Therapeutics
Review: Selective digestive decontamination reduces mortality more than chlorhexidine in general ICU patients
Price R, Maclennan G, Glen J; SuDDICU Collaboration. Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis. BMJ. 2014;348:g2197.
Clinical impact ratings: h ★★★★★✩✩ I ★★★★★✩✩ c ★★★★★✩✩ Question
*Information provided by author.
In patients in general intensive care units (ICUs), what is the relative efficacy of selective digestive tract decontamination (SDD), selective oropharyngeal decontamination (SOD), and topical oropharyngeal chlorhexidine for preventing mortality?
For correspondence: Dr. R. Price, Royal Alexandra Hospital, Paisley, Scotland, UK. E-mail [email protected]. ■
Commentary
Review scope Included studies compared SDD (poorly absorbable antibiotics applied to the oropharynx and stomach plus empirical IV antibiotics), SOD (poorly absorbable antibiotics applied to the oropharynx only), or topical oropharyngeal chlorhexidine (chlorhexidine applied to the oropharynx) with placebo or usual care in adults in general ICUs. Studies that included children only or specialized populations (such as cardiac surgery); assessed combinations of oropharyngeal plus gastric application of antibiotics, or gastric or subglottic application; or delivered active topical drugs to both groups or empirical IV antibiotics to the control group were excluded. The outcome was mortality.
Review methods MEDLINE, EMBASE/Excerpta Medica, and Cochrane Register of Clinical Trials (all 1984 to Dec 2012); published meta-analyses and congress abstracts (2005 to 2012); and controlled-trials.com were searched for randomized controlled trials (RCTs). 29 RCTs {n = 14 723}* met the selection criteria. 14 RCTs assessed SDD, 3 assessed SOD, 11 assessed chlorhexidine, and 1 assessed SDD and SOD. Sequence generation was adequate in 18 RCTs, and allocation concealment was adequate in 20 RCTs.
Main results A generalized linear modelling framework was used for analysis of mixed treatment comparisons that combined data from direct and indirect comparisons. Mixed treatment comparisons are shown in the Table.
Conclusion In patients in general intensive care units, selective digestive tract decontamination reduces mortality more than chlorhexidine or placebo or usual care; selective oropharyngeal decontamination reduces mortality more than chlorhexidine. Mixed treatment comparisons for mortality in patients in general intensive care units† Comparisons
Source of funding: No external funding.
Odds ratio (95% credible interval)
SDD vs placebo or usual care
0.74 (0.63 to 0.86)
SDD vs chlorhexidine
0.61 (0.47 to 0.78)
SOD vs placebo or usual care
0.82 (0.62 to 1.02)
SDD vs SOD
0.91 (0.70 to 1.19)
SOD vs chlorhexidine
0.67 (0.48 to 0.91)
Chlorhexidine vs placebo or usual care
1.23 (0.99 to 1.49)
Of all the questions that have been addressed by RCTs in critical care, none has shown a more consistent result, nor engendered more controversy, than that of the utility of SDD. The rationale for SDD dates back 40 years to the work of van der Waaij and colleagues, who described a key role for the anaerobic gut flora in preventing pathologic colonization by gram-negative organisms, such as Pseudomonas species (1). Anaerobes vastly outnumber aerobes in the healthy gastrointestinal tract and play important roles in gut development, absorptive capacity, and mucosal antibacterial defenses. SDD selectively targets aerobic gram-negative organisms and fungi, leaving the anaerobic and gram-positive flora intact. SDD is not gut sterilization but rather ablation of pathologic overgrowth and support of the normal indigenous flora. Chlorhexidine exerts much broader antimicrobial activity, including against anaerobes. Although the systematic review by Price and colleagues included small individual studies, their pooled conclusions are consistent and congruent with the conclusions of other trials that did not meet the inclusion criteria of the systematic review. The lingering concern with SDD is that it might result in the emergence of resistant organisms. Systematic reviews have not shown this (2), but the long-term effects of broad adoption of this prophylactic strategy are uncertain. The available evidence argues compellingly that we should abandon routine use of chlorhexidine and adopt SDD as a more efficacious alternative. Yet, there is a disconnect between the evidence and what clinicians are comfortable doing. The most productive resolution of this remarkably durable controversy could be a welldesigned RCT that addresses not only individual patient benefit but also communal microbial ecology. John C. Marshall, MD St. Michael’s Hospital, University of Toronto Toronto, Ontario, Canada References 1. van der Waaij D, Berghuis-de Vries JM, Lekkerkerk van der Wees JEC. Colonization resistance of the digestive tract in conventional and antibiotic treated mice. J Hyg (Lond). 1971;69:405-411. 2. Daneman N, Sarwar S, Fowler RA, Cuthbertson BH; SuDDICU Canadian Study Group. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13:328-41.
†SDD = selective digestive tract decontamination (poorly absorbable antibiotics applied to the oropharynx and stomach plus empirical IV antibiotics); SOD = selective oropharyngeal decontamination (poorly absorbable antibiotics applied to the oropharynx only).
19 August 2014 | ACP Journal Club | Volume 161 • Number 4
© 2014 American College of Physicians
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/930674/ by a Tufts University User on 08/02/2017
JC9
Review: Selective digestive decontamination reduces mortality more than chlorhexidine in general ICU patients
Price R, Maclennan G, Glen J; SuDDICU Collaboration. Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis. BMJ. 2014;348:g2197.
Clinical impact ratings: h ★★★★★✩✩ I ★★★★★✩✩ c ★★★★★✩✩ Question
*Information provided by author.
In patients in general intensive care units (ICUs), what is the relative efficacy of selective digestive tract decontamination (SDD), selective oropharyngeal decontamination (SOD), and topical oropharyngeal chlorhexidine for preventing mortality?
For correspondence: Dr. R. Price, Royal Alexandra Hospital, Paisley, Scotland, UK. E-mail [email protected]. ■
Commentary
Review scope Included studies compared SDD (poorly absorbable antibiotics applied to the oropharynx and stomach plus empirical IV antibiotics), SOD (poorly absorbable antibiotics applied to the oropharynx only), or topical oropharyngeal chlorhexidine (chlorhexidine applied to the oropharynx) with placebo or usual care in adults in general ICUs. Studies that included children only or specialized populations (such as cardiac surgery); assessed combinations of oropharyngeal plus gastric application of antibiotics, or gastric or subglottic application; or delivered active topical drugs to both groups or empirical IV antibiotics to the control group were excluded. The outcome was mortality.
Review methods MEDLINE, EMBASE/Excerpta Medica, and Cochrane Register of Clinical Trials (all 1984 to Dec 2012); published meta-analyses and congress abstracts (2005 to 2012); and controlled-trials.com were searched for randomized controlled trials (RCTs). 29 RCTs {n = 14 723}* met the selection criteria. 14 RCTs assessed SDD, 3 assessed SOD, 11 assessed chlorhexidine, and 1 assessed SDD and SOD. Sequence generation was adequate in 18 RCTs, and allocation concealment was adequate in 20 RCTs.
Main results A generalized linear modelling framework was used for analysis of mixed treatment comparisons that combined data from direct and indirect comparisons. Mixed treatment comparisons are shown in the Table.
Conclusion In patients in general intensive care units, selective digestive tract decontamination reduces mortality more than chlorhexidine or placebo or usual care; selective oropharyngeal decontamination reduces mortality more than chlorhexidine. Mixed treatment comparisons for mortality in patients in general intensive care units† Comparisons
Source of funding: No external funding.
Odds ratio (95% credible interval)
SDD vs placebo or usual care
0.74 (0.63 to 0.86)
SDD vs chlorhexidine
0.61 (0.47 to 0.78)
SOD vs placebo or usual care
0.82 (0.62 to 1.02)
SDD vs SOD
0.91 (0.70 to 1.19)
SOD vs chlorhexidine
0.67 (0.48 to 0.91)
Chlorhexidine vs placebo or usual care
1.23 (0.99 to 1.49)
Of all the questions that have been addressed by RCTs in critical care, none has shown a more consistent result, nor engendered more controversy, than that of the utility of SDD. The rationale for SDD dates back 40 years to the work of van der Waaij and colleagues, who described a key role for the anaerobic gut flora in preventing pathologic colonization by gram-negative organisms, such as Pseudomonas species (1). Anaerobes vastly outnumber aerobes in the healthy gastrointestinal tract and play important roles in gut development, absorptive capacity, and mucosal antibacterial defenses. SDD selectively targets aerobic gram-negative organisms and fungi, leaving the anaerobic and gram-positive flora intact. SDD is not gut sterilization but rather ablation of pathologic overgrowth and support of the normal indigenous flora. Chlorhexidine exerts much broader antimicrobial activity, including against anaerobes. Although the systematic review by Price and colleagues included small individual studies, their pooled conclusions are consistent and congruent with the conclusions of other trials that did not meet the inclusion criteria of the systematic review. The lingering concern with SDD is that it might result in the emergence of resistant organisms. Systematic reviews have not shown this (2), but the long-term effects of broad adoption of this prophylactic strategy are uncertain. The available evidence argues compellingly that we should abandon routine use of chlorhexidine and adopt SDD as a more efficacious alternative. Yet, there is a disconnect between the evidence and what clinicians are comfortable doing. The most productive resolution of this remarkably durable controversy could be a welldesigned RCT that addresses not only individual patient benefit but also communal microbial ecology. John C. Marshall, MD St. Michael’s Hospital, University of Toronto Toronto, Ontario, Canada References 1. van der Waaij D, Berghuis-de Vries JM, Lekkerkerk van der Wees JEC. Colonization resistance of the digestive tract in conventional and antibiotic treated mice. J Hyg (Lond). 1971;69:405-411. 2. Daneman N, Sarwar S, Fowler RA, Cuthbertson BH; SuDDICU Canadian Study Group. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13:328-41.
†SDD = selective digestive tract decontamination (poorly absorbable antibiotics applied to the oropharynx and stomach plus empirical IV antibiotics); SOD = selective oropharyngeal decontamination (poorly absorbable antibiotics applied to the oropharynx only).
19 August 2014 | ACP Journal Club | Volume 161 • Number 4
© 2014 American College of Physicians
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/930674/ by a Tufts University User on 08/02/2017
JC9
