Randomized, Multicenter, Phase III, Controlled Clinical Trial, to Demonstrate the no Inferiority of Reduced Antibiotic Treatment vs a Broad Spectrum Betalactam Antipseudomonal Treatment in Patients With Bacteremia by Enterobacteriaceae
Overview
- Phase
- Phase 3
- Intervention
- Antipseudomonal beta-lactam antibiotic
- Conditions
- Enterobacteriaceae Infections
- Sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Enrollment
- 344
- Locations
- 21
- Primary Endpoint
- Clinical cure at day 3-5 after treatment.
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The continuous increase in the bacterial resistance rate and the slow arrival of new therapeutic options have turned into an antibiotic crisis. One of the strategies proposed by stewardship programs to try to change this situation described worldwide is the use of antibiotics with the lowest possible antimicrobial spectrum.
Enterobacteriaceae bacteremia is a good example of how this strategy would be applied. The empirical treatment of nosocomial bacteremia by Enterobacteriaceae comprises in several cases one or two antibiotics with antipseudomonal activity, being much less common than desirable a subsequent change to narrower spectrum antibiotics based on susceptibility data ("de escalation"). This is because the safety of de escalation is based only on expert advice and some observational studies, so their efficacy and safety is questioned by many clinicians and therefore its use is lower than desired. In fact, a recent systematic review of the Cochrane Library concluded that randomized studies to support this practice are needed. Investigators propose a "real clinical practice-based" randomized trial to compare the efficacy and safety of continuing with an antipseudomonal agents vs. de-escalation according to a pre-specified rule, in patients with bacteraemia due to Enterobacteriaceae.
Investigators
Eligibility Criteria
Inclusion Criteria
- •≥18 years old hospitalized patients with bacteremia from any source with isolation of an enterobacteria in blood cultures.
- •Active empiric treatment with antipseudomonal betalactamic at 48 hours from the symptoms of sepsis and the blood culture.The patient could have received any other type of antibiotic therapy up to 24 hours after blood extraction.
- •Microorganism susceptible at least one treatment from the experimental arm.
- •Patients with intravenous treatment at least 3 days from the randomization o 5 days from the initial blood culture.
- •Patients to sign the informed consent form.
Exclusion Criteria
- •Palliative care or life expectance \< 90 days.
- •Pregnancy or lactation period.
- •To isolate the Extended-spectrum β-lactamases producing Enterobacteriaceae
- •Late randomization \>48 hours after the enterobacteriaceae blood culture´s identification
- •Severe neutropenic (\< 500 céls/mm3) at the randomization.
- •Treatment of infection \> 28 days (endocarditis and osteomyelitis) or meningitis.
Arms & Interventions
Antipseudomonal beta-lactam antibiotic
1. Ampicillin 2g IV/6h 2. Trimethoprim/sulfamethoxazole 160/800 mg IV/8 -12h 3. Cefuroxime 750-1000 mg IV/8h 4. Cefotaxime 1-2g IV/8h ó ceftriaxone 1 g/12-24h 5. Amoxicillin/clavulanate 1000/125 mg IV/8h 6. Ciprofloxacin 400 mg IV/12h 7. Ertapenem 1-2g/24h.
Intervention: Antipseudomonal beta-lactam antibiotic
De-escalation(short-spectrum antibiotic)
* Piperacillin/tazobactam 4/0.5 g IV/8h * Meropenem 1-2 g IV/8h * Imipenem 0.5 g IV/6h - 1g IV/6h * Aztreonam 1-2 g IV/8h * Ceftazidime 1-2 g IV/8h * Cefepime 2 g IV/8-12h
Intervention: De-escalation(short-spectrum antibiotic)
Outcomes
Primary Outcomes
Clinical cure at day 3-5 after treatment.
Time Frame: Day 3-5 after end of treatment.
Clinical cure: complete resolution of infection symptoms (bacteremia) present at the day on which the assessment is done and patient is alive.
Secondary Outcomes
- Late clinical and microbiological response.(Day 60)
- Treatment duration.(It is not allowed treatment duration more than 28 days)
- Early clinical and microbiological response.(After 5 days of treatment)
- Mortality(At 7,14 and 30 days)
- Length of hospital stay(At 7,14 and 30 days)
- Impact of the study treatment on intestinal microbiota(Screening, Day 7-14, Day 12-21, Day 30)
- Secondary infections.(60 days)
- Safety of antibiotic treatment(60 days)
- Recurrences (relapse or reinfection) rate(Day 60 after treatment)