Selective decontamination of the digestive tract and oropharynx

Price, Richard J.; Cuthbertson, Brian H.

doi:10.1097/mcc.0000000000000281

Cited by 7 publications

(3 citation statements)

References 42 publications

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“…Recent systematic reviews [30] show that chlorhexidine increased mortality with an odds ratio (OR) of 1.25 (95% confidence interval (CI) 1.05–1.50). This corresponds to a risk ratio of 1.18 (95% CI 1.04–1.33) and an absolute reduction in mortality of 5% (95% CI 1%–6%).…”

Section: Methodsmentioning

confidence: 99%

Protocol for a multi-centered, stepped wedge, cluster randomized controlled trial of the de-adoption of oral chlorhexidine prophylaxis and implementation of an oral care bundle for mechanically ventilated critically ill patients: the CHORAL study

Dale

Rose

Carbone

et al. 2019

Trials

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BackgroundRoutine application of chlorhexidine oral rinse is recommended to reduce risk of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Recent reappraisal of the evidence from two meta-analyses suggests chlorhexidine may cause excess mortality in non-cardiac surgery patients and does not reduce VAP. Mechanisms for possible excess mortality are unclear. The CHORAL study will evaluate the impact of de-adopting chlorhexidine and implementing an oral care bundle (excluding chlorhexidine) on mortality, infection-related ventilator-associated complications (IVACs), and oral health status.MethodsThe CHORAL study is a stepped wedge, cluster randomized controlled trial in six academic intensive care units (ICUs) in Toronto, Canada. Clusters (ICU) will be randomly allocated to six sequential steps over a 14-month period to de-adopt oral chlorhexidine and implement a standardized oral care bundle (oral assessment, tooth brushing, moisturization, and secretion removal). On study commencement, all clusters begin with a control period in which the standard of care is oral chlorhexidine. Clusters then begin crossover from control to intervention every 2 months according to the randomization schedule. Participants include all mechanically ventilated adults eligible to receive the standardized oral care bundle. The primary outcome is ICU mortality; secondary outcomes are IVACs and oral health status. We will determine demographics, antibiotic usage, mortality, and IVAC rates from a validated local ICU clinical registry. With six clusters and 50 ventilated patients on average each month per cluster, we estimate that 4200 patients provide 80% power after accounting for intracluster correlation to detect an absolute reduction in mortality of 5.5%. We will analyze our primary outcome of mortality using a generalized linear mixed model adjusting for time to account for secular trends. We will conduct a process evaluation to determine intervention fidelity and to inform interpretation of the trial results.DiscussionThe CHORAL study will inform understanding of the effectiveness of de-adoption of oral chlorhexidine and implementation of a standardized oral care bundle for decreasing ICU mortality and IVAC rates while improving oral health status. Our process evaluation will inform clinicians and decision makers about intervention delivery to support future de-adoption if justified by trial results.Trial registrationClinicalTrials.gov, NCT03382730. Registered on December 26, 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-019-3673-0) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Protocol for a multi-centered, stepped wedge, cluster randomized controlled trial of the de-adoption of oral chlorhexidine prophylaxis and implementation of an oral care bundle for mechanically ventilated critically ill patients: the CHORAL study

Dale

Rose

Carbone

et al. 2019

Trials

Self Cite

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“…Other meta-analyses suggest SDD is not associated with the development of antimicrobial resistance in patients in the ICU, although the effect of decontamination on ICU-level antimicrobial resistance rates is understudied 13 – 16 …”

Section: Introductionmentioning

confidence: 99%

Selective digestive tract decontamination to prevent healthcare associated infections in critically ill children: the PICNIC multicentre randomised pilot clinical trial

Pathan,

Woolfall,

Popa

et al. 2023

Sci Rep

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Healthcare-associated infections (HCAIs) are a major cause of morbidity and mortality in critically ill children. Data from adult studies suggest Selective Decontamination of the Digestive tract (SDD) may reduce the incidence of HCAIs and improve survival. There are no data from randomised clinical trials in the paediatric setting. An open label, parallel group pilot cRCT and mixed-methods perspectives study was conducted in six paediatric intensive care units (PICUs) in England. Participants were children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 h. Sites undertook standard care for a period of 9 weeks and were randomised into 3 sites which continued standard care and 3 where SDD was incorporated into infection control practice for eligible children. Interviews and focus groups were conducted for parents and staff working in PICU. 434 children fulfilled eligibility criteria, of whom 368 (85%) were enrolled. This included 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering SDD, the majority (98%) of children received at least one dose of SDD and of these, 68% commenced within the first 6 h. Whilst admission swabs were collected in 91% of enrolled children, consent for the collection of additional swabs was low (44%). Recruited children were representative of the wider PICU population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cRCT of 3 children/site/week, based on data from all UK PICUs. Parents (n = 65) and staff (n = 44) were supportive of the aims of the study, suggesting adaptations for a larger definitive trial including formulation and administration of SDD paste, approaches to consent and ecology monitoring. Stakeholders identified preferred clinical outcomes, focusing on complications of critical illness and quality-of-life. A definitive cRCT in SDD to prevent HCAIs in critically ill children is feasible but should include adaptations to ecology monitoring along with the dosing schedule and packaging into a paediatric specific format. A definitive study is supported by the findings with adaptations to ecology monitoring and SDD administration.Trial Registration: ISRCTN40310490 Registered 30/10/2020.

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“…Although surgeons routinely decontaminate the intestinal tract with antibiotics prior to surgery to prevent infection, this practice carries the unintended consequence of causing antibiotic resistance. 2 Furthermore, overuse of antibiotics can destroy the microbiome, which normally protects against high risk pathogens. 3 A more evolutionarily stable strategy to this problem would be to develop compounds that can suppress pathogen virulence rather than kill bacteria.…”

Section: Introductionmentioning

confidence: 99%

De Novo Synthesis of Phosphorylated Triblock Copolymers with Pathogen Virulence-Suppressing Properties That Prevent Infection-Related Mortality

Mao

Zaborin

Poroyko

et al. 2017

ACS Biomater. Sci. Eng.

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Phosphate is a key and universal “cue” in response to which bacteria either enhance their virulence when local phosphate is scarce or downregulate it when phosphate is adundant. Phosphate becomes depleted in the mammalian gut following physiologic stress and serves as a major trigger for colonizing bacteria to express virulence. This process cannot be reversed with oral supplementation of inorganic phosphate because it is nearly completely absorbed in the proximal small intestine. In the present study, we describe the de novo synthesis of phosphorylated polyethylene glycol compounds with three defined ABA (hydrophilic/-phobic/-philic) structures, ABA-PEG10k-Pi10, ABA-PEG16k-Pi14, and ABA-PEG20k-Pi20, and linear polymer PEG20k-Pi20 absent of the hydrophobic block. The 10k, 16k, and 20k demonstrate the molecular weights of the poly(ethylene glycol) block, and Pi10, Pi14, and Pi20 represent the repeating units of phosphate. Polymers were tested for their efficacy against Pseudomonas aeruginosa virulence in vitro and in vivo by assessing the expression of the phosphate sensing protein PstS, the production of key virulence factor pyocyanin, and Caenorhabditis elegans killing assays. Results indicate that all phosphorylated polymers suppressed phosphate sensing, virulence expression, and lethality in P. aeruginosa. Among all of the phosphorylated polymers, ABA-PEG20k-Pi20 displayed the greatest degree of protection against P. aeruginosa. To define the role of the hydrophobic core in ABA-PEG20k-Pi20 in the above response, we synthesized PEG20k-Pi20 in which the hydrophobic core is absent. Results indicate that the hypdrophobic core of ABA-PEG20k-Pi20 is a key structure in its protective effect against P. aeruginosa, in part due to its ability to coat the surface of bacteria. Taken together, the synthesis of novel polymers with defined structures and levels of phosphorylation may elucidate their antivirulence action against clinically important and lethal pathogens such as P. aeruginosa.

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Selective decontamination of the digestive tract and oropharynx

Abstract: Current evidence suggests that selective decontamination reduces mortality without increasing antibiotic resistances; this will be tested again in two huge international trials.

Cited by 7 publications

References 42 publications

Protocol for a multi-centered, stepped wedge, cluster randomized controlled trial of the de-adoption of oral chlorhexidine prophylaxis and implementation of an oral care bundle for mechanically ventilated critically ill patients: the CHORAL study

Protocol for a multi-centered, stepped wedge, cluster randomized controlled trial of the de-adoption of oral chlorhexidine prophylaxis and implementation of an oral care bundle for mechanically ventilated critically ill patients: the CHORAL study

Selective digestive tract decontamination to prevent healthcare associated infections in critically ill children: the PICNIC multicentre randomised pilot clinical trial

De Novo Synthesis of Phosphorylated Triblock Copolymers with Pathogen Virulence-Suppressing Properties That Prevent Infection-Related Mortality

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