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Study on Reduced Antibiotic Treatment vs Broad Spectrum Betalactam in Patients With Bacteremia by Enterobacteriaceae

Phase 3
Completed
Conditions
Enterobacteriaceae Infections
Interventions
Drug: Antipseudomonal beta-lactam antibiotic
Drug: De-escalation(short-spectrum antibiotic)
Registration Number
NCT02795949
Lead Sponsor
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
344
Inclusion Criteria
  1. ≥18 years old hospitalized patients with bacteremia from any source with isolation of an enterobacteria in blood cultures.
  2. 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.
  3. Microorganism susceptible at least one treatment from the experimental arm.
  4. Patients with intravenous treatment at least 3 days from the randomization o 5 days from the initial blood culture.
  5. Patients to sign the informed consent form.
Exclusion Criteria
  1. Palliative care or life expectance < 90 days.
  2. Pregnancy or lactation period.
  3. To isolate the Extended-spectrum β-lactamases producing Enterobacteriaceae
  4. Late randomization >48 hours after the enterobacteriaceae blood culture´s identification
  5. Severe neutropenic (< 500 céls/mm3) at the randomization.
  6. Treatment of infection > 28 days (endocarditis and osteomyelitis) or meningitis.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Antipseudomonal beta-lactam antibioticAntipseudomonal beta-lactam antibiotic1. 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.
De-escalation(short-spectrum 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
Primary Outcome Measures
NameTimeMethod
Clinical cure at day 3-5 after treatment.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 Outcome Measures
NameTimeMethod
Late clinical and microbiological response.Day 60

The infection was completely resolved at day 60 (patients without infection symptoms)

Treatment duration.It is not allowed treatment duration more than 28 days

Evaluate the study treatment duration.

Early clinical and microbiological response.After 5 days of treatment

The infection was completely resolved after 5 days of treatment (patients without infection symptoms and a negative blood culture).

MortalityAt 7,14 and 30 days

Death for any reason

Length of hospital stayAt 7,14 and 30 days

Defined as the from admission to hospital discharge

Impact of the study treatment on intestinal microbiotaScreening, Day 7-14, Day 12-21, Day 30

Effect of study treatment on colonization of the intestinal tract with multi drug resistant gram negative bacilli

Secondary infections.60 days

Evaluate the development of secondary infections other than the initial bacteremia.

Safety of antibiotic treatment60 days

Gathering any related adverse event from the informed consent form signature up to 60 days

Recurrences (relapse or reinfection) rateDay 60 after treatment

Trial Locations

Locations (21)

Son Espases Hospital

🇪🇸

Palma de Mallorca, Spain

University Hospital Donostia

🇪🇸

San Sebastian, Gipúzcoa, Spain

University Hospital of Bellvitge

🇪🇸

Barcelona, Spain

Cruces Hospital

🇪🇸

Baracaldo, País Vasco, Spain

La Coruña Hospital

🇪🇸

La Coruña, Spain

San Juan de Dios del Aljarafe Hospital

🇪🇸

Bormujos, Sevilla, Spain

Universitary Hospital of Leon

🇪🇸

León, Spain

University Hospital La Princesa

🇪🇸

Madrid, Spain

University Clinic of Navarra

🇪🇸

Pamplona, Spain

Universitary Hospital of Orense

🇪🇸

Orense, Spain

University Hospital La Paz

🇪🇸

Madrid, Spain

Universitary Hospital of Vigo

🇪🇸

Vigo, Spain

University Hospital Puerta del Mar

🇪🇸

Cádiz, Spain

Puerto Real Hospital

🇪🇸

Cádiz, Spain

University Hospital Virgen Macarena

🇪🇸

Seville, Spain

University Hospital Marqués de Valdecilla

🇪🇸

Santander, Spain

University Hospital Mutua de Tarrasa

🇪🇸

Barcelona, Spain

University General Hospital of Alicante

🇪🇸

Alicante, Spain

University Hospital of Zaragoza

🇪🇸

Zaragoza, Spain

La Línea de La Concepción Hospital

🇪🇸

La Línea de La Concepción, Cádiz, Spain

Jerez de la Frontera Hospital

🇪🇸

Jerez de la Frontera, Cádiz, Spain

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