Multidrug-Resistant Acinetobacter baumannii

多重耐药鲍曼不动杆菌

• 批准号: 7569097
• 负责人: Yohei Doi
• 金额: $ 16.06万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-18 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7569097
• 关键词: Acinetobacter baumannii; Address; Afghanistan; Amikacin; Antibiotics; Antimicrobial Resistance; Bacteremia; Clinical; Colistin; Disease Outbreaks; Environment; Epidemiologic Studies; Epidemiology; Fingerprint; Future; Hand; Health Personnel; Hospitals; Imipenem; Infection; Infection Control; Institution; Instruction; International; Iraq; Knowledge; Laboratories; Lactose; Lead; Methods; Military Personnel; Minisatellite Repeats; Molecular; Multi-Drug Resistance; Nosocomial Infections; Organism; Patients; Pneumonia; Pulsed-Field Gel Electrophoresis; Resistance; Resistance development; Scheme; Therapeutic Agents; United States; Ventilator; antimicrobial; base; design; improved; novel therapeutics; pathogen; rRNA methylase; resistance mechanism; surveillance study; tigecycline; tool; transmission process

DESCRIPTION (provided by applicant): Acinetobacter baumannii is a Gram-negative, non-lactose-fermenting organism that causes serious nosocomial infections such as ventilator-associated pneumonia and bacteremia. A. baumannii is characterized by its tendency to acquire resistance to various classes of antimicrobials that are otherwise effective against this organism. In Pittsburgh, there is a surge in imipenem-resistant and amikacin-resistant A. baumannii, necessitating use of salvage agents such as colistin and tigecycline. Despite the potential magnitude of the problem caused by these multidrug-resistant (MDR) A. baumannii strains, little is known about the mechanisms of resistance to these antimicrobials in A. baumannii in the United States. Current epidemiological studies using pulsed-field gel electrophoresis (PFGE) reveal that A. baumannii causes nosocomial outbreaks, spreading from patient to patient mostly by contact with the contaminated hands of healthcare workers or the hospital environment. A molecular typing method that is more standardized and objective than PFGE is needed for use in surveillance studies to investigate national and international epidemiology of A. baumannii. The hypotheses of the application are: (1) OXA-type carbapenemases (e.g., OXA-23) and ArmA 16S ribosomal RNA methylase are the primary mechanisms by which A. baumannii develops resistance to imipenem and amikacin, (2) The multi-locus variable number of tandem repeats analysis (MLVA) scheme of molecular typing accurately and reliably discriminates clinical strains of A. baumannii and offers advantages over PFGE. To address these hypotheses, the following specific aims have been formulated: (1) Characterize the molecular mechanisms of imipenem and amikacin resistance in MDR A. baumannii clinical strains, (2) Evaluate objective molecular typing methods of A. baumannii. Typing results for MLVA will be compared with PFGE and MLST. The proposed study will enhance the level of understanding in how A. baumannii acquires multidrug resistance and lead to a strategy to best utilize the existing classes of antimicrobials to manage the infections. This will also form the basis for efforts in designing novel therapeutic agents and strategies that will overcome or evade the existing and emerging resistance mechanisms. Objective molecular typing methods will serve as an essential tool for future studies that will address the global epidemiology of MDR A. baumannii. RELEVANCE (See instructions): Acinetobacter baumannii is a problematic pathogen that causes serious infections in patients admitted to hospitals. The project aims to examine how it acquires resistance to two important antibiotics, imipenem and amikacin, and also develop an objective method to "fingerprint" the strains. Such knowledge will help in optimizing use of existing antibiotics and improving infection control practices.

描述（由申请人提供）：鲍曼尼杆菌是一种革兰氏阴性，非乳糖发酵生物体，会引起严重的医生感染，例如呼吸机相关性肺炎和细菌。 鲍曼尼氏曲霉的特征是它倾向于获得对这种有效反对这种生物的各种抗菌剂的抵抗力。在匹兹堡，抗甲哌丁象抗性和抗氨基甲霉素的baumannii有激增，需要使用诸如colistin和tigecycline之类的保水剂。尽管这些抗性（MDR）A。Baumannii菌株引起的问题的潜在幅度却很少，但美国对这些抗菌素的抗性机制知之甚少。当前使用脉冲场凝胶电泳（PFGE）的流行病学研究表明，鲍曼尼a。A.baumannii会导致医院爆发，从患者到患者的传播主要是通过与污染的医护人员或医院环境接触。在监视研究中使用比PFGE更为标准化和客观的分子分型方法，以研究鲍曼尼A. Baumannii的国家和国际流行病学。 The hypotheses of the application are: (1) OXA-type carbapenemases (e.g., OXA-23) and ArmA 16S ribosomal RNA methylase are the primary mechanisms by which A. baumannii develops resistance to imipenem and amikacin, (2) The multi-locus variable number of tandem repeats analysis (MLVA) scheme of molecular typing accurately and reliably区分鲍曼尼曲霉的临床菌株，并具有优于PFGE的优势。为了解决这些假设，已经提出了以下特定目的：（1）表征MDR A. baumannii临床菌株中亚替姆和氨基甲酸抗性的分子机制，（2）评估鲍曼尼曲霉的客观分子分型方法。将MLVA的键入结果与PFGE和MLST进行比较。拟议的研究将提高鲍曼尼a。如何获得多药耐药性的理解水平，并导致一种策略，以最好地利用现有的抗菌剂类型来管理感染。这也将构成设计新颖的治疗剂和策略的努力，这些治疗剂和策略将克服或逃避现有的抗药性机制。客观的分子分型方法将成为未来研究的重要工具，该研究将解决MDR A. Baumannii的全球流行病学。相关性（请参阅说明）：鲍曼尼杆菌是一种有问题的病原体，会引起医院入院患者的严重感染。该项目旨在研究如何获得对两种重要的抗生素（Imipenem和amikacin）的抗性，并开发出一种客观的方法来“指纹”菌株。这种知识将有助于优化现有抗生素的使用并改善感染控制实践。