TO THE EDITOR—The recent systematic review of 157 studies of pneumonia prevention methods in the intensive care unit (ICU) by Roquilly et al is of great interest [1]. Two of their findings—the importance of systemic antimicrobial therapy in selective decontamination of the digestive tract (SDD) and the apparent benefit among 29 randomized studies of SDD with 6089 patients vs its insignificance in a single, large-cluster. randomized study with 4035 patients—are novel [1]. However, are their findings safe? Have the column headings in Figure 3A been transposed? Is a study included in Figure 3B and 3C with a relative risk >2 missing from Figure 3A? They have otherwise classified some studies that others would have classified as SDD [2]. Some of their data are incorrect. For example, the mortality numbers that they used were mortality percentages in the original studies [3]. For 10 studies, the control group patients that they identified as randomized were, in fact, randomly assigned to receive either the systemic antimicrobial component of SDD (duplex studies) or to ICUs that did not use SDD.
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Is Selective Decontamination of the Digestive Tract Safe?
Is each of the following without effect in this context: concurrent group study design, duplex design, and the use of placebo to achieve blinding? [4–7]. In this regard, I have replotted the mortality proportions for the control and intervention groups from studies of digestive prophylactic methods using the data and study design properties provided by Roquilly et al [1]. These box plots (Figure 1) demonstrate similar mortality proportions for all categories of control and intervention groups with one exception. For the concurrent control groups from SDD studies with observer blinding achieved through placebo administration, the mortality is approximately 10 percentage points higher. The apparent effect of SDD on mortality, as for bacteremia [7] and ventilator associated pneumonia (VAP) [5] incidences, requires a cautious interpretation and consideration of direct vs indirect (contextual) mediations. Among 206 such studies, the mean VAP and bacteremia incidences among control groups of concurrent control trials of SDD are unusually high compared with groups within studies of comparable populations either without any study intervention or studies with a nonantibiotic-based method of intervention [5]. For bacteremia incidence, these incidences are more than 2-fold higher [7]. Moreover, the incidences among concurrent control groups of SDD studies are higher than those among studies of SDD for which the control group was either nonconcurrent or concurrent and receiving only the systemic component of SDD. Presumably, topical placebo application and concurrency underlie this contextual risk, whereas systemic antibiotics and nonconcurrency mitigate against this contextual risk [4–7]. I ask Roquilly et al whether their findings may have a different interpretation. Is the insignificant benefit for the SDD study that was cluster randomized attributable to the absence of an SDD contextual effect? In regard to the association between increase in relative risk and higher
rates of control group mortality (their Figure 3C), which is causal? Is it possible that their observations can be explained by an increased risk of mortality for control group patients concurrently located in the ICU with SDD group patients via a contextual effect? Crucially, is SDD safe?
Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
James C. Hurley1,2 1
Rural Health Academic Center, Melbourne Medical School, University of Melbourne, Parkville, and 2 General Medicine, Ballarat Health Services, and St John of God Hospital and Ballarat Health Services, Victoria, Australia
Supplementary Data References Supplementary materials are available at Clinical Infectious Diseases online (http://cid.oxford journals.org). Supplementary materials consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all supplementary data are the sole responsibility of the authors. Questions or messages regarding errors should be addressed to the author.
Notes Financial support. This work was supported by the Australian Government Department of Health and Ageing through the Rural Clinical Training and Support program. Potential conflict of interest. Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
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1. Roquilly A, Marret E, Abraham E, Asehnoune K. Pneumonia prevention to decrease mortality in intensive care unit: a systematic review and meta-analysis. Clin Infect Dis 2014; 60: 64–75. 2. Silvestri L, Van Saene HKF, 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; 65:187–203. 3. Tryba M. Risk of acute stress bleeding and nosocomial pneumonia in ventilated intensive care unit patients: sucralfate versus antacids. Am J Med 1987; 83:117–24. 4. Hurley JC. The perfidious effect of topical placebo: calibration of Staphylococcus aureus ventilator-associated pneumonia incidence within selective digestive decontamination
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studies versus the broader evidence base. Antimicrob Agents Chemother 2013; 57: 4524–31. 5. Hurley JC. Ventilator associated pneumonia prevention methods using topical antibiotics: herd protection or herd peril? Chest 2014; 146:890–8. 6. Hurley JC. Prophylaxis with enteral antibiotics in ventilated patients: selective decontamination or selective cross-infection? Antimicrob Agents Chemother 1995; 39:941–7. 7. Hurley JC. Topical antibiotics as a major contextual hazard toward bacteremia within selective digestive decontamination studies: a meta-analysis. BMC Infect Dis 2014; 14:714. Correspondence: James C. Hurley, MB BS, PhD, D Med Sci, Internal Medicine Service, Ballarat Health Services, PO Box 577, Ballarat 3353, Australia ([email protected]; hurleyjc@ unimelb.edu.au). Clinical Infectious Diseases® 2015;60(11):1729–30 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/civ125
Downloaded from http://cid.oxfordjournals.org/ at North Dakota State University on May 16, 2015
Figure 1. Box plots of mortality proportions for component (control and intervention) groups from 69 studies of digestive prophylactic methods classified by study intervention and blinding (see Supplementary Material). The box represents the median and interquartile range. Test for equality of group mean mortality percentage by 1-way analysis of variance for intervention groups (P = .30) and control groups (P = .034). Abbreviations: CC, concurrent control; NC, non-concurrent; SDD, selective decontamination of the digestive tract.
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CID 2015:60 (1 June)
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1729
Downloaded from http://cid.oxfordjournals.org/ at North Dakota State University on May 16, 2015
Is Selective Decontamination of the Digestive Tract Safe?
Is each of the following without effect in this context: concurrent group study design, duplex design, and the use of placebo to achieve blinding? [4–7]. In this regard, I have replotted the mortality proportions for the control and intervention groups from studies of digestive prophylactic methods using the data and study design properties provided by Roquilly et al [1]. These box plots (Figure 1) demonstrate similar mortality proportions for all categories of control and intervention groups with one exception. For the concurrent control groups from SDD studies with observer blinding achieved through placebo administration, the mortality is approximately 10 percentage points higher. The apparent effect of SDD on mortality, as for bacteremia [7] and ventilator associated pneumonia (VAP) [5] incidences, requires a cautious interpretation and consideration of direct vs indirect (contextual) mediations. Among 206 such studies, the mean VAP and bacteremia incidences among control groups of concurrent control trials of SDD are unusually high compared with groups within studies of comparable populations either without any study intervention or studies with a nonantibiotic-based method of intervention [5]. For bacteremia incidence, these incidences are more than 2-fold higher [7]. Moreover, the incidences among concurrent control groups of SDD studies are higher than those among studies of SDD for which the control group was either nonconcurrent or concurrent and receiving only the systemic component of SDD. Presumably, topical placebo application and concurrency underlie this contextual risk, whereas systemic antibiotics and nonconcurrency mitigate against this contextual risk [4–7]. I ask Roquilly et al whether their findings may have a different interpretation. Is the insignificant benefit for the SDD study that was cluster randomized attributable to the absence of an SDD contextual effect? In regard to the association between increase in relative risk and higher
rates of control group mortality (their Figure 3C), which is causal? Is it possible that their observations can be explained by an increased risk of mortality for control group patients concurrently located in the ICU with SDD group patients via a contextual effect? Crucially, is SDD safe?
Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
James C. Hurley1,2 1
Rural Health Academic Center, Melbourne Medical School, University of Melbourne, Parkville, and 2 General Medicine, Ballarat Health Services, and St John of God Hospital and Ballarat Health Services, Victoria, Australia
Supplementary Data References Supplementary materials are available at Clinical Infectious Diseases online (http://cid.oxford journals.org). Supplementary materials consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all supplementary data are the sole responsibility of the authors. Questions or messages regarding errors should be addressed to the author.
Notes Financial support. This work was supported by the Australian Government Department of Health and Ageing through the Rural Clinical Training and Support program. Potential conflict of interest. Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
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1. Roquilly A, Marret E, Abraham E, Asehnoune K. Pneumonia prevention to decrease mortality in intensive care unit: a systematic review and meta-analysis. Clin Infect Dis 2014; 60: 64–75. 2. Silvestri L, Van Saene HKF, 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; 65:187–203. 3. Tryba M. Risk of acute stress bleeding and nosocomial pneumonia in ventilated intensive care unit patients: sucralfate versus antacids. Am J Med 1987; 83:117–24. 4. Hurley JC. The perfidious effect of topical placebo: calibration of Staphylococcus aureus ventilator-associated pneumonia incidence within selective digestive decontamination
CORRESPONDENCE
studies versus the broader evidence base. Antimicrob Agents Chemother 2013; 57: 4524–31. 5. Hurley JC. Ventilator associated pneumonia prevention methods using topical antibiotics: herd protection or herd peril? Chest 2014; 146:890–8. 6. Hurley JC. Prophylaxis with enteral antibiotics in ventilated patients: selective decontamination or selective cross-infection? Antimicrob Agents Chemother 1995; 39:941–7. 7. Hurley JC. Topical antibiotics as a major contextual hazard toward bacteremia within selective digestive decontamination studies: a meta-analysis. BMC Infect Dis 2014; 14:714. Correspondence: James C. Hurley, MB BS, PhD, D Med Sci, Internal Medicine Service, Ballarat Health Services, PO Box 577, Ballarat 3353, Australia ([email protected]; hurleyjc@ unimelb.edu.au). Clinical Infectious Diseases® 2015;60(11):1729–30 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/civ125
Downloaded from http://cid.oxfordjournals.org/ at North Dakota State University on May 16, 2015
Figure 1. Box plots of mortality proportions for component (control and intervention) groups from 69 studies of digestive prophylactic methods classified by study intervention and blinding (see Supplementary Material). The box represents the median and interquartile range. Test for equality of group mean mortality percentage by 1-way analysis of variance for intervention groups (P = .30) and control groups (P = .034). Abbreviations: CC, concurrent control; NC, non-concurrent; SDD, selective decontamination of the digestive tract.
