Antibiotic-resistant bacteria colonization patterns in different neonatal populations across European neonatal intensive care units

Background: Colonisation pressure is a major contributor to the spread of resistant bacteria in neonatal units Pre-trial colonisation feasibility study to characterize baseline colonization pressure at neonatal-unit level Feasibility study to inform NeoDeco study* (*Optimising kangaroo care to reduce neonatal severe infection/sepsis and resistant bacterial colonisation among high-risk infants in neonatal intensive care: a pragmatic, multicentre, parallel cluster randomised hybrid implementation-effectiveness study) Gaps in knowledge with Kangaroo Care: Unknown effects of immediate and prolonged skin-to-skin contact on bacterial resistance colonisation pressure Unknown if skin-to-skin contact has the same beneficial effects on sepsis and mortality of highrisk infants in HIC as it has in LMICs Methods: Feasibility study: 4 cross-sectional surveys (point-prevalence surveys, PPS) in 1-month – variable intervals of 4, 7 and 14 days 23 sites (8 European countries) Skin swabs and faecal samples collected from all infants present on unit on day of survey Data collected on REDCap Infants present on multiple surveys contributed longitudinal data Infants born <32 weeks’ gestational age defined as “high-risk” DNA extraction (NucliSENS easyMAG, bioMérieux) RT-qPCR detection of: carbapenemases in stool (CBPs; Carbaplex-IVD PCR, Bruker); extended-spectrum-beta-lactamases in stool (ESBLs; Ba04646149_s1, Ba04646127_s1, ThermoFisher); vancomycin-resistant enterococci in stool (VREs; VRE, Geneproof); Methicillin-resistant Staphylococcus aureus (MRSA) in skin swabs (MRSA; Diarella MRSA-SeqC, Gerbion). Results: 20.5% (288/1399) stool samples positive for ARBs 36/92 surveys did not identify any ARB colonisation (varied by country) Overall, ESBLs (14.4%, blaCTX-M group1) were most prevalent, followed by CBPs (7.1%; mainly blaKPC and blaVIM), and VREs (4.1%, vanA). 38.5% of colonized samples were from high-risk infants (111/614, 18.1%), compared to 61.5% from low-risk infants (177/785, 22.5%) (p=0.04) Resistant colonization differed significantly by country and site (p<0.001, range 0.0%-94% for individual sites) Gut colonization rate stability over time was ARB/ARG-dependent CBP and ESBL positivity remained stable over time (p>0.05); only VRE colonization increased significantly from 2%-7.7% during the study period (p= 0.001); MRSA skin colonization was rare (2.7%) By risk group: CBP and ESBL positivity remained stable over time significant difference in the proportion of ESBL-colonised samples (low>high-risk, 16.3% vs. 12.1%) VRE colonisation increased significantly for low-risk infants from 2%-9.6% (p= 0.001) Conclusions: Antibiotic-resistant bacteria/gene (ARB/ARG) colonization prevalence varied considerably across Countries and neonatal units, being highest in southern Europe. Stability of colonization rate/PPS varied for different ARBs/ARGs. ARB colonization prevalence not associated with proportion of high-risk infants on the unit The proportion of colonized low-risk infants was significantly higher.