Oral cephalosporins: current perspectives

Oral cephalosporins had been, for years, a small group of compounds belonging to the first or second-generation cephalosporins, with a limited antimicrobial spectrum. New oral first-generation cephalosporins include cefprozil and loracarbef, similar to cefadroxil and cefaclor, respectively, with activity similar to cefaclor but with pharmacokinetic improvements. Second-generation oral cephalosporins are esters of already available cephalosporins, and third-generation oral cephalosporins include a number of drugs whose activity is similar to available parenteral drugs, showing pharmacokinetic advantages and, some of them, better resistance to hydrolysis mediated by extended wide-spectrum β-lactamases. They may be a good alternative against mild to moderate ENT infections, UTIs, STDs, lower respiratory tract and skin and soft tissue infections, mainly in the outpatient setting.     

反相高效液相色谱对多种头孢菌素的分离和测定

目的：建立一种同时分离测定多种头孢菌素的高效液相色谱法，让各种头孢菌素在同一流动相中排序，既可用于鉴别又可用于定量测定。方法：以磷酸盐缓冲液(pH2．6)-甲醇(79：21)为流动相；检测波长为254nm。结果：在同一流动相中可分离检测6种头孢菌素，保留时间在22min之内。并且每一种头孢菌素都有良好的线性。结论：方法简便、快速、准确。     

Bactericidal activity of oral beta-lactam antibiotics in plasma and urine versus isogenic Escherichia coli strains producing broad- and extended-spectrum beta-lactamases

Bacteria harbouring extended-spectrum β-lactamases (ESBLs), derived by mutation from TEM-1, TEM-2 or SHV-1 β-lactamases, have been described world-wide. The in vitro activities of these enzymes against β-lactam antibiotics, including oral cephalosporins, are well recognised. The aim of this investigation was to assess the bactericidal activity of oral β-lactam antibiotics available in Croatia (amoxicillin/clavulanate, cephalexin, cefuroxime, cefadroxil and ceftibuten), in biological fluids against isogenic Escherichia coli strains producing broad-spectrum (TEM-1, TEM-2 and SHV-1) and extended-spectrum β-lactamases (SHV-2, SHV-3, SHV-4, SHV-5, SHV-12). Bactericidal activity of oral β-lactams in plasma and urine was tested in time-kill experiments and by determining bactericidal titres at different time intervals post-dose. The killing rate of antibiotics in urine was slower than in plasma, but faster than in Mueller–Hinton broth. High bactericidal titres in urine were only maintained throughout the whole dosing interval by ceftibuten against strains producing broad-, SHV-2 and SHV-3 β-lactamases. The older generation cephalosporins can be considered for the therapy of urinary tract infections caused by E. coli harbouring TEM-1, TEM-2 and SHV-1 β-lactamases but a shorter dosing interval is needed. Ceftibuten can be recommended with caution in ESBL producing E. coli except those producing SHV-4, SHV-5 and SHV-12 that confer resistance to it. If these enzymes are produced, fluoroquinolones or carbapenems could be considered.     

我院头孢菌素类基本药物的应用分析

目的:为临床合理应用头孢菌素类药物提供参考。方法:根据是否为基本药物、药物分代、药物名称和给药途径,将我院2010年全年使用的头孢菌素类药物进行分类,对其用药金额及比例、用药频度、日均费用和排序比进行统计、分析。结果:2010年我院共使用27类头孢菌素类药物,销售总金额为10044255.78元,其中基本药物的销售金额占总金额的0.20%,用药频度和日均费用少,排序比均大于1。第3代头孢菌素类药物和头孢菌素类注射剂的销售金额占头孢类总金额的比例分别为61.08%和96.14%。结论:我院2010年头孢菌素类抗菌药物的使用不尽合理。     

注射用头孢菌素类抗生素细菌内毒素动态比浊定量法的研究

目的:应用动态比浊定量法研究头孢菌素类抗生素细菌内毒素。方法:通过对样本中定量添加标准内毒素的干扰预试验,将头孢菌素类抗生素制备成5种浓度系列,测得回收率,并筛选出最佳检测浓度,最后进行3个批号的试验。结果:内毒素的回收率分别为92.48%(头孢曲松钠舒巴坦钠),111.1%(头孢拉啶),99.39%(头孢他啶),73.31%(头孢曲松钠),111.9%(头孢呋辛),109.2%(头孢噻肟钠),133.3%(头孢哌酮钠舒巴坦钠),133.6(头孢硫脒)。头孢菌素类抗生素浓度小于等于1mg/mL的条件下,对动态比浊定量法无干扰作用,可用于有效的日常细菌内毒素检查。结论:动态比浊定量法为头孢菌素类抗生素的细菌内毒素的定量检测提供了一种全新的、高效的方法。     

头孢哌酮和哌拉西林与β内酰胺酶抑制剂对大肠埃希菌和肺炎克雷伯菌的后效应研究

目的测定头孢哌酮和哌拉西林与克拉维酸、舒巴坦、三唑巴坦3种β内酰胺酶抑制剂的不同复方的最低抑菌浓度（MIC）、抗生素后效应（PAE）、β内酰胺酶抑制剂后效应（PLIE）和亚抑菌浓度后效应（PASME）。方法以肉汤稀释法测定MIC；以菌落计数法测定菌落形成单位（CFU），根据CFU做生长曲线，计算PAE、PLIE、PASME。结果不同比例复方对产β内酰胺酶菌株的MIC较单方呈2—256倍的降低。无论单方还是复方均无长PAE。3种β酰胺酶抑制剂的PLIE对于大肠埃希菌有正有负（－2．25h～〉5h），而对于肺炎克雷伯菌均为正值（0．34h～5．37h）。对于肺炎克雷伯菌，0．2MIC的头孢哌酮／舒巴坦（1／1）的PASME为0．32h，0．1MIC、0．2MIC的哌拉西林／克拉维酸（8／1）的PASME分别为2．96h、4．41h。结论同时具有长PLIE及PASME的复方，PLIE、PASME较其半衰期在给药方案的设计中更为重要；PAE、PLIE、PASME作为重要的药效动力学参数，可应用于评价新抗菌药物的药效学和优化给药方案。     

头孢菌素致过敏性休克459例文献分析

目的：了解头孢菌素致过敏性休克的情况,探究其发生规律。方法：检索《万方数据》和《中国知网》中有关头孢菌素引起过敏性休克的文献资料（1998～2011年）,筛选收集过敏性休克的病例报告,按患者年龄、性别、给药途经、原患疾病、发生时间、愈后等进行统计分析。结果：检索获得头孢菌素引起过敏性休克的病例共459例,以第三代头孢菌素及其酶抑制药复合制剂为主（62.31%）;居前3位的品种为头孢曲松（20.48%）、头孢噻肟（12.85%）、头孢哌酮/舒巴坦（12.85%）。给药途径以静脉用药为主（85.40%）;多发于用药后10 min内（61.66%）;1 min～24 h内缓解或痊愈（87.58%）;有48例（10.46%）死亡。结论：临床应重视头孢菌素引起的过敏性休克,鼓励、推广头孢的皮试工作,以确保用药安全。     

A comparative study of capillary zone electrophoresis and pH-potentiometry for determination of dissociation constants

Acidity constants of six cephalosporin antibiotics, cefalexin, cefaclor, cefadroxil, cefotaxim, cefoperazon and cefoxitin are determined using capillary zone electrophoresis (CZE) and pH-potentiometric titrations. Since CZE is a separation method, it is not necessary for the samples to be of high purity and known concentration because only mobilities are measured. The effect on determination of dissociation constants of different matrices (serum, 0.9% NaCl, fermentation matrix) was examined. The advantages of CZE can be utilized in those fields where potentiometry has limitations (sample quantity, solubility, purity, simultaneous determinations), although pK_a values that are close to each other can be determined by potentiometry with more accuracy.     

310例头孢菌素类药物不良反应临床调查

目的：了解头孢菌素类药物不良反应的相关因素,提高合理用药水平。方法：对310例头孢菌素类药物不良反应进行回顾性调查。结果：头孢菌素类药物不良反应主要为过敏反应,与患者年龄相关,与给药浓度似有一定关系,与性别无关。结论：医护人员熟练掌握头孢菌素类药物的适应证和给药方法,对于提高疗效和减少不良反应的发生具有积极意义。