Optimal Antibiotic Treatment of Moderate to Severe Bacterial Infections (CDSS)

Optimal Antibiotic Treatment of Moderate to Severe Bacterial Infections: Integration of PCR Technology and Medical Informatics/Artificial Intelligence

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.

Study Overview

• Status: Completed
• Conditions: Nosocomial Infections; Community-associated Infections; Health-care Acquired Infections
• Intervention / Treatment: Other: antibiotic treatment of by TREAT/PCR

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Petah Tikvah, Israel, 49100
    • Rabin Medical Center, Beilinson Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Management by TREAT/PCR; The 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.	Other: antibiotic treatment of by TREAT/PCR; Management by TREAT/PCR. The 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. On day 2, when results of blood cultures and other cultures become available TREAT will be re-consulted and will issue a new recommendation based on the full microbiological investigation (negative and positive results).
No Intervention: Usual management; Patients will be managed by physicians as in regular clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical success defined as 30-day survival and clinical stability on day 4	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).	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival		30 days
Appropriate empirical antibiotic treatment	Appropriateness of the antibiotic treatment given during the first 48 hours, before identification of the causative pathogen and its antibiotic susceptibilities	48 hours
Hospital stay	Length of hospital stay	30 days
Antibiotic miuse of broad spectrum antibiotics and total costs of antibiotic treatment Superfluous antibiotic treatment	Use of broad spectrum antibiotics and total costs of antibiotic treatment	30 days
Costs	Costs incurred during hospital stay	30 days
Adverse events	Allergy, nephrotoxicity, diarrhea, clostridium-difficile associated diarrhea and others	30 days

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Investigators: Principal Investigator: Mical Paul, MD, Rabin Medical Center; Principal Investigator: Leonard Leibovici, Prof, Rabin Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): May 13, 2019
• Study Completion (Actual): May 13, 2019

Study Registration Dates

• First Submitted: March 30, 2011
• First Submitted That Met QC Criteria: April 17, 2011
• First Posted (Estimated): April 19, 2011

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 7, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: PCR; antibiotic treatment; computerized decision support system
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Iatrogenic Disease; Infections; Communicable Diseases; Bacterial Infections; Cross Infection; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: 6036 (CTEP)