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

Overview

Journal Clin Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2024 Jun 25

PMID 38917034

Authors

Sophie C H Wen

Patrick N A Harris

Brian Forde

Budi Permana

Mark D Chatfield

Colleen L Lau

Geoffrey Spurling

Michelle J Bauer

Ross Balch

Henry Chambers

Luregn J Schlapbach

Julia E Clark

Sonia Dougherty

Christopher C Blyth

Philip N Britton

Vanessa Clifford

Gabrielle M Haeusler

Brendan McMullan

Ushma Wadia

David L Paterson

Adam D Irwin

Affiliations

Soon will be listed here.

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.

References

Lipworth S, Vihta K, Chau K, Barker L, George S, Kavanagh J . Ten-year longitudinal molecular epidemiology study of Escherichia coli and Klebsiella species bloodstream infections in Oxfordshire, UK. Genome Med. 2021; 13(1):144. PMC: 8414751. DOI: 10.1186/s13073-021-00947-2. View

Inouye M, Dashnow H, Raven L, Schultz M, Pope B, Tomita T . SRST2: Rapid genomic surveillance for public health and hospital microbiology labs. Genome Med. 2014; 6(11):90. PMC: 4237778. DOI: 10.1186/s13073-014-0090-6. View

Thompson G, Barker C, Folgori L, Bielicki J, Bradley J, Lutsar I . Global shortage of neonatal and paediatric antibiotic trials: rapid review. BMJ Open. 2017; 7(10):e016293. PMC: 5652566. DOI: 10.1136/bmjopen-2017-016293. View

Hallmaier-Wacker L, Andrews A, Hope R, Demirjian A, Lamagni T, Collin S . Incidence of infant Gram-negative invasive bacterial infections in England, 2011-2019: an observational study using population-wide surveillance data. Arch Dis Child. 2023; 108(9):762-767. DOI: 10.1136/archdischild-2023-325569. View

Lipworth S, Vihta K, Davies T, Wright S, Tabirao M, Chau K . Molecular epidemiology and antimicrobial resistance phenotype of paediatric bloodstream infections caused by Gram-negative bacteria. Commun Med (Lond). 2022; 2:101. PMC: 9372158. DOI: 10.1038/s43856-022-00161-0. View

Al Yazidi L, Outhred A, Britton P, Kesson A . Culture-proven Bloodstream Infections at a Specialist Pediatric Hospital. Pediatr Infect Dis J. 2020; 39(6):500-506. DOI: 10.1097/INF.0000000000002605. View

Forde B, Bergh H, Cuddihy T, Hajkowicz K, Hurst T, Playford E . Clinical Implementation of Routine Whole-genome Sequencing for Hospital Infection Control of Multi-drug Resistant Pathogens. Clin Infect Dis. 2022; 76(3):e1277-e1284. DOI: 10.1093/cid/ciac726. View

Feudtner C, Feinstein J, Zhong W, Hall M, Dai D . Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation. BMC Pediatr. 2014; 14:199. PMC: 4134331. DOI: 10.1186/1471-2431-14-199. View

Pfaller M, Carvalhaes C, Smith C, Diekema D, Castanheira M . Bacterial and fungal pathogens isolated from patients with bloodstream infection: frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (2012-2017). Diagn Microbiol Infect Dis. 2020; 97(2):115016. DOI: 10.1016/j.diagmicrobio.2020.115016. View

10.

Sands K, Carvalho M, Portal E, Thomson K, Dyer C, Akpulu C . Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries. Nat Microbiol. 2021; 6(4):512-523. PMC: 8007471. DOI: 10.1038/s41564-021-00870-7. View

11.

Tamma P, Sharara S, Pana Z, Amoah J, Fisher S, Tekle T . Molecular Epidemiology of Ceftriaxone Non-Susceptible Enterobacterales Isolates in an Academic Medical Center in the United States. Open Forum Infect Dis. 2019; 6(8):ofz353. PMC: 6736082. DOI: 10.1093/ofid/ofz353. View

12.

Agyeman P, Schlapbach L, Giannoni E, Stocker M, Posfay-Barbe K, Heininger U . Epidemiology of blood culture-proven bacterial sepsis in children in Switzerland: a population-based cohort study. Lancet Child Adolesc Health. 2018; 1(2):124-133. DOI: 10.1016/S2352-4642(17)30010-X. View

13.

Harris P, Taylor R, Thielke R, Payne J, Gonzalez N, Conde J . Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2008; 42(2):377-81. PMC: 2700030. DOI: 10.1016/j.jbi.2008.08.010. View

14.

Dinsmore N, McRae J, Quinn H, Glover C, Dougherty S, McMinn A . Paediatric Active Enhanced Disease Surveillance (PAEDS) 2019: Prospective hospital-based surveillance for serious paediatric conditions. Commun Dis Intell (2018). 2021; 45. DOI: 10.33321/cdi.2021.45.53. View

15.

Russell N, Stohr W, Plakkal N, Cook A, Berkley J, Adhisivam B . Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS). PLoS Med. 2023; 20(6):e1004179. PMC: 10249878. DOI: 10.1371/journal.pmed.1004179. View

16.

Cole B, Ilikj M, McCloskey C, Chavez-Bueno S . Antibiotic resistance and molecular characterization of bacteremia Escherichia coli isolates from newborns in the United States. PLoS One. 2019; 14(7):e0219352. PMC: 6611611. DOI: 10.1371/journal.pone.0219352. View

17.

Bolger A, Lohse M, Usadel B . Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014; 30(15):2114-20. PMC: 4103590. DOI: 10.1093/bioinformatics/btu170. View

18.

Pitout J, Peirano G, Chen L, DeVinney R, Matsumura Y . Escherichia coli ST1193: Following in the Footsteps of E. coli ST131. Antimicrob Agents Chemother. 2022; 66(7):e0051122. PMC: 9295538. DOI: 10.1128/aac.00511-22. View

19.

Paioni P, Kuhn S, Strassle Y, Seifert B, Berger C . Risk factors for central line-associated bloodstream infections in children with tunneled central venous catheters. Am J Infect Control. 2019; 48(1):33-39. DOI: 10.1016/j.ajic.2019.06.027. View

20.

Magiorakos A, Srinivasan A, Carey R, Carmeli Y, Falagas M, Giske C . Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2011; 18(3):268-81. DOI: 10.1111/j.1469-0691.2011.03570.x. View