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Optimal Antibiotic Treatment of Moderate to Severe Bacterial Infections

Not Applicable
Completed
Conditions
Nosocomial Infections
Community-associated Infections
Health-care Acquired Infections
Interventions
Other: antibiotic treatment of by TREAT/PCR
Registration Number
NCT01338116
Lead Sponsor
Rabin Medical Center
Brief Summary

Severe bacterial infections are associated with mortality of about 30%. Patients with moderate to severe bacterial infections given early and appropriate empirical antibiotic treatment are at a lesser risk for a fatal outcome, with odds ratios ranging from 1.6 to 6.9. However only about 2/3 of patients worldwide are given early and appropriate empirical antibiotic treatment. About 40% of patients treated with antibiotics are given superfluous treatment.

TREAT is a computerized decision support system for antibiotic treatment in inpatients with common bacterial infections. TREAT is based on a state of the art stochastic model of the domain (a causal probabilistic network) and uses a cost benefit model for antibiotic treatment, including costs assigned to future resistance. It was tested in a randomized controlled trial in 3 countries and shown to improve the percentage of appropriate empirical antibiotic treatment while at the same time reduce hospital stay and the use of broad-spectrum antibiotics. The main limitation of TREAT is inherent in the limited information available within hours of presentation.

A second attractive approach to improve antibiotic treatment is to use techniques that do not depend on cultures, and thus shorten the time to identification of the pathogen to a few hours only. The LightCycler® SeptiFast test from Roche performs in vitro nucleic acid amplification test for pathogens causing bloodstream infections.

The purpose of the clinical trial is to show that the combined system TREAT/PCR assays will improve the outcome of inpatients with moderate to severe bacterial infections, while at the same time reducing the use of broad-spectrum antibiotics, with no or little additional costs. A secondary objective will be to assess the sensitivity and specificity of whole blood PCR, using TREAT as the reference standard.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
600
Inclusion Criteria

The rationale of the study will be to address patients for whom antibiotic treatment is, or should be, considered. Thus we will include consecutive patients detected in medical departments according to the following criteria:

  1. Patients from whom blood cultures were drawn or

  2. All patients for whom antibiotic treatment (but not prophylaxis or intra-peritoneal, inhalation or local antibiotics therapy ) is started within the last 96 days or

  3. Patients fulfilling the CDC diagnostic criteria for any infection (see appendix C) or

  4. Patients with temperature ≥38.3 measured orally (or 38 axillary or 38.5 rectal) on a single measurement or ≥38 / < 36 on at least 2 consecutive measurements separated at least 1 hr apart and one of the next criteria:

    (a) heart rate >90 beats/minute; (b) respiratory rate >20 breaths/minute or partial pressure of CO2 <32 mm Hg; and (c) white blood cell count >12,000/ L, <4000 L, or >10% immature (band) forms. or

  5. Patients with shock compatible with septic shock. As defined as hypotension (arterial blood pressure <90 mmHg systolic, or 40 mmHg less than patient's normal blood pressure) for at least 1 h despite adequate fluid resuscitation; Or Need for vasopressors to maintain systolic blood pressure >90 mmHg or mean arterial pressure >70 mmHg and a suspected source of infection.

Exclusion Criteria
  1. HIV positive patients with opportunistic infection (suspected or proven)and / or AIDS defining illness in the last 6 months prior to data collection.
  2. Children<18 years.
  3. Suspected travel infections.
  4. Suspected tuberculosis.
  5. Pregnancy.
  6. We will exclude patients not able to sign informed consent or not having a legal guardian willing to do so.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Management by TREAT/PCRantibiotic treatment of by TREAT/PCRThe data available at the time of patient recruitment will be entered into TREAT. TREAT will provide advice for the empirical antibiotic treatment and unless the caring physician can justify a deviation from this recommendation, TREAT's recommendation will be implemented (yes or no antibiotic treatment and type of antibiotic). TREAT will also recommend whether a blood sample for PCR should be obtained. Blood will be collected aseptically and the test will be performed once daily between 1000AM-1700PM (results available daily at 1700 PM). PCR results and a PCR-revised TREAT recommendation will be reported to the patient's physician in charge and treatment will be revised accordingly.
Primary Outcome Measures
NameTimeMethod
Clinical success defined as 30-day survival and clinical stability on day 430 days

patient alive at day 30; on day 4: no fever, no intra-tracheal tube, hemodynamic stable, no vasopressor support, empirical treatment appropriate (and thus not changed).

Secondary Outcome Measures
NameTimeMethod
Appropriate empirical antibiotic treatment48 hours

Appropriateness of the antibiotic treatment given during the first 48 hours, before identification of the causative pathogen and its antibiotic susceptibilities

Hospital stay30 days

Length of hospital stay

Antibiotic miuse of broad spectrum antibiotics and total costs of antibiotic treatment Superfluous antibiotic treatment30 days

Use of broad spectrum antibiotics and total costs of antibiotic treatment

Costs30 days

Costs incurred during hospital stay

Adverse events30 days

Allergy, nephrotoxicity, diarrhea, clostridium-difficile associated diarrhea and others

Survival30 days

Trial Locations

Locations (1)

Rabin Medical Center, Beilinson Hospital

🇮🇱

Petah Tikvah, Israel

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