INterest of the Negative Predictive Value of Integrons in the reduCtion of Large Broad-spectrum anTibiotics Consumption for Urinary Tract infectionS: a Randomized Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 204
- 试验地点
- 7
- 主要终点
- Number of days with large broad-spectrum antibiotic therapy
研究概览
简要总结
Urinary tract infections (UTI), mainly driven by Gram-negative bacteria (GNB) are a frequent cause of hospitalization and the second cause of antibiotic prescription after lower respiratory tract infections. Integrons play a major role in the dissemination of antibiotic resistance among GNB. In the prospective INVICTUS project, whose ultimate objective is to reduce the use of large broad-spectrum antibiotics, our hypothesis is that, in adult patients with a non-severe UTI (qSOFA<2) and a former documentation with a 3GC-resistant GNB in the previous 6 months, integrons search could reduce the empirical use of large broad-spectrum antibiotics.
详细描述
The promotor conducted a multicenter prospective study, IRIS (Interest of integrons as predictive markers of acquired antibiotic Resistance in patients with urinary or Intra-abdominal Sepsis) which showed that integrons have a high negative predictive value (NPV) for antibiotic resistance. Among the 343 patients admitted in the ED or intensive care units (ICU) with a urinary sepsis, the NPV of integrons, by detecting them directly form urine samples, was 96.6% (CI:94.0-98.6%) for resistance to 3GC. Whether the detection of integrons to predict antibiotic resistance could efficiently guide empirical antibiotic therapy of patients with a UTI remains to determine. INVICTUS aims at providing the front-line ED physician with additional valuable information using molecular detection of integrons, to best guide adequate first-line antibiotic therapy, while sparing large broad-spectrum antimicrobial agents. In the experimental arm, empirical parenteral antibiotic therapy will be guided based on the detection of integrons. If integrons detection is positive, a large broad spectrum therapy with ureidopenicillin and β-lactamase inhibitors combinations (Piperacillin-Tazobactam) or carbapenems (Imipenem, Meropenem) will be prescribed. If integrons detection is negative, patient will receive a parenteral 3GC (Ceftriaxone, Cefotaxime, Ceftazidime or Cefepime). In the control arm, the comparative treatment will be an empirical antibiotic therapy with ureidopenicillin and β-lactamase inhibitors combinations (Piperacillin-Tazobactam) or carbapenems (Imipenem, Meropenem) at clinician's discretion. For the primary analysis, the number of days with large broad-spectrum antibiotic therapy during the first week will be compared between the two groups using a Student t-test.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old; Hospitalized or admitted to the Emergency department;
- •Diagnosis of non-severe (qSOFA < 2) urinary tract infection coupled with fever ≥ 38°C or < 36°C
- •Presence of bacteria in the fresh urine sample and/or GNB on the Gram stain
- •Empirical parenteral antibiotic therapy required; Hospitalization required;
- •Former documentation of a 3GC-resistant GNB on a microbiological sample in the previous six months
- •Informed consent of the patient or their representative
排除标准
- •Pregnant and/or breastfeeding
- •Neutropenia (absolute neutrophil count < 500 / mm3)
- •Severe UTI with sepsis (qSOFA ≥ 2) or septic shock
- •Urinary derivation required (ureteral catheter/per-cutaneous nephrostomy) except for simple urinary catheterization
- •Known allergy to β-lactams
- •Patients with a former documentation with carbapenemase-producing Enterobacterales in the last 6 months
- •Ongoing antibiotic treatment with 3GC, piperacillin-tazobactam or carbapenem
- •Not affiliated to Social Security
研究组 & 干预措施
Empirical parenteral antibiotic therapy based on the detection of integrons
In the experimental arm, empirical parenteral antibiotic therapy will be guided based on the detection of integrons. If integrons detection is positive, a large broad spectrum therapy with ureidopenicillin and β-lactamase inhibitors combinations (Piperacillin-Tazobactam) or carbapenems (Imipenem, Meropenem) will be prescribed. If integrons detection is negative, patient will receive a parenteral 3GC (ceftriaxone, cefotaxime, ceftazidime or cefepime). The treatment will be started after the integron detection
干预措施: Detection of integrons (Diagnostic Test)
Empirical antibiotic therapy with ureidopenicillin and β-lactamase inhibitors combinations
In the control arm, the comparative treatment will be an empirical antibiotic therapy with ureidopenicillin and β-lactamase inhibitors combinations (Piperacillin-Tazobactam) or carbapenems (Imipenem, Meropenem) at clinician's discretion. The treatment will be started after the randomization
干预措施: Gold standard (Other)
结局指标
主要结局
Number of days with large broad-spectrum antibiotic therapy
时间窗: Day 7
Number of days with large broad-spectrum antibiotic therapy (ureidopenicillin and β-lactamases inhibitor combinations or carbapenems) during the first week of treatment (i.e., until Day 7 after admission) in the experimental arm compared to the number of days with large broad-spectrum antibiotic therapy in the control arm
次要结局
- Proportion of patients with clinical resolution of UTI(Day 7)
- Proportion of patients for whom the empirical antibiotic therapy(Day 7)
- Proportion of patients, for whom the integron detection result was consistent with the AST(Day 7)
- Proportion of resistant bacteria for the clinically-relevant antibiotics(Day 7)