Should selective digestive decontamination be used in critically ill patients?
Cite this as: BMJ 2012;345:e6697
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We read with interest the uncertainties page entitled ‘Should selective digestive decontamination (SDD) be used in critically ill patients?’ by Walden et al . However, we would like to raise several points that deserve attention.
Firstly, the authors acknowledge the efficacy in reducing serious infection of lower airways and mortality by SDD defined as an antimicrobial prophylaxis using parenteral and enteral antimicrobials applied in throat and gut. However, they express uncertainty about SDD due to the theoretical possibility of antimicrobial resistance. Although they discuss the two recent Dutch trials [2,3] with respect to their efficacy, they fail to mention the resistance data from these two trials. De Jonge et al conducted an RCT in 934 critically ill adult patients . Carriage of aerobic Gram-negative bacilli (AGNB) resistant to polymyxin E, tobramycin, ceftazidime, ciprofloxacin and imipenem was significantly reduced in SDD patients compared with controls (16 vs 26%; p = 0.001). Similarly, de Smet et al  showed that there were fewer patients with AGNB in rectal swabs resistant to the marker antibiotics in the SDD group when compared to the group who received selective oral decontamination (SOD), a modified SDD protocol without the parenteral and enteral gut component. In addition, bloodstream infections due to highly resistant pathogens was significantly reduced by SDD compared with SOD (OR 0.37, 95% CI 0.16-0.85) .
Secondly, the authors state that they believe a new trial with the endpoint of resistance is required to address the aforementioned area of uncertainty. The R-GNOSIS group is planning a cluster randomised clinical trial across Europe in countries with higher levels of resistance. This study will compare SOD, oral decontamination with chlorhexidine without the parenteral component of the calssic SDD regimen with standard care. It is remarkable that the classic SDD regimen is not included in that study, since this should be considered the gold-standard in this type of approach. Nor is it clear whether surveillance samples of throat and/or gut (carriage of resistance) or diagnostic samples of lower airways (colonisation/infection with resistant bacteria) are obtained in this new trial. It is generally accepted that surveillance samples are the most sensitive samples to detect resistance . Of course R-GNOSIS will generate interesting resistance data but this trial cannot answer the original question ‘Does SDD cause resistance?’
1. Walden AP, Bonten MJ, Wise MP. Should selective digestive decontamination be used in critically ill patients? BMJ 2012; doi: 10.1136/bmj.e6697.
2. de Jonge E, Schultz M, Spanjaard L et al. Effects of selective decontamination of the digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised, controlled trial. Lancet 2003; 363: 1101-1016.
3. de Smet AMGA, Kluytmans JAJW, Cooper BS et al. Decontamination of the digestive tract and oropharynx in ICU-patients. N Engl J Med 2009; 360: 20-31.
4. de Smet AM, Kluytmans AJ, Blok HE et al. Selective digestive 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; 11: 372-380.
5. D'Agata EM, Venkataraman L, DeGirolami P et al. Colonization with broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units during a nonoutbreak period: prevalence, risk factors, and rate of infection. Crit Care Med 1999; 27: 1090-1095.
Competing interests: None declared
Gelre Hospitals, Apeldoorn, The Netherlands
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This opinion piece fails to note three observations that remain unexplained among the broad range of interventions other than SDD that have been studied to prevent VAP.
Firstly, the VAP incidence within the SDD evidence base is unusual in two respects versus the evidence base for other methods of VAP prevention and versus observational studies; the mean VAP incidence in the control groups of SDD studies is >13 percentage points higher and the dispersion is greater than among control groups from studies of non-antibiotic methods of VAP prevention [1, 2]. Most strikingly, these disparities are most apparent among groups of VAP prevention studies rated with higher study quality due for example to study blinding achieved through the use of topical placebo . Why?
Second, how does SDD work? It appears not to be through reductions in rates of Pseudomonas aeruginosa VAP .
Third, is it possible that the use of topical placebo is itself a vehicle for cross infection which is compounded by ecological effect associated with the use of SDD? If, as you report, colonization with antibiotic resistant Gram negative bacteria increases after cessation of SOD and SDD , would not this ecological effect carry over into periods of standard care and complicated the interpretation of even a cross over study ?
Until the fundamental question why the rates of VAP in control groups are generally higher than expected and yet this is not the case for non-antibiotic methods of VAP prevention then SDD has not been proven to be safe let alone effective.
1. Hurley JC. Profound effect of study design factors on ventilator-associated pneumonia incidence of prevention studies: benchmarking the literature experience. J Antimicrob Chemother 2008;61:1154–61.
2. Hurley JC. Paradoxical ventilator associated pneumonia incidences among Selective Digestive Decontamination studies versus other studies of mechanically ventilated patients. Benchmarking systematic review data. Crit Care 2011;15:R7.
3. Hurley JC. Lack of impact of Selective Digestive Decontamination on Pseudomonas aeruginosa ventilator associated pneumonia: benchmarking the evidence base. J Antimicrob Chemother 2011;66:1365-73
4. Oostdjik EAN, de Smet AMGA, Blok HEM, et al. Ecological effects of selective decontamination on resistant gram negative colonization. Am J Respir Crit Care Med 2010;181:452–7.
5. Raoofi M, Hurley JC. Selective Decontamination crossover study. Lancet Infectious Diseases 2012;12:179-80
Competing interests: None declared
University of Melbourne, Mair st., Ballarat, Victoria, Australia
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