Simplified Selective Digestive Tract Decontamination for the Prevention of Intensive Care Unit Acquired Infections

Phase 2

• Conditions: Ventilator Associated Pneumonia; Bacteremia; Bacteremia Associated With Intravascular Line
• Interventions: Drug: Neomycin Colistin Nystatin Vancomycin

• Registration Number: NCT01798537
• Lead Sponsor: Rambam Health Care Campus

Brief Summary

A simplified graded gut decontamination protocol combined with rigorous bi-weekly screening and appropriate bacterial prophylaxis, will lead to a 25% reduction in the acquisition of blood stream infections and to a 25% reduction in lower airway colonization with multi drug resistant organisms. There will be no concomitant rise in gram-positive or fungal infection or a surgency of new resistance patterns.

Detailed Description

Simplified Selective Digestive Tract Decontamination for the prevention of ICU infections in a setting of high-level antibiotic resistance

Scientific Background:

Aerobic gram-negative bacilli (AGNB), Gram-positive bacteria and fungi are responsible for hospital acquired infections. This problem is especially typical in intensive care units (ICUs) due to the complexity of disease and wide use of invasive procedures. The common use of empiric wide-range antibiotic therapy had lead to the development significant resistance of these pathogens and this group of bacteria was defined as Multi-Drug Resistant Organisms (MDRO). Among these bacteria the most important and virulent are: Carbapenem Resistant Enterobacteriaceae (CRE), Extended Spectrum Beta Lactamases (ESBL), Methicillin Resistant Staphylococcus Aureus (MRSA), Vancomycin Resistant Enterococci (VRE) as well as Fluconazol resistant Candida.

The main reservoir of these organisms is the intestinal tract, which raises the possibility that their primary eradication may lead to control of the MDRO epidemic.

Selective Digestive tract Decontamination (SDD) has been studied extensively over the last 10-15 years and there is a body of evidence that shows that this method can reduce acquired infections, bacterial drug resistance and mortality in various ICU settings. It should be pointed out however that many of these studies were performed in units with a low prevalence of infection from MDROs and that they were never performed in units were CREs are endemic. According to the described protocols, SDD was performed as a combination of an a oral antibiotic paste - Selective Oropharyngeal Decontamination (SOD) together with enteral medication given through a gastric feeding tube, as well as a few days of prophylactic intra-venous treatment with an early generation cephalosporin.

This treatment method did not become a standard of care - mostly due to the concern that new resistance will develop to the prescribed enteral antibiotics, or that there will be a rise in the prevalence of other enteral infections as VRE, Clostridium difficile or MRSA acquired infections. Despite evidence that during the SDD treatment period there was actually a reduction of drug resistance, the Center for Disease Control and prevention (CDC) and the protocols of the surviving sepsis campaign do not recommend SDD as a means of coping with the MDRO epidemic. In published SDD protocols there was a use of wide-spectrum antibiotics that covered the range of gram-positive, gram-negative bacteria and fungi, without correlation to the results of primary screening in these patients. Even though this approach did not lead to a rise in bacterial resistance, it raised enough anxiety and resistance within the caregivers to prevent its penetration to daily use. The endemic spread of CRE infection at Rambam Medical Center has lead us to focus on these pathogens in our SDD program, while performing rigorous bi-weekly screening for all bacteria. We gave enteral antibiotic treatment (Neomycin + Polymixin E) targeting AGNB, and only if the primary screening found MRSA or Fungi, did we prescribe enteral preventive treatment against them (Vancomycin or Nystatin). Therefore, a prospective study was performed during 2011 at Rambam department of critical care medicine, on the influence of a simplified SDD protocol on the acquisition of AGNB infection in the ICU. The results show a significant reduction in blood stream infections and a change in the epidemiology of colonization of the respiratory tract - from resistant to sensitive bacteria. There was a concomitant reduction in the use of MDRO- targeted antibiotics.

The proposed multi-center study is based on this successful experience and will focus on the influence of a simplified SDD protocol on colonization and infection with MDROs in israeli ICUs where CREs are endemic.

Study Timeline

• Status Verified: 2013-02
• Study First Submitted: 2013-02-17
• Study First Submitted QC: 2013-02-25
• Last Update Submitted: 2013-02-25
• Study First Posted: 2013-02-26
• Last Update Posted: 2013-02-26
• Study Start: 2013-06
• Primary Completion: 2015-07
• Study Completion: 2015-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 2400

Inclusion Criteria

1. Expected to be in the ICU > 72 hours
2. Has an enteral feeding tube and can receive enteral medication
3. Has a tracheal tube

Exclusion Criteria

1. Pt. is moribund - not expected to survive > 28 days
2. Pt. or legal representative refuse to participate

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Neomycin Colistin Nystatin Vancomycin	Neomycin Colistin Nystatin Vancomycin	All participating study arm patients will receive SDD from admission to discharge according to the following plan: ENTERAL MEDICATION (via feeding tube) x 4 times daily: 375 mg Neomycin 100 mg Colistin Sulphate 1 million units Nystatin \* 250 mg Vancomycin \* Nystatin will be prescribed only if there is a positive sputum or urine culture for yeast or candida Vancomycin will be prescribed only in case of a positive screen or culture for MRSA

Primary Outcome Measures

Name	Time	Method
Number of Intensive care acquired infections per 1000 device days	two years	A simplified graded SDD protocol combined with rigorous bi-weekly screening and appropriate bacterial prophylaxis, will lead to a reduction in the acquisition of central venous line blood-stream infections and to a reduction in ventilator associated pneumonia. There will be no concomitant rise in gram-positive or fungal infection or a surgency of new resistance patterns.

Secondary Outcome Measures

Name	Time	Method
The effect of SDD on the morbidity and mortality from MDRO on israeli ICU patients.	two years

Trial Locations

Locations (1)

Rambam Health Care Campus; 🇮🇱 Haifa, Israel