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。     

抗生素引起多脏器功能衰竭

本文报告1例老年患者,因不明热在院外服用头孢氨苄和肌注庆大霉素引起肾功能不全和肝功能损害,入院后换用头孢唑啉钠、丁胺卡那霉素和头孢哌酮,出现黄疸,无尿和皮疹,肝肾功能进一步恶化。因高热持续不退又改用头孢三嗪,引起的白色念珠菌感染、鼻衄、呕血和黑便,最后患者死于多脏器功能衰竭(肝、肾、消化道和皮肤)。提示氨基糖甙抗生素的肾损害,头孢氨苄的肝毒性和头孢哌酮、头孢三嗪的消化道出血的副作用是严重的。本文还讨论了这些抗生素的副作用发生机理,以提醒我们重视抗生素的合理应用。     

3-硝基-5-(6-溴己酰胺)苯甲酸的合成及其作为头孢菌素酰化酶产生菌筛选指示剂的研究

为筛选头孢菌素Ｃ酰化酶产生菌,由环己酮和３－硝基－５－乙酰胺基苯甲酸出发,合成了一种新的生色物质３－硝基－５－（６－溴己酰胺）苯甲酸（３－Ｎｉｔｒｏ－５－（６－ｂｒｏｍｏｈｅｘａｎｏｙｌａｍｉｎｏ）ｂｅｎｚｏｉｃａｃｉｄ,ＮＢＨＡＢ）。通过红外光谱法、核磁共振法、质谱法鉴定了其结构。ＧＬ－７ＡＣＡ酰化酶和青霉素Ｇ酰化酶（ｐｅｎｉｃｉｌｉｎＧＡｃｙｌａｓｅ,ＰＧＡ）及其产生菌对该化合物的作用表明,该物质能够检测头孢菌素酰化酶活力,用来筛选头孢菌素Ｃ酰化酶产生菌,其灵敏性有待进一步提高。     

头孢他美（Cefetamet）的合成

２－甲肟基－２－（２－氨基－４－噻唑）乙酸经Ｖｉｌｓｍｅｉｅｒ试剂活化后，与带有保护基的７－ＡＤＣＡ缩合得到头孢他美。     

我院住院患者头孢菌素类药物利用分析

目的：了解医院头孢菌素类药物的使用情况及其合理性,促进临床合理用药。方法：根据医院计算机药品信息管理系统的原始数据资料,采用世界卫生组织（WHO）推荐的限定日剂量法,以限定日剂量（DDD）、用药频度（DDDs）、药物利用指数（DUI）为指标对2007年我院住院患者头孢菌素类药物使用情况进行统计分析。结果：2007年我院住院患者应用头孢菌素类药物有25个品种,占总抗菌药金额的59．39％,其中,第三代头孢菌素类药物及其复方制剂和氧头孢烯类药物销售金额占75．14％,成为临床治疗的主导药物。结论：2007年我院住院患者应用头孢菌素类药物基本合理,应严格控制第三代头孢菌素类药物及其复方制剂的应用,掌握用药指征,以提高疗效,延缓细菌耐药。     

Drug-specific history,skin and in vitro tests can reduce the need for drug provocation tests in betalactam-hypersensitivity

BackgroundMany patients report questionable drug hypersensitivity reactions (DHR) to betalactam antibiotics. A workup is required for objectivation. Direct drug provocation tests (DPTs) omitting a prior allergy workup are increasingly recommended as the primary diagnostic approach. However, apart from the risk of severe side effects, DPTs often are a scarce resource in overloaded healthcare-systems. We investigated how many cases can be solved by drug-specific history, drug-specific IgE, and skin tests obviating the need for DPT.MethodsWe conducted a chart review in a retrospective cohort of 932 patients in an allergy outpatient centre from 2016 to 2017. Patients had been submitted to drug-specific history and specific IgE-, skin prick-, intradermal- and patch-tests with early and late readings with a series of penicillins and cephalosporins but DPTs were no option.ResultsOverall, positive in vitro and/or skin tests were found in 96/932 (10.3%) patients. Drug-specific IgE was detected in 40/932 (4.3%) patients, 61/787 (7.8%) patients had positive skin tests. In vitro tests to Pencillin V showed the highest rate of positivity 24/479 (5.0%) and early readings of ampicillin the highest amongst the skin tests (3/49, 6.1%). Immediate skin tests were more often positive than delayed ones (75:45). The combination of all parameters including drug-specific history solved 346/932 (37.1%) cases while 586/932 (62.9%) remained unresolved. Self-reported DHR could be less often confirmed in females and young children (p < 0.05).ConclusionsTesting with betalactams applying simple, cheap, and safe skin and blood tests can solve a third of DHR-cases on a high throughput scale.     

头孢菌素类药物不良反应与对策

目的：探讨头孢菌素类抗生素的不良反应及对策。方法选取2012年1月－2014年1月医院使用头孢菌素治疗致严重不良反应的132例患者的临床资料,对不良反应类型、诱发因素及防治措施进行统计分析。结果诱发患者不良反应的因素包括：患者个体因素、药物因素、疾病因素、气候和环境因素等;不良反应类型包括：严重过敏反应、消化系统不良反应、神经系统不良反应、泌尿系统和血液系统不良反应,需采取积极地预防措施。结论头孢菌素类不良反应类型及诱发因素多样,临床上应针对患者的体质和病情进行全面判断,控制用法用量,预防不良反应发生。     

Comparison of interactions between warfarin and cephalosporins with and without the N-methyl-thio-tetrazole side chain

Cephalosporins with an N-methyl-thio-tetrazole (NMTT) side chain interact with warfarin by reducing the production of blood clotting factors. However, cephalosporins without the NMTT side chain also enhance the effects of warfarin. Thus, we aimed to compare the effects of warfarin modified by cephalosporins with and without the NMTT side chain, using a Japanese health insurance claims database. The inclusion criteria were patients who (1) intravenously received second- or third-generation cephalosporins between April 2010 and March 2017 and (2) received warfarin during cephalosporin therapy. Patients were administered either cephalosporins with the NMTT side chain (NMTT group) or those without NMTT (non-NMTT group). After matching patient data by propensity score, the following outcomes were compared between the two groups: (1) proportion of patients administered vitamin K, (2) proportion of bleeding events, and (3) changes in the daily dose of warfarin. Among 203 patients, 100 patients (50 per group) were matched by the propensity score. The proportion of patients administered vitamin K was 6.0% in both groups. These patients intravenously received a single dose of menatetrenone; no bleeding was observed. The proportion of patients subjected to a reduction in the daily dose of warfarin was 6.5% and 4.3% in the NMTT and non-NMTT groups, respectively. As our study had a small sample size, we could not determine whether the risk of over anticoagulation of warfarin is affected by cephalosporins with or without NMTT side chain. However, we showed the bleeding risk was sufficiently low regardless of the presence/absence of the NMTT side chain.     

Clostridium difficile bacteremia and meningitis as a complication of prolonged cephalosporin therapy in a case of staphylococcal pyogenic arthritis

With increasing incidence of Clostridium difficile (C. difficile) associated diarrhea and pseudomembranous colitis, several extra-intestinal manifestations of the organism have been unmasked which include-bacteremia, brain abscess, pericarditis etc. We report a rare and interesting case of C. difficile bacteremia and subsequent meningitis in a 10 year old child. The child was immune competent, which further raises the question about the virulent possibilities of the organism and its implications in the near future. The condition resulted from a prolonged treatment with intravenous (I.V.) cefotaxime for staphylococcal pyogenic arthritis. The child recovered from the septic arthritis but on the 7th day post-admission developed features of bacteremia. The child was later treated with intravenous metronidazole and vancomycin and he was discharged on the 21st day post-admission. No recurrence of symptoms was noted.     

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus

ObjectivesCefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens.MethodsWe included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT _{> 4 × MIC}.ResultsThirty-nine patients with a median (range) age of 7 (0.1–17) years and a BW of 21 (2.8–79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m² were the best schemes to reach the PK target of 100% fT _{> 4 × MIC}.ConclusionsIn critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT _{> 4 × MIC} in children with normal and augmented renal function.