Urinary Infections due to Escherichia Coli with Reduced Quinolone Susceptibility

喹诺酮敏感性降低的大肠杆菌引起的尿路感染

• 批准号: 8582191
• 负责人: EBBING LAUTENBACH
• 金额: $ 15.04万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-21 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8582191
• 关键词: Ambulatory Care; Antibiotic Therapy; Antibiotic susceptibility; Antibiotics; Bacterial Infections; Characteristics; Clinical; Escherichia coli; Escherichia coli Infections; Evolution; Fluoroquinolones; Future; In Vitro; Infection; Intervention; Levaquin; Minimum Inhibitory Concentration measurement; Mutation; Organism; Outpatients; Predisposition; Quinolones; Reporting; Research; Resistance; Risk Factors; Site; Staging; Treatment Failure; Urinary tract infection; Work; base; design; economic implication; fluoroquinolone resistance; insight; meetings; novel; pressure; prevent; public health relevance; resistance mechanism; resistant strain; urinary

DESCRIPTION (provided by applicant): Resistance to the fluoroquinolone (FQ) antibiotics is particularly concerning for Escherichia coli, the most common cause of outpatient urinary tract infections (UTIs). UTIs are the most common outpatient bacterial infection with significant clinical and economic implications. Antibiotic susceptibility is typically reported as "susceptible, "intermediate", or "resistant". However, it has been suggested that FQ-susceptible E. coli (FQSEC) can be further divided into two groups based on the minimum inhibitory concentration (MIC) value: 1) "Low-MIC FQSEC" (or LM-FQSEC) (levofloxacin MIC d0.12 mcg/ml); and 2) "High-MIC FQSEC" (or HM- FQSEC) (levofloxacin MIC >0.12 but <4 mcg/ml). These groups have also been referred to as "fully susceptible" and "reduced susceptible" strains, respectively. There is a clear rationale for distinguishing HM- FQSEC and LM-FQSEC. Specifically, while still within the susceptible range, HM-FQSEC isolates typically harbor at least one FQ resistance mechanism (e.g., gyrA mutation). Treatment of an HM-FQSEC with a FQ agent exerts selective pressure on the organism to acquire additional FQ resistance mechanisms. This not only increases the likelihood of treatment failure, but also drives further increases in the reservoir o FQ- resistant organisms. Risk factors for HM-FQSEC UTI are unknown. Furthermore, the impact of HM-FQSEC on FQ treatment failure has not been studied. Finally, the relationship between HM-FQSEC and underlying FQ resistance mechanisms and strain type are unknown. This study has two specific aims: Aim 1: To identify risk factors for HM-FQSEC among outpatient UTIs; Aim 2: To determine the association between HM-FQSEC and treatment failure among outpatients with UTIs who receive FQ therapy. The primary hypotheses for these aims are: 1) prior FQ use is associated with HM-FQSEC; and 3) HM-FQSEC is associated with FQ treatment failure. This study also has two secondary aims: Secondary Aim 1: To determine the impact of organism characteristics (i.e., FQ resistance mechanisms, strain type) on risk factors for HM-FQSEC. Secondary Aim 2: To determine the impact of organism characteristics (i.e., FQ resistance mechanisms, strain type) on the association between HM-FQSEC and FQ treatment failure. This study will provide important insights with regard to which modifiable variables might be targeted to curtail further emergence of FQ resistance. This work will also be invaluable in informing antibiotic prescribing for E. coli UTIs. Finally, this study will provide critical detail of the relationship between HM-FQSEC and the underlying FQ resistance mechanism(s) and strain type 1.

描述（由申请方提供）：对氟喹诺酮类（FQ）抗生素的耐药性尤其值得关注的是大肠埃希菌，这是门诊尿路感染（UTIs）的最常见原因。尿路感染是最常见的门诊细菌感染，具有重要的临床和经济意义。抗生素敏感性通常报告为“敏感”、“中间”或“耐药”。然而，已经有人提出，易感染大肠杆菌的E.基于最小抑制浓度（MIC）值，可以将大肠杆菌（MIC SEC）进一步分为两组：1）“低MIC MIC MIC MIC SEC”（或LM-MIC SEC）（左氧氟沙星MIC d0.12mcg/ml）;和2）“高MIC MIC MIC SEC”（或HM-MIC SEC）（左氧氟沙星MIC >0.12但<4 mcg/ml）。这些群体也分别被称为“完全敏感”和“降低敏感”菌株。有一个明确的理由来区分HM-β-SEC和LM-β-SEC。具体而言，虽然仍在易感范围内，但HM-HMSEC分离株通常具有至少一种FQ抗性机制（例如，gyrA突变）。用FQ试剂处理HM-FQSEC会对生物体施加选择性压力，以获得额外的FQ耐药机制。这不仅增加了治疗失败的可能性，而且还进一步增加了FQ抗性生物体的储存库。HM-MSEC UTI的风险因素未知。此外，还没有研究HM-HMSEC对FQ治疗失败的影响。最后，HM-GISSEC与潜在的FQ抗性机制和菌株类型之间的关系尚不清楚。本研究有两个具体的目的：目的1：确定门诊UTI患者中HM-MIBSEC的危险因素;目的2：确定接受FQ治疗的门诊UTI患者中HM-MIBSEC与治疗失败之间的相关性。这些目的的主要假设是：1）既往使用FQ与HM-β SEC相关; 3）HM-β SEC与FQ治疗失败相关。本研究还有两个次要目的：次要目的1：确定生物体特征的影响（即，FQ耐药机制，菌株类型）对HM-EASSEC风险因素的影响。次要目的2：确定微生物特征的影响（即，FQ耐药机制、菌株类型）对HM-GISSEC和FQ治疗失败之间的关联的影响。这项研究将提供重要的见解，关于哪些可修改的变量可能 有针对性地减少FQ耐药性的进一步出现。这项工作也将是非常宝贵的通知抗生素处方为E。coli UTI。最后，本研究将提供HM-GISSEC与潜在的FQ抗性机制和菌株类型1之间关系的关键细节。