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: 8724334
• 负责人: EBBING LAUTENBACH
• 金额: $ 28万
• 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 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8724334
• 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（由申请人提供）：对氟喹诺酮（FQ）抗生素的抗性特别关乎大肠杆菌，这是门诊尿路感染（UTI）的最常见原因。 UTI是最常见的门诊细菌感染，具有重大的临床和经济影响。 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）“高-MIC FQSEC”（或HM-FQSEC）（左氧霉素MIC> 0.12，但<4 mcg/ml）被称为“完全易感”和“易感性”。通常，至少有一种FQ电阻机制（例如，Gyra突变）对HM-FQSEC的处理会对有机体施加选择性的压力，以获得其他FQ抗性机制。 HM-FQSEC UTI的危险因素尚不清楚。此外，尚未研究HM-FQSEC对FQ治疗失败的影响。最后，HM-FQSEC与基础FQ抗性机制和应变类型之间的关系尚不清楚。这项研究有两个具体的目的：目标1：确定门诊UTI中HM-FQSEC的危险因素； AIM 2：确定HM-FQSEC和门诊病人与接受FQ治疗的UTI之间的关联。这些目的的主要假设是：1）先前的FQ使用与HM-FQSEC相关联； 3）HM-FQSEC与FQ治疗失败有关。这项研究还具有两个次要目标：次要目标1：确定生物特征（即FQ抗性机制，应变类型）对HM-FQSEC风险因素的影响。次要目的2：确定生物体特征（即FQ抗性机制，应变类型）对HM-FQSEC和FQ治疗失败之间关联的影响。这项研究将提供重要的见解，以了解哪些可修改变量可能 目标是降低FQ抗性的进一步出现。这项工作对于向大肠杆菌UTI的抗生素处方提供了非常宝贵的宝贵。最后，这项研究将为HM-FQSEC与基础FQ抗性机理和应变类型1之间的关系提供关键细节。