Mortality and hospital stay associated with resistant Staphylococcus aureus and Escherichia coli bacteremia: estimating the burden of antibiotic resistance in Europe.
Mortality and hospital stay associated with resistant Staphylococcus aureus and Escherichia coli bacteremia: estimating the burden of antibiotic resistance in Europe.
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DOI：
10.1371/journal.pmed.1001104
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发表时间：
2011-10
期刊：
影响因子：
15.8
通讯作者：
BURDEN study group
中科院分区：
文献类型：
--
作者：
de Kraker ME;Davey PG;Grundmann H;BURDEN study group
作者计算了欧洲与耐抗生素细菌血流感染（金黄色葡萄球菌和大肠杆菌）相关的超额死亡率、超额住院时间和相关医院支出。人类疾病的相对重要性通常是通过特定病因的死亡率、发病率和经济影响来评估的。目前对抗生素耐药细菌引起的感染的估计没有得到定量经验数据的充分支持。本研究确定了参与欧洲抗菌素耐药性监测系统（EARSS）的31个国家中，与耐甲氧西林金黄色葡萄球菌（MRSA）和第三代耐头孢菌素大肠杆菌（G3CREC）引起的血流感染（bsi）相关的过量死亡人数、住院天数和住院费用。MRSA和G3CREC引起的脑梗死数量是根据EARSS患病率数据和国家卫生保健统计数据推断的。2007年在参与EARSS的医院进行的前瞻性队列研究提供了估计MRSA或G3CREC引起的脑损伤相关的额外30天死亡率和住院时间的参数。医院支出来源于可公开获得的成本模型。EARSS建立的趋势被用来确定MRSA和G3CREC的流行轨迹，直到2015年。2007年，在参与国，MRSA bsi的27,711次发作与5,503例额外死亡和255,683例额外住院日相关，而G3CREC bsi的15,183次发作与2,712例额外死亡和120,065例额外住院日相关。MRSA和G3CREC bsi的额外住院总费用分别为440万欧元和1810万欧元（6310万和2970万国际美元）。根据目前的趋势，G3CREC引起的bsi数量可能会迅速增加，在不久的将来超过MRSA bsi的数量。MRSA和G3CREC引起的脑损伤相关的超额死亡率是显著的，住院时间的延长给卫生保健系统带来了相当大的负担。可预见的抗生素耐药性负担从革兰氏阳性感染向革兰氏阴性感染的转变将加剧这一情况，值得关注。抗菌素耐药性——使用和误用抗菌素药物的后果——发生在微生物对以前敏感的抗菌素药物产生耐药性（通常通过突变或获得耐药基因）的时候。然后，标准治疗变得无效，导致持续感染，并可能传播给其他人。除了一些明显的例外，如结核病、艾滋病毒、疟疾和淋病，大多数可归因于抗菌素耐药性的疾病负担是由机会性细菌病原体引起的医院相关感染引起的。这些细菌通常会导致危及生命或难以控制的疾病，如深层组织、伤口或骨骼感染，或下呼吸道、中枢神经系统或血流感染。世界范围内最常见的两种引起血流感染的原因是金黄色葡萄球菌和大肠杆菌。尽管在过去十年中，与医院有关的感染引起了广泛关注，但这一日益严重的现象对人类健康和医疗服务的总体影响仍有待充分量化。研究人员建议通过估计欧洲两种耐药生物的抗生素耐药性的影响——发病率、死亡率和对卫生保健服务的需求来填补这一信息空白，这两种耐药生物通常与多种抗生素的耐药有关，可以被视为耐甲氧西林金黄色葡萄球菌和第三代耐头孢菌素大肠杆菌的耐药替代标记。最近，欧洲国家耐药性和疾病负担项目收集了有关整个欧洲抗菌素耐药性临床影响的代表性数据。利用并结合来自欧洲抗生素耐药性监测系统的2007年流行数据，研究人员计算了与耐甲氧西林金黄色葡萄球菌和第三代耐头孢菌素大肠杆菌血流感染相关的疾病负担。这种疾病负担表现为过量的死亡人数、过量的住院天数和过量的费用。利用统计模型，研究人员预测了欧洲地区31个参与国家到2015年的基于趋势的耐药性轨迹。在他们的分析中，研究人员包括来自31个国家的1293家医院，通常覆盖大多数国家所有可用急性护理病床的47%。金黄色葡萄球菌的血流感染估计总数为108,434例，其中27,711例（25.6%）对甲氧西林耐药。大肠杆菌引起163476例血流感染，其中15183例（9.3%）对第三代头孢菌素耐药。估计有5,503例额外死亡与耐甲氧西林金黄色葡萄球菌引起的血流感染有关（预计英国和法国的额外死亡率最高），2,712例额外死亡与第三代耐头孢菌素大肠杆菌引起的血流感染有关（预计土耳其和英国最高）。研究人员还发现，耐甲氧西林金黄色葡萄球菌和第三代耐头孢菌素大肠杆菌引起的血流感染分别造成了255,683和120,065个额外的住院日，估计额外费用为6200万欧元（9280万国际美元）。在他们的趋势分析中，研究人员发现，预计2015年将有97,000例耐药血流感染和17,000例相关死亡，同时住院时间和费用也会增加。重要的是，研究人员估计，在不久的将来，与第三代耐头孢菌素大肠杆菌相关的疾病负担可能会超过与耐甲氧西林金黄色葡萄球菌相关的疾病负担。这些发现表明，尽管所研究的血流感染仅占与抗生素耐药性相关的疾病总负担的一小部分，但由耐甲氧西林金黄色葡萄球菌和第三代耐头孢菌素大肠杆菌引起的与这些感染相关的额外死亡率很高，并且相关的住院时间延长给欧洲的卫生保健系统带来了相当大的负担。重要的是，抗生素耐药性负担可能从革兰氏阳性感染转变为革兰氏阴性感染，这一点令人担忧。这些预测表明，尽管预计在控制耐甲氧西林金黄色葡萄球菌方面取得进展，但由第三代耐头孢菌素革兰氏阴性病原体（如大肠杆菌）引起的感染数量不断增加，可能很快就会超过这一成就。这一日益加重的负担将对已经捉襟见肘的卫生系统产生重大影响。请通过本摘要的在线版本（http://dx.doi.org/10.1371/journal.pmed.1001104）访问这些网站。世界卫生组织有一份关于一般抗菌素耐药性的情况介绍。美国疾病控制和预防中心关于抗生素/抗菌素耐药性的网页包括有关教育运动和资源的信息。欧洲疾病控制中心通过一个互动数据库提供有关欧洲耐药性流行情况的数据
The authors calculate excess mortality, excess hospital stay, and related hospital expenditure associated with antibiotic-resistant bacterial bloodstream infections (Staphylococcus aureus and Escherichia coli) in Europe. The relative importance of human diseases is conventionally assessed by cause-specific mortality, morbidity, and economic impact. Current estimates for infections caused by antibiotic-resistant bacteria are not sufficiently supported by quantitative empirical data. This study determined the excess number of deaths, bed-days, and hospital costs associated with blood stream infections (BSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) and third-generation cephalosporin-resistant Escherichia coli (G3CREC) in 31 countries that participated in the European Antimicrobial Resistance Surveillance System (EARSS). The number of BSIs caused by MRSA and G3CREC was extrapolated from EARSS prevalence data and national health care statistics. Prospective cohort studies, carried out in hospitals participating in EARSS in 2007, provided the parameters for estimating the excess 30-d mortality and hospital stay associated with BSIs caused by either MRSA or G3CREC. Hospital expenditure was derived from a publicly available cost model. Trends established by EARSS were used to determine the trajectories for MRSA and G3CREC prevalence until 2015. In 2007, 27,711 episodes of MRSA BSIs were associated with 5,503 excess deaths and 255,683 excess hospital days in the participating countries, whereas 15,183 episodes of G3CREC BSIs were associated with 2,712 excess deaths and 120,065 extra hospital days. The total costs attributable to excess hospital stays for MRSA and G3CREC BSIs were 44.0 and 18.1 million Euros (63.1 and 29.7 million international dollars), respectively. Based on prevailing trends, the number of BSIs caused by G3CREC is likely to rapidly increase, outnumbering the number of MRSA BSIs in the near future. Excess mortality associated with BSIs caused by MRSA and G3CREC is significant, and the prolongation of hospital stay imposes a considerable burden on health care systems. A foreseeable shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections will exacerbate this situation and is reason for concern. Please see later in the article for the Editors' Summary Antimicrobial resistance—a consequence of the use and misuse of antimicrobial medicines—occurs when a microorganism becomes resistant (usually by mutation or acquiring a resistance gene) to an antimicrobial drug to which it was previously sensitive. Then standard treatments become ineffective, leading to persistent infections, which may spread to other people. With some notable exceptions such as TB, HIV, malaria, and gonorrhea, most of the disease burden attributable to antimicrobial resistance is caused by hospital-associated infections due to opportunistic bacterial pathogens. These bacteria often cause life-threatening or difficult-to-manage conditions such as deep tissue, wound, or bone infections, or infections of the lower respiratory tract, central nervous system, or blood stream. The two most frequent causes of blood stream infections encountered worldwide are Staphylococcus aureus and Escherichia coli. Although hospital-associated infections have gained much attention over the past decade, the overall effect of this growing phenomenon on human health and medical services has still to be adequately quantified. The researchers proposed to fill this information gap by estimating the impact—morbidity, mortality, and demands on health care services—of antibiotic resistance in Europe for two types of resistant organisms that are typically associated with resistance to multiple classes of antibiotics and can be regarded as surrogate markers for multi-drug resistance—methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli. Recently, the Burden of Resistance and Disease in European Nations project collected representative data on the clinical impact of antimicrobial resistance throughout Europe. Using and combining this information with 2007 prevalence data from the European Antibiotic Resistance Surveillance System, the researchers calculated the burden of disease associated with methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli blood stream infections. This burden of disease was expressed as excess number of deaths, excess number of days in hospital, and excess costs. Using statistical models, the researchers predicted trend-based resistance trajectories up to 2015 for the 31 participating countries in the European region. The researchers included 1,293 hospitals from the 31 countries, typically covering 47% of all available acute care hospital beds in most countries, in their analysis. For S. aureus, the estimated number of blood stream infections totaled 108,434, of which 27,711 (25.6%) were methicillin-resistant. E. coli caused 163,476 blood stream infections, of which 15,183 (9.3%) were resistant to third-generation cephalosporins. An estimated 5,503 excess deaths were associated with blood stream infections caused by methicillin-resistant S. aureus (with the UK and France predicted to experience the highest excess mortality), and 2,712 excess deaths with blood stream infections caused by third-generation cephalosporin-resistant E. coli (predicted to be the highest in Turkey and the UK). The researchers also found that blood stream infections caused by both methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli contributed respective excesses of 255,683 and 120,065 extra bed-days, accounting for an estimated extra cost of 62.0 million Euros (92.8 million international dollars). In their trend analysis, the researchers found that 97,000 resistant blood stream infections and 17,000 associated deaths could be expected in 2015, along with increases in the lengths of hospital stays and costs. Importantly, the researchers estimated that in the near future, the burden of disease associated with third-generation cephalosporin-resistant E. coli is likely to surpass that associated with methicillin-resistant S. aureus. These findings show that even though the blood stream infections studied represent only a fraction of the total burden of disease associated with antibiotic resistance, excess mortality associated with these infections caused by methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli is high, and the associated prolonged length of stays in hospital imposes a considerable burden on health care systems in Europe. Importantly, a possible shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections is concerning. Such forecasts suggest that despite anticipated gains in the control of methicillin-resistant S. aureus, the increasing number of infections caused by third-generation cephalosporin-resistant Gram-negative pathogens, such as E. coli, is likely to outweigh this achievement soon. This increasing burden will have a big impact on already stretched health systems. Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001104. The World Health Organization has a fact sheet on general antimicrobial resistance The US Centers for Disease Control and Prevention webpage on antibiotic/antimicrobial resistance includes information on educational campaigns and resources The European Centre for Disease Control provides data about the prevalence of resistance in Europe through an interactive database
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影响因子：
82.9
作者：
McCormick, AW;Whitney, CG;Lipsitch, M
通讯作者：
Lipsitch, M
DOI：
10.1016/j.diagmicrobio.2004.05.003
发表时间：
2004-09-01
影响因子：
2.9
作者：
Biedenbach, DJ;Moet, GJ;Jones, RN
通讯作者：
Jones, RN
DOI：
10.1007/s10096-008-0545-z
发表时间：
2008-11-01
影响因子：
4.5
作者：
Marchaim, D.;Zaidenstein, R.;Weinberger, M.
通讯作者：
Weinberger, M.
影响因子：
14.2
作者：
Benfield, T.;Espersen, F.;Skinhoj, P.
通讯作者：
Skinhoj, P.
影响因子：
14.2
作者：
Asgeirsson, H.;Gudlaugsson, O.;Kristjansson, M.
通讯作者：
Kristjansson, M.