Urinary Infections due to Escherichia Coli with Reduced Quinolone Susceptibility

描述（由申请人提供）：对氟喹诺酮类（FQ）抗生素的耐药性对大肠杆菌尤其令人担忧，大肠杆菌是门诊尿路感染（uti）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”、“中等”或“耐药”。但有研究认为，fq敏感大肠杆菌（FQSEC）可根据最低抑菌浓度（MIC）值进一步分为两组：1)“Low-MIC FQSEC”（或LM-FQSEC）（左氧氟沙星MIC d0.12 mcg/ml）；2)“高MIC FQSEC”（或HM- FQSEC）（左氧氟沙星MIC >0.12但<4微克/毫升）。这些群体也分别被称为“完全易感”和“降低易感”菌株。区分HM- FQSEC和LM-FQSEC的基本原理是明确的。具体来说，尽管HM-FQSEC仍在易感范围内，但其分离株通常至少具有一种FQ抗性机制（例如，gyrA突变）。用FQ剂处理HM-FQSEC会对生物体施加选择性压力，以获得额外的FQ抗性机制。这不仅增加了治疗失败的可能性，而且还推动了FQ耐药菌库的进一步增加。HM-FQSEC尿路感染的危险因素尚不清楚。此外，HM-FQSEC对FQ处理失败的影响尚未研究。最后，HM-FQSEC与潜在的FQ抗性机制和应变类型之间的关系尚不清楚。本研究有两个具体目的：目的1：确定门诊尿路感染中HM-FQSEC的危险因素；目的2：确定在接受FQ治疗的uti门诊患者中HM-FQSEC与治疗失败之间的关系。这些目标的主要假设是：1)先前的FQ使用与HM-FQSEC有关；3) HM-FQSEC与FQ治疗失败相关。本研究还有两个次要目的：次要目的1：确定生物体特性（即FQ抗性机制、菌株类型）对HM-FQSEC危险因素的影响。次要目标2：确定生物体特性（即FQ抗性机制，菌株类型）对HM-FQSEC与FQ治疗失败之间关系的影响。这项研究将提供重要的见解，关于哪些可修改的变量可能

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.