Characterization of Gram-negative Bloodstream Infections in Hospitalized Australian Children and Their Clinical Outcomes

Abstract

Background: Gram-negative bloodstream infections (GNBSIs) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSIs in children that relate the clinical presentation, pathogen characteristics, and outcomes.; Methods: A 3-year prospective study of GNBSIs in children aged <18 years was conducted in 5 Australian children's hospitals between 2019 and 2021. The clinical characteristics, disease severity, and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing.; Results: There were 931 GNBSI episodes involving 818 children. Median age was 3 years (interquartile range, 0.6-8.5). A total of 576/931 episodes (62%) were community onset, though 661/931 (71%) occurred in children with comorbidities and a central venous catheter was present in 558/931 (60%). Central venous catheter (145/931) and urinary tract (149/931) were the most common sources (16% each). One hundred of 931 (11%) children required intensive care unit admission and a further 11% (105/931) developed GNBSIs in intensive care unit. A total of 659/927 (71%) isolates were Enterobacterales, of which 22% (138/630) were third-generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes were confirmed in 65/138 (47%) 3GCR Enterobacterales. Most common extended spectrum beta-lactamase genes were blaCTX-M-15 (34/94, 36%) and blaSHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted odds ratio, 3.2; 95% confidence interval, 1.6-6.4).; Conclusions: GNBSIs in children are frequently healthcare associated and affect children younger than age 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritize future antimicrobial clinical trials.; Competing Interests: Potential conflicts of interest . D. L. P. reports research grants from Shionogi, Pfizer, Merck, bioMérieux, BioVersys, Gilead, and consultancies with AMR Action Fund, CARB-X, Innoviva, Pfizer, Merck, bioMérieux, Cepheid, Aurobac, Arrepath, Spero, Shionogi. P. N. A. H. reports research grants from Gilead, has served on advisory boards for OpGen, Merck, and Sandoz, and has received honoraria from OpGen, Sandoz, Pfizer, and BioMérieux. S. C. H. W. has received honoraria for participation in MSD expert forum for pneumococcal disease, which was paid to Children's Health Queensland. U. W. received travel and accommodation support for meeting attendances by Pfizer and Moderna. A. D. I. has received honoraria for lectures from BioMérieux and Gilead that were paid to the University of Queensland. L. J. S. is a recipient of grants from Swiss National Science Foundation, Swiss Personalized Health Network (SPHN), NHMRC, NIH, NOMIS Foundation, Doris and Thomas Ammann Foundation. L. J. S. is also on the advisory board for the Lancet Child Adolescent Health Journal. HC receives grants from NIH and NIAID and payment from Merck for participation in Molnupiravir clinical trial. H. C. receives payment as senior editor for Sanford Guide to Antimicrobial Therapy and holds stocks in Moderna and Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)