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Decontamination strategies to remove potentially harmful bacteria from the mouth, throat and gut of critically ill patients don’t reduce the risk of intensive care unit-acquired bloodstream infections or deaths from bacteria that were resistant to antibiotics. The study was carried out in 13 intensive care units across Europe, including the UK, with moderate to high levels of antibiotic resistance (extended resistance in more than 5% of all bloodstream infections). This fills an important gap in the evidence as most previous studies have been in units with lower levels of resistant organisms.
Infections with multi-drug resistant gram-negative bacteria are a frequent problem for ventilated patients on intensive care wards. In this trial of 8,665 patients, the use of chlorhexidine mouthwash, selective digestive tract decontamination, or selective mouth and throat decontamination were compared to standard care, involving daily body washings with chlorhexidine and a hand hygiene improvement programme.
The decontamination strategies were not associated with a significant difference in multi-drug resistant bloodstream infections, suggesting that they should not be used in the UK as a strategy to reduce antibiotic resistance in hospitals with similar extended resistance rates.
Why was this study needed?
Approximately 30% of critically ill patients contract a hospital-acquired infection, which can result in increased complications, healthcare costs and deaths. One way of preventing them is using antibiotics to selectively destroy gram-negative bacteria in the digestive tract (SDD) or the mouth and throat (SOD), which are a common cause of such infections. Although both strategies have been associated with improved patient outcomes in intensive care units (ICUs) with low levels of antibiotic resistance, a lack of data from settings with higher levels means they haven’t been widely adopted. Only around 5% of UK hospitals use SDD.
More common is the use of chlorhexidine (CHX) mouthwash, which is associated with a reduced incidence of ventilator-associated pneumonia but has been linked to higher death rates. This trial aimed to identify whether the above strategies reduce the risk of bloodstream infections among ventilated patients in ICUs with moderate to high levels of antibiotic resistance.
What did this study do?
This was a randomised trial of 8,665 mechanically ventilated patients, conducted in 13 European ICUs (including the UK) with moderate to high levels of antibiotic resistance.
All began with a baseline period of six to 14 months, during which patients were given daily body washings with CHX and staff followed a hand hygiene improvement program. Next followed three sequential six-month intervention periods, consisting of treatment with CHX 2% mouthwash; SOD (involving a colistin, tobramycin, and nystatin mouthpaste); or SDD (involving the same mouthpaste plus a gastrointestinal suspension of the same antibiotics), four times a day.
The study was designed to compare each intervention to standard care but not to each other, which may limit its applicability. Long-term effects of the interventions were also not evaluated.
What did it find?
- Decontamination strategies with either antibiotics (SDD or SOD) or CHX mouthwash were not associated with significant reductions in ICU-acquired bloodstream infections with multi-drug resistant gram-negative bacteria. Absolute risk reductions were 0.3% for CHX mouthwash (95% confidence interval [CI] −0.6% to 1.1%); 0.6% for SOD (95% CI −0.2% to 1.4%); and 0.8% for SDD (95% [CI] 0.1% to 1.6%), compared to baseline treatment.
- Neither were the interventions associated with a significant difference in mortality at 28 days. Absolute risk reductions were −1.1% for CHX mouthwash (95% CI −3.9% to 1.8%); −0.5% for SOD (95% CI −3.3% to 2.3%); and −2.2% for SDD (95% CI −5.0% to 0.7%), compared to baseline.
- The unit-wide prevalence of antibiotic-resistant bacteria did not change during the interventions compared to baseline. The overall prevalence of multi-drug resistant gram-negative bacteria ranged from 17.1% to 25.3% in rectal samples, and from 10.2% to 15.2% in respiratory tract samples, without statistically significant differences between the study groups.
What does current guidance say on this issue?
Joint guidelines published by the Faculty of Intensive Care Medicine and the Intensive Care Society in 2015, stress that hand hygiene, cleaning and antimicrobial stewardship are key to keeping healthcare-acquired infections at bay.
They say that the use of oral chlorhexidine for the prevention of ventilator-associated pneumonia should not be recommended except for cardiac surgery patients, and further trials are needed in the general ICU population. This evidence provides useful reinforcement of this guidance.
What are the implications?
Decontamination strategies involving antibiotics or chlorhexidine mouthwash are unlikely to reduce infection rates among ventilated patients on ICUs with moderate or high antibiotic resistance rates (more than 5%).
Hand hygiene, cleaning of the environment and antimicrobial stewardship should continue to be the primary strategies for keeping ICU infections at bay, in these units.
Citation and Funding
Wittekamp BH, Plantinga NL, Cooper BS et al. Decontamination strategies and bloodstream infections with antibiotic-resistant microorganisms in ventilated patients: a randomized clinical trial. JAMA. 2018;320(20):2087-98.
This study was funded by the European Commission under the Seventh Framework Programme (FP7-HEALTH-2011 single-stage, grant agreement number 282512).
Bibliography
Canter RR, Harvey E, Harrison DA, et al. Observational study of current use of selective decontamination of the digestive tract in UK critical care units. Br J Anasth. 2014;113(4): 610-7.
The Faculty of Intensive Care Medicine. Guidelines for the Provision of Intensive Care Services. London: The Faculty of Intensive Care Medicine; 2016.
Vandenbroucke-Grauls CMJE, van der Meer JWM. Decontamination of oral or digestive tract for patients in the intensive care unit. JAMA. 2018;320(20):2081-83.
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