿单胞菌的体外抗菌活性。结果在临床分离的182株铜绿假单胞菌中,亚胺培南敏感性最高为85.71%,依次为头胞他啶(80.77%)、氨曲南(80.22%)、丁胺卡那(70.88%);在99株下呼吸道感染的铜绿假单胞菌中,亚胺培南的耐药率为24.24%,头孢他啶的耐药率为28.28%,明显高于其它部位;而在38株产β-内酰胺酶的铜绿假单胞菌中,耐药率最高的为哌拉西林(100%),其次为头孢唑啉(97.37%)和头孢噻肟(94.74%),明显高于非产酶株。结论铜绿假单胞菌感染中产β-内酰胺酶较为常见。产酶株铜绿假单胞菌的耐药性明显高于非产酶株铜绿假单胞菌的耐药性。其产生的β-内酰胺酶,是造成临床上铜绿假单胞菌对β-内酰胺类抗生素耐药的主要原因。     

Design of Lipid Matrix Particles for Fenofibrate: Effect of Polymorphism of Glycerol Monostearate on Drug Incorporation and Release

The effect of polymorphism of glycerol monostearate (GMS) on drug incorporation and release from lipid matrix particles (LMPs) was investigated using fenofibrate as a model drug. X-ray powder diffraction and differential scanning calorimetry were used to study the polymorphism change of GMS and the drug incorporation in GMS matrix. When medium-chain triglycerides (MCT) was absent, melted GMS was frozen to α-form of GMS with drug molecularly dispersed, whereas β-form of GMS was formed with part of drug crystallized out when the ratio of GMS/MCT in the lipid matrix was 2:1 (w/w). For LMP composed of GMS/MCT (2:1, w/w) prepared, GMS was in α-form when the particles were in nanometer range, whereas GMS was in β-form when lipid particles were in micrometer range. The model drug was molecularly dispread in α-form lipid nanoparticles, whereas part of drug was expulsed out from microparticles because of the denser crystalline packing than α-form of GMS, and caused a faster drug release from lipid microparticles than that from nanoparticles. During the storage, the transformation of GMS from α-form into the more stable β-form promoted drug expulsion and caused drug precipitation. In conclusion, the polymorphism of GMS is an important factor determining particle stability, drug incorporation, and the release of the drug from LMP. Critical attention should be paid on the investigation as well as control of the lipid polymorphism when formulating lipid-based matrix particles.     

The configuration of beta-eucaine and beta-isoeucaine

The configurations of the two isomers, β-eucaine (benzamine hydrochloride B.P.C. 1954) and β-isoeucaine have been deduced. As a result of a study of the nuclear magnetic resonance spectra and of catalytic hydrogenation and oxidation, the α-form has been assigned an equatorial hydroxyl group on C-4 and the β-form an axial hydroxyl group in this position.     

氨曲南和亚胺培南对β－内酰胺酶稳定性和抑酶效应的研究

用紫外分光光度法．以其它青霉素类、头孢菌素类抗生素为对照．研究氨曲南（Ａｚｔｒｅｏｎａｍ．ＡＺ）和亚胺培南（Ｉｍｉｐｅｎｅｍ．ＩＭＰ）对１１种标准β－内酰胺酶的稳定性及抑酶作用。结果表明．ＡＺ．ＩＭＰ与第三代头孢菌素头孢噻甲羧肟．头孢氨噻类似，对１１种标准β－内酰胺酶均高度稳定。除酶Ｋ１对头孢氨噻相对水解率达２５％外．其余均不超过１５％．其余的青霉素类及第一、二代头孢菌素类，除头孢西丁酶稳定性较好外．均对β－内酰胺酶不稳定．大多数相对水解率１００％以上。抑酶结果表明．ＡＺ或ＩＭＰ对β－内酰胺酶抑制，除与β－内酰胺酶类型有关外．还与ＡＺ或ＩＭＰ本身浓度密切关联。     

Pharmacokinetics of Aztreonam and Imipenem in Critically Ill Patients with Pneumonia

Study Objective . To evaluate the pharmacokinetic profiles of aztreonam and imipenem in critically ill trauma patients with pneumonia. Methods . Trauma patients in intensive care units who were intubated within 3 days of hospital admission were eligible for the study. Patients with the clinical diagnosis of pneumonia were consecutively randomized to receive either aztreonam plus vancomycin or imipenem-cilastatin. Serial blood samples were taken and sputum was collected to determine aztreonam and imipenem concentrations after 2–3 days and 7–8 days of therapy. Pharmacokinetics of both agents were estimated and compared with estimates from healthy volunteers. Results . Twenty patients were enrolled in the study, 10 patients received imipenem-cilastatin, and 10 received aztreonam plus vancomycin. Steady-state volume of distribution (V_ss) for aztreonam at 2–3 days and 7–8 days was significantly greater in patients than in historical controls, whereas the V_ss for imipenem was greater at 2–3 days. The β-half-life for aztreonam at both sampling periods was significantly greater in patients than in controls. No significant changes in pharmacokinetics occurred over time for either antibiotic. Sputum concentrations of aztreonam and imipenem were highly variable when sampled 2 hours after the infusion. Conclusion . Larger volumes of distribution were observed for both aztreonam and imipenem in trauma patients than in volunteers, suggesting that standard initial dosages of the antibiotics may result in lower concentrations in these critically ill patients. Both antibiotics penetrated into the sputum of most patients; however, the degree of penetration was highly variable in relation to serum concentrations.     

CONFORMATIONAL STABILITY OF A SNAKE CARDIOTOXIN

A snake cardiotoxin from the venom of the Formosan cobra, Naja naja atra, is a basic polypeptide. The protein can be denatured in 6.0 M guanidine hydrochloride or at elevated temperatures. Its conformation remains virtually the same in solvents of lower polarity than water such as 1, 2-ethanediol or 1-propanol and 1, 2-ethanediol (1:1 v/v). The circular dichroism spectrum is atypical in water in that the peptide chromophores show a small negative CD band at 214 nm and a large positive one at 195 nm. To some extent the CD pattern resembles that of the β-form but differs in specific positions and magnitudes. Considering that the theoretical CD of the reverse β-bend and the characteristics of model polypeptides in β-form manifest a similar pattern, we suggest that cobra cardiotoxin is rich in β structure including β pleated-sheets and β reverseturns.     

Impact of storage on the physico-chemical properties of microparticles comprising a hydrogenated vegetable oil matrix and different essential oil concentrations

Microparticles made from hydrogenated sunflower oil without essential oil and with different essential oil concentrations (75–300?g/kg; g of essential oil per kg of microparticles) were stored for 1 or 2 months at 25 or 37?°C. Before and after storage the essential oil concentration, flowability, optical appearance, melting behaviour and crystalline structure of the microparticles were investigated. Essential oil recovery, melting behaviour and crystalline structure were identical for the essential oil containing microparticles and were not affected during storage. The surface structure of the microparticles varied with their essential oil concentration. While the particles containing 75?g/kg essential oil were covered by erect fat crystals, those with 225?g/kg and higher were mostly smooth with some round shaped dumps. However, the surface of all essential oil containing microparticle batches had reached their final stage after production already and did not change during storage. Microparticles without essential oil presented two melting peaks; all microparticle batches with essential oil had one peak. Peaks in the X-ray scattering powder diffraction signal of the essential oil-free microparticles after production can be associated with the α-form of the hydrogenated vegetable oil. During storage, a conversion of the α-form to the stable β-form was observed. Microscopy showed that these microparticles also developed strong fat crystals throughout storage. The triglycerides in microparticles with essential oil seem to directly take on the stable β-form. The formation of robust microparticle agglomerates during storage was prevalently observed for the fat crystal forming product batches, meaning the products without or with low essential oil concentration.     

24株洋葱伯克霍尔德菌耐药性分析及β-内酰胺酶耐药基因检测

目的 了解洋葱伯克霍尔德菌耐药情况及耐药基因,为临床用药提供指导.方法 琼脂稀释法检测洋葱伯克霍尔德菌对10种抗生素的最低抑菌浓度(MIC); PCR法测定β-内酰胺酶耐药基因.结果 洋葱伯克霍尔德菌对头孢呋辛耐药率最高,达71.5%,其次氨曲南69.9%,左旋氧氟沙星66.7%,美罗培南66.6%,氯霉素62%;耐药...