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

Abstract

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.

Short-duration selective decontamination of the digestive tract infection control does not contribute to increased antimicrobial resistance burden in a pilot cluster randomised trial (the ARCTIC Study)

“…The PICnIC pilot trial was a scoping study and not powered to identify clinical significant effects of SDD on patients. 16 This substudy was designed to gather baseline data to inform sample size for a larger multicentre clinical trial. A larger cohort with more frequent and longer-term post-treatment sampling would help determine the effects of SDD on the maturing microbiome.…”

“…The PICnIC Study 16 enrolled 368 children. Phase one recruited 207 children to SC, with phase two recruiting 161 children.…”

“…The protocol for the pilot SDD trial was previously reported by Brown et al, 15 (ISRCTN40310490 19 ) with further details available from Pathan et al 16 The study consisted of five periods: prestudy ecology (1 week), baseline phase (phase one) (8 weeks), pre-intervention ecology (1 week), intervention phase (phase two) (9 weeks) and post-study ecology (1 week). The intervention phase was divided into SC and SDD, with three hospitals randomly assigned to each arm.…”

“…The oropharyngeal microbiome can be considered a lowbiomass biome, as such the majority (80%, IQR 66-86%) of shotgun metagenomic sequencing reads were from host DNA. After correcting for host reads and normalisation, we examined the alpha and beta diversity of the oropharyngeal 16 Briefly, children arriving in the PICU who required mechanical ventilation were assessed by clinicians, and patients judged to require greater than 48 hours of invasive respiratory support became eligible. Patients were not eligible if they were known to be allergic to colistin, tobramycin or nystatin, or if they were known to be colonised by a microorganism resistant to any of the three previous drugs.…”

“…Children became eligible for the substudy upon enrolment to the PICnIC Study. Inclusion into PICnIC is outlined by Brown et al15 and Pathan et al16 Briefly, children arriving in the PICU who required mechanical ventilation were assessed by clinicians, and patients judged to require greater than 48 hours of invasive respiratory support became eligible. Patients were not eligible if they were known to be allergic to colistin, tobramycin or nystatin, or if they were known to be colonised by a microorganism resistant to any of the three previous drugs.…”