Selective Digestive Decontamination

Reviewed and revised 26 January 2014

OVERVIEW

Selective Digestive Decontamination (SDD) is a prophylactic strategy to prevent or minimize nosocomial endogenous and exogenous infections in critically ill patients

• SDD uses non-absorbable oral and enteric antibiotics and parenteral antibiotics
• aim  is to prevent or eradicate, if present, the oropharyngeal and intestinal abnormal carriage of potentially pathogenic microorganisms (PPMs), such as aerobic Gram-negative microorganisms (AGNB), methicillin-sensitive Staphylococcus aureus and yeasts
• first used in 1982, first RCT in 1987 and over 60 RCTs and several meta-analyses in approximately 15,000 patients, over a period of 25 years
• it is the best evaluated therapy in intensive care medicine yet has had minimal uptake

RATIONALE

• nosocomial infection is a major ICU problem — e.g. healthy individuals (eg Staph aureus, E coli and C albicans) and opportunistic, aerobic Gram-negative bacilli (eg Klebsiella, Pseudomonas Acinetobacter)
• critical illness alters normal body flora causing overgrowth of normal and abnormal flora
• gut overgrowth (i.e. ≥105 colonies per ml of saliva or faeces) is a critical event which precedes endogenous infections and is a risk factor for antimicrobial resistance
• only ~15 PPMs are responsible for the majority of infections in ICU, so SDD mainly targets these microorganisms
• ICU infections are caused by: primary endogenous infections > secondary endogenous infections > exogenous infections

PROTOCOL

Full 4-step protocol targets normal and abnormal flora, but only those that are likely to cause infection

• application of topical PTA (polymyxin E, tobramycin and amphotericin B) + IV cefotaxime

1. short course (4 days) of IV antibiotics to control primary endogenous infections caused by PPMs present in the patient’s admission flora.
   — previously healthy:  β-lactam, such as cefotaxime 80-100 mg/kg/day,
   —  chronic underlying disease (e.g. DM, COPD, hospital transfer):  combination therapy or an anti-pseudomonal cephalosporin (e.g. ceftazidime)
2. enteral antimicrobials given throughout ICU stay to control secondary oropharyngeal and intestinal carriageand subsequent secondary endogenous infections due to PPMs acquired in the ICU.
   —  e.g. polymyxin E, tobramycin, and amphotericin B (PTA)
   — 0.5g of paste or gel containing 2% PTA is applied in the oropharyngeal cavity with a gloved finger Q6H + h 10 ml suspension of  100 mg of polymyxin E, 80 mg of tobramycin and 500 mg of amphotericin B via NG q6h
   — if methicillin-resistant S. aureus (MRSA) endemic (>1 case/month  with a diagnostic sample positive for MRSA over a 6 month perioid): add oropharyngeal gel and/or intestinal solution of vancomycin
3. high level of hygiene to prevent exogenous infections
   — also topical  PTA on the tracheostomy in tracheostomized patients to control exogenous lower airway infections
4. surveillance cultures of throat and rectum
   — on admission and twice weekly
   — monitor the effectiveness and to detect resistance

Variations from the original protocol have also been used and studied:

• intestinal antimicrobials only
• administration of enteral antimicrobials without the parenteral component
• selective oropharyngeal decontamination (SOD), omitting both the parenteral and the intestinal components
• different choice of antibiotics

EVIDENCE

Over 60 RCTs with >15,000 patients (mostly in Europe) show benefits in terms of:

• mortality (NNT ~18)
• overall infection
• lower airway infections
• blood stream infections
• oropharyngeal carriage
• rectal carriage
• MODS
• ICU length of stay

Patient groups studied include general ICU, burns, gastrointestinal surgery and transplant patients.

PROBLEMS

• The number of trials with good scientific methods are few
• In the trials that suggested benefit, there was baseline variance in patient demographics and overall care
• There is a suggestion that selective oral decontamination is equally as effective as SDD, so the iv cephalopsporins are not required
• potential for antibiotic resistance and modification of ICU flora (especially in the longterm) — though the (flawed) evidence does not suggest an increase in MROs; proponents of SDD argue that by limiting bacterial overgrowth antibiotic resistance may be curtailed
• efficacy and safety primarily seen in ICUs with a low prevalence of  resistant organisms (such as MRSA and/or VRE), mostly in Europe (e.g. Netherlands and Germany)
• In seven RCTs conducted in ICUs in which MRSA was endemic there was a trend toward higher MRSA infection rates in patients receiving SDD (other studies suggest the addition of vancomycin prevents this)
• Hurley 2013’s reanalysis of published data suggests that the topical placebo used in some studies may have been a vehicle for S. aureus and led to increased VAP, thus inflating the beneficial effect of SDD

BARRIERS TO ADOPTION

• protocols driven by local flora and practice
• concerns regarding antibiotic resistance
• requires considerable commitment from intensivists, nursing staff, microbiologists, and pharmacists in patient’s monitoring, processing surveillance samples, and preparing SDD drugs
• not supported by Big Pharma
• lack of opinion leader support

AN APPROACH

• SDD is not generally practiced in the Australia and New Zealand or North American settings
• Despite the impressive body of evidence for efficacy of SDD, it is unclear if this is generalised to the ANZ setting, to ICUs with higher rates of resistant organisms and what the longterm consequences on antimicrobial ecology and resistance will be
• Await the SuDDICU trial, a multinational trial that seeks to find the definitive answer to whether SDD saves lives (LITFL’s Paul Young is one of the Chief Investigators)…

References and Links

Journal articles

• 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. PMID: 14522530.
• de Smet AM, Kluytmans JA, Cooper BS, et al. Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med. 2009 Jan 1;360(1):20-31. PMID: 19118302.
• Hurley JC. The perfidious effect of topical placebo: A calibration of Staphylococcus aureus Ventilator Associated Pneumonia incidence within Selective Digestive Decontamination (SDD) studies versus the broader evidence base. Antimicrob Agents Chemother. 2013 Jul 8. PMID: 23836178
• Liberati A, D’Amico R, Pifferi S, Torri V, Brazzi L, Parmelli E. Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD000022. PMID: 19821262.
• Oostdijk EA et al. Ecological effects of selective decontamination on resistant gram-negative bacterial colonization. Am J Respir Crit Care Med. 2010 Mar 1;181(5):452-7. PMID: 19965807.
• Silvestri L, van Saene HK. Selective decontamination of the digestive tract: an update of the evidence. HSR Proc Intensive Care Cardiovasc Anesth. 2012;4(1):21-9. PMC3484923.

FOAM and web resources

• Crit-IQ blog — Selective Digestive Decontamination – Right time for prime time? (includes a comment by Ian Seppelt about SuDDICU)