氧头孢烯类抗生素的研究进展

拉氧头孢是第一个用于临床的氧头孢烯类抗生素,是新的β-内酰胺类抗生素研究中很有希望的一种药物,不仅对革兰氏阴性菌作用明显,而且还改善了药代动力学性质.拉氧头孢不仅广谱、耐霉,血浓度也较高和持久.     

第一个碳头孢烯类抗生素Loracarbef

碳头孢烯类为一类新的β-内酰胺类抗生素。其结构与头孢菌素相似,不同点在于,头孢菌素分子中头孢烯环上的1位硫原子被亚甲基所替代。这一结构上的变化使碳头孢烯类比头孢菌素类包括头孢克洛的化学稳定性明显增高,尚可制成混悬剂,以利于儿童服用。loracarbef(LR)为第一个碳头孢烯类抗生素,本文对其抗菌活性、药代动力学、临床试用及不良反应等方面作一综述。 1 体外抗菌活性 肺炎球菌、化脓性链球菌、β-溶血链球菌     

克拉霉素的特点和临床应用

克拉霉不为14元半合成红霉素衍生物，作用于细菌50S核糖体亚基，抑制细菌蛋白质的合成，克拉霉素对大多数需氧菌的体外活性与红霉素相似，对流感嗜血菌和胞内分枝杆菌－－鸟分枝杆菌复合体的活性显著强于红霉素；对酸稳定，口服吸收（生物利用度55％）好于红霉素，在组织和体液中分布良好；在临床上适用于呼吸道感染、分枝杆菌病、弓形体病、螺杆菌病等感染性疾病的治疗；毒性较低，人体耐受性良好，胃肠道不良反应的发生率（10.6％）低于红霉素和罗红霉素。     

妥布霉素的药理学特点及其临床应用

<正>妥布霉素（Tobramycin,TOB）由 Streptomyces teredrar-ius菌所产生的雷布霉素（Nedramycin）复合物中分离而得,系一种单一的氨基糖苷类抗生素,游离碱为白色或类白色粉末,易溶于水,极微溶解于乙醇,10％溶液的pH为9～11。制造注射液时,加入适量硫酸,调节pH至5.8。 TOB适用于绿脓杆菌、变形杆菌、大肠杆菌、克雷伯菌属、肠杆菌属、沙雷菌属及葡萄球菌（包括青霉素G与耐甲氧西林菌株）所致的各种感染。本品用于绿脓杆菌脑膜炎或脑室炎时可同时鞘内注射给药;用于支气管及肺部感染时可同时气溶吸入本品作为辅助治疗。TOB对多数D组链球菌感染无效。     

纳他霉素等多烯类抗生素作用机制及研究方法

目的介绍纳他霉素的作用机制及近年来的研究方法。方法综合国内外文献报道,简述纳他霉素等多烯类抗生素的性质、作用机制及研究方法。结果研究抗真菌药物的作用机制有利于研发新型药物和改善己有药物的药学特性,并且能够指导临床合理的联合用药,新技术新方法的应用将有助于深入研究多烯类抗真菌抗生素的作用机制。结论本文为研究纳他霉素作用机制及国内拥有自主知识产权的产品开发提供参考。     

纳他霉素等多烯类抗生素作用机制及研究方法

目的 介绍纳他霉素的作用机制及近年来的研究方法。方法 综合国内外文献报道,简述纳他霉素等多烯类抗生素的性质、作用机制及研究方法。结果 研究抗真菌药物的作用机制有利于研发新型药物和改善己有药物的药学特性,并且能够指导临床合理的联合用药,新技术新方法的应用将有助于深入研究多烯类抗真菌抗生素的作用机制。结论 本文为研究纳他霉素作用机制及国内拥有自主知识产权的产品开发提供参考。     

头孢匹胺的特点与临床应用

头孢匹胺(cefpiramide,CPM,日本住友药品工业公司商品名Sepatren)是注射用半合成的第三代头孢菌素.1985年10月首次上市.头孢匹胺化学名为(6R,7R)-7-[(R)-2-(4-羟基-6-甲基-3-吡啶基羧酰胺基)-2-(对羟基苯基)乙酰胺基]-3-[[(1-甲基-1H-四唑-5-基)硫]甲基]-8-氧代-5-硫杂-1-氮杂二环[4,2,O]辛-2-烯-2-羧酸钠,分子式为C_(25)H_(23)N_8NaO_7S_2,分子量634.62,1g头孢匹胺钠含钠3.62mg.化学结构见图1.     

头孢硫脒的抗菌活性和临床应用综述

头孢硫脒（cefathiamidine,商品名：仙力素）是由我国自行研制并首先应用于临床的半合成头孢菌素,属第一代头孢菌素,对G^＋球菌,尤其是葡萄球菌属和肠球菌属具有很强的抗菌活性。本文拟从作用机制、体内外抗菌活性、临床应用和不良反应等方面对其作一综述。     

克拉霉素的临床应用

克拉霉素是新一代14-元环半合成的新型大环内酯类抗生素，化学名为6-O-甲基红霉素，分子式C38H69NO13，它是从红霉素A出发，经肟化、醚化、硅烷化、甲基化和还原制成^[1]。具有稳定性好，杀菌能力强，低pH条件下易溶解，口服吸收好，不良反应少，患者耐受性高等优点。其药理学特点为：主要通过与细胞核糖体上的50S亚基结合，阻滞转肽酶和易位作用，抑制细菌蛋白质的合成，从而发挥其杀菌或抑菌作用^[2]。     

Combined action of cephamycin and aminoglycoside antibiotics

The combined actions of cefoxitin (CFX) with amikacin (AMK), gentamicin (GM) and dibekacin (DKB) were studied against Gram-positive and Gram-negative bacteria. The following results were obtained. The synergistic actions of CFX with AMK, GM and DKB were observed on S. aureus, S. epidermidis, E. coli, S. marcescens, K. pneumoniae, Proteus spp. and Acinetobacter by checker board titration method. The combination of CFX with AMK was most effective. In case of the combination of CFX with AMK, the simultaneous administration showed the highest bactericidal effect, followed by the case of addition of AMK after adding CFX. The phase-contrast microscopic observation on S. marcescens revealed that the bacterial cell prolonged with CFX showed a filament-like form and with AMK almost a normal form. In the combination, lysed cells were observed. The therapeutic experiment of S. marcescens infection in mice demonstrated that the combination of CFX with AMK showed superior effect than that of each drug alone.     

Studies on oxacephems, an artificial type of beta-lactam antibiotics

A pioneering work in the field of oxacephem antibiotics which had been carried out in our research laboratories is reviewed. Our research of beta-lactam antibiotics was started in 1974 with the policy to make chemical modification at the nuclei but not the side chain of the existing beta-lactam antibiotics, with an expectation to discover a new type of antibiotics. After the success in establishing an efficient synthetic method for 3'-norcephalosporin, we started oxacephem research in 1975. We succeeded in developing three synthetic methods starting from penicillins which efficiently served to prepare numerous oxacephem (1-oxa-1-dethia-cephalosporin) derivatives. It turned out that the oxacephem nucleus was much more distorted with an increased ring strain, resulting in reduction of the beta-lactam amide resonance to a greater extent than the cephalosporin nucleus. This physicochemical properties conferred an increased chemical reactivity on the nucleus as evidenced by an increased hydrolysis rate as compared with the corresponding 1-thia counterpart. This increased chemical reactivity coupled with the reduced hydrophobicity of the oxacephem nucleus as evidenced by the lower distribution constant in a water-octanol system, characterized unique biological properties of oxacephem derivatives. These include (1) 2-16 times increase in antibacterial activity with emphasis against gram-negative bacteria; (2) increased protecting effect in vivo parallel to the increased in vitro activity; (3) reduction of the stability to beta-lactamases leading to decreased antibacterial activity against the beta-lactamase producing strains; (4) 1.6-3.2 times increase in penetrability through the outer membrane of certain gram-negative bacteria, the increase being due to the increased hydrophilicity of the oxacephem nucleus; (5) remarkably reduced binding to human serum albumin improving the efficacy of the oxacephems in the blood; (6) a remarkable change in the excretion pattern, i.e. recovery in the bile reduced and that in the urine increased. These biological characteristics are generally favorable for antibacterial agents against pathogenic diseases except for the reduced stability to beta-lactamases. This unfavorable property of the oxacephem nucleus was the only barrier for developing a new agent of the oxacephem nucleus. However, this problem was relatively easily solved by introduction of (1) the methoxy group at 7 alpha and (2) appropriately alpha-substituted acyl amide chain at 7 beta; the former and the latter substituent effectively stabilized the oxacephems to various kinds of penicillinases and cephalosporinases, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)     

Interaction of clavulanic acid, sulbactam and cephamycin antibiotics with beta-lactamases

The inhibitory effects of clavulanic acid, sulbactam and cephamycin antibiotics on chromosomally-mediated or plasmid-mediated beta-lactamases were investigated. The inhibition constants were determined by a non-linear regression analysis. Clavulanic acid and sulbactam had high affinities for the purified plasmid-mediated beta-lactamases such as SHV-1, TEM-1 and PSE-4, and were potent inhibitors as shown by their low Ki values. Except for Bacteroides beta-lactamase, which is sensitive to inhibition by cephamycin antibiotics, clavulanic acid and sulbactam were found not to be as effective against chromosomally-mediated beta-lactamases. The cephamycin antibiotics were better inhibitors of chromosomally-mediated beta-lactamases than those that are plasmid mediated. Except for P99 beta-lactamase, against which sulbactam and clavulanic acid were inactive, the cephamycin antibiotics were less effective inhibitors than sulbactam and clavulanic acid.     

Clinical study on transfer into lung tissue and postoperative prophylactic effect of new cephamycin antibiotics, particularly cefotetan and cefbuperazone

The following findings were obtained in our clinical study on the transfer of cefotetan (CTT) and cefbuperazone (CBPZ), new antibiotics of cephamycin series, into the lung tissue and on their postoperative prophylactic effect. 1. The mean serum concentration 30 minutes after the start of an intravenous drip infusion of 1 g of CTT over a period of 30 minutes was 99.4 micrograms/ml, and it decreased gradually thereafter with the half-life of 2.45 hours. After an intravenous drip infusion of 1 g of CTT over a period of 1 hour, the mean peak concentration of 104.1 micrograms/ml appeared 1 hour after the start of the infusion, and mean concentrations at 2, 4 and 6 hours after the infusion were 63.4, 34.3 and 27.0 micrograms/ml, respectively, with the half-life of 2.35 hours during phase beta. 2. Following 30 minutes of an intravenous drip infusion of CTT, the tissue CTT level in normal lung tissues was Tmax 1.82 hours and Cmax 19.8 micrograms/g. After 1 hour of an intravenous drip infusion the mean concentration in the tissues was at the peak of 39.7 micrograms/g in 2 hours after the start of an administration, while mean levels at 3, 4 and 6 hours after an administration were 32.2, 22.2 and 8.76 micrograms/g, respectively, with Tmax of 1.82 hours and Cmax of 30.5 micrograms/g. 3. Following an intravenous drip infusion of 1 g of CBPZ over a period of 1 hour, the mean serum drug concentration 1 hour after the start of infusion was at its peak, 83.3 micrograms/ml, while mean values at 2, 4 and 6 hours after the start of an administration were, respectively, 40.4, 19.8 and 9.62 micrograms/ml, with the beta-phase half-life of 2.03 hours. 4. By 1 hour after the start of intravenous drip infusion of CBPZ, the mean tissue level in normal lung tissues was at the peak of 31.6 micrograms/g, while mean levels at 3, 4 and 8 hours after an administration were 16.2, 11.0 and 4.56 micrograms/g, respectively, with Tmax of 1.67 hours and Cmax of 21.9 micrograms/g. 5. Infused CBPZ was transferred into bronchiole tissues. Drug concentrations in these tissues at 3 and 5 hours after the start of the infusion were 7.87 and 4.85 micrograms/g, respectively, with their ratios to the peak serum level were 9.4 and 5.8%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical use of cefoxitin, a new semisynthetic cephamycin.

Cefoxitin, a new semi-synthetic cephamycin, has been studied in the treatment of patients with a variety of infections. Included have been a number of patients who have impaired renal function. The drug proved to be effective in treating gram-positive, gram-negative and anaerobic infections, and can be given by the intravenous or intramuscular route. Adverse effects occurred in six of 34 patients. These were not usually serious. The presence of renal failure did not interfere significantly with the efficacy of cefoxitin in treating urinary tract infection and it is considered, in contrast to the aminoglycosides, that this preparation can be used successfully without the necessity for measuring blood or urine levels in patients with reduced or unknown renal function.     

急诊内科中抗生素的临床合理应用及耐药分析

目的 分析急诊内科中抗生素的合理应用及耐药情况.方法 选择2012年1月～2013年4月本院急诊内科开具的2015张抗生素应用处方为研究对象,分析抗生素合理用药情况,并随机选取其中500例抗生素应用患者进行药敏试验及细菌培养,观察抗生素的耐药性情况.结果 实际应用中2种抗生素联用者占50.22％,明显高于1种抗生素、3种及以上抗生素联用的比例,差异有统计学意义（P＜0.05）;头孢类抗生素应用比例（占72.70％）明显高于其他种类抗生素（P＜0.05）;119例存在不合理用药现象,占5.91％,主要为药物配伍不合理、给药方式不合理、溶媒不对等.结论 临床中抗生素有严格的应用原则,但临床依然存在诸多用药不合理现象,应用时还需考虑其耐药性,合理选择药物种类.     

择期剖宫产预防性应用抗生素的临床研究

目的探讨择期剖宫产预防性应用抗生素的方法。方法130例择期剖宫产孕妇随机分为观察组和对照组各65例,观察组于术前30min给予头孢呋辛钠1.5g加入生理盐水250ml快速静脉滴注,术后给予甲硝唑1.0g静脉滴注,距术前用药6h再用等量头孢呋辛钠静脉滴注1次,以后不再应用任何抗生素。对照组术前不给药,术后常规给予头孢呋辛钠1.5g加入生理盐水250ml中静脉滴注,每天2次,共3d。观察2组术后平均体温、产褥病率、腹部切口愈合情况、白细胞计数、住院时间及医疗费用等。结果观察组产褥病发生率低于对照组,差异有统计学意义（P〈0.05）;且观察组住院时间短于对照组,住院费用多于对照组,差异均有统计学意义（P〈0.05）。结论剖宫产围术期给予抗生素1～2次,能有效预防感染,减轻产妇经济负担。     

剖宫产围手术期预防性应用抗生素的临床分析

目的　探讨择期剖宫产围手术期预防性应用抗生素用药时间、剂量与术后感染的关系。方法　回顾性分析 6 5例择期剖宫产手术病人 ,根据预防性用药方法不同分为 3组 :A组 (围手术期用药组 ) 2 1例 ,选用甲硝唑与头孢噻肟钠 ,于手术前 30min内单次静脉冲击给药 ,术中冲洗宫腔、子宫切口及腹腔留置 ;B组 (手术期及术后用药组 ) 2 4例 ,术中甲硝唑冲洗宫腔、子宫切口及腹腔留置 ,术后头孢噻肟钠用药 3d ;C组 (传统术后用药组 )2 0例 ,术后头孢噻肟钠 +甲硝唑全身用药 5d。结果　术后最高体温、退热时间 3组间差异有统计学意义 (P <0 0 5 ) ;术后病率、腹部伤口感染、子宫内膜炎 3组间差异无统计学意义 (P >0 .0 5 ) ;术后副反应中白细胞计数、胃肠道反应及药物性皮疹 3组间差异无统计学意义 (P >0 .0 5 )。结论　择期剖宫产围手术期预防性使用抗生素安全、有效 ,且剂量小、疗程短 ,优于术后用药。     

抗生素在自然分娩会阴侧切术中预防应用的临床观察

目的观察自然分娩会阴侧切术预防应用抗生素的临床观察效果,评价其临床可行性。方法选取足月妊娠自然分娩,并且符合会阴侧切术指征的产妇260例,随机分为观察组和对照组,各130例。对照组常规会阴切开,缝合,消毒及护理;观察组在对照组的基础上预防性应用抗生素,手术当日加用,比较两组会阴切开术后切口感染,切口愈合情况,最高体温及子宫复旧情况。结果两组术后切口感染,切口愈合,最高体温及子宫复旧情况差异无统计学意义(P>0.05)。结论预防性应用抗生素不能预防切口感染,术后不必应用抗生素。     

合理应用抗菌药物

药物作为能查明、改变机体生理功能和病理状态,用以预防、治疗和诊断疾病的物质,对人类的贡献是不言而喻的,其中抗菌药物更是起着举足轻重的作用.但是长期以来,人们对抗菌药物的认识和应用存在很多误区,比如,抗菌药物越贵越好;广谱抗菌药物成为人们用药的首选;注射、静脉滴注成为首选治疗方式等等.来自WHO的一份报告提示,现在可治愈的疾病,如咽炎、结核病,有可能成为无法治愈的疾病,这种危险来自于细菌的耐药性,也就是滥用抗菌药物造成的.