Diversity of Antimicrobial Use and Emergence of Resistance in Pseudomonas

抗菌药物使用的多样性和假单胞菌耐药性的出现

• 批准号: 7500794
• 负责人: DARREN R. LINKIN
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7500794
• 关键词: Acute; Affect; Aminoglycosides; Antimicrobial Resistance; Carbapenems; Caring; Cephalosporins; Class; Clinical; Data; Development; Drug Efflux; Drug resistance; Drug usage; Effectiveness of Interventions; Epidemiology; Fluoroquinolones; Future; Hospitals; Individual; Infection; Inpatients; Intervention; Knowledge; Lactamase; Lead; Monobactams; Morbidity - disease rate; Patients; Penicillins; Pharmaceutical Preparations; Prevalence; Pseudomonas; Pseudomonas Infections; Pseudomonas aeruginosa; Public Health; Randomized Controlled Trials; Repression; Research Design; Resistance; Testing; antimicrobial; antimicrobial drug; design; efflux pump; mathematical model; mortality; research study; resistance mechanism

DESCRIPTION (provided by applicant): Antimicrobial resistance is a common problem of great clinical and public health significance due to the associated increase in morbidity and mortality. Antimicrobial use is a critical factor in the development of antimicrobial resistance. Antimicrobial cycling-sequential use of antimicrobial agents with cycle periods of several months-has had mixed results in studies aiming to decrease antimicrobial resistance. Mathematical modeling studies suggest that diversity of use of antimicrobials, essentially a cycling period of zero, would be optimal to limit antimicrobial resistance. We are performing an interventional study to test the hypothesis that an increase in antimicrobial diversity of agents typically used to treat Pseudomonas infections (antipseudomonals) will lead to a decrease in Pseudomonas aeruginosa antimicrobial resistance. We will determine the effect of a diversity of use of anti-Pseudomonal agents on the prevalence of phenotypic anti-Pseudomonal resistance (to any anti-Pseudomonal) in P. aeruginosa clinical isolates obtained from clinical cultures. Our study will also determine the effect of a diversity use of anti-Pseudomonal antimicrobials on the prevalence of specific mechanisms of anti-Pseudomonal resistance. We will utilize a quasi-experimental study design with multiple pre- and post-intervention observations hospital-wide in an intervention hospital versus two control hospitals. The intervention will increase the diversity of anti-Pseudomonal agent use by increasing the evenness of use of available anti-pseudomonals. The results of our study will be used as preliminary data to propose a cluster-randomized controlled trial to further investigate this intervention. If our current and future studies demonstrate that diversity of antimicrobial use limits antimicrobial resistance, it will affect antimicrobial prescribing for all hospitalized patients and be a wedge against the thus far inexorable rise in antimicrobial resistance. Diversity of Antimicrobial Use and Emergence of Resistance in Pseudomonas Public Health Statement Antimicrobial resistance in hospitalized patients is a common problem of great clinical and public health significance due to the associated increase in morbidity and mortality. We hypothesize that increasing the diversity of antimicrobials used in the treatment of hospitalized patients will lead to a decrease in Pseudomonas aeruginosa antimicrobial resistance. The results of our study will be generalizable to inpatients in tertiary acute care centers everywhere.

描述（由申请人提供）：由于发病率和死亡率的增加，抗菌素耐药性是一个临床和公共健康意义的常见问题。抗菌使用是抗菌耐药性发展的关键因素。抗菌循环及时使用具有几个月周期的抗菌剂，在旨在降低抗菌耐药性的研究中，结果混合了。数学建模研究表明，抗菌药物使用的多样性（本质上是零骑自行车时期）将是限制抗微生物耐药性的最佳选择。我们正在进行一项介入研究，以检验以下假设：通常用于治疗假单胞菌感染的药物的抗菌多样性增加（抗抑郁症）将导致铜绿假单胞菌抗镁性耐药性的降低。我们将确定使用抗峰值剂的多样性对从临床培养物获得的铜绿假单胞菌临床分离株中表型抗质子抗性的流行（对任何抗质量符号）的流行。我们的研究还将确定抗峰值抗菌剂对抗峰值抗抗性特定机制的普遍性的多样性使用的影响。我们将利用一项准实验研究设计，在干预医院与两家对照医院进行多个干预前和干预后的观察结果。干预措施将通过增加使用可用的抗质量符号的均匀性来增加抗峰值剂使用的多样性。我们的研究结果将用作初步数据，以提出一项集群随机对照试验，以进一步研究此干预措施。如果我们目前和未来的研究表明，抗菌素使用的多样性限制了抗菌素的耐药性，它将影响所有住院患者的抗菌处方，并成为对迄今为止抗菌耐药性无可避免升高的楔子。抗菌素使用的多样性和抗药性出现在医院患者中的假单胞菌公共卫生声明抗菌抗药性是由于发病率和死亡率的增加，这是一个很大的临床和公共卫生意义的问题。我们假设增加用于治疗住院患者的抗菌剂的多样性将导致铜绿假单胞菌抗菌素耐药性降低。我们的研究结果将可以推广到各地三级急性护理中心的住院患者。

项目成果

Risk factors for gyrA and parC mutations in Pseudomonas aeruginosa.

• DOI: 10.1017/ice.2014.87
• 发表时间: 2015-04
• 期刊: INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
• 影响因子: 4.5
• 作者: Cluzet, Valerie C.;Lautenbach, Ebbing;Nachamldn, Irving;Cary, Mark S.;Fishman, Neil O.;Shih, Natalie N. C.;Morales, Knashawn H.;Linkin, Darren R.
• 通讯作者: Linkin, Darren R.