Multidrug-Resistant Acinetobacter baumannii

描述（由申请人提供）： 鲍曼不动杆菌是一种革兰氏阴性、非乳糖发酵微生物，可引起严重的院内感染，如呼吸机相关性肺炎和菌血症。 A.鲍曼不动杆菌的特征在于其倾向于获得对各种类型的抗微生物剂的抗性，这些抗微生物剂在其它情况下对该生物体有效。在匹兹堡，耐亚胺培南和阿米卡星的A。鲍曼不动杆菌，需要使用补救药物，如粘菌素和替加环素。尽管这些多药耐药（MDR）A.鲍曼不动杆菌菌株中，人们对这些抗菌药物的耐药机制知之甚少。鲍曼不动杆菌在美国目前流行病学研究采用脉冲场凝胶电泳（PFGE）显示，A。鲍曼不动杆菌引起医院内爆发，主要通过接触医护人员受污染的手或医院环境在病人之间传播。因此，需要一种比脉冲场凝胶电泳更标准化、更客观的分子分型方法，用于国内和国际甲型H1N1流感流行病学的监测研究。鲍曼不动杆菌。本申请的假设是：（1）OXA型碳青霉烯酶（例如，OXA-23）和阿尔马16 S核糖体RNA甲基化酶是A.（2）多位点可变数目串联重复序列分析（MLVA）分子分型方案能准确可靠地区分鲍曼不动杆菌临床菌株;鲍曼不动杆菌，并提供优于PFGE的优点。为阐明这些假说，本研究的具体目标如下：（1）研究MDR A对亚胺培南和阿米卡星耐药的分子机制。（2）评价鲍曼不动杆菌客观分子分型方法;鲍曼不动杆菌。MLVA的分型结果将与PFGE和MLST进行比较。该研究将有助于加深对A.鲍曼不动杆菌获得多药耐药性，并导致最佳利用现有类别的抗微生物剂来控制感染的策略。这也将成为设计新的治疗药物和策略的基础，这些药物和策略将克服或避免现有的和新出现的耐药机制。目的分子分型方法将作为未来研究的重要工具，解决MDR A的全球流行病学问题。鲍曼不动杆菌。相关性（见说明书）：鲍曼不动杆菌是一种有问题的病原体，可导致住院患者严重感染。该项目旨在研究它如何获得对两种重要抗生素亚胺培南和阿米卡星的耐药性，并开发一种客观的方法来“指纹”菌株。这些知识将有助于优化现有抗生素的使用和改善感染控制实践。

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.