Articles
Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis

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Summary

Background

Many meta-analyses have shown reductions in infection rates and mortality associated with the use of selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD) in intensive care units (ICUs). These interventions have not been widely implemented because of concerns that their use could lead to the development of antimicrobial resistance in pathogens. We aimed to assess the effect of SDD and SOD on antimicrobial resistance rates in patients in ICUs.

Methods

We did a systematic review of the effect of SDD and SOD on the rates of colonisation or infection with antimicrobial-resistant pathogens in patients who were critically ill. We searched for studies using Medline, Embase, and Cochrane databases, with no limits by language, date of publication, study design, or study quality. We included all studies of selective decontamination that involved prophylactic application of topical non-absorbable antimicrobials to the stomach or oropharynx of patients in ICUs, with or without additional systemic antimicrobials. We excluded studies of interventions that used only antiseptic or biocide agents such as chlorhexidine, unless antimicrobials were also included in the regimen. We used the Mantel-Haenszel model with random effects to calculate pooled odds ratios.

Findings

We analysed 64 unique studies of SDD and SOD in ICUs, of which 47 were randomised controlled trials and 35 included data for the detection of antimicrobial resistance. When comparing data for patients in intervention groups (those who received SDD or SOD) versus data for those in control groups (who received no intervention), we identified no difference in the prevalence of colonisation or infection with Gram-positive antimicrobial-resistant pathogens of interest, including meticillin-resistant Staphylococcus aureus (odds ratio 1·46, 95% CI 0·90–2·37) and vancomycin-resistant enterococci (0·63, 0·39–1·02). Among Gram-negative bacilli, we detected no difference in aminoglycoside-resistance (0·73, 0·51–1·05) or fluoroquinolone-resistance (0·52, 0·16–1·68), but we did detect a reduction in polymyxin-resistant Gram-negative bacilli (0·58, 0·46–0·72) and third-generation cephalosporin-resistant Gram-negative bacilli (0·33, 0·20–0·52) in recipients of selective decontamination compared with those who received no intervention.

Interpretation

We detected no relation between the use of SDD or SOD and the development of antimicrobial-resistance in pathogens in patients in the ICU, suggesting that the perceived risk of long-term harm related to selective decontamination cannot be justified by available data. However, our study indicates that the effect of decontamination on ICU-level antimicrobial resistance rates is understudied. We recommend that future research includes a non-crossover, cluster randomised controlled trial to assess long-term ICU-level changes in resistance rates.

Funding

None.

Introduction

Hospital-acquired infections affect a quarter of critically ill patients, and can double the risk of a patient dying.1, 2 Because hospital-acquired infections are preceded by colonisation with pathogenic bacteria, prophylactic antimicrobial treatment might have the potential to reduce the burden of pathogens in a patient's respiratory and gastrointestinal tract, and thereby prevent the onset of invasive infections such as ventilator-associated pneumonia.

Selective digestive decontamination (SDD) is defined as the prophylactic application of topical, non-absorbable antimicrobials in the oropharynx and stomach, with the goal of eradicating potentially pathogenic microorganisms but preserving the protective anaerobic microbiota. Selective oropharyngeal decontamination (SOD) is the application of such treatments to only the oropharynx. SDD is usually, and SOD is rarely, accompanied by systemic antimicrobials, which might also pre-emptively treat undetected infections. We refer to SDD, SOD, or both under the umbrella term of selective decontamination.

Selective decontamination is not a new idea; it has been assessed in more than 40 randomised controlled trials, with clinical benefits summarised in many meta-analyses.3, 4, 5, 6, 7, 8, 9, 10, 11 This intervention has shown consistent reductions in hospital-acquired infection rates (most notably ventilator-associated pneumonia), and might reduce overall mortality in intensive care units (ICUs).5, 12 However, there has been little uptake of selective decontamination in ICUs and little or no endorsement in guidelines issued by professional organisations.13, 14 The barriers to uptake of selective decontamination were explored in an international survey and Delphi panel of multidisciplinary expert stakeholders, including critical care and infectious diseases specialists.15, 16 The predominant concern expressed was that use of selective decontamination will promote the development of antimicrobial-resistant pathogens.

The possibility of promoting resistance is a serious concern, especially in view of ICUs already being the epicentre of antimicrobial use and resistance within most hospitals.1 Calls for reduced antimicrobial use through improved antimicrobial stewardship are being made worldwide,17, 18 and have already shown some success in helping curtail antimicrobial resistance in some ICUs.19, 20 Proponents of selective decontamination counter that the body of research has not documented a clear signal of increased antimicrobial resistance, and that this intervention could even potentially reduce resistance rates.21

By contrast with meta-analyses assessing the effect of selective decontamination on infection and mortality rates, no such assessment has been done to measure the effect of selective decontamination on antimicrobial resistance. Therefore, we aimed to systematically review the effect of selective decontamination on rates of colonisation or infection with antimicrobial-resistant pathogens in patients in ICUs.

Section snippets

Search strategy and selection criteria

We did our systematic review and meta-analysis in accordance with the PRISMA guidelines.22 To ensure that we captured all relevant studies we searched Medline, Embase, and Cochrane databases without any restriction on date of publication, language, country, sex, age, outcome measures, and study design or study quality. Search terms for selective decontamination included “digestive decontamination”, “oral decontamination”, “oropharyngeal decontamination”, “bowel decontamination”,

Results

We identified 64 studies of selective decontamination,12, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87 35 of which were included in our systematic analysis (figure 1 and table 1). The study selection criteria showed good reproducibility (unweighted κ score 0·92).

Studies of selective

Discussion

We did not detect an increased incidence of colonisation or infection with antimicrobial resistant pathogens in recipients of selective decontamination compared with non-recipients in an ICU setting. For all pathogens other than MRSA, the pooled OR estimate showed a lower level of antibiotic-resistance in patients who received selective decontamination compared with patients who did not. This reduction in resistance was statistically significant for polymyxin-resistant and third-generation

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