Antimicrobial Susceptibility Patterns and Outcomes of Neonatal Early-Onset Sepsis over a Decade: Implications for Empirical Therapy in a Tertiary NICU.

Background

The goal of this study was to characterize the microbial etiology, antimicrobial susceptibility, and temporal resistance trends of early-onset neonatal sepsis (EOS) pathogens in a tertiary neonatal intensive care unit over 10 years (2014-2023), assessing empirical therapy adequacy and mortality associations.

Methods

Retrospective analysis was performed on the positive blood cultures of neonates with confirmed EOS, born between 1 January 2014 and 31 December 2023. Blood was aseptically collected into PEDS Plus/BC bottles, incubated using the BACTEC system, with pathogen identification by biochemical assays or MALDI-TOF MS. Susceptibility testing followed EUCAST disk-diffusion standards, with additional resistance assays.

Results

Among 6631 NICU admissions, 39 neonates met EOS criteria (31 preterm, 8 term). In preterm infants, Gram-negative Enterobacterales-mainly E. coli (n = 20)-predominated, while GBS was most common in term infants. All GBS isolates (n = 7) were susceptible to benzylpenicillin and vancomycin. Although 90% of E. coli were ampicillin-resistant, 90-95% remained susceptible to third-generation cephalosporins, piperacillin-tazobactam, and aminoglycosides. Two E. coli isolates produced ESBL but remained susceptible to aminoglycosides and carbapenems. Mortality was higher in E. coli EOS (50%) than in GBS (0%) or other pathogens (25%), with borderline significance (p = 0.0547; adjusted RR 1.55, 95% CI 0.54-4.41). Ampicillin resistance was not associated with increased mortality. No annual resistance trends were observed.

Conclusions

In this 10-year NICU cohort, the etiology of EOS differed markedly between preterm and term neonates. Recommended empirical ampicillin-aminoglycoside therapy demonstrated in vitro efficacy against most neonatal bloodstream isolates pending pathogen identification. However, the widespread ampicillin resistance, particularly among E. coli strains, supports consideration of cephalosporin-aminoglycoside combinations or meropenem monotherapy when rapid beta-lactam bactericidal activity is clinically essential. Mortality was higher in E. coli EOS, though not statistically significant, and unrelated to ampicillin resistance.