Urinary Infections due to Escherichia Coli with Reduced Quinolone Susceptibility

描述(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，它是门诊尿路感染(UTIs)最常见的原因。尿路感染是最常见的门诊细菌感染，具有重大的临床和经济影响。抗生素敏感性通常被报告为“敏感”、“中间”或“耐药”。然而，有人建议，根据最低抑菌浓度(MIC)值，FQ敏感的大肠杆菌(FQSEC)可进一步分为两组：1)低MIC FQSEC(或LM-FQSEC)(左氧氟沙星MIC d0.12微克/毫升)；2)高MIC FQSEC(或HM-FQSEC)(左氧氟沙星MIC&>0.12 BUT&lt；4微克/毫升)。这两组病毒也分别被称为“完全敏感”和“低敏感”菌株。区分HM-FQSEC和LM-FQSEC有明确的理由。具体地说，虽然HM-FQSEC分离株仍在敏感范围内，但通常至少有一种FQ耐药机制(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抗性机制。这不仅增加了治疗失败的可能性，而且进一步增加了对氟喹诺酮耐药微生物的数量。HM-FQSEC UTI的风险因素尚不清楚。此外，还没有研究HM-FQSEC对FQ治疗失败的影响。最后，HM-FQSEC与潜在的FQ抗性机制和菌株类型之间的关系尚不清楚。本研究有两个具体目的：目的1：在门诊尿路感染患者中确定HM-FQSEC的危险因素；目的2：确定接受FQ治疗的门诊尿路感染患者中HM-FQSEC与治疗失败的关系。这些目的的主要假设是：1)既往的FQ使用与HM-FQSEC相关；3)HM-FQSEC与FQ治疗失败相关。这项研究还有两个次要目标：第二目标1：确定生物特性(即FQ耐药机制、菌株类型)对HM-FQSEC危险因素的影响。第二个目标：确定生物特性(即FQ耐药机制、菌株类型)对HM-FQSEC和FQ治疗失败之间的关联的影响。这项研究将提供关于哪些可修改变量可能 成为目标，以遏制FQ抵抗的进一步出现。这项工作在为大肠杆菌尿路感染提供抗生素处方方面也将是非常有价值的。最后，这项研究将提供HM-FQSEC与潜在的FQ抗性机制(S)和1型毒株之间的关系的关键细节。

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.