Evolution of Antimicrobial Resistance in Neonatal Sepsis: A Narrative Review

Antimicrobial resistance is a growing threat in neonatal intensive care units (NICUs) worldwide, challenging the management of neonatal sepsis for decades. The aim of this narrative review is to compare the epidemiology and resistance patterns of neonatal sepsis in NICUs between two periods, 2000-2005 and 2020-2025, and to identify key insights that may inform future practices to limit the emergence and dissemination of antimicrobial resistance in NICUs. During the early 2000s, resistant pathogens, including extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales, vancomycin-resistant Enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and coagulase-negative Staphylococci (CoNS), were increasingly reported in NICUs. The increasing prevalence of antimicrobial resistant strains was associated with the widespread use of broad-spectrum antibiotics, exerting selective pressure that contributed to the emergence of multidrug-resistant pathogens in the 2020s, including carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Acinetobacter baumannii, and to the further dissemination of resistant strains in NICUs. The evolution of antimicrobial resistance over the past twenty years highlights that preserving the effectiveness of antibiotics, through rational antibiotic use, is a key strategy to limit the emergence of resistant pathogens. This is of particular importance for the neonatal population due to the limited therapeutic options. Although antimicrobial stewardship programs have been implemented in numerous NICUs with encouraging results, optimization of antibiotic use requires the identification of biomarkers that can promptly and accurately diagnose sepsis and the development of new effective antimicrobial agents against multidrug-resistant pathogens. Future research is expected to improve diagnostic precision, therapeutic options, and stewardship strategies to limit the spread of antimicrobial resistance.