416 - Effect of an Empirical Antibiotic Protocol on Multidrug-Resistant Organisms in Nosocomial Late-Onset Sepsis

Publication Number: 2404.416

世冠 杨, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong, China (People's Republic); xiaopeng zhao, Guangzhou Women and Children's Medical Center, guangzhou, Guangdong, China (People's Republic)

Background: Nosocomial late-onset sepsis (LOS) poses a significant clinical challenge due to its high incidence and serious outcomes. The prevalent overuse of antibiotics in the NICU represents a major driver, contributing to the increasing emergence of multidrug-resistant organisms.

Objective: This study assessed the efficacy of an empirical antibiotic protocol to reduce multidrug-resistant organisms in nosocomial late-onset sepsis in the NICU.

Design/Methods: We conducted a retrospective cohort study of neonates with hospital-acquired late-onset sepsis (LOS) at two campuses of our academic medical center between January 2018 and December 2024. Hospital-acquired LOS was defined as a positive blood or cerebrospinal fluid culture obtained >72 hours after birth and >48 hours after hospital admission. Exclusion criteria were fungal infections or incomplete medical records. The primary outcome was the impact of the empirical antibiotic protocol on the incidence of multidrug-resistant organisms. Secondary outcomes included pathogen distribution and temporal trends in multidrug resistance.

Results: The study analyzed 441 bacterial culture-positive specimens, comprising 388 (88.0%) blood and 53 (12.0%) cerebrospinal fluid isolates. Pathogen distribution and MDR proportions are shown in Figure 1. The patient populations differed markedly-all inborn in Campus A versus 77.6% (204/263) transfers in Campus B-which was accompanied by a significantly higher overall multidrug resistance rate in Campus B (66.9% [176/263] vs. 56.2% [100/178]; χ²=4.78, p=0.029).In 2020, our hospital implemented an empirical antibiotic protocol of ampicillin and cefotaxime for early-onset sepsis (EOS). Following this, the multidrug resistance (MDR) rate in Campus A decreased from 86.7% in 2020 to 28.1% in 2024. The MDR rate in Campus B remained above 57% during the same period.A multivariable logistic regression model showed a statistically significant difference in the temporal trends of MDR rates between the campuses (OR, 0.668; 95% CI, 0.542-0.824; p < 0.001). The same model also showed that Gram-negative bacteria had a lower risk of multidrug resistance than Gram-positive bacteria (OR, 0.507; 95% CI, 0.334-0.768; P = 0.001). These findings suggest that the difference in MDR trends between the two campuses may be related to differences in pathogen distribution.

Conclusion(s): Geographic heterogeneity in multidrug resistance rates is driven by variations in pathogen sources and distribution, making the rigorous enforcement of an institutional empirical antibiotic protocol a critical control strategy.

Bacterial Isolates Distribution in Two Campuses
Figure1. Distribution of pathogenic bacteria and multidrug-resistant organisms (MDROs) in two hospital campuses, 2018-2024. Donut charts depict pathogen composition for Campus A (left) and Campus B (right). The outer ring shows pathogen frequency and percentage; the inner ring shows MDRO frequency and proportion relative to total pathogens from that campus.Strain distribution analysis revealed that Campus A, with 178 specimens (178/441, 40.4%), was predominantly composed of gram-negative bacilli (109/178, 61.2%). In contrast, Campus B, comprising 263 specimens (263/441, 59.6%), was primarily characterized by gram-positive cocci (167/263, 63.5%). The distribution of multidrug-resistant organisms (MDROs) differed between the two campuses. In Campus A, the predominant MDROs and their respective proportions were: coagulase-negative staphylococci (43/100, 43.0%), Klebsiella spp. (26/100, 26.0%), and Escherichia coli (12/100, 12.0%). Conversely, in Campus B, the distribution was: coagulase-negative staphylococci (110/176, 62.5%), Escherichia coli (25/176, 14.2%), and Klebsiella spp. (19/176, 10.8%).

Multidrug Resistance Analysis in Two Campuses
Figure2. Epidemiology of multidrug resistant organisms (MDROs) in 2 hospital campuses, 2018-2024. Panel A shows the overall merged MDRO rates for the entire study period. Campus A had an MDRO rate of 56.2%, compared with 66.9% for Campus B. Panel B illustrates the annual trends in MDRO rates. Campus A (blue line) peaked in 2020 and subsequently declined consistently, while Campus B (orange line) maintained a higher prevalence throughout the period without a similar sustained decrease. The size of each data point in the right panel corresponds to the number of MDRO isolates for each year and campus.