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

Bacteremia Clinical Trial

— SDDICU  

Official title:

Simplified Selective Digestive Tract Decontamination for the Prevention of ICU Infections in the Setting of High-level Antibiotic Resistance

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01798537
• Other study ID #: 0401-12-RMB CTIL
• Secondary ID: NIHP Israel
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• First received: February 17, 2013
• Last updated: February 25, 2013
• Start date: June 2013
• Est. completion date: July 2015

Study information

• Verified date: February 2013
• Source: Rambam Health Care Campus
• Contact: Yaron P Bar-Lavie, M.D.
• Phone: ++972-50-206-2027
• Email: y_barlavie[@]rambam.health.gov.il
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2400
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bacteremia
• Bacteremia Associated With Intravascular Line
• Pneumonia, Ventilator-Associated
• Ventilator Associated Pneumonia

Intervention

Drug:
• Neomycin Colistin Nystatin Vancomycin
All participating study arm patients will receive SDD from admission to discharge

Locations

Country	Name	City	State
Israel	Rambam Health Care Campus	Haifa

Sponsors (1)

Lead Sponsor	Collaborator
Rambam Health Care Campus

Country where clinical trial is conducted

Israel, 

References & Publications (6)

de Jonge E, Schultz MJ, Spanjaard L, Bossuyt PM, Vroom MB, Dankert J, Kesecioglu J. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet. 2003 Sep 27;362(9389):1011-6. — View Citation

de Smet AM, Kluytmans JA, Blok HE, Mascini EM, Benus RF, Bernards AT, Kuijper EJ, Leverstein-van Hall MA, Jansz AR, de Jongh BM, van Asselt GJ, Frenay IH, Thijsen SF, Conijn SN, Kaan JA, Arends JP, Sturm PD, Bootsma MC, Bonten MJ. Selective digestive tract decontamination and selective oropharyngeal decontamination and antibiotic resistance in patients in intensive-care units: an open-label, clustered group-randomised, crossover study. Lancet Infect Dis. 2011 May;11(5):372-80. doi: 10.1016/S1473-3099(11)70035-4. Epub 2011 Mar 21. — View Citation

de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Bogaers-Hofman D, van der Meer NJ, Bernards AT, Kuijper EJ, Joore JC, Leverstein-van Hall MA, Bindels AJ, Jansz AR, Wesselink RM, de Jongh BM, Dennesen PJ, van Asselt GJ, te Velde LF, Frenay IH, Kaasjager K, Bosch FH, van Iterson M, Thijsen SF, Kluge GH, Pauw W, de Vries JW, Kaan JA, Arends JP, Aarts LP, Sturm PD, Harinck HI, Voss A, Uijtendaal EV, Blok HE, Thieme Groen ES, Pouw ME, Kalkman CJ, Bonten MJ. Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med. 2009 Jan 1;360(1):20-31. doi: 10.1056/NEJMoa0800394. — View Citation

Schultz MJ, Haas LE. Antibiotics or probiotics as preventive measures against ventilator-associated pneumonia: a literature review. Crit Care. 2011;15(1):R18. doi: 10.1186/cc9963. Epub 2011 Jan 13. Review. — View Citation

Silvestri L, van Saene HK, Milanese M, Gregori D, Gullo A. Selective decontamination of the digestive tract reduces bacterial bloodstream infection and mortality in critically ill patients. Systematic review of randomized, controlled trials. J Hosp Infect. 2007 Mar;65(3):187-203. Epub 2007 Jan 22. Review. — View Citation

van Saene HK, Petros AJ, Ramsay G, Baxby D. All great truths are iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth. Intensive Care Med. 2003 May;29(5):677-90. Epub 2003 Apr 10. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The effect of SDD on bacteriological screening of Israeli ICU patients		two years	No
Primary	Number of Intensive care acquired infections per 1000 device days	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.	two years	Yes
Secondary	The effect of SDD on the morbidity and mortality from MDRO on israeli ICU patients.		two years	No