P-458. Genomic Characterization of Invasive and Colonizing Antibiotic-Resistant Enterobacterales in Infants

TL;DR

This study compares antibiotic-resistant Enterobacterales in infants that cause infections versus those that just colonize, finding that E. coli ST131 is a key strain with more virulence genes in invasive cases.

Contribution

The study identifies specific virulence genes in E. coli isolates from invasive infections that are less common in colonizing strains, offering insights for future screening and interventions.

Findings

E. coli ST131 was the most common strain in invasive infections and also colonized healthy infants.

Eight virulence genes were significantly more frequent in invasive E. coli isolates.

Invasive isolates had genes related to adhesion, invasion, and iron uptake, suggesting targets for intervention.

Abstract

Infants are vulnerable to bacterial infections, including those caused by antibiotic-resistant Enterobacterales (AR-E). These bacteria can asymptomatically colonize the gut of young infants or cause invasive infections leading to morbidity and mortality. The objective of this study is to characterize differences between AR-E that cause invasive infections and those that are asymptomatic stool colonizers.Clinical Characteristics of Patients with Antibiotic-Resistant Enterobacterales by GroupMicrobiologic Characteristics of Antibiotic-Resistant Enterobacterales by GroupBolded sections represent E. coli ST Types that were observed > 2 times in this study

Clinical Characteristics of Patients with Antibiotic-Resistant Enterobacterales by Group

Microbiologic Characteristics of Antibiotic-Resistant Enterobacterales by Group

Bolded sections represent E. coli ST Types that were observed > 2 times in this study

AR-E isolates causing bacteremia and urinary tract infection (UTI) in infants less than 12 months of age over the past 10 years were retrieved from hospital clinical microbiology lab archives. Concurrently, AR-E were identified in stool of healthy community infants for an observational study titled “The Acquisition of Resistant Bacteria (ACQUIRE).” Invasive blood and urine isolates were compared to colonizing stool isolates.

Bacterial DNA was extracted then sequenced on the MiSeq Platform. De novo genome assembly was performed using SPAdes. Genomes were annotated using the RAST tool kit. A phylogenetic tree was constructed to visualize strain relatedness. Virulence genes were identified and compared between groups, with Benjamini-Hochberg correction for multiple comparisons.Phylogenetic Tree of AR-E IsolatesEach label represents an AR-E isolate and the distance between isolates is a function of their relatedness. Clustering isolates with a more recent common ancestor are more closely related.Virulence Gene Presence in E. coli Isolates by Group(a) All E. coli isolates that were identified in this study are included.(b) Only E. coli isolates from healthy infants are included, those without any medical history per chart review (e.g. no prematurity, no urogenital anomaly, no central line, etc.)*Adjusted p value < 0.05

Phylogenetic Tree of AR-E Isolates

Each label represents an AR-E isolate and the distance between isolates is a function of their relatedness. Clustering isolates with a more recent common ancestor are more closely related.

Virulence Gene Presence in E. coli Isolates by Group

(a) All E. coli isolates that were identified in this study are included.

(b) Only E. coli isolates from healthy infants are included, those without any medical history per chart review (e.g. no prematurity, no urogenital anomaly, no central line, etc.)

*Adjusted p value < 0.05

We identified 15 cases of AR-E bacteremia, 45 cases of AR-E UTI, and 30 stool colonizing AR-E in infants. Characteristics of these patients and isolates are described in Table 1 and Table 2, respectively. A phylogenetic tree demonstrated clustering of invasive isolates as these were predominantly E. coli, most commonly strain ST131 (Figure 1). Eight virulence genes were significantly more frequent in E. coli isolates causing invasive infection rather than those asymptomatically colonizing healthy infants (Table 3).

While many AR-E colonize the gut of healthy young infants, invasive infection was disproportionately caused by E. coli. The global pandemic E. coli strain ST131 was found to be both an asymptomatic colonizer and invasive pathogen. Compared to colonizing isolates, E. coli isolates causing invasive infection in healthy infants were more likely to have virulence genes implicated in bacterial adhesion, invasion, and iron uptake. These genes may inform future screening for virulent bacteria, or targeted interventions to reduce invasive infection.

Cecilia Thompson, PhD, D(ABMM), bioMerieux: Honoraria|NaviDX Consulting: Consulting

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