432 - Epidemiology of multiple infections in NICU infants

Publication Number: 2420.432

Sarah A. Coggins, Children's Hospital of Philadelphia, Philadelphia, PA, United States; David A. Kaufman, University of Virginia School of Medicine, Charlottesville, VA, United States; Mark R. Conaway, University of Virginia School of Medicine, Charlottesville, VA, United States; Dustin D. Flannery, Children's Hospital of Philadelphia, Wynnewood, PA, United States; Pablo J. Sanchez, Nationwide Children's Hospital -OSU, Columbus, OH, United States; Joern-Hendrik Weitkamp, Vanderbilt University School of Medicine, Nashville, TN, United States; Robert L. Schelonka, Oregon Health & Science University School of Medicine, Portland, OR, United States; Michael T. Favara, ChristianaCare, Media, PA, United States; Kristin Weimer, Duke University School of Medicine, Durham, NC, United States; Margaret Gilfillan, St. Christopher's Hospital for Children, Philadelphia, PA, United States; Kathryn Ziegler, Sidney Kimmel Medical College at Thomas Jefferson University, Abington, PA, United States; Andrew Berenz, Rush Medical College of Rush University Medical Center, Chicago, IL, United States; Katia C. Halabi, Nationwide Children's Hospital, Morristown, NJ, United States; Sagori Mukhopadhyay, Childrens Hospital of Philadelphia, Philadelphia, PA, United States

Background: Large neonatal infection studies often report only a first late-onset episode of bacteremia or meningitis, with limited attention to urinary tract infections (UTI) or additional infection episodes, leaving patterns of multiple infections poorly characterized.

Objective: To describe the epidemiology of multiple late-onset infections (bloodstream infection, meningitis, and UTI) in a multicenter NICU cohort.

Design/Methods: Retrospective cohort of infants admitted to 12 U.S. and Canadian level III-IV NICUs from March 2018-July 2022. We analyzed all culture-confirmed bacterial or fungal infections from blood, CSF, or urine occurring after 3 days of age with >5 days of antimicrobial therapy. UTI was defined as growth of a single pathogen from urine of >10,000 CFU/mL. A new infection was defined as isolation of a new pathogen at any time relative to a prior infection; recurrent infection had the same pathogen isolated >10 days after finishing therapy for a prior infection. We compared infants with single vs. multiple infections and described multiple episodes using descriptive statistics (significance at p< 0.05). We described source patterns of frequently-recurring pathogens with Sankey plots.

Results: Among 46,516 infants, 1,347 (3%) experienced 1,637 infection events. Of these, 223 infants (16%) had multiple infections, totaling 513 infection events; most infants had two infections (175/233, 78%). Infants with multiple infections had lower gestational age and birthweight and were older at initial infection onset compared to those with single infections (Table 1). Coagulase-negative staphylococci (CoNS) predominated as first events, whereas gram-negatives were more common in subsequent events.

Among 223 infants with multiple infections, 133 (60%) had new infections with different pathogens, 61 (27%) had same-pathogen recurrences, and 29 (12%) experienced both of these patterns. The interval between infections was shorter for new than for recurrent infections (28 vs 38 days, p=0.004). Among 100 same-pathogen recurrences, 53% were due to gram-negative bacteria; K. pneumoniae (23%), E. coli (19%), and Enterococcus (10%) were the most common non-CoNS pathogens (Table 2). Most recurrences were from the same culture source (82/100), with 11 transitioning from blood to urine and 7 from urine to blood (Figure).

Conclusion(s): Multiple late-onset infections in NICU infants often involved discordant pathogens across sources, particularly blood and urine. Same-pathogen recurrences were predominantly due to gram-negative bacteria. Defining these infection patterns may help identify reservoirs and targets for prevention.

Figure 1
Sankey diagrams showing source transition sites between multiple late-onset infections caused by E.coli, Klebsiella, and Enterococcus.

Table 1: Demographics of infants with single vs multiple infections


Table 2: Pathogens causing single and multiple infections in NICU infants