2011—2013年北京市中关村医院呼吸科头孢菌素类抗菌药物应用分析

目的:了解北京市中关村医院(以下简称"我院")呼吸科头孢菌素类抗菌药物的使用情况。方法:采用世界卫生组织推荐的用药频度(DDDs)分析法,通过医院信息系统,统计2011—2013年我院呼吸科使用的头孢菌素类抗菌药物的药品名称、规格、数量等,计算出DDDs和销售金额并对其进行排序、分析。结果:近3年来,我院呼吸科使用的头孢菌素类抗菌药物的DDDs和销售金额均呈上升趋势;第3代头孢菌素使用的种类最多,且其DDDs和销售金额排序也居首位;第4代头孢菌素的DDDs和销售金额明显低于第3代和第2代头孢菌素。结论:我院呼吸科使用头孢菌素类抗菌药物较合理,但应严格控制第3代头孢菌素的用药指征,以提高疗效、延缓细菌耐药性的产生。     

头孢菌素类衍生物的中间体合成研究

本文简述了从青霉素（Ｇ或Ｖ）经化学转化制取头孢菌素类衍生物的中间体。     

In vitro andin vivo evaluations of LB10517, a novel parenteral broad-spectrum cephalosporin

Thein vitro activity of LB10517, a new catechol-substituted cephalosporin, was compared with those of E-1077, cefpirome and ceftazidime against 1034 clinical isolates collected in Japan. LB10517 showed a broad-spectrum antibacterial activity against a wide range of gram-positive and gram-negative bacteria including non-glucose fermenting rods,Pseudomonas aeruginosa. Against the methicillin-susceptible strains ofStaphylococcus aureus (MSSA) andStreptococcus pyogenes, the MIC₉₀ values of LB10517 which required to inhibit 90% of the strains were 3.13 μg/ml and 0.1 μ/ml, respectively. It was as active as E-1077 but more active than cefpirome and ceftazidime. Methicillin-resistant strains ofS. aureus (MRSA) andEnterococcus spp. were highly resistant to all the test compounds. LB10517 was highly active against most members of the familyEnterobacteriaceae, 90% of which were inhibited at a concentration of less than 0.78 μg/ml, except forEnterobacter cloacae (1.56 μg/ml) andSerratia marcescens (3.13 μg/ml). Its activity was comparable to those of E-1077 and cefpirome but it was greater than that of ceftazidime. AgainstPseudomonas aeruginosa, LB10517 showed the most potent antibacterial activity among the compounds tested. Ninety percent ofP. aeruginosa isolates were susceptible at the concentration of 0.39 μg/ml. Its activity was 32- to 128-fold higher than those of E-1077, cefpirome and ceftazidime. Against imipenem- or ofloxacinresistantP. aeruginosa, LB10517 with MIC₉₀s of 6.25 μg/ml and 3.13 μg/ml, respectively, showed 16-fold more potent activity than the other test compounds. LB10517 showed a relatively high plasma level and long plasma elimination half-life in rats (t_1/2(β), 52 min) and dogs (t_1/2(β), 103 min).     

生物制药生产中的在线产量预测及经济效益优化

针对生物发酵生产波动大、大量经典优化控制手段难以奏效的特点,本文从建立过程的经济效益函数入手,提出了一种将在线动态优化和稳态调度优化相结合的总体优化方案。效益函数由物料、能量衡算获得,它集产率、得率及产品质量指标于一体,是各罐批创利状况的客观评价函数。效益优化的前提之一是产量预测,故文中叙述了进行在线产量预测的两个方法,即基于模型的和基于人工神经网络的方法。前者采用滚动参数辨识技术,利用现有模型对过程进行短期预测,后者则是适用于一般过程的滚动学习－预测。关于动态效益优化,本文给出了设计思想并基于头孢菌素Ｃ参数自适应模型给出了一个实例。关于人工神经网络,本文结合青霉素发酵生产,证实了神经网络预估器在发酵中、后期的高预测精度和强鲁棒性。这使后继工作,即基于效益函数的统计分析和预测进行稳态调度优化和异常罐批早期诊断等,得以展开。     

Management of patients with a history of allergy to beta-lactam antibiotics

Patients with a history of penicillin allergy pose a treatment dilemma. Unnecessary avoidance of this relatively nontoxic class of drugs exposes the patient to potentially more toxic drugs, increases health care costs, and contributes to the development of antibiotic resistance. Yet for those who truly have allergy or other serious adverse reactions to beta-lactams, the use of alternate drugs is a must. This article reviews current management strategies to determine which patients are good candidates for reintroduction of beta-lactams and which patients should continue avoidance.     

氨噻肟唑头孢菌素的合成

本文以7-ACA为原料制备了7-ACT,再以DCC为缩合剂与侧链2(2-氯乙酰氨基噻唑-4)-(Z)-2甲氧亚胺乙酸进行缩合,使用N-甲基二硫代氨基甲酸甲胺盐脱保护基,以葡聚糖凝胶LH-20精制合成了氨噻肟唑头孢菌素;总收率35.8％。产物经~1H核磁确证为顺式构型化合物。     

Extended spectrum β-lactamase-producing Escherichia coli faecal carriage in Spanish travellers returning from tropical and subtropical countries

The aim of this study was to investigate the prevalence of extended-spectrum β-lactamase (ESBL) -producing Escherichia coli in stool samples from 457 patients with travellers’ diarrhoea who had travelled to tropical and subtropical countries. Ninety-seven ESBL-producing E. coli strains were isolated from 17.9% of the patients (82/457). CTX-M-15 was the most prevalent enzyme (80%) and India was the most visited country and showed the highest prevalence of positive samples (37.4%).     

Fatal Cephalosporin-Induced Acute Hypersensitivity Myocarditis

A frequently fatal, although rare, side effect of cephalosporin antibiotics is noninfectious myocarditis. We report two cases of hypersensitivity myocarditis secondary to administration of cephalosporin antibiotics. In both cases, acute hypersensitivity myocarditis was not suspected clinically, and the diagnosis was made postmortem. Histology revealed intense eosinophilic infiltration of the endomyocardium with eosinophil degranulation and myocyte damage, Clinically, death in both cases was due to cardiac failure. When suspected early, appropriate management may be lifesaving.     

Clinical and Molecular Epidemiology of Community-Onset Bacteremia Caused by Extended-Spectrum β-Lactamase-Producing Escherichia coli over a 6-Year Period

Although extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) has emerged as a significant community-acquired pathogen, there is little epidemiological information regarding community-onset bacteremia due to ESBL-EC. A retrospective observational study from 2006 through 2011 was performed to evaluate the epidemiology of community-onset bacteremia caused by ESBL-EC. In a six-year period, the proportion of ESBL-EC responsible for causing community-onset bacteremia had increased significantly, from 3.6% in 2006 to 14.3%, in 2011. Of the 97 clinically evaluable cases with ESBL-EC bacteremia, 32 (33.0%) were further classified as healthcare-associated infections. The most common site of infection was urinary tract infection (n=35, 36.1%), followed by biliary tract infections (n=29, 29.9%). Of the 103 ESBL-EC isolates, 43 (41.7%) produced CTX-M-14 and 36 (35.0%) produced CTX-M-15. In the multilocus sequence typing (MLST) analysis of 76 isolates with CTX-M-14 or -15 type ESBLs, the most prevalent sequence type (ST) was ST131 (n=15, 19.7%), followed by ST405 (n=12, 15.8%) and ST648 (n=8, 10.5%). No significant differences in clinical features were found in the ST131 group versus the other group. These findings suggest that epidemic ESBL-EC clones such as CTX-M-14 or -15 type ESBLs and ST131 have disseminated in community-onset infections, even in bloodstream infections, which are the most serious type of infection.