北京地区2003-2013年头孢吡肟不良反应分析

目的:统计分析北京地区近10年来头孢吡肟的不良反应报告,为头孢吡肟的安全合理应用提供依据。方法:收集2003年10月-2013年10月北京市药品不良反应监测中心数据库中头孢吡肟不良反应报告,并对283例不良反应进行统计分析。结果:头孢吡肟致不良反应(ADR)以老年人及成年人发生率较高,54.67%的ADR发生于首次输液后。这可能与用药例数多有关。临床表现复杂多样,涉及机体多个器官或系统,严重的不良反应为过敏性休克、肾功能损害和癫痫发作等。主要的不良反应为皮肤和神经系统的不良反应等。结论:头孢吡肟的安全性是临床应关注的问题,应在合理使用的基础上,监测并及时处理其不良反应。     

盐酸头孢吡肟在小鼠肺内的药代动力学研究

目的研究盐酸头孢吡肟在小鼠肺组织内的药动学特征。方法小鼠尾静脉注射盐酸头孢吡肟后,于不同时间点取小鼠肺组织并以HPLC测定肺内药物含量,采用DAS3.1软件处理,计算药动学参数并进行统计学分析。结果小鼠肺内盐酸头孢吡肟的主要药动学参数t1/2为0.267h,Cmax为20.279μg·g-1,AUC0^t为9.897μg·h·g-1,MRT0t为9.897μg·h·g-1,MRT0^t为1.954h。结论小鼠尾静脉注射盐酸头孢吡肟后,在肺组织内分布较快,呈一室模型,提示盐酸头孢吡肟静脉给药能有效治疗敏感菌引起的肺部感染。     

Relationship between pharmacokinetics and pharmacodynamics of β-lactams and outcome

The in-vitro susceptibility of an organism and the pharmacokinetics of an antimicrobial agent are two basic factors on which the choice of standardised treatment regimens is based. However, the inter-individual variability of these factors, which modifies the exposure of bacteria to an antibiotic in terms of time and quantity, is not usually taken into account. In 87 patients treated with beta-lactams (ceftriaxone, cefepime or piperacillin), the probability of failure was greater when the infectious process was located in tissues with barriers to the distribution of beta-lactams. Mean MICs of piperacillin and cefepime, but not ceftriaxone, were below the breakpoints in cases of both recovery and failure, but organisms isolated from patients with a poor outcome had higher MICs. Therefore, the use of breakpoints to determine the susceptibility of microorganisms was not satisfactory in predicting the outcome for a large number of patients. If MICs are determined and plasma concentrations are monitored, dosages can be adjusted according to these parameters, thereby allowing antibiotic treatment to be individualised.     

High-dose cefepime as an alternative treatment for infections caused by TEM-24 ESBL-producing Enterobacter aerogenes in severely-ill patients

This study evaluated retrospectively the efficacy of treatment with cefepime vs. a carbapenem, in combination with amikacin or ciprofloxacin, for seriously-ill patients infected with ESBL-producing Enterobacter aerogenes who were admitted to an intensive care unit. Forty-four episodes of infection were investigated in 43 patients: 21 treated with cefepime; 23 with a carbapenem. The two treatment groups did not differ statistically in terms of age, APACHE II scores, and infection sites, but the average duration of antibiotic exposure was significantly shorter in the cefepime group (8.5 days vs. 11.4 days; p 0.04). Clinical improvement was seen in 62% of patients receiving cefepime vs. 70% of patients receiving a carbapenem (p 0.59). Bacteriological eradication was achieved in 14% of patients receiving cefepime vs. 22% of patients receiving a carbapenem (p 0.76). The 30-day mortality rates related to infection were 33% in the cefepime group and 26% in the carbapenem group (p 0.44). Thus, outcome parameters did not differ significantly between the two groups. Nevertheless, a statistically significant increase in failure to eradicate ESBL-producing E. aerogenes was observed as the MICs of cefepime rose (p 0.017). Pulsed-field gel electrophoresis revealed three distinct clones, but one predominant clone harbouring the bla(TEM-24) gene was associated with most (42/44) of the episodes of infection. It was concluded that cefepime may be an alternative agent for therapy of severe infections caused by TEM-24 ESBL-producing E. aerogenes, although further studies are required to confirm these observations.     

Treatment of bone and joint infections caused by Gram-negative bacilli with a cefepime–fluoroquinolone combination

A 3-year retrospective study evaluated the effectiveness and safety of cefepime plus a fluoroquinolone for treating bone and joint infections caused by Gram-negative bacilli (GNB) in 28 patients. Intra-operative cultures yielded primarily Pseudomonas spp. and Enterobacter cloacae. Full recovery (cure) was observed in 79% of patients. There were no serious adverse effects and no resistant organisms were isolated. The results of the study confirmed the safety and effectiveness of cefepime combined with a fluoroquinolone for the treatment of bone and joint infections caused by Gram-negative bacilli.     

紫外双波长、系数倍率法测定头孢吡肟与甲硝唑配伍的稳定性

目的 :考察头孢吡肟与 0 .5%甲硝唑配伍的稳定性。方法 :用紫外双波长、系数倍率法分别测定头孢吡肟与甲硝唑的含量。结果 :在 0 ,1,2 ,4 ,6h内 ,2药合用的含量、pH及外观基本不变。该方法的平均回收率头孢吡肟为 (10 0 .9± 0 .4 ) % (n =5) ,甲硝唑为 (99.8± 0 .6 ) % (n =5)。结论 :2种药物配伍 6h内基本稳定。用双波长、系数倍率法分别测定其稳定性 ,方法简便、准确、实用性广。     

Comparison of the boronic acid disk potentiation test and cefepime-clavulanic acid method for the detection of ESBL among AmpC-producing Enterobacteriaceae

Purpose: Extended spectrum β-lactamase (ESBL) and AmpC β-lactamase are important mechanisms of betalactam resistance among Enterobacteriaceae. The ESBL confirmation test described by Clinical Laboratory Standards Institute (CLSI) is in routine use. This method fails to detect ESBL in the presence of AmpC. Therefore, we compared two different ESBL detection methods against the CLSI confirmatory test. Materials and Methods: A total 200 consecutive clinical isolates of Enterobacteriaceae from various clinical samples were tested for ESBL production using (i) CLSI described phenotypic confirmatory test (PCT), (ii) boronic acid disk potentiation test and (iii) cefepime–CA disk potentiation method. AmpC confirmation was done by a modified three-dimensional test. Results: Among total 200 Enterobacteriaceae isolates, 82 were only ESBL producers, 12 were only AmpC producers, 55 were combined ESBL and AmpC producers, 14 were inducible AmpC producers and 37 isolates did not harboured any enzymes. The CLSI described PCT detected ESBL-producing organisms correctly but failed to detect 36.3% of ESBLs among combined enzyme producers. The boronic acid disk potentiation test reliably detected all ESBL, AmpC, and combined enzyme producers correctly. The cefepime–CA method detected all ESBLs correctly but another method of AmpC detection has to be adopted. Conclusion: The use of boronic acid in disk diffusion testing along with the CLSI described PCT enhances ESBL detection in the presence of AmpC betalactamases.     

头孢吡肟对铜绿假单胞菌防突变浓度的研究

目的研究头孢吡肟对铜绿假单胞茵的防突变浓度（MPC）,考察头孢吡肟对耐药突变株的选择能力,为临床优化抗菌药物的给药方案。方法采用肉汤法富集铜绿假单胞茵ATCC27853和10株临床分离茵,采用琼脂平板二倍稀释法测定头孢吡肟对铜绿假单胞茵的MIC、MPC值,计算MIC90、MPC90、选择指数SI。结果头孢吡肟对铜绿假单胞茵临床分离菌株的MIC90为32μg·mL^-1,MPC90〉2048μg·mL^-1,SI〉64。结论头孢吡肟在临床的应用容易筛选出铜绿假单胞茵耐药突变株。     

盐酸头孢吡肟的合成

以7－ACA为原料，经“一勺烩”得到关键中间体7－氨基－3－[（1－甲基－1－吡咯烷）甲基]头孢－3－烯－4羧酸盐酸盐（Ⅶ），Ⅶ与苯并噻唑硫醇活性酯（Ⅷ）综合得到第四代头孢菌素类抗生素盐酸头孢吡肟，总收率为24.7%。