摘要
背景:抗菌药物作为预防和治疗感染性疾病的主要药物,在医院中的使用非常普遍。但近二十多年来,世界各地抗菌药物不合理使用的情况越来越严重,不仅导致住院患者承受不必要的经济和健康负担,而且导致细菌耐药性日趋严重、地球生态环境被破坏等严重的社会后果。抗菌药物不合理使用已经成为一个全球性的重大公共卫生问题。
了解临床抗菌药物使用现状,分析抗菌药物使用影响因素是促进临床合理使用抗菌药物的基础。根据现有文献资料的报告,国内研究大多局限在某一医院或某一疾病人群,或者某一确定日期住院患者抗菌药物使用情况研究,没有一个相对固定人群几年的住院期间抗菌药物使用趋势的详细研究,更缺乏我国实施《抗菌药物临床应用指导原则》前后抗菌药物使用变化情况研究,很难准确、全面反映我国住院患者抗菌药物使用情况。
目的:本次研究的目的是调查分析2003~2009年抗菌药物使用现状及变化趋势,全面揭示当前抗菌药物使用构成、变迁和经济负担,探讨产生目前状况的主要影响因素,并就减少抗菌药物不合理使用提供基础数据。具体内容包括:
(1)全面分析2003~2009年研究对象抗菌药物使用率、描述抗菌药物联合用药、不同用药途径、细菌学检查、各类抗菌药物构成情况以及变化趋势,揭示目前抗菌药物使用的基本现况。
(2)评价住院患者抗菌药物使用的费用负担,以及各类抗菌药物费用负担构成及变化趋势。
(3)通过分析计算各类抗菌药物的DDDs值,描述当期住院抗菌药物使用总量、构成和变化趋势,计算DDDc (日均费用)并以此评估费用负担,分析每百住院日抗菌药物DDDs值和居民每人每年抗菌药物DDDs值。
(4)分析单纯性甲状腺肿手术患者和住院分娩产妇的抗菌药物使用情况,反映清洁手术患者抗菌药物使用情况;分析不同支付类型的急性单纯性阑尾炎患者抗菌药物使用情况,揭示医疗保险支付方式对抗菌药物使用的影响。
(5)分析研究对象使用率最高的左氧氟沙星和使用金额最大的头孢哌酮舒巴坦使用情况。
方法:采用回顾性研究方法,对研究对象进行全样本的分析。
(1)研究对象:本次研究对象为由湖南省医疗工伤生育保险管理服务局经办管理的湖南省省本级城镇职工基本医疗保险参保人员2003年1月1日~2009年12月31日出院患者。7年间每年参保人数在20-30万之间,7年累计参保人数为180.41万人。采取全样本分析方法,出院患者共计245322人。
(2)数据来源及组成:本研究资料来源于湖南省医疗工伤生育保险管理服务局医疗保险管理信息系统数据库,该系统直接与医院信息系统(HIS)对接,自动从HIS系统中获取数据进行医疗保险费用结算。对于没有HIS系统的医院,医院当天会根据医疗费用发生情况,如实将每一类药物及医疗服务发生情况及费用明细录入该系统前台,数据实时传输,出院时进行医疗保险费用结算。本次研究数据由软件开发商直接从医疗保险管理信息系统数据库导出。
所引用的编码体系主要有:疾病编码——ICD-10国际疾病分类标准;各类费用及支付方式编码由软件开发公司(创智公司)自行定义;其他编码,如性别、疗效等使用国家标准编码。
收集资料的内容包括:一般情况(姓名、性别、年龄、民族、公务员级别、工作状况、单位性质、就诊医院、就诊医院级别、临床诊断ICD-10分类、入院日期、出院日期、住院天数及疗效判断)、住院(含西药费、手术费)等各项医疗费用、抗菌药物名称、剂型、规格、使用数量、给药方式、抗菌药物费用、临床微生物检查(含病原微生物镜检、培养、鉴定及药物敏感试验)次数和费用。
(3)真实性评判:包括日常真实性评判和研究抽查制度。①医疗保险工作人员每月抽查住院患者的5%-1O%的数据,核对住院患者实际接受治疗的诊疗项目、药品数量和费用情况与医疗保险信息系统中数据是否一致。确定一致后,方能进行结算;②此次研究中,研究人员抽查了千分之一的数据,逐一与医院病历进行数据核对,准确无误后方进行统计分析。
(4)筛选标准:对参保人员住院数据进行清理,有以下条件之一的参保人员数据予以删除:①各参与分析的主要变量缺失(如:出院时间、年龄、诊断、ICD-10、抗菌药物使用情况等);②在长沙市以外地区住院;③住院费用小于100元(多为患者住院后尚未实际实施住院诊疗就因某种原因出院所致);④住院天数小于1天;⑤各项住院费用之和不等于总费用;⑥各项支付费用之和不等于总费用。⑦年龄小于18岁。
研究期间研究对象共计245322例,数据清理后符合研究要求的住院人员共240158例,构成本研究的总体,占全部参保人员的97.90%。本研究的研究单位(即:例)为出院人次,如果同一人多次住院,计为不同人次。
(5)数据整理:①按照筛选标准进行数据删除工作。②主要对抗菌药物的名称、规格进行转换。2007年《处方管理办法》出台前,医院药品使用商品名开具处方,给统计分析带来很大困难,此次研究对于每一个商品名药品统一修改为通用名,并按照世界卫生组织所规定的化学结构和药理作用分类编码(即ATC编码),同时将剂型规格按照ATC/DDD编码转换成统一的国际单位,进行分类统计分析。
(6)分析方法
住院费用资料一般呈正偏态分布,应该分别应用中位数和四分位数间距描述其集中趋势和离散趋势。但由于卫生部的规定和各医疗部门的长期习惯,以及中位数的非加和性,本研究在费用描述中同时给出中位数和算术均数。统计分析方法包括描述性统计分析、t检验、单因素方差分析、χ2检验、多元回归分析等。计数资料用χ2检验。P值为双尾,P≤0.05认为有显著性差异。采用DBF进行数据转换,利用SPSS17.0软件进行数据处理和统计分析。
(7)质量控制
本研究数据直接采自湖南省医疗工伤生育保险管理服务局的医疗保险管理信息系统,数据量大,内容真实、可靠,并经过严格的数据筛选,保证了数据的准确和完整。数据的采集、转换由专门的Oracle数据库技术人员专人负责,确保数据转换过程无误。
结果
(一)一般情况
2003~2009年湖南省省本级城镇职工基本医疗保险参保人员共有24.02万人在102家医院接受住院治疗,其中男性13.80万人(57.45%),女性10.22万人(42.55%),年龄59.8±14.9岁,住院时间18.2±20.8天。其中三级医院(20家)住院人数为13.00万人(54.12%),二级医院(32家)6.83万人(28.46%),一级医院(50家)4.18万人(17.43%)。在职人员8.81万人,占总人数的36.70%。退休人数15.20万人,占总人数的63.30%。研究对象中手术人数39981人,手术人数比例为16.65%。研究对象中进行了细菌培养检查和药敏试验的人数为33772人,占总人数的14.06%。
(二)抗菌药物使用情况
1、抗菌药物使用总体情况
(1)总体情况:抗菌药物使用人数为16.83万,使用率为70.07%,给药途径以注射为主(92.19%),使用抗菌药物患者中平均使用2.66种抗菌药物。男性患者抗菌药物使用率为71.02%,略高于女性患者68.78%;20~30岁年龄段患者抗菌药物使用率最高,为84.28%。而50~60岁年龄段使用率最低,为65.39%。在职患者抗菌药物使用率为72.89%,略高于退休患者68.43%;收入最低的0~1000元等级和和收入高的5000元以上住院患者抗菌药物使用率分别为72.65%和72.39%,略高于其他收入等级住院患者抗菌药物使用率。
(2)不同级别医院情况:一级医院使用率最高,为73.15%,二级医院居中为71.36%,三级医院为68.39%。非手术患者抗菌药物使用率为64.65%,明显低于手术患者抗菌药物使用率为97.16%。16.83万名抗菌药物使用患者中3.38万人进行了细菌培养,细菌培养率为20.07%。近80%的抗菌药物使用者未进行任何细菌培养和药敏实验,主要根据临床经验用药。抗菌药物使用比例最高的一级医院细菌培养率最低,仅为3.84%,二级医院细菌培养率最高为30.09%,三级医院居中为20.16%。
(3)联合用药情况:使用了抗菌药物的住院患者人均每次住院使用2.69种。其中使用一种抗菌药物人数为4.76万人,占抗菌药物使用总人数的28.29%。71.71%的患者联合使用了两种及两种以上抗菌药,43.24%的患者使用三种及三种以上抗菌药物。60.09%的注射药物使用者使用了两种及两种以上注射类抗菌药物,使用三种及三种以上者有4.39万人,占28.31%。
2、抗菌药物使用变化趋势
(1)使用率变化趋势:2003-2009年间住院患者抗菌药物使用率呈逐年下降趋势。由2003年的78.96%,下降到2008年的66.17%和2009年的66.26%。
(2)给药途径变化趋势:2003-2009年间住院人员中口服用药比例,从2003年的35.63%增加到2009年的38.72%。注射用药人员比例从2003年的73.91%下降到2009年的59.13%。
(3)抗菌药物使用种数变化趋势:2003年至2009年人均使用抗菌药物种类呈下降趋势,从2003年人均2.79种下降到2009年的人均2.57种。2003-2009年人均注射类抗菌药物使用种数也呈明显下降趋势,从2.22种下降到1.71种。在此期间口服抗菌药物使用种数略有上升,从0.57种上升到0.86种。两种及以上抗菌药物联合使用人员比例从74.36%%降至70.64%%,使用四种以上人员比例由2003年14.44%下降到2009年的10.74%%。
(4)不同级别医院使用率变化趋势:一级医院由2003年的79.78%%下降到2009年的71.61%%。二级医院由2003年的80.54%%下降到2009年的67.8%,下降了12.74个百分点。三级医院下降最明显,从2003年78.24%%下降到2009年的63.03%%。
(5)细菌培养比例:2003-2009年间细菌培养比例略有增加,从2003年的17.25%增加到2009年的21.86%。
3、抗菌药物构成分析
(1)总体构成:抗生素类抗菌药物使用率64.40%(头孢菌素类抗生素使用率为45.72%,青霉素类抗生素使用率为25.48%%),人工合成抗菌药物使用率为36.57%。抗分支杆菌和抗真菌药物使用率分别为4.93%和1.82%。抗菌药物使用率前三名的药品依次为左氧氟沙星(13.34%%)、头孢噻肟(8.14%)和头孢哌酮舒巴坦(8.03%)。
(2)头孢菌素使用构成:头孢菌素使用率为45.72%。第三代头孢菌素的使用率最高,为36.64%。头孢菌素使用人次占同期抗菌药物使用人次的65.25%,占同期抗生素使用人次的70.99%。头孢菌素使用频数为15.67万。使用头孢菌素的患者平均使用种数为1.43。
(3)青霉素类抗生素构成:青霉素类使用率为25.48%,从2003年的38.91%逐年下降至2009年的20.23%。窄谱青霉素使用率为4.76%,由2003年12.53%下降至2009年2.83%;耐霉青霉素使用率4.85%,7年下降了2个百分点;广谱和复方青霉素使用率最高22.54%,是窄谱青霉素和耐霉青霉素使用率的5倍,7年问由33.47%下降到17.94%。
(4)人工合成抗菌药物构成:喹诺酮类使用率最高(29.71%),7年中呈下降趋势,从2003年的38.89%下降到2009年的24.28%;其次为硝基咪唑类(11.89%),使用其他类人工合成抗菌药物的患者最少(1.29%)。
(5)广谱抗菌药物使用率为59.37%,从2003年62.43%降至2009年的57.21%,广谱抗菌药物使用人次占抗菌药物使用总人次的比例从79.07%逐年上升,到2009年达86.34%,分析发现广谱抗菌药物使用人员平均使用了2.19种广谱抗菌药物,有逐年下降趋势。
4、抗菌药物费用负担:
(1)总体费用负担:2003-2009年住院人员抗菌药物费用2.87亿元,占使用抗菌药物患者住院医疗总费用16.37亿元的17.53%,占其西药费用6.97亿元的41.17%。抗菌药物费用中抗生素费用为2.40亿元,占抗菌药物总金额的比例83.03%,人工合成抗菌药金额为0.44亿元,占抗菌药物总金额的比例为15.23%,抗分枝杆菌药和抗真菌药物金额分别占总金额的0.24%和1.49%。
抗菌药物费用占医疗总费用比例从2003年的19.07%下降到2009年的17.71%,抗菌药物占西药费比例也从2003年的42.3%下降到2009年为40.62%,下降值均在两个百分点以内。
住院人员抗菌药物使用金额以注射剂型为主,共计27553.49万元,占总金额28923.33万元的95.26%。
(2)不同级别医院情况:三级医院次均住院抗菌药物使用金额最高,7年平均为2139.05元,二级医院次之,为1445.36元,一级医院最低为863.30元。然而一级医院人均抗菌药物费用占住院费用的比例最高,为27.24%,二级医院为19.28%,三级医院最低16.19%,一级医院次均抗菌药物费用863.30占次均西药费用1573.83的比例为54.85%,二级医院次均抗菌药物费用1445.36元是次均西药费用3084.24元的46.86%,三级医院该比例则为38.13%。
(3)抗菌药物费用负担:头孢菌素1.57亿元,占抗生素药物金额比例为65.7%,由2003年的62.82%逐步上升至2009年的67.21%,占抗菌药物总金额的54.37%;青霉素类药物金额占抗生素总金额的比例为20.04%,从24.55%降至16.19%。人工合成抗菌药物以喹诺酮类为主,占人工合成抗菌药物的86.57%。
抗菌药物使用金额排名前三位的是头孢哌酮舒巴坦、左氧氟沙星、头孢他啶,排名前10位的药物中头孢菌素占据了8种,除头孢呋辛为头孢二代外,其余均为头孢三代;另外一种是哌拉西林三唑巴坦,十种药物均为广谱抗菌药物。
头孢三代金额明显上升,从2003年74.12%,上升到2006年85.66%,到2009年略有下降,为82.49%。广谱及复方青霉素占青霉素类抗菌药物费用的66.92%。
(4)广谱抗菌药物情况:广谱抗菌药物累计费用为22891.5万元,占总抗菌药物费用28923.33万元的79.15%。从2003年的83.56%降至2009年的76.07%。
(5)全人群抗菌药物经济负担:人均参保人员每年住院消费抗菌药物金额为160.32元,从2003年的130.22元/人/年,增长至2009年的212.39元,注射费用从从2003年的124.23元/人/年,增长至2009年的196.73元,口服费用每年为7.59元。
5、抗菌药物DDDs变化情况
(1)总体情况:将能获取药物规格的注射类抗菌药物169019人次进行分析,平均药物DDDs值为7.39,从2003年的8.02略有下降,到2006年降至7.13,然后又逐步回升,到2009年的7.5。一级医院每种药物次均DDDs值为9.17,明显高于二级医院平均值的6.9和三级医院平均值6.81。
(2)抗菌药物DDDs值构成:在抗菌药物DDDs构成中头孢菌素为56.29万DDDs,其次为青霉素类抗菌药物26.40万DDDs,分别占总数的45.10%和21.15%,头孢菌素类抗菌药物占总数比例有逐年增加趋势,从2003年的37.54%,增加至2009年的51.03%,占到了抗菌药物总DDDs的一半以上。
青霉素抗生素DDDs值占比最大的为广谱青霉素及复方制剂,其DDDs值为202389.42,占总数的76.79%,从2003年的74.2%上升到2009年的85.8%,各代头孢菌素DDDs构成中,头孢三代占比例最高,DDDs值为440882.31,占总数的78.25%,由2003年的67.54%,逐年增长至2006年的81.70%,后略有下降。
2003-2009年DDD值排名前三位的药物分别为左氧氟沙星,12.72万DDDs,占总数的10.19%,其次为头孢噻肟钠,占9.61%,头孢哌酮舒巴坦钠6.57%
(3)广谱抗菌药物DDDs值变化趋势:广谱注射类抗菌药物DDDs值为1026605,占同期抗菌DDDs值的比例为82.25%,从2003年的77.87%上升到2009年的84.39%。
(4)全人群抗菌药物DDDs值。住院人员注射类抗菌药物DDDs值总和由2003年25.72万,增加至2009年48.52万,除以当期参保人员数量,计算出平均参保人每年住院注射类抗菌药物DDDs值为1.39,从2003年1.2,增加至2009年的1.55。每百住院日注射类抗菌药物DDDs值为57.58,由2003年的68.74,下降到2009年的54.11。
6、部分疾病抗菌药物应用情况
(1)结节性甲状腺肿手术患者抗菌药物使用
667名住院患者中665人使用了抗菌药物,使用率为99.3%。注射类抗菌药物使用人数为653人,使用率为97.90%,平均为1.92±0.90。使用抗菌药物92.80万元,占医疗总费用的18.76%。人均抗菌药物费用为1374.87±841.79元,中位数为1407元。头孢菌素类抗生素62.04万元,占抗菌药物费用的67.16%。其次为青霉素类抗菌药物22.72万元,占抗菌药物费用的22.72%。使用率前三位为头孢地尼14.24%、青霉素13.64%和头孢尼西11.24%。金额前三名为头孢尼西、美洛西林舒巴坦和头孢孟多酯。
(2)不同付费方式的急性单纯性阑尾炎患者抗菌药物使用
206名阑尾炎患者抗菌药物使用率为100%,平均每人抗菌药物使用种数为2.83±1.19,100%的患者使用了注射剂型的抗菌药物,平均2.50种。单病种付费人员抗菌药物使用种数为2.43±1.18,按项目付费人员抗菌药物种数为3.05±1.14。平均抗菌药物使用金额为1055.43±894.35元,占人均西药费用1705.61元的61.88%。按项目付费人员平均抗菌药物使用金额1374.72±959.73,单病种付费平均抗菌药物费用485.78±283.08元,平均每个住院患者使用了1.23种头孢菌素类药物和0.825种硝基咪唑类药物。其他各项如头孢菌素、青霉素类、喹诺酮类和硝基咪唑类抗菌药物,按项目付费人员均高于按单病种付费人员。项目付费人员头孢菌素频次费用为675.94元,是按单病种付费人员头孢菌素频次费用的2.71倍。
(3)参保产妇住院分娩期间抗菌药物使用:6834名住院分娩产妇中只有11人未使用任何抗菌药物,抗菌药物使用率为99.84%。
住院分娩产妇平均使用抗菌药物种数为2.48±1.19种。75.23%的产妇联合使用了两种或两种以上抗菌药物,47.31%的产妇使用三种及三种以上抗菌药物。阴道分娩产妇注射抗菌药物使用率为90.4%,低于剖宫产产妇的98.72%。阴道分娩产妇平均使用抗菌药物种类为1.95±1.06,低于剖宫产产妇的2.84±1.13种。抗菌药物费用占西药费用的55.92%。
7、左氧氟沙星和头孢哌酮舒巴坦使用情况
(1)左氧氟沙星:左氧氟沙星是抗菌药物使用中使用率最高的抗菌药物,此次研究中连续七年注射类使用率均排名第一,平均使用率为13.34%,从2003年的20.01%,下降到2009年的7.64%。一级医院使用率逐年上升,从10.39%上升至2008年的23.02%,7年平均使用率为17.36%。二三级医院使用率逐年下降,7年平均使用率分别为15.28%和11.03%。左氧氟沙星费用1612.4万元,以注射类为主,7年累计为1469.78万元,占左氧氟沙星总费用的91.15%。注射剂型左氧氟沙星使用人次费用从691.38元逐年下降,至2009年将为342.62元,平均每个医疗保险参保人员每年有8.15元用于住院使用注射剂型左氧氟沙星。
7年平均值为7.34个DDD,一级医院次均DDDs最大,为8.97。二级医院次之为7.43,三级医院为5.92。左氧氟沙星的DDDc值从2003年的116.29元逐年下降至2009年的42.06元,7年平均DDDc为64.54元。三级医院最高,91.37元,二级医院63.84元,一级医院最低为30.41元。
(2)头孢哌酮舒巴坦:孢哌酮舒巴坦此次研究中是抗菌药物使用金额最高的抗菌药物,7年平均使用率为8.03%,从2003年的7.46%,逐步上升,到2005年达10.27%,后不断下降到2009年的7.13%。
一级医院使用率逐年上升,从2003年1.24%上升至2008年的11.87%,2009年有下降,10.82%,7年平均使用率为8.59%。三级医院使用率均从2003年的8.36%,上升到2005年的11.65%,后逐步下降到2009年的3.68%,平均使用率为6.34%。二级医院平均使用率最高达10.90%,7年来一直波动在8.57%到13.94%之间。头孢哌酮舒巴坦使用金额2062.80万元,占注射类抗菌药物总额的7.49%。头孢哌酮舒巴坦使用人员次均费用从1828.13元逐年下降,2006年达到最低,794.27元,后逐步上升至2009年的969.1元,平均为1069.47元。
7年次均DDDS为7.97,7年波动在8.21至7.33之间。其中三级医院次均DDDs最大,为8.59。二级医院次之为7.93,一级医院为7.03。DDDc是指每日剂量价格,反映了该药品的经济负担,头孢哌酮舒巴坦的DDDc值从2003年的222.57元逐年下降至2009年的124.83元,7年平均DDDc为134.14元。
结论
(一)研究样本七年间的抗菌药物使用率为70.07%;以注射给药途径为主、联合用药比例高、细菌学检查和培养率过低、广谱抗菌药物使用率高(59.37%)等为主要特征。每百住院日注射类抗菌药物DDDs值为57.58。
(二)在抗菌药物使用构成中,抗生素类使用率为64.40%,人工合成抗菌药物使用率为36.57%。左氧氟沙星的使用率最高(为13.34%),药品费用最高为头孢哌酮舒巴坦(占注射类抗菌药物费用的7.49%)。
(三)抗菌药物使用者的次均费用、药费均高于未使用抗菌药物的被调查对象,参保人员人均每年住院消费抗菌药物金额为160.32元。
(四)七年间抗菌药物使用的变化趋势主要表现为:抗菌药物的总体使用率逐年下降;注射途径给药逐年降低,口服途径给药逐年增高;人均抗菌药物使用种数缓慢下降;广谱抗菌药物使用率逐年下降,但其在抗菌药物使用人次中的比例逐年上升;抗菌药物使用的人均DDDs和DDDc两项指标均呈逐年下降趋势。
(五)影响抗菌药物使用的主要因素为支付类型、工资分层、手术与否、年龄、和住院天数。
主要创新点:
(1)研究了长达7年时间跨度的相对固定人群住院抗菌药物使用率、各类抗菌药物构成及变化趋势。
(2)首次研究了住院抗菌药物使用人员的抗菌药物DDDs值、每百床日抗菌药物DDDs值以及全人口的住院年均抗菌药物DDDs值及变化趋势。
(3)分析了住院人员的抗菌药物费用负担,首次研究了全人口的抗菌药物费用负担变化趋势。
(4)首次研究了不同医疗保险支付方式对抗菌药物使用和费用负担的影响。
Background:
As a major tool for the prevention and treatment of infectious diseases, the antibacterial drugs are commonly used in hospitals. But over the past twenty years, the irrational administration of antibacterial drugs become more and more serious around the world, which not only leads to heavier economic and health burden on inpatients, but also increases bacterial resistance, worsens the global environment and results in other serious social problems. Irrational administration of antibacterial drugs has become a major global public health problem.
Understanding the current situation of the clinical use of antibacterial drug and analyzing the influence factors of the clinical use of antibacterial drugs are the basis for promoting the rational use of antibacterial drugs. Existing literatures reports that most domestic studies are limited to the research of using antibacterial drugs within a certain group or on a certain date, while there is no such a detailed study for the antibacterial use and utility trends of a relatively fixed population, let alone the lack of study about antibacterial drugs use before and after implementation of the "Guiding Principles of clinical use of antibiotics". So it is difficult to accurately and fully reflect the antibacterial drugs use of inpatients under the circumstances.
Objective:
The objectives of this study are to investigate the situation and trends of antibacterial drugs use from 2003 to 2009, fully reveal the current constitution, changes and economic burden of antibacterial drugs administration, analyze the main factors affecting the current situation, and develop proper interventions to reduce the irrational administration of antibacterial drugs. Specific objectives are:
(1) To employ a comprehensive analysis on the situation and trends of prescription rate, combination administration, administration route, bacterial culture, drug type of antibacterial drugs of inpatients in 102 hospitals from 2003 to 2009.
(2) To evaluate the economic burden of antibacterial drugs on inpatients, and the composition of the economic burden of various antibacterial drugs on patients as well as its trend of change.
(3) By analyzing the value of various types of DDDs of antibacterial drugs, to describe the total usage, composition and change trends of antibacterial drugs, calculate DDDc (medication daily price), evaluate the economic burden, analyze DDDs value per thousand inpatients, and compare those data with international data.
(4) By analyzing the antibacterial drugs administration of patients with simple goiter and puerperal to the administration of antibiotics of patients with reflect antibiotics administration of patients with clearing operation. By analyzing antibacterial drugs administration of acute simple appendicitis patients with different types of payment to reveal how medical insurance payment influences antibacterial drugs administration.
(5) To analyze the administration status of levofloxacin which is most frequently prescribed and Cefoperazone Sulbactam which costs patients most.
Methods:A retrospective study is applied to conduct a full-sample analysis.
(1) Subjects:the subjects of this study are in-patients which are hospitalized from January 1,2003 to December 31,2009; those patients are covered by Hunan provincial basic medical insurance which is managed by Medical Insurance Bureau of Hunan Province. The number of the insured staff is 200~300 thousand per year; 7-year cumulative insured staffs are 1.8041 million. Using full sample analysis, the antibiotics administration situation of 245322 in-patients are studied in this study.
(2) Data sources and its composition:Data from this paper comes from the management information system database of Medical Insurance Bureau of Hunan Province. This system is directly connected with the hospital information system (HIS) system, and automatically access data from the HIS system to settle on medical insurance expenses. As for those hospitals which has no hospital HIS system, medication administration, medical services and expenses are faithfully recorded into system. The research data was directly exported from the medical insurance management information system by software developers.
Coding systems introduced into this study are:disease coding-ICD-10 International Classification of Diseases; fees and payment code are defined by software development company (Chuangzhi Company); other codes, such as gender, therapeutic effect is national standard codes.
Data include:general data (name, gender, age, nationality, civil servants level, work status, nature of one's work, visiting hospital, the level of visiting hospital, clinical diagnosis ICD-10 classification, admission date, discharge date, length of hospitalization stay and therapeutic effect), medical expense (including medicine fees, surgery fees), name, dosage forms, specifications, quantities, administration methods of antimicrobial drug, antimicrobial drug costs, time and cost of clinical microbiological examination (including pathogenic microorganisms microscopy, culture, identification and drug sensitivity test).
(3) Authenticity:including routine Authenticity and research sampling principles.①Medical insurance staff do sampling check on the medical records of 5%-10% inpatients every month, matching the actual inpatient treatment programs, drug amounts and costs of medical insurance. Only data in medical record is in accordance with the medical insurance system, accounts can be settled;②In this study, the researchers took 1‰data to match with the hospital medical records one by one for data verification, so as to make sure the accuracy of the data, then statistical analysis was conducted。
(4) Selection criteria:the data of insured inpatients was cleaned up; data that fits with one of the following conditions should be deleted:①The absence of the main variables in the analysis (such as:discharge time, age, diagnosis, ICD-10 antimicrobial drug administration, etc.);②Hospitalization outside Changsha city;③hospitalization costs less than 100 Yuan;④Hospital stay is less than 1 day;⑤The sum of every hospital expense is not equal to the total cost;⑥The payment of fees and not equal to the total cost.⑦The patient is younger than 18 years old;⑧The sum of the cost of antimicrobial agents is negative.
(5) Data processing:①Delete data in accordance with the screening criteria.②Focus on translating the name and specifications of antibiotics. Before "Prescription Management Principles" took into effect in 2008, hospital prescription drugs were recorded in their trade names, which have brought great difficulties to the statistical analysis. Thus each brand name was changed into a common name in this study, and each drug was coded in accordance with the chemical structure and classification of the World Health Organization (i.e., ATC code), while specification was conversed to unified international units in accordance with the ATC/DDD, then statistical analysis was conducted.
(6) Analysis methods:
Hospital cost data, often on positively skewed distribution, should be described with its central tendency and dispersion tendency using the median and interquartile range respectively. Considering the regulations of the Ministry of Health and the health sector's long-term habits, and the median of the non-additive, the median and arithmetic mean were given when described the cost in this study. Statistical methods include descriptive statistics, t test, ANOVA,χ2 test, multiple regression analysis. Application of Kolmogorov-Simonov measurement data and Levine test to determine the normal distribution and the overall homogeneity of variance. Normal distribution was analyzed by Student's t test, non-normal distribution was analyzed by Mann-Whitney U test to compare the mean. Administrationχ2 test to analyze Count Data. Two-tailed P value, P< 0.05 was considered significant difference. DBF was administration for data conversion, SPSS17.0 software for data processing and statistical analysis.
(7) Quality control:
The data comes from the management information system database of Medical Insurance Bureau of Hunan Province. Data capacity is abundant; its content is true and reliable; data was screened rigorously to ensure data accuracy and integrity. Data acquisition and conversion were monitored by a specific staff person who is responsible for Oracle database technology to ensure accurate data conversion process.
Results:
(A) General situation:
A total of 240,2 thousand insured people had received treatment in 102 hospitals from 2003 to 2009, who participated in Hunan Province's basic medical insurance for urban workers. Among them,138 thousand were (57.45%) male patients,102.2 thousand (42.55%) were female patients, whose age ranged from 59.8 plus or minus 14.9 years old, and their hospitalized time almost 20.8 plus or minus 18.2 days on average. There are 130 thousand (54.12%) inpatients in 20 tertiary hospitals,68.3 thousand (28.46%) in 32 Second-level hospitals, and 41.8 thousand (17.43%) inpatients in First-level hospitals.88.1 thousand inpatients were occupied personnel, made up 36.70% of the total number, while 152 thousand retired inpatients which made up 63.30%.39,981 inpatients received operation, which accounted for 16.65% of all research numbers in this study. The number of receiving bacterial culture and sensitivity test were 33,772, which made up 14.06% of all research numbers.
(B) The situation of using antimicrobial drugs
1. The general situation of using antimicrobial drugs
(1) The general situation:The number of using antimicrobial was 168,3 thousand, and the prescription rate is 70.07%. The main administration method is injection, which made up 92.19%. The inpatients who received treatment with antimicrobial agents administration average 2.66 kinds antimicrobial drugs. As for the prescription rate of Antimicrobial drugs, male patients was 71.02%, much higher than female patients whose prescription rate was 68.78%; for different age, the group of 20-30 year-old was the highest, whose prescription rate was 84.28%.While the group of 50-60 year-old was the lowest, whose prescription rate was 65.39%.Prescription rate of Antimicrobial drugs of occupied people was 72.89%, slightly higher than retired people (68.43%). The prescription rate of the people with lowest income levels (0-1000 Yuan per month) and those with the highest income levels (≥5000 Yuan per month) were 72.65% and 72.39% respectively, slightly higher than people with other income level.
(2) Situations in different levels of hospitals:The prescription rate in first-class hospitals was the highest (73.15%). The second-class hospitals were in the middle (71.36%). The third-class hospitals were the lowest (68.39%). The prescription rate of antimicrobial drugs of non-operational patients was 64.65%, obviously lower than operational patients (97.16%). Among 168,3 thousand clients using antibacterial drugs,33.8 thousand people had done bacterial cultivation (20.07%). Nearly 80% of the patients using antibacterial drugs did not have any bacterial cultivation or drug sensitive test. Doctors prescribe antibacterial drugs mainly based on their clinical experiences. The bacterial cultivation rate in first-class hospitals was the lowest (only 3.84%).the bacterial cultivation in the second-class hospital was the highest (30.09%), the third-class hospitals was in the middle (20.16%).
(3) Situation of combination drugs:Hospitalized patients who apply antibacterial drugs apply 2.69 kinds'antibacterial drugs per inpatient. Among them,47.6 thousand patients use only one kind antibacterial drug, accounting for 28.29% of the total people of antibacterial drugs usage.71.71% of patients practice two or more kinds of antibacterial drugs.43.24% of the patients use three or more kinds of antibacterial drugs.60.09% of injective drugs patients administered two or more than two injective antibacterial drugs. There were 43.9 thousand patients who received there or more injective antibacterial drugs, accounting for 28.31%.
2. Trends of antibacterial drugs administration:
(1) Trends of the total prescription rate. The total prescription rate of antibacterial drugs decreased year by year between 2003 and 2009. The total prescription rate was 78.96% in 2003, decreased to 66.17% in 2008 and 66.26% in 2009.
(2) Trends of administration route:the administration rate of oral drugs rose from 2003 to 2009. The administration n rate increased from 35.63% in 2003 to 38.72% in 2009, while the administration rate of injecting drugs fell from 73.91% in 2003 to 59.13% in 2009.
(3) Trends of antibacterial drugs species:the antibacterial drugs species of per capita declined from 2003 to 2009, from 2.79 kinds per capita in 2003 per capita fell to 2.57 kinds in 2009. The injective antibacterial drugs species of per capita also significantly decreased from 2.22 kinds per capita in 2003 per capita fell to 1.71 kinds in 2009. During this period the species of oral antimicrobial drugs increased slightly, from 0.57 kinds in 2003 to 0.86 kinds in 2009.Combination administration rate of two and more than two kinds antibacterial drugs reduced from 70.64% to 74.36%, Combination administration rate of four and more than four kinds antibacterial drugs fell from 14.44% in 2003 to 10.74% in 2009.
(4) Trends of the total prescription rate with different levels hospitals:the total prescription rate in the first-level hospitals decreased from 79.78% in 2003 to 71.61% in 2009. This declined trend also presented in the second-level hospitals, from 80.54% in 2003 to 67.80% in 2009. The most obvious decline was in tertiary hospitals, fell down from 78.24% in 2003 to 63.03% in 2009.
(5) Trends of the bacterial cultivation rate:the bacterial cultivation rate increased slightly from 17.25% in 2003 to 21.86% in 2009.
3. Antibacterial drugs constitution analysis:
(1) The overall constitution of antibacterial drugs:The prescription rate of antibiotics was 64.6% (cephalosporin antibiotics was 45.72% and penicillin antibiotics was 25.48%), the prescription rate of synthetic antibacterial drugs was 36.57%. the prescription rate of Antifungal drugs and the drugs resisted of Mycobacterium were 4.93% and 1.82% respectively. The drugs which the prescription rates were in top three were levofloxacin (13.34%), cefotaxime (8.14%) and cefoperazone -sulbactam (8.03%).
(2) The constitution of cephalosporin:the prescription rate of cephalosporin was 45.72%. The prescription rate of third-generation cephalosporin was the highest (36.64%). The administration frequency of cephalosporin was 156.7 thousand times. The patient's administration cephalosporin administrated 1.43 kinds cephalosporin.
(3) The constitution of penicillin antibiotics:the prescription rate of penicillin was 25.48%, from 38.91% in 2003 decreased to 20.23% in 2009. The prescription rate of Narrow-spectrum penicillin was 4.76%, from 12.53% in 2003 decreased to 2.83 in 2009. the prescription rate of penicillin-resistant mold was 4.85%, down 2 percentage points; the highest prescription rates was broad-spectrum and compound penicillin (22.54%),which was 5 times of that of narrow spectrum penicillin and penicillin-resistant mold.
(4) The constitution of synthetic antibacterial drugs:fluoroquinolones had the highest prescription rate (29.71%). There was a downward trend between 2003 and 2009, from 38.89% in 2003 down to 24.28% in 2009. Nitroimidazole (11.89%) followed fluoroquinolones. the prescription rate of other types of synthetic antibacterial drugs was low (1.29%).
(5) The constitution of broad spectrum antibacterial drugs:the prescription rate of broad spectrum antibacterial drugs was 59.37%, from 62.43% in 2003 to 57.21% in 2009.2.19 kinds broad spectrum antibacterial drugs were administrated by patients who received broad spectrum antibacterial drugs therapy.
4. Expense analysis of antibacterial drugs
(1) The total expense of antibacterial drugs:the total expense of antibacterial drugs was 287 million Yuan from 2003 to 2009, which accounting for 17.53% of the total expense (1637 million Yuan) of inpatients who administrated antibacterial drugs, accounts for 41.17% of the medicine expense (679 million Yuan), and both the proportions decreased. The expense of antibiotics was 240 million Yuan, accounting for 83.03% of the total expense of antibacterial drugs. The expense of synthetic antibacterial drugs was 44 million Yuan, accounting for 15.23% of the total expense of antibacterial drugs. The expense of antifungal drugs and the drugs resisted of Mycobacterium respectively accounted for 0.24% and 1.49% of the total expense of antibacterial drugs.
The proportion of antibacterial drugs expense in the medical expense decreased from 19.07% in 2003 down to 17.71% in 2009. The proportion of Antibacterial drugs expense in medicine expense also fell from 42.3% in 2003 to 40.62% in 2009.
The expense of injective antibacterial drugs was 276 million Yuan, accounting for 95.25% of the total expense (287 million Yuan) of antibacterial drugs.
(2) The expense of antibacterial drugs for different levels hospitals:per captia expense of antibacterial drugs (on average 2139.05yuan) in tertiary hospitals was highest. Second-class hospitals followed tertiary hospitals with on average 1445.36 Yuan. First-class hospitals were lowest with 863.30yuan. However, the rate of per captia expense of antibacterial drugs in medical expense was 27.24% in first-class hospitals, which was the highest rate. Second-class hospitals followed first-class hospitals (19.28%). tertiary-class hospitals was lowest with 16.29%.
(3) The expense of different antibacterial drugs:The expense of Cephalosporin was 157 million Yuan, accounting for 65.7% of the expense of antibiotics and 54.37% of the expense of antibacterial drugs. The expense of penicillin was 47.95 million Yuan, accounting for 19.97% of the expense of antibiotics and 16.58% of the expense of antibacterial drugs. The expense of synthetics antibacterial drugs was 44.05 million Yuan, accounting for 15.23% of the expense of antibacterial drugs.
According to expense, the top three antibacterial drugs are Cefoperazone sulbactam, levofloxacin, ceftazidime. Cephalosporins accounted 8 kinds in the top 10 drugs, in addition to second-generation cephalosporin---cefuroxime; others are three-generation cephalosporin. The top 10 antibacterial drugs were all broad-spectrum antibacterial drugs.
(4) The expense of broad-spectrum antibacterial drugs:The total expense of broad-spectrum antibacterial drugs was 229 million Yuan, accounting for 79.15% of the expense of antibacterial drugs, which proportion declined from 83.56% in 2003 to 6.07% in 2009.
(5) Antibacterial drugs expense of the population:every insured people consumed antibacterial drugs 160.32 Yuan every year, this expense increased from 130.22yuan in 2003 to 212.39 Yuan per person per year. The expense of injective antibacterial drugs every insured people consumed increased from 124.23 Yuan in 2003 to 196.73 Yuan per person per year. The expense of oral antibacterial drugs was 7.59yuan per person per year.
5. Changes of antibacterial drugs DDDs
(1) General situation:drug specifications can be got from only 1690 thousand patients in this study. The average DDDs of antibacterial drugs was 7.39. The DDDs of every kind antibacterial drug per time was 9.17 in the first-class hospitals, significantly higher than the secondary hospitals (6.9) and tertiary hospitals (6.81).
(2) DDDs constitution of antibacterial drugs:cephalosporin DDDs (562.9 thousand) was the highest in all antibacterial drugs, which accounting for 45.10%total antibacterial drugs DDDs. Penicillin DDDs (264.0 thousand) followed cephalosporin, which accounting for 21.25%.the proportion of cephalosporin DDDs in total antibacterial drugs DDDs raised year by year, from 37.54% in 2003 to 51.03% in 2009.
The broad spectrum and the compound penicillin DDDs (202.4 thousand) were the highest in Penicillin DDDs, accounting for 76.79% of Penicillin DDDs. the third-generation cephalosporin DDDs (440.9 thousand) were the highest in cephalosporin DDDs, accounting for 78.25% of Penicillin DDDs.
According to DDDs, the three top antibacterial drugs were levofloxacin (127.2thousand DDDs, accounting for 10.19%of all antibacterial drugs DDDs), cefotaxime sodium (9.61%), and cefoperazone sulbactam sodium (6.57%).
(3) DDDs of broad spectrum antibacterial drugs:the DDDs of broad spectrum injective antibacterial drugs were 257.2 thousand, which accounted for 82.25% of total antibacterial drugs DDDs in the same period. This proportion increased from 77.87% in 2003 to 84.39% in 2009.
(4) Antibacterial drugs DDDs of the population:injective antibacterial drug DDDs per insured person per year was 1.39, which lightly rose from 1.2 in 2003 to 1.55 in 2009. Injective antibacterial drug DDDs per 100 bed-days was 57.58, which declined from 68.74 in 2003 to 54.11 in 2009.
6. Antibacterial drugs administration in some diseases
(1) Antibacterial drugs administration for patients with tuberous strums surgery: 665 inpatients with tuberous strums surgery administration antibacterial drugs, the prescription rate was 99.3%.665 inpatients received Injective antibacterial drugs therapy, the prescription rate was 97.90%. The species of antibacterial drugs were 1.92±0.90 on average. The expense of antibacterial drugs was 928 thousand Yuan, accounting for 18.76% of the total medical expense. The per capita expense of antibacterial drugs was 1374.87±841.79 Yuan, median was 1,407 Yuan. The expense of cephalosporin was 620.4 thousand Yuan, accounting for 67.16% of antibacterial drugs expense. The expense of penicillin antibiotics was 227.2 thousand Yuan, accounting for 22.72% of antibacterial drugs expense. The top three of prescription rate of antibacterial drugs were cefdinir (14.24%), penicillin (13.64%) and Cefonicid (11.24%). The top three of expense were Cefonicid, Bangladesh mezlocillin sulbactam and cephalosporins more esters.
(2) Antibacterial drugs administration of inpatients with acute simple appendicitis in different medical insurance payment
Antibacterial drugs prescription rate of 206 patients with appendicitis was 100%, average species of antibacterial drugs per patient were 2.83±1.19. injective antibacterial drugs prescription rate also was 100% and average species were 2.50. antibacterial drug average species of patients with single DRGS (diseases related groups) was 2.43±1.18, average species of patients with fee for service was 3.05±1.14. Average expense of patients with acute simple appendicitis was 1055.43±894.35 Yuan, accounting for 61.88% of per captia medical expense (1705.61yuan). The average expense of patients with fee for service was 1374.72±959.73 Yuan and that of patients with single DRGS was 485.78±283.08 Yuan. Frequency expense of cephalosporin, penicillin, Fluoroquinolones and nitroimidazole of patients with fee for service was higher than that of patients with single DRGS. Frequency expense of cephalosporin of patients with fee for service was 675.94 Yuan, which was 1.71 multiple high than that of patients with single DRGS.
(3) Antibacterial drugs administration of parturient with fertility insurance during parturition:The total administration rate of antibacterial drugs was 99.84%.2.48±1.19 kinds of antibacterial drugs were administration on average as for parturient who administrated antibacterial drugs. The main administration route was injection; the rate of drug combination was 75.23%. prescription rate of antibacterial drugs of parturient with vaginal delivery was 90.4%,which was slightly lower than that of parturient with cesarean section(98.72%).1.95±1.06 kinds of antibacterial drugs on average were administrated by parturient with vaginal delivery, this number was much lower than that of parturient with cesarean section (2.84±1.13 kind of antibacterial drugs were administrated). The expense of antibacterial drugs accounts for 12.84% of the total medical expense of parturient who administrated antibacterial drugs, accounts for 55.92% of the medicine expense.
7. Administration situation of levofloxacin and cefoperazone sulbactam
(1) Levofloxacin:Prescription rate of levofloxacin on average was 13.34%, which was the highest prescription rate in all antibacterial drugs. Prescription rate of levofloxacin increased year by year in the first-class hospitals, which was 17.36% between 2003 and 2009. However, prescription rate was decreased year by year in the second-class and tertiary hospitals, which were 15.28% and 11.03% respectively on average. The total expense of levofloxacin was 16.12 million Yuan. The expense of injective levofloxacin was 14.70 million Yuan, accounting for 91.15% of the total expense of levofloxacin. Attendance expense of injective levofloxacin was 691.38 Yuan in 2003, which was declined year by year, the expense was 342.62 Yuan in 2009.every insured person consumed 8.15 injective levofloxacin on average.
The DDD of levofloxacin was 7.34 on average between 2003 and 2009. The DDD is the largest in first-class hospitals (8.97), followed by the second-class hospitals (7.43). The DDD is the lowest in tertiary hospitals (5.92). DDDc is the daily dose price, reflecting the economic burden of the drug. The DDDc of levofloxacin was 64.54 Yuan on average between 2003 and 2009, this number decreased from 116.29 Yuan in 2003 to 42.06yuan in 2009. The DDDc of levofloxacin was. the highest in tertiary hospitals (91.37yuan), followed by that of the second-class hospitals (63.84yuan). The DDDc was the lowest in the first-class hospitals (30.41 Yuan).
(2) Cefoperazone sulbactam:the total expense of cefoperazone sulbactam was the highest in all antibacterial drugs in this study. Prescription rate of cefoperazone sulbactam was 8.03% on average. The total expense of this drug was 20.63 million Yuan, accounting for 7.49% of the expense of injective antibacterial drugs. Attendance expense of cefoperazone sulbactam was 1828.13 Yuan in 2003, which was declined year by year; the expense was 794.27 Yuan until 2006. After that the expense was increased,342.62 Yuan in 2009.
The DDD of cefoperazone sulbactam was 7.97 on average between 2003 and 2009. The DDD is the largest in tertiary hospitals (8.59), followed by the second-class hospitals (7.93). The DDD is the lowest in the first-class hospitals (7.03). The DDDc of cefoperazone sulbactam was 134.14 Yuan on average between 2003 and 2009, and this number decreased from 222.57yuan in 2003 to 124.83 Yuan in 2009.
Conclusion
(1) Prescription rate of antibacterial drugs was 70.7%; The high rate of injection administration, The high rate of combination drugs, The low rate of bacterial cultivation and drug sensitive test, Prescription rate of broad spectrum antibacterial drugs was 59.37%, njective antibacterial drug DDDs per 100 bed-days was 57.58.
(2) Prescription rate of antibiotics, synthetic antibacterial drugs were 64.40%, 36.57% respectively. Prescription rate of levofloxacin on average was 13.34%, which was the highest prescription rate in all antibacterial drugs. The total expense of cefoperazone sulbactam was the highest in all antibacterial drugs in this study, accounting for 7.49% of the expense of injective antibacterial drugs.
(3) The medical expense and medicine expense per captia who administrated antibacterial drugs were higher than these of who didn't administrated antibacterial drugs. Every insured people consumed antibacterial drugs 160.32 Yuan every year on average in this study.
(4) The trend of prescription of antibacterial drugs between 2003 and 2009 includes:Prescription rate of antibacterial drugs, the rate of injection administration, the kinds'antibacterial drugs per inpatient, the prescription rate of broad spectrum antibacterial drugs, the antibacterial drugs DDDs per captia and DDDc decreased year by year;
(5)Medical insurance payment, salary, operation, age and hospitalization period are main factors influencing antibacterial drugs administration.
The major innovative points
(1) This study analyzes and assesses the trend of prescription rate of anti-bacterial drugs and the constitution of anti-bacterial drugs of inpatients from 2003-2009.
(2) For the first time in China, the study depicts the changing trend of DDDs per capita, DDDs per 100 bed-days, and DDDs per inhabitant per year of antibacterial drug of inpatient during 7 years.
(3) This study researches the cost burden of inpatient using antimicrobial drugs and reports the financial burden and its trend of antimicrobial drug of the whole population for the first time in china.
(4) This study analyzes the impact of the different medical insurance payment on antimicrobial drugs administration and cost burden
引文
[1]周宏灏 药理学科学出版社[M]2003,397
[2]WHO collaborating centre for drug statistics methodology. The WHO collaborating centre for drug statistics methodology ATC/DDD index 2010[WB/OL].. http://www.whocc.no/atc_ddd_index
[3]赵健,李野.遏制抗生素滥用是药品监管的重要责任[J].中国药业,2004;13(12):4-5
[4]崔兰贵,张磊,朱铁梁.抗菌药物滥用与医院感染管理[J]中华医院感染学杂志,2009;19(15):2011-12
[5]WHO Drug Management Program, Interventions and strategies to improve the use of antimicrobials in developing countries [M] 20012 http://whqlibdoc.who.int/hq/2001/who_CDS_CSR_DRS_2001.9.pdf
[6]朱会英,曹洪涛,韩丽萍,等.综合性医院抗菌药物应用调查分析与管理对策[J].中华医院感染学杂志,2003,13(2):152.
[7]Franak Ansari, The European Surveillance of Antimicrobial Consumption (ESAC) Point-Prevalence Survey of Antibacterial Use in 20 European Hospitals in 2006[J] Clinical Infectious Diseases2009;49:1496-1504
[8]Gaye Usluer A multicenter point-prevalence study:antimicrobial prescription frequencies in hospitalized patients in turkey [J] Annals of Clinical Microbiology and Antimicrobials 2005; 4:16-20
[9]Seaton. R.A. Nathwani, Burton P et al Point prevalence survey of antibiotic use in Scottish hospitals utilising the Glasgow Antimicrobial Audit Tool (GAAT) [J] International Journal of Antimicrobial Agents 2007; 29:693-699
[10]卫生部医院感染管理规范(卫医发[2000]431号)47条2000年11月20日http://www.moh.gov.cn/publicfiles/business/htmlfiles/mohyzs/s3593/200804/186 26.htm
[11]全国医药经济信息网.中国医院药品商情数据分析[J].中国医院药品商情,2003;1(3):5
[12]孙海英,温燕,陈万生.上海市11家医院2003—2005年抗感染药物应用分析[J]第二军医大学学报2007;28(8):884-887
[13]张上淳,张鸿仁,萧美玲:台湾地区公立医院抗生素使用情形之调查研究[J]微免感志 1998;31:125-321
[14]蔡秀军,丁勇合理使用抗菌药物的管理体会[J]中华医学杂志2005;85(37): 2598-2600
[15]Ruifang Zhang, Karen Eggleston, VincentRotim, et al·Antibiotic resistance as a global threat:Evidence from China, Kuwait and the United States[J]Globalization and Health,2006; 2(6):1
[16]卫生部全国细菌耐药监测2006-2007年度报告关于进一步加强抗菌药物临床应用管理的通知,卫办医发(2008)48号http://www.moh.gov.cn/ publicfiles/business/htmlfiles/mohbgt/pw10805/200804/33289. htm
[17]Okumura J, Osaka K, Okabe N. Widespread multi-antimicrobial-resistant Shigella in Asia:What does it mean? Thailand,430 March-273 Okumu [abstract AM 011].2nd International Conference on Improving Use of Medicines, Chiang Mai,April 2004.
[18]陆铸今,张灵恩,陆国平等.2001年儿科医院重症监护室细菌耐药性监测[J].中国抗感染化疗杂志,2003,3(2):97-98.
[19]钟慧.老年患者二重真菌感染与抗菌药物应用分析[J].中国药房杂志,2002,13(3):155.
[20]北京市药品不良反应监测中心.2005年北京市药品不良反应监测数据分析[J].药物不良反应监测工作简报,2006,l:7-15.
[21]汪复.合理应用抗菌药物是当务之急[J].临床药物治疗杂志。2006,(4)5,1-2
[22]杨莉,肖永红,抗菌药物不合理使用对住院费用的影响[J]北京大学学报(医学版)2010(3)279-283
[23]肖永红,侯芳,王进抗菌药物不良反应的社会与经济后果调查[J]中国卫生经济卷2010,29(5):94-96
[24]Dajani AS. Adherence to physicians'instructions as a factor in managing streptococcal pharyngitis [J]. Pediatrics 1996; 97:976-80.
[25]Pechere JC. Parameters important in short antibiotic courses [J]. J Int Med Res 2000;28(Suppl 1):3-12
[26]Sclar DA, Tartaglione TA, Fine MJ. Overview of issues related to medical compliance with implications for the outpatient management of infectious diseases [J]. Infect Agents Dis 1994; (3):266-73.
[27]张浩军,张映华,王燕等,1453例住院患者抗菌药物临床应用回顾性调查分析[J],中华医院感染学杂志2009;19(2):193-195
[28]黄丽萍,吴伟,潘曼等,5302例住院患者抗菌药物使用的调查[J],中华医院感染学杂志2006;16(4):431-433
[29]冯建军等24771例住院病人抗生素使用调查分析[J]川北医学院学报 2002;17(4):135-136
[30]吴安华,任南,文细毛等,我国178所医院住院患者横断面抗菌药物使用率调查[J]中华医院感染学杂志2002;(12):881-884
[31]吴安华、任南等151家医院2003年度住院患者日抗菌药物使用率的调查分析[J]中华流行病学杂志2005;(6):24-26
[32]任南,文细毛,吴安华.165所医院住院患者抗菌药物临床应用横断面调查[J]中国医师杂志,2007;(05):633-635
[33]冷萍,曹玉,丁海燕住院患者抗菌药物的使用实施干预的调查研究[J]中华医院感染学杂志2009;(19):199-201
[34]陈莹莹行政干预前后抗菌药物临床应用分析[J]中华医院感染学杂志2009;(19):196-198
[35]陈炜抗菌药物综合干预管理的研究[J]中华医院感染学杂志2007;(17):1260-1262
[36]刘洪光住院精神病患者医院感染抗生素使用情况分析[J]华北煤炭医学院学报2007;(9)45-48
[37]徐菁莉等 肿瘤病人抗生素使用情况的调查[J]卫生职业教育2006;(24)97-98
[38]Conan MacDougall Ronald E Variability in Rates of Antibacterials Among 130 US Hosptials and Risk-Adjustment Models for Interhospital Comparison[J] Infection Control and Hospital Epidemiology 2008; (29) 203-211
[39]Gastmeier P, Sohr D, Forster D et al. Identifying outliers of antibiotic usage in prevalence studies on nosocomial infections [J]. Infect Control Hosp Epidemiol 2002; (21):324-8
[40]Kanerva M, Ollgren J, Lyytikainen O Antimicrobial use in Finnish acute care hospitals:data from national prevalence survey,2005 [J], Journal of Antimicrobial Chemotherapy 2007;60(2):440-4
[41]Shija R, Malele RS. A Baseline Survey of the Pharmaceutical Sector in Tanzania. [J] WHO; 2002; 62(http://whqlibdoc.who.int/hq/2002/a87428_eng.pdf)
[42]Kulkarni R et al. Surveillance of Antimicrobial Use at All Levels of the Health Sector:An Intervention in Itself? http://archives.who.int/icium/icium2004/ posterbadd.html
[43]Gray A et al. Antimicrobial Use and Resistance Surveillance Pilot Project: Lessons from the Durban Site http://archives.who.int/icium/icium2004/ posterbadd.html
[44]WHO International Working Group for Drug Statistics Methodology, Introduction to Drug Utilization Research [M].2003 38 [WB/OL] http://apps.who.int/medicinedocs/en/d/Js4876e/7.html
[45]卫生部 关于施行《抗菌药物临床应用指导原则》的通知卫医发[2004]285号[WB/OL] http://www.cfs.gov.cn/cmsweb/webportal/W4247/A63999500. html.
[46]Mainous AG Ⅲ, Hueston WJ, Davis MP, Pearson WS. Trends in antimicrobial prescribing for bronchitis and upper respiratory infections among adults and children[J]. Am J Public Health.2003;93:1910-4.
[47]Christianne L. Roumie, Natasha B. Halasa, Carlos G. Grijalva, Trends in Antibiotic Prescribing for Adults in the United States—1995 to 2002[J] J GEN INTERN MED 2005; 20:697-702
[48]The U.S.Agency for International Development(USAID)s.How to Investigate Antimicrobial Drug Use in Hospitals:Selected Indicators(M):Management Sciences for Health. Page 7
[49]朱会英,曹洪涛,韩丽萍,等.综合性医院抗菌药物应用调查分析与管理对策[J].中华医院感染学杂志2003;13(2):152.
[50]缪晓辉.抗菌药物临床应用中的问题与对策[J]中华医院管理杂志2005;21(2);122-125
[51]卫生部卫生统计中心2003-2009年中国卫生事业发展统计公报http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/pwstj/index.htm
[52]Guven GS, Uzun O:Principles of good use of antibiotics in hospitals [J]. J Hosp Infect 2003,53:91-96.
[53]Hecker MT, Aron DC, Patel NP, Lehmann MK, Donskey CJ:Unnecessary use of antimicrobials in hospitalized patients [J]. Arch Intern Med 2003,163:972-978.
[54]Knox K, Lawson W, Dean B, Holmes A:Multidisciplinary antimicrobial management and the role of the infectious diseases pharmacist-a UK perspective [J]. J Hosp Infect 2003,53:85-90.
[55]Hu S, Liu X, Peng Y:Assessment of antibiotic prescription in hospitalized patients at a Chinese university hospital [J]. J Hosp Infect 2003; 46:161-3
[56]SKOOGG, CARSO, SKARLUNDK, et al. Large scale nationwide point prevalence study of indications for antibiotic use in 54 Swedish hospitals in 2003[J]. Clinical Microbiology and Infection,2004,10:Supplement3,105-112.
[57]MCLAUGHLIN CM, BODASING N, BOYTER A, et al. Pharmacy- implemented guidelines on switching from intravenous to oral antibiotics:an intervention study[J]. Q J Med,2005,98:745-752.
[58]陈纯,林瑾文2002-2006年福州医保头孢类抗生素的使用情况分析[J].海峡药学,2007,19(11):98-99.
[59]Sang-Oh Lee Reduced Use of Third-Generation Cephalosporins Decreases The Acquisition of Extended-Spectrum Beta-Lactamsase-Producing Klebsiella Pneumoniae[J]. Infection Control and Hospital Epidemiology,2004,25(10): 832-836.
[60]杜斌;陈德昌;刘大为,等.限制使用三代头孢菌素可降低感染相关病死率[J].中国实用外科杂志,2004,24(6):348-351.
[61]2009年城镇职工医疗保险参保人数[WB/OL] http://www.gov.cn/jrzg/2010-06/10/content 1625109.htm
[62]DUNCAN RA. Controlling use of antimicrobial agents [J], Infect Control Hosp Epidemiology.1997,18(4):260-266.
[63]HARBARTH S, ALBRICH W, BRUM-BUISSON C Sociocultural Perspective on Outpatient Antibiotic Use and Prevalence of Antibiotic-Resistant Pneumococci:A Comparison between Two Large European Countries [J]. Emerging Infectious Diseases 2002; 8(12),1460-1467
[64]DIMASI JA, HANSEN RW, GRABOWSKI HG. The price of innovation:new estimates of drug development costs [J]. J Health Econ 2003; 22(10):151-185.
[65]MCGOMAN JE. Antimicrobial resistance in hospital organisms and its relation to antibiotic use. [J] Rev Infect Dis.1983; 5(6):1033-48.
[66]KUMARASAMY KK, TOLEMAN MA, WALSH TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK:a molecular, biological, and epidemiological study [J]. Lancet Infect Dis,2010, 10(9):597-602.
[67]MacDougall C, Harpe SE, Powell JP, et al Pseudomonas aeruginosa, Staphylococcus aureus, and fluoroquinolone use [J]. Emerg Infect Dis,2005,11: 1197-1204.
[68]王进,李家泰,李耘.氟喹诺酮类抗菌药物对2554株细菌的抗菌活性分析[J].中国抗感染化疗杂志,2004,4(1):14.
[69]R. Janknegt, A. Oude Lashof, I. M. Gould Antibiotic use in Dutch hospitals 1991-1996[J]. Antimicrob. Chemother.2000,45 (2):251-256.
[70]RAUL-ALL AN KIIVET, MARJA-LIISA DAHL, ADRIA'N LLERENA, Antibiotic Use in 3 European University Hospitals [J] Scand J Infect Dis 1998 30:277-280.
[71]王湘玲,郭小兰,汤萍.甲状腺大部切除围手术期抗生素应用的调查分析[J]中国药业,2004,13(5):56.
[72]张丽辉,林俊平,张华生,等.围手术期抗菌药物应用1235例调查分析[J]中国全科医学,2004,7(13):9811
[73]史占军,张亚莉,景宗森,等.规范化与长期应用抗生素预防术后伤口感染的效果对比[J].中华医院感染学杂志,2003,13(1):572-579
[74]黎沾良.手术后抗生素相关性肠炎[J].中华胃肠外科杂志,2005,8(2):110.
[75]黄丽萍,吴伟.妇产科抗菌药物临床调查分析[J].海南医学院学报,2007,13(4):331-333
[76]王选华,钱小毛剖宫产术前预防用药对预防切口感染效果的研究[J]中华医院感染学杂志2009,19(16):2170-2171
[77]黄晓华,马珩 抗菌药物在产科的预防性应用及管理[J]中华医院感染学杂志2002;12(10):726-727
[78]文宗萍,某三级甲等综合性医院感染现患率及抗菌药物应用调查研究[J]。中国药房2010;21(10):893-895
[79]孙旦萍.谢胜新.抗菌药物使用的调查分析[J]中国医院药学杂志2007;27(7):973-974
[80]Bodasing N, Cahill S, Seaton RA. Survey of antimicrobial prescribing in West Glasgow hospitals [J]. J Infect 2002; 44:113.
[81]McLaughlin CM, Bodasing N, Boyter A, Fenelon C, Fox JG, Seaton RA. Pharmacy-implemented guidelines on switching from intravenous to oral antibiotics:an intervention study [J]. Q J Med 2005; 98:745-52.
[82]董鹏,张立峰.普通外科480例住院患者抗菌药物应用情况分析[J].华西医学2010,25(4):777-779
[83]段蓉,王瑞臣,闫晨.我院2007年3月-2008年3月肝病住院患者抗菌药物应用调查分析[J].中国药房2010;21(10):885-888
[84]郑晓燕,阴赪宏,王超.2004年友谊医院抗菌药物应用调查及研究[J].中华医院感染学杂志2006;16(7):801-804
[85]van Zanten AR, Engelfriet PM, van Dillen K et al. Importance of nondrug costs of intravenous antibiotic therapy [J]. Crit Care 2003; 7:184-90.
[86]Pestotnik SL, Classen DC, Evans RS et al. Implementing antibiotic practice guidelines through computer-assisted decision support:linical and financial outcomes [J]. Ann Intern Med 1996; 124:884-90.
[87]Hamilton-Miller JM. Switch therapy:the theory and practice of early change from parenteral to non-parenteral antibiotic administration [J].Clin Microbiol Infect 1996; 2:12-9.
[88]Fraser GL, Stogsdill P, Dickens JD Jr et al. Antibiotic optimization. An evaluation of patient safety and economic outcomes [J]. Archntern Med 1997; 157:1689-94.
[89]Hitt CM, Nightingale CH, Quintiliani R et al. Streamlining anti-microbial therapy for lower respiratory tract infections [J]. Clin Infect Dis 1997; 24 (Suppl 2): 231-7.
[90]杨刚英国牛津地区医院抗生素使用介绍[J]中国药物与临床2007;7(1):61-63
[91]Duncan RA. Controlling use of antimicrobial agents [J]. Infection trol Hosp Epidemiol 1997; 18:260-6.
[92]沈志君.2007-2009年医院抗菌药物使用调查分析[J]中华医院感染学杂志2010:20(12):1774-1776
[93]孙旦萍,谢胜新.抗菌药物使用的调查分析[J]中国医院药学杂志2007;27(7):973-974
[94]穆英,刘东,陶曙光.国内防止抗生素不合理使用的制度[J].护理实践与研究.2008;5(3):52-53
[95]孙海英,温燕,陈万生等上海市11家医院2003—2005年抗感染药物应用分析[J]第二军医大学学报2007;(28)8:884-887
[96]卫生部2009年我国卫生事业发展情况简报[WB/OL] 2010-02-02 http:// www.moh.gov.cn/publicfiles/business/htmlfiles/mohwsbwstjxxzx/s8208/201001 /45652.htm
[97]Fleming A. Penicillin:Nobel Lecture,11 December 1945 [WB/OL] http:// nobelprize.org/nobel_prizes/medicine/laureates/1945/feming-lecture.pdf,
[98]World Health Organizaiotn. The world health report 2007:A safer future.global public health security in the 21st century[M].23 [WB/OL] http://www. who. int/whr/2007/en/index. html
[99]ARuifang Zhang, Karen Eggleston, Vincent Rotimi, et al. antibiotic resistance as a global threat:Evidence from China, Kuwait and the United States [J] Globalization and Health 2006,2:61-14
[100]Chavers LS, Moser SA, Benjamin WH, et al. Vancomycin resistant enterococci:15 years and counting [J]. J Hosp Infect,2003,53(4):159-171.
[101]Niederman MS. Impact of antibiotic resistance on clinical outcomes and the cost of care [J]. Crit Care Med 2001; 29(Suppl):S114-S120.
[102]Andersson Dl, Levin BR. The biological cost of antibiotic resistance [J]. Curr Opinion Microbial 1999; 2:489-493.
[103]Enne VI, Livermore DM, Stephens P, Hall LM. Persistence of sulphonamide resistance in Escherichia coli in the UK despite national prescribing restriction [J]. Lancet 2001; 357:1325-1328.
[104]Belongia EA, Sullivan BJ, Chyou PH, et al. A community intervention trial to promote judicious antibiotic use and reduce penicillin-resistant Streptococcus pneumoniae carriage in children [J].Pediatrics 2001; 108:575-583.
[105]S Molstad, M Erntell, H Hanberger Sustained reduction of antibiotic use and low bacterial resistance:10-year follow-up of the Swedish Strama [J] Lancet Infect Dis 2008; 8:125-32
[106]Berild D, Abrahamsen TG, Andresen S, eta.l A controlled intervention study to improve antibiotic use in aRussian paediatric hospital [J]. Int J Antimicrob Agents,2008,31(5):478-483.
[107]Dajani AS. Adherence to physicians'instructions as a factor in managing streptococcal pharyngitis [J]. Pediatrics 1996; 97:976-80.
[108]Pechere JC. Parameters important in short antibiotic courses [J] J Int Med Res 2000;28(Suppl 1):3A-12A
[109]Timothy H. Dellit,Robert C. Owens,John E. McGowan, Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship [J]. Clinical Infectious Diseases 2007; 44:159-77
[1]周宏灏.药理学[M].北京:科学出版社2003,397.
[2]罗佳,尹桃,李湘平.长沙市居民药店购买抗菌药的调查[J].中国药师,2009,12(5):613-615.
[3]Raz R,Edelstein H,Grigoryan L,et al.Self-medication with antibiotics by a population in northern Israe1[J].Isr Medical Association.2005 Nov, 7(11):722-725.
[4]Saradammaa RD.Social factors influencing the acquisition of antibiotics without prescription in Kerala State, south India[J].Soc Sci Med,2000,50:891-903.
[5]赵健,李野.遏制抗生素滥用是药品监管的重要责任[J].中国药业,2004,13(12):4-5.
[6]缪晓辉.抗菌药物临床应用中的问题与对策[J].中华医院管理杂志,2005,2,21(2):122-125.
[7]陈坚,方维军.上海市松江区21家医疗机构门诊处方合理用药国际指标调研[J].中国药房,2009,20(19):1517-1518
[8]孙强,闫赟,王伟.山东、宁夏农村地区县、乡、村医疗机构药品合理使用分析[J].中国卫生事业管理,2010,(8):535-538.
[9]王淑兰,全英南,鲁云鹤.我院门诊病人抗菌药物应用调查及合理性分析[J].中华医院管理杂志,2005,12,21(12):822-824.
[10]赵晓东,卢仲毅,杨锡强,等.重庆医科大学儿童医院1996-2001年抗生素使用情况分析[J].中华儿科杂志,2000,8,40(8):467-469.
[11]How to Investigate Antimicrobial Use in Hospitals: Selected Indicators[M]. Strengthening Pharmaceutical Systems,October 2008:20-33.
[12]崔兰贵,张磊,朱铁梁,等.抗菌药物滥用与医院感染管理[J].中华医院感染学杂志,2009,19(15):2011-2012.
[13]朱会英,曹洪涛,韩丽萍,等.综合性医院抗菌药物应用调查分析与管理对策[J].中华医院感染学杂志,2003,13(2):152.
[14]刘敬伟,甘霖,肖水源,等.2003-2009年102家医院住院患者抗菌药使用的趋势研究[J].中国全科医学,2011,1(14):102-104.
[15]吴安华,任南,文细毛,等.151家医院2003年度住院患者日抗菌药物使用率的调查分析[J].中华流行病学杂志,2005,6,26(6):451-454.
[16]Franak Ansari, The European Surveillance of Antimicrobial Consumption (ESAC) Point-Prevalence Survey of Antibacterial Use in 20 European Hospitals in 2006 Clinical Infectious Diseases[J].2009;49:1496-1504.
[17]Conan MacDougall Ronald E Variability in Rates of Antibacterials Among 130 US Hosptials and Risk-Adjustment Models for Interhospital Comparison[J]. Infection Control and Hospital Epidemiology 2008(29)203-211.
[18]Gaye Usluer A multicenter point-prevalence study:antimicrobial prescription frequencies in hospitalized patients in turkey[J]. Annals of Clinical Microbiology and Antimicrobials 2005,4:16-20.
[19]张上淳,张鸿仁、萧美玲.台湾地区公立医院抗生素使用情形之调查研究[J].微免杂志,1998,31:125-321.
[20]R.A. Seaton. Nathwani, Point prevalence survey of antibiotic use in Scottish hospitals utilising the Glasgow Antimicrobial Audit Tool (GAAT) [J]. International Journal of Antimicrobial Agents,2007,29:693-699.
[21]中华医学会,中华医院管理学会药事管理专业委员会,中国药学会医院药学专业委员会.抗菌药物临床应用指导原则[J].中华医学杂志,2004,84(23):2026-2056.
[22]孙海英,温燕,陈万生,等.上海市11家医院2003-2005年抗感染药物应用分析[J].第二军医大学学报,2007,28(8):884-887.
[23]金蜀蓉,杜蕾.重庆地区20家医院2006-2008年用药分析[J].中国药房,2010,21(14):1273-1276.
[24]张吉,孟玲,邹颖.南京地区22家医院2006—-2008年抗感染药物应用分析[J].中国新药与临床杂志,2010,6,29(6):462-465.
[25]郑晓燕,阴赪宏,王超.2004年友谊医院抗菌药物应用调查及研究[J].中华医院感染学杂志,2006,16(7):801-804.
[26]李烈坚,甘燕.300例儿科住院患者抗生素使用情况调查分析[J].广西医学,2007,12,29(12):1925-1926.
[27]文宗萍.某三级甲等综合性医院感染现患率及抗菌药物应用调查研究[J].中国药房,2010,21(10):893-895.
[28]孙旦萍,谢胜新.抗菌药物使用的调查分析[J].中国医院药学杂志,2007,27(7):973-974.
[29]董鹏,张立峰.普通外科480例住院患者抗菌药物应用情况分析[J].华西医学,2010,25(4):777-779.
[30]段蓉,王瑞臣,闫晨,等.我院2007年3月-2008年3月肝病住院患者抗菌药物应用调查分析[J].中国药房,2010,21(10):885-888.
[31]沈志君.2007-2009年医院抗菌药物使用调查分析[J].中华医院感染学杂志,2010,20(12):1774-1776.
[32]穆英,刘东,陶曙光.国内防止抗生素不合理使用的制度[J].护理实践与研究,2008,5(3):52-53.
[33]WHO—Promoting rational use of medicines:core components[M]. WHO Policy Perspectives on Medicines, World Health Organization,2002.
[34]蔡秀军,丁勇.合理使用抗菌药物的管理体会[J].中华医学杂志,2005,,85(37):2598-2600.
[35]杨莉,肖永红,聂垚.抗菌药物不合理使用对住院费用的影响[J].北京大学学报(医学版),2010,1(3):279-283.
[36]杨小娟,宋军燕.640例住院病历抗菌药物使用分析[J].陕西医学杂志,2005,8,34(8):1006-1008.
[37]Guven GS, Uzun O:Principles of good use of antibiotics in hospitals. [J]. Hosp Infect 2003,53:91-96.
[38]Hecker MT, Aron DC, Patel NP, Lehmarm MK, Donskey CJ:Unnec-essary use of antimicrobials in hospitalized patients[J]. Arch Intern Med 2003,163:972-978.
[39]Knox K, Lawson W, Dean B, Holmes A:Multidisciplinary antimicrobial management and the role of the infectious diseases pharmacist-a UK perspective [J]. Hosp Infect 2003,53:85-90.
[40]Hu S, Liu X, Peng Y:Assessment of antibiotic prescription in hospitalized patients at a Chinese university hospital [J]. Hosp Infect 2003,46:161-3.
[41]全国医药经济信息网.《中国医院药品商情》数据分析[J].中国医院药品商情,2003,1(3):5.
[42]李大魁.医院环境下的药物经济学工作[J].中国药学杂志,1999,1,34卷(1):50-51.
[43]黄继勋,赵广玉.2006-2008年我院用抗菌药物的回顾分析[J].中国新药杂志,2010,19(15):1380-1384.
[44]Wei J, Li BP, Zhao YG, et a.l Development of an automatic monitoring system for the rational use of antibiotics [J]. Chin J Hosp Admin,2004,8:479-481.
[45]Huskins WC, Soule BM, OBoyle C. Hospital infection prevention and control: a model for improving the quality of hospitalcare in low-and middle-income countries [J]. Infect Control Hosp Epidemiol,1998,19 (2):125-135.
[46]赵晖,于建华.持续质量改进理论在抗菌药物管理中的应用[J].山东医药2006,46(22):39.
[47]任真年.现代医院医疗质量管理[M].北京:人民军医出版社,2002.65-70.
[48]陈解语.PDCA循环在合理使用抗菌药物管理中的应用[J].中华医院感染学 杂志,2007,17(1):75-77.
[49]石娜,徐卫,舒雪芹,等PDCA循环在抗菌药物管理中的应用[J].中国药学杂志,2007,8,42(16):1270-1272.
[50]戴兴凌,刘文萍,程轶波,等.合理用药监测系统应用体会[J].中国药房,2005,16(17):1303-1304.
[51]钟初雷,张国荣,陈文光.抗菌药物合理应用系统的建立与应用[J].中华医院感染学杂志,2007,17(2):199-200.
[52]张慧芬,盛炳义,方曙,等.抗菌药物分级使用情况调查[J].中国医院药学杂志,2006,26(2):215-216.
[53]Goldmann DA, Weinstein RA, WenzelRP, Tablan OC, Duma RJ,Gaynes RP, et al·Strategies to prevent and control the emergence and spread of antimicrobial-resistantmicroorganisms in hospitals·A challenge to hospital leadership-JAMA 1996,275:234-240.
[54]蔡秀军,丁勇.合理使用抗菌药物的管理体会[J].中华医学杂志,2005,9,85(37):2598-2600.
[55]穆英,刘东,陶曙光,等.国内防止抗生素不合理使用的制度[J].护理实践与研究,2008,5(3):52-53.
[56]BonhoefferS, LipsitchM, Levin BR-Evaluating treatment protocols to prevent antibiotic resistance[J]. ProcNatlAcad Sci USA 1997,94:12106-12111.