Impact of the Choice of 3rd Generation Cephalosporins on the Emergence of Resistance in the Microbiota Intestinal.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- The area under the curve of the 3rd generation cephalosporins resistant enterobacteria in the intestinal microbiota between D0 and D7.
研究概览
简要总结
CEREMI is an open, randomised prospective study in parallel groups in healthy volunteers. This study compare the effect of a monotherapy by ceftriaxone or cefotaxime on the emergence of resistance of enterobacteria to 3rd-generation cephalosporins within the intestinal microbiota. Each volunteer will be treated for 3 days by either ceftriaxone (1 gram per day) or cefotaxime (1 gram every 8 hours).
详细描述
Selection of resistant bacteria within the microbiota constitutes the main mechanism for the emergence and the diffusion of bacterial resistance to antibiotics. Ceftriaxone is a 3rd generation cephalosporin that exposes the intestinal microbiota to an important selecting pressure, due to its high biliary clearance. It is thereby suspected to have an important role in the emergence of resistance of enterobacteria to 3rd generation cephalosporins. Its pharmacokinetics features allow a once daily administration, and it is more largely used than cefotaxime, which requires ter in die injections but whose mainly urinary elimination suggest a lower impact on the intestinal microbiota.
Our hypothesis is that ceftriaxone exerts a higher selecting pressure on the intestinal microbiota than cefotaxime.
Our main objective is to compare the effect of a monotherapy by ceftriaxone or cefotaxime on the emergence of resistance of enterobacteria to 3rd-generation cephalosporins within the intestinal microbiota.
Secondary objectives include :
- Comparison of the effect of ceftriaxone and cefotaxime on the counts of (i) total enterobacteria, (ii) 3rd generation cephalosporins resistant enterobacteria according to the resistance mechanism, (iii) colonisation resistance in the intestinal microbiota
- Pharmacokinetic analysis of cefotaxime and ceftriaxone at steady-state, and link between plasma and fecal expositions to each antimicrobial
- Analysis of the association between individual exposition to ceftriaxone and cefotaxime and their impact on the intestinal microbiota.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 18 and 65 years
- •Volunteer regarded as healthy after detailed examination
- •Subject whose entourage (person living under the same roof) does not present any chronic disease throughout the course and did not receive antibiotics within 15 days.
- •Effective contraception for women in reproductive age and negative pregnancy test before inclusion
- •Normal intestinal passage (one stool per day)
- •Negative urinalysis for toxic substances
- •Normal blood test (including blood and platelets counts, prothrombin, ionograms, Liver function tests)
- •Negative HIV and HCV (hepatitis C virus) test, no HBV (hepatitis B virus)chronic infection
- •Normal weight (BMI comprised between 19 and 29 kg/m²)
- •Freely obtained consent
- •Health insurance beneficiary
排除标准
- •Antibiotic therapy in the previous 6 months
- •Hospitalisation in the previous 12 months;
- •Active infection
- •Ongoing treatment
- •Any chronic disease
- •Allergy to one of the study drugs
- •Any contraindications to β-lactam therapy in particular to penicillins or cephalosporins
- •Pregnancy or no effective contraception, suckling women
- •Subject, as determined by the investigating physician, could not observing during the study, or unable to communicate because of language or mental disorders barrier;
- •Subject participating simultaneously in another biomedical research
- •Subject can not be contacted in case of emergency;
- •Subject about legally protected under tutorship or curators;
- •Subject deprived of freedom under judicial or administrative constraints
- •Secondary exclusion criteria
- •No pre-treatment stool sample obtained
- •More than one stool sample missing from D1 to D7
研究组 & 干预措施
ceftriaxone
healthy volunteer who receive ceftriaxone
干预措施: ceftriaxone (Drug)
cefotaxime
healthy volunteer who receive cefotaxime
干预措施: Cefotaxime (Drug)
结局指标
主要结局
The area under the curve of the 3rd generation cephalosporins resistant enterobacteria in the intestinal microbiota between D0 and D7.
时间窗: within the first 7 days
次要结局
- The area under the curve of enterobacteriaceae resistant to C3G accounts (regardless of the resistance mechanism) from D0 to D15 in each treatment group.(within the first 15 days)
- Proportion of patients with 3rd generation cephalosporins resistant enterobacteria in the intestinal microbiota (regardless of the resistance mechanism) at D30 at D90 and at D180 in each treatment group.(D30, D90 and D180)
- Area under the curve of enterobacteriaceae resistant to C3G accounts distinguishing the resistance mechanism (B lactamase,plasmid cephalosporinase or cephalosporinase) from D0 to D15 in each treatment group.(within the first 15 days)
- Proportion of patients with 3rd generation cephalosporins resistant enterobacteria in the intestinal microbiota (distinguishing the resistance mechanism) at D30 at D90 and at D180 in each treatment group.(D30, D90 and D180)
- Area under the curve of total coliform accounts from D0 to D 7 and D0 to D15 in each treatment group.(within the first 15 days)
- Change in total coliform accounts between D0 and D30 between D0 and D90 and between D0 and D180 in each treatment group.(D30, D90 and D180)
- The area under the curve of aeruginosa accounts, S. aureus, Enterococcus spp., Clostridium difficile and yeasts from D0 to D7 and D0 to D15 in each treatment group.(within the first 15 days)
- The area under the curve of β-lactamase activity of the intestinal microbiota from D0 to D7 and D0 to D15 in each treatment group.(within the first 15 days)
- Proportion of patients with β-lactamase activity in the stools at D30, D90 and D180 in each treatment group.(D30, D90 and D 180)