Background: There has been little decline in neonatal mortality rates over recent decades, and this is now further challenged by the rising prevalence of antimicrobial resistance (AMR). In Australia, the incidence of neonatal sepsis is low on a global scale, yet there are increasingly frequent outbreaks of multidrug-resistant (MDR) infections in neonatal intensive care units, alongside rising rates of colonisation with MDR bacteria. Methods: We analysed positive blood and cerebrospinal fluid (CSF) cultures collected from infants (aged 0 to 180 days) across five clinical sites in Australia between 2010 and 2019, to determine evolving antimicrobial susceptibility profiles. Results: After excluding presumed contaminants, we analysed 743 pathogenic bacterial isolates cultured from 624 neonates and infants with early (</=72 hours), late (>72 hours to </=28 days), and very late-onset (>28 days to </=180 days) infections. Escherichia coli (37%) and Streptococcus agalactiae (31%) were the primary pathogens responsible for early-onset bloodstream infections, whilst coagulase-negative staphylococci, E. coli and Staphylococcus aureus were responsible for most infections in older neonates and infants. Antimicrobial susceptibility to currently-recommended empiric regimens remains high; however, gram-negative bacteria - including MDR bacteria - were responsible for an increasing proportion of very late-onset infections over the study period (22% in 2010-2014 versus 34% in 2015-2019; p=0.07). Conclusions: Although empiric antimicrobial regimens remain adequate for most pathogens causing infections in neonates and infants in Australia, there is an increasing burden of invasive infections caused by gram-negative bacteria. Ongoing surveillance is necessary to ensure empiric antimicrobial guidelines remain efficacious and appropriate.

The authors have declared no competing interest.

This study did not receive any funding, but Phoebe CM Williams is supported by an NHMRC investigator grant on neonatal sepsis.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee of Sydney Children's Hospital Network gave ethical approval for this work.

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All data produced in the present study are available upon reasonable request to the authors.