Letters to the Editor / Journal of Hospital Infection 86 (2014) 276e279 S. Bambia,* A. Lucchinib M. Giustic a University of Florence, Emergency and Trauma Intensive Care Unit, DAI-DEA, Azienda Ospedaliero Universitaria Careggi, Florence, Italy b General Intensive Care Unit, Ospedale San Gerardo Monza, Monza, Italy c
Emergency Department, Ospedale Santa Maria Annunziata, Azienda Sanitaria di Firenze, Florence, Italy * Corresponding author. Address: University of Florence, Emergency and Trauma Intensive Care Unit, DAI-DEA, Azienda Ospedaliero Universitaria Careggi, Largo Brambilla 3 e 50134, Florence, Italy. Tel.: þ39 0557947473; fax: þ39 0557947821. E-mail address: [email protected] (S. Bambi). Available online 20 February 2014
ª 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jhin.2014.01.008
Oropharyngeal without intestinal decontamination does not make sense Madam, We read with interest the systematic review and metaanalysis by Li et al. on oral topical decontamination for the prevention of ventilator-associated pneumonia (VAP).1 The authors included all randomized controlled trials (RCTs) using oral decontamination with antibiotics (three studies) or antiseptics (10 studies on chlorhexidine, two studies on povidone iodine). The results suggest that both oral antibiotics and antiseptics are effective in reducing VAP, but they have no effect on mortality. We would like to comment on these results. The finding that oral decontamination with antibiotics, also called ‘selective oropharyngeal decontamination’ (SOD), reduced pneumonia and not mortality is not new. The authors were only able to find three RCTs; one of these studies also used the parenteral antibiotic cefotaxime in the test arm, and parenteral antibiotics were used in both test and control groups in the other two studies. A previous meta-analysis on SOD identified nine RCTs, and showed an 83% reduction in lower respiratory tract infection in 849 patients [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.07 to 0.43].2 Remarkably, mortality was not reduced in a meta-analysis of 4733 patients (OR 0.93, 95% CI 0.81e1.07). The effectiveness of oral chlorhexidine was explored recently in a meta-analysis of 22 RCTs including 4277 patients.3
DOI of original article: http://dx.doi.org/10.1016/j.jhin.2013.04. 012.
277
Chlorhexidine significantly reduced the incidence of nosocomial pneumonia (OR 0.66, 95% CI 0.51e0.85) and VAP (OR 0.68, 95% CI 0.53e0.87). Mortality was not affected. Interestingly, this meta-analysis found that the chlorhexidine manoeuvre mainly affected ‘normal’ flora, such as meticillin-sensitive Staphylococcus aureus, Haemophilus influenzae and Streptococcus pneumoniae. ‘Abnormal’ flora, such as aerobic Gram-negative bacilli including Klebsiella spp., Proteus spp., Morganella spp., Enterobacter spp., Citrobacter spp., Serratia spp., Acinetobacter spp., Pseudomonas spp., Stenotrophomonas maltophilia, Burkholderia cepacia and meticillin-resistant S. aureus, were not affected by oral chlorhexidine. The reason why both manoeuvres may reduce pneumonia is obvious. In preventing oropharyngeal acquisition and secondary carriage of potentially pathogenic micro-organisms, the first step in the pathogenesis of VAP, both SOD and chlorhexidine may prevent endogenous lower airway infection. The authors suggest two reasons for the absence of a reduction in mortality: the low attributable mortality of VAP and the low sample sizes. However, we believe that the rationale behind the absence of a survival benefit of SOD and chlorhexidine, even in a sample of more than 4000 patients, is based on the observation that these two manoeuvres only control the oropharyngeal ‘normal’ flora without affecting gut carriage of ‘abnormal’ micro-organisms, and, therefore, without reducing other severe infections, such as bloodstream infections. Only the full protocol of selective digestive decontamination (SDD) including parenteral and enteral antimicrobials (throat and gut for the whole treatment period) has been shown to control severe infections of the lower airways and the bloodstream, and to reduce mortality.4 The observation that gut decontamination is important for a reduction in mortality comes from meta-analyses of SDD RCTs; the full protocol of SDD reduced mortality by 29% (OR 0.71, 95% CI 0.61e0.82), reaching a 42% reduction (OR 0.58, 95% CI 0.45e0.77) when the gut was decontaminated successfully. The answer to the authors’ question about what type of decontamination has a superior effect, lower cost and fewer adverse events is already in the literature; only the full protocol of SDD reduces pneumonia, bloodstream infection and mortality at lower cost without the emergence of resistance.4,5 Conflict of interest statement None declared. Funding sources None.
References 1. Li J, Xie D, Li A, Yue J. Oral topical decontamination for preventing ventilator-associated pneumonia: a systematic review and metaanalysis of randomised controlled trials. J Hosp Infect 2013;84:283e293. 2. Silvestri L, van Saene HKF, Zandstra DF, Viviani M, Gregori D. SDD, SOD or oropharyngeal chlorhexidine to prevent pneumonia and to reduce mortality in ventilated patients: which manoeuvre is evidence based? Intensive Care Med 2010;31:1436e1437. 3. Silvestri L, Weir I, Gregori D, et al. Effectiveness of oral chlorhexidine on nosocomial pneumonia, causative micro-organisms and mortality in critically ill patients: a systematic review and
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Letters to the Editor / Journal of Hospital Infection 86 (2014) 276e279
meta-analysis. Minerva Anestesiol; 2013. published ahead of print. 4. Silvestri L, de la Cal MA, van Saene HKF. Selective decontamination of the digestive tract: the mechanism of action is gut overgrowth. Intensive Care Med 2012;38:1738e1750. 5. 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: 328e341.
V. Damjanovica L. Silvestrib N. Taylora H.K.F. van Saenea,* N. Piacenteb a Institute of Ageing and Chronic Diseases, University of Liverpool, Liverpool, UK b Department of Emergency, Unit of Anaesthesia and Intensive Care, Presidio Ospedaliero, Gorizia, Italy
* Corresponding author. Address: Institute of Ageing and Chronic Diseases, Duncan Building, University of Liverpool, Liverpool L69 3GA, UK. Tel.: þ44 (0) 151 706 4923; fax: þ44 (0) 151 706 5803. E-mail address: [email protected] (H.K.F. van Saene). Available online 25 February 2014 ª 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jhin.2013.11.011
Oral topical decontamination for preventing ventilator-associated pneumonia: a systematic review and metaanalysis of randomized controlled trials e authors’ response Madam, Saene et al. commented in their letter that selective digestive decontamination (SDD) is overall superior to selective oropharyngeal decontamination (SOD) in the way that SDD can reduce both incidences of ventilator-associated pneumonia (VAP) and mortality without the emergence of resistance, whereas SOD has no influence on mortality. Our study revealed that the incidence of VAP was reduced by oral decontamination with either antiseptics or antibiotics. When only the best-designed studies are included, however, this benefit is no longer present (odds ratio: 0.87; 95% confidence interval: 0.60e1.26).1 This lack of mortality reduction by SOD agrees strongly with Saene and colleagues’ review.
DOI of original article: http://dx.doi.org/10.1016/j.jhin.2013.04. 012, http://dx.doi.org/10.1016/j.jhin.2013.11.011.
Several recent guidelines have suggested SOD and SDD for prevention of VAP. However, compared with SOD, SDD may pose a higher risk for emergence of antibiotic resistance. This risk is debatable.2e4 Data from several high-quality studies have indicated that SDD has low risk for emergence of resistance to antibiotics. One randomized controlled trial showed that SDD could decrease colonization with resistant Gram-negative aerobic bacteria.5 In an ecological study of 38 intensive care units, the introduction of SOD/SDD was followed by statistically significant reductions in resistance rates for all antimicrobial agents.6 A study with large sample size (5939 participants) also confirmed the low levels of antibiotic resistance with SDD (highly resistant microorganisms’ acquisition rate was 15% during standard care versus 8% with SDD).7 For reduction in mortality and low risk of resistance, we agree that SDD is the type of decontamination with superior effect and fewer adverse events.5,7,8 Conflict of interest statement None declared. Funding sources None.
References 1. Li J, Xie D, Li A, Yue J. Oral topical decontamination for preventing ventilator-associated pneumonia: a systematic review and metaanalysis of randomized controlled trials. J Hosp Infect 2013;84:283e293. 2. Daneman N, Sarwar S, Fowler RA, Cuthbertson BH. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infect Dis 2013;13:328e341. 3. Halaby T, Al Naiemi N, Kluytmans J, van der Palen J, VandenbrouckeGrauls CM. Emergence of colistin resistance in Enterobacteriaceae after the introduction of selective digestive tract decontamination in an intensive care unit. Antimicrob Agents Chemother 2013;57:3224e3229. 4. Lubbert C, Faucheux S, Becker-Rux D, et al. Rapid emergence of secondary resistance to gentamicin and colistin following selective digestive decontamination in patients with KPC-2-producing Klebsiella pneumoniae: a single-centre experience. Int J Antimicrob Agents 2013;42:565e570. 5. de Jonge E, Schultz MJ, Spanjaard L, et al. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet 2003;362:1011e1016. 6. Houben AJ, Oostdijk EA, van der Voort PH, Monen JC, Bonten MJ, van der Bij AK. Selective decontamination of the oropharynx and the digestive tract, and antimicrobial resistance: a 4 year ecological study in 38 intensive care units in the Netherlands. J Antimicrob Chemother 2014;69:797e804. 7. de Smet AM, Kluytmans JA, Blok HE, et al. Selective digestive tract decontamination and selective oropharyngeal decontamination and antibiotic resistance in patients in intensive-care units: an openlabel, clustered group-randomised, crossover study. Lancet Infect Dis 2011;11:372e380. 8. Bonten MJ, Oostdijk EA, van der Bij AK. Selective decontamination of the oropharynx and the digestive tract, and antimicrobial resistance: a 4 year ecological study in 38 intensive care units in the Netherlands e authors’ response. J Antimicrob Chemother 2014; 69:861.
Emergency Department, Ospedale Santa Maria Annunziata, Azienda Sanitaria di Firenze, Florence, Italy * Corresponding author. Address: University of Florence, Emergency and Trauma Intensive Care Unit, DAI-DEA, Azienda Ospedaliero Universitaria Careggi, Largo Brambilla 3 e 50134, Florence, Italy. Tel.: þ39 0557947473; fax: þ39 0557947821. E-mail address: [email protected] (S. Bambi). Available online 20 February 2014
ª 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jhin.2014.01.008
Oropharyngeal without intestinal decontamination does not make sense Madam, We read with interest the systematic review and metaanalysis by Li et al. on oral topical decontamination for the prevention of ventilator-associated pneumonia (VAP).1 The authors included all randomized controlled trials (RCTs) using oral decontamination with antibiotics (three studies) or antiseptics (10 studies on chlorhexidine, two studies on povidone iodine). The results suggest that both oral antibiotics and antiseptics are effective in reducing VAP, but they have no effect on mortality. We would like to comment on these results. The finding that oral decontamination with antibiotics, also called ‘selective oropharyngeal decontamination’ (SOD), reduced pneumonia and not mortality is not new. The authors were only able to find three RCTs; one of these studies also used the parenteral antibiotic cefotaxime in the test arm, and parenteral antibiotics were used in both test and control groups in the other two studies. A previous meta-analysis on SOD identified nine RCTs, and showed an 83% reduction in lower respiratory tract infection in 849 patients [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.07 to 0.43].2 Remarkably, mortality was not reduced in a meta-analysis of 4733 patients (OR 0.93, 95% CI 0.81e1.07). The effectiveness of oral chlorhexidine was explored recently in a meta-analysis of 22 RCTs including 4277 patients.3
DOI of original article: http://dx.doi.org/10.1016/j.jhin.2013.04. 012.
277
Chlorhexidine significantly reduced the incidence of nosocomial pneumonia (OR 0.66, 95% CI 0.51e0.85) and VAP (OR 0.68, 95% CI 0.53e0.87). Mortality was not affected. Interestingly, this meta-analysis found that the chlorhexidine manoeuvre mainly affected ‘normal’ flora, such as meticillin-sensitive Staphylococcus aureus, Haemophilus influenzae and Streptococcus pneumoniae. ‘Abnormal’ flora, such as aerobic Gram-negative bacilli including Klebsiella spp., Proteus spp., Morganella spp., Enterobacter spp., Citrobacter spp., Serratia spp., Acinetobacter spp., Pseudomonas spp., Stenotrophomonas maltophilia, Burkholderia cepacia and meticillin-resistant S. aureus, were not affected by oral chlorhexidine. The reason why both manoeuvres may reduce pneumonia is obvious. In preventing oropharyngeal acquisition and secondary carriage of potentially pathogenic micro-organisms, the first step in the pathogenesis of VAP, both SOD and chlorhexidine may prevent endogenous lower airway infection. The authors suggest two reasons for the absence of a reduction in mortality: the low attributable mortality of VAP and the low sample sizes. However, we believe that the rationale behind the absence of a survival benefit of SOD and chlorhexidine, even in a sample of more than 4000 patients, is based on the observation that these two manoeuvres only control the oropharyngeal ‘normal’ flora without affecting gut carriage of ‘abnormal’ micro-organisms, and, therefore, without reducing other severe infections, such as bloodstream infections. Only the full protocol of selective digestive decontamination (SDD) including parenteral and enteral antimicrobials (throat and gut for the whole treatment period) has been shown to control severe infections of the lower airways and the bloodstream, and to reduce mortality.4 The observation that gut decontamination is important for a reduction in mortality comes from meta-analyses of SDD RCTs; the full protocol of SDD reduced mortality by 29% (OR 0.71, 95% CI 0.61e0.82), reaching a 42% reduction (OR 0.58, 95% CI 0.45e0.77) when the gut was decontaminated successfully. The answer to the authors’ question about what type of decontamination has a superior effect, lower cost and fewer adverse events is already in the literature; only the full protocol of SDD reduces pneumonia, bloodstream infection and mortality at lower cost without the emergence of resistance.4,5 Conflict of interest statement None declared. Funding sources None.
References 1. Li J, Xie D, Li A, Yue J. Oral topical decontamination for preventing ventilator-associated pneumonia: a systematic review and metaanalysis of randomised controlled trials. J Hosp Infect 2013;84:283e293. 2. Silvestri L, van Saene HKF, Zandstra DF, Viviani M, Gregori D. SDD, SOD or oropharyngeal chlorhexidine to prevent pneumonia and to reduce mortality in ventilated patients: which manoeuvre is evidence based? Intensive Care Med 2010;31:1436e1437. 3. Silvestri L, Weir I, Gregori D, et al. Effectiveness of oral chlorhexidine on nosocomial pneumonia, causative micro-organisms and mortality in critically ill patients: a systematic review and
278
Letters to the Editor / Journal of Hospital Infection 86 (2014) 276e279
meta-analysis. Minerva Anestesiol; 2013. published ahead of print. 4. Silvestri L, de la Cal MA, van Saene HKF. Selective decontamination of the digestive tract: the mechanism of action is gut overgrowth. Intensive Care Med 2012;38:1738e1750. 5. 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: 328e341.
V. Damjanovica L. Silvestrib N. Taylora H.K.F. van Saenea,* N. Piacenteb a Institute of Ageing and Chronic Diseases, University of Liverpool, Liverpool, UK b Department of Emergency, Unit of Anaesthesia and Intensive Care, Presidio Ospedaliero, Gorizia, Italy
* Corresponding author. Address: Institute of Ageing and Chronic Diseases, Duncan Building, University of Liverpool, Liverpool L69 3GA, UK. Tel.: þ44 (0) 151 706 4923; fax: þ44 (0) 151 706 5803. E-mail address: [email protected] (H.K.F. van Saene). Available online 25 February 2014 ª 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jhin.2013.11.011
Oral topical decontamination for preventing ventilator-associated pneumonia: a systematic review and metaanalysis of randomized controlled trials e authors’ response Madam, Saene et al. commented in their letter that selective digestive decontamination (SDD) is overall superior to selective oropharyngeal decontamination (SOD) in the way that SDD can reduce both incidences of ventilator-associated pneumonia (VAP) and mortality without the emergence of resistance, whereas SOD has no influence on mortality. Our study revealed that the incidence of VAP was reduced by oral decontamination with either antiseptics or antibiotics. When only the best-designed studies are included, however, this benefit is no longer present (odds ratio: 0.87; 95% confidence interval: 0.60e1.26).1 This lack of mortality reduction by SOD agrees strongly with Saene and colleagues’ review.
DOI of original article: http://dx.doi.org/10.1016/j.jhin.2013.04. 012, http://dx.doi.org/10.1016/j.jhin.2013.11.011.
Several recent guidelines have suggested SOD and SDD for prevention of VAP. However, compared with SOD, SDD may pose a higher risk for emergence of antibiotic resistance. This risk is debatable.2e4 Data from several high-quality studies have indicated that SDD has low risk for emergence of resistance to antibiotics. One randomized controlled trial showed that SDD could decrease colonization with resistant Gram-negative aerobic bacteria.5 In an ecological study of 38 intensive care units, the introduction of SOD/SDD was followed by statistically significant reductions in resistance rates for all antimicrobial agents.6 A study with large sample size (5939 participants) also confirmed the low levels of antibiotic resistance with SDD (highly resistant microorganisms’ acquisition rate was 15% during standard care versus 8% with SDD).7 For reduction in mortality and low risk of resistance, we agree that SDD is the type of decontamination with superior effect and fewer adverse events.5,7,8 Conflict of interest statement None declared. Funding sources None.
References 1. Li J, Xie D, Li A, Yue J. Oral topical decontamination for preventing ventilator-associated pneumonia: a systematic review and metaanalysis of randomized controlled trials. J Hosp Infect 2013;84:283e293. 2. Daneman N, Sarwar S, Fowler RA, Cuthbertson BH. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infect Dis 2013;13:328e341. 3. Halaby T, Al Naiemi N, Kluytmans J, van der Palen J, VandenbrouckeGrauls CM. Emergence of colistin resistance in Enterobacteriaceae after the introduction of selective digestive tract decontamination in an intensive care unit. Antimicrob Agents Chemother 2013;57:3224e3229. 4. Lubbert C, Faucheux S, Becker-Rux D, et al. Rapid emergence of secondary resistance to gentamicin and colistin following selective digestive decontamination in patients with KPC-2-producing Klebsiella pneumoniae: a single-centre experience. Int J Antimicrob Agents 2013;42:565e570. 5. de Jonge E, Schultz MJ, Spanjaard L, et al. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet 2003;362:1011e1016. 6. Houben AJ, Oostdijk EA, van der Voort PH, Monen JC, Bonten MJ, van der Bij AK. Selective decontamination of the oropharynx and the digestive tract, and antimicrobial resistance: a 4 year ecological study in 38 intensive care units in the Netherlands. J Antimicrob Chemother 2014;69:797e804. 7. de Smet AM, Kluytmans JA, Blok HE, et al. Selective digestive tract decontamination and selective oropharyngeal decontamination and antibiotic resistance in patients in intensive-care units: an openlabel, clustered group-randomised, crossover study. Lancet Infect Dis 2011;11:372e380. 8. Bonten MJ, Oostdijk EA, van der Bij AK. Selective decontamination of the oropharynx and the digestive tract, and antimicrobial resistance: a 4 year ecological study in 38 intensive care units in the Netherlands e authors’ response. J Antimicrob Chemother 2014; 69:861.
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