Introduction

Infants colonized with antibiotic-resistant bacteria (ARB) are at high-risk of developing severe bacterial infections, that can ultimately lead to sepsis, particularly when born at <32 weeks gestation (high-risk). However, overall prevalence and burden of specific antibiotic resistance genes (ARGs) in a high-income setting is largely unknown.

Methodology

In the pan-European NeoIPC project, skin swabs (N=929) and stool samples (N=754) were collected during four point-prevalence surveys (PPSs) interspaced with 4-, 7-, or 14-day intervals from all infants (<1 year, N=468) present in 14 NICUs across six European countries. DNA was extracted (NucliSENS easyMAG, bioMérieux) followed by RT-qPCR detection of carbapenemases (CBPs), extended-spectrum-beta-lactamases (ESBLs), and vancomycin-resistant enterococci (VREs) in stools, as well as methicillin-resistant Staphylococcus aureus (MRSA) in skin swabs. Collected anonymized data were analyzed per sample per PPS.

Results

Overall, 26% (217/754) stool samples were ARG-positive (ESBL, CBP, or VRE) across four PPSs, and in 8.8% (66/754) ≥2 ARGs were detected. ESBLs (19%, blaCTX-M group1) were most prevalent, followed by CBPs (10%; mainly blaKPC and blaVIM), and VREs (7.2%, vanA). In contrast, MRSA skin colonization was rare (2.7%). While not specifically screened for, methicillin-resistant coagulase-negative staphylococci (MRCoNS) were detected by the MRSA assay in majority of the skin swabs (88%, 821/929). 40% of high-risk infants were colonized, compared to 60% of non-high-risk infants (Pearson’s χ2, p=0.3), and high-risk infants were more frequently ESBL-colonized (21% vs. 16%, p=0.086). Gut ARG colonization varied by country and site (p<0.001), ranging from 0.0%-94% for individual sites, and was most common in Greece. Colonization rate stability over time was found to be ARG/ARB-dependent; only VRE colonization increased from 3.8%-13% during the study period (p=0.002), while the CBP, MRSA, ESBL, and MRCoNS positivity remained stable over time (p>0.05).

Conclusion

• We observed remarkable variation in ARG prevalence across countries and NICU sites.
• Stability of colonization rate/PPS was found to vary for different ARGs.
• Although non-significant, gut colonization with ESBLs, specifically blaCTX-M group 1, was more frequent in high-risk infants.