Evaluation of the Non-inferiority of Cefoxitin Versus Imipenem/Cilastatin in the Treatment of Urinary Tract Infections Caused by ESBL-producing Escherichia Coli
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Control urine culture negative
研究概览
简要总结
Background Information: Infections caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are becoming increasingly common owing to incorrect use of antibiotics and cross-transmission in healthcare establishments. These give rise to major problems in standard clinical practice: penicillins and cephalosporins cannot be used, and resistance to the other classes of antibiotics normally used, such as fluoroquinolones or cotrimoxazole, is very frequently observed. The current therapeutic strategy involves the use of a carbapenem, which represents the last effective solution on an individual level. However, the growing use thereof is contributing, collectively, to the development of resistance due to the production of carbapenemases, which will become a major public health problem, with a potential therapeutic dead-end. This observation is particularly worrying due to the very small number of antibiotic agents currently in development.
Infectious disease specialists and microbiologists are thus examining alternative agents to carbapenems in the management of infections caused by ESBL-producing E. coli. One of the avenues which could be developed is the use of known agents, already on the market, which are active in vitro on ESBL-producing E. coli, but which are not currently recommended for this indication in standard practice due to the lack of conclusive studies. Cefoxitin, an antibiotic belonging to the cephamycin group, could thus represent an alternative of particular interest in the treatment of infections caused by ESBL-producing E. coli, and help limit the use of carbapenems.
The implementation of a prospective, randomized, non-inferiority study on ertapenem and cefoxitin is of the most interest from a methodological perspective. It will enable recommendations to be drawn up, with a high level of evidence, very long-awaited in the field.
Primary objective: To evaluate the bacteriological non-inferiority of cefoxitin versus imipenem in the treatment of non-severe urinary tract infections (other than cystitis) caused by ESBL-producing E. coli susceptible in vitro to cefoxitin.
Secondary objectives:
- To evaluate the clinical non-inferiority of cefoxitin versus imipenem in the treatment of non-severe urinary tract infections (other than cystitis) caused by ESBL-producing E. coli susceptible in vitro to cefoxitin.
- To evaluate the impact of cefoxitin and imipenem on the emergence of multiresistant bacteria in the gut flora.
详细描述
Rationale:
Commensal enterobacteriaceae of the digestive tract, mostly represented by E.coli, can cause a wide range of infections such as urinary tract infections or severe bacteraemia. For several years now, the misuse of antibiotics and cross-transmission in hospitals have led to the emergence of Enterobacteriaceae producing extended-spectrum β-lactamases (ESBL). The rising prevalence of ESBL is estimated at 8.2% in healthcare settings and at 6.2% in the community.
Carbapenems are considered the reference treatment for ESBL-producing E.coli (EESBL) infections. They often remain the last effective treatment on an individual level. But on a larger scale, their increasing use contributes to the emergence of resistance that might soon become a major public health issue.
Although the prevalence of ESBL remains low, the rate of ESBL epidemics in French hospitals has increased hugely since 2004. This could become a cause of concern especially because very few antibacterial agents are currently in development.
So infectiologists and microbiologists have to consider alternatives to carbapenems to treat infections caused by EESBL, which is stipulated in the new recommendations from the French High Council for Public Health and the Infectious Disease Society of America.
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
- •Patient admitted to any medical or surgical department in the participating centre
- •Documented urinary tract infection (other than cystitis), with or without bacteremia, caused by ESBL-producing E. coli susceptible in vitro to cefoxitin (minimal inhibition concentration <= 8 mg/L and /or diameter ≥ 19 mm according to CA-SFM 2015) and resistant to fluoroquinolones and to association trimethoprim-sulfamethoxazole. An E. Coli urinary tract infection is defined according to SPILF 2014 Clarification by a leucocytury ≥ 104/mL and clinical significant limit at 103 UFC/ml, for the men or the women.
- •Medical examination prior to inclusion
- •Informed consent signed by the patient
- •Patient affiliated to a French Sécurité Social regimen
排除标准
- •Serious infection (severe sepsis, septic shock)
- •Pregnant or breast-feeding women
- •Chronic kidney failure (creatinine clearance < 30 ml/min) and/or dialysis
- •Hypersensibility to imipenem/cilastatine, to cefoxitine
- •Hypersensibility to another antibiotics of cephalosporine class
- •Hypersensibility to another antibiotics of carbapenem class
- •Severe hypersensibility (ex :anaphylactic reaction, or serious cutaneous reaction) to all other antibiotics from beta lactamines family (ex : penicillins, monobactam)
- •Treatment with ganciclovir and/or valproic acid
- •Infection on the urinary cathether
- •Empirical antibiotic therapy including an aminoglycoside
- •Patient being treated with antibiotic(s) for another infection
- •Patient participating to another interventional study
- •Patient not compliant according to the investigator's opinion
- •Patient under guardianship
研究组 & 干预措施
cefoxitin
Cefoxitin 2 g administered intravenously three times a day. during 10 days for the treatment of pyelonephritis during 21 days for the treatment of prostatitis
干预措施: Cefoxitin (Drug)
imipenem
Imimpenem 1 g administered intravenously three times a day. during 10 days for the treatment of pyelonephritis during 21 days for the treatment of prostatitis
干预措施: imipenem (Drug)
结局指标
主要结局
Control urine culture negative
时间窗: 7 days after the end of treatment
次要结局
- presence of multiresistant bacteria in a rectal swab(7 days after the end of treatment)
- absence of fever(3 days after the beginning of study treatment)
- Composite outcome measure consisting of resolution of clinical signs observed on diagnosis(7 days after the end of treatment)