Pre-HCT Resistome Disruption Predicts ESBL Gene Expansion in Pediatric Transplant Recipients: A Prospective...

Area of Science:

• Microbiology
• Genomics
• Pediatric Medicine

Background:

• Infections are the primary cause of mortality post-pediatric hematopoietic cell transplant (HCT).
• Gut microbiome organisms are the source of up to 90% of bacteremias in pediatric HCT patients.
• The selection mechanisms for resistance genes like Extended-spectrum β-lactamase (ESBL) in these microbiomes are not well understood.

Purpose of the Study:

• To investigate changes in multidrug-resistant bacteria within the gut microbiome of pediatric HCT recipients during the early post-transplant period.
• To understand the factors driving the expansion of ESBL genes in the gut microbiome of these vulnerable patients.

Main Methods:

• Prospective stool sample collection from 133 pediatric HCT recipients across five centers.
• Shotgun metagenomic sequencing of bacterial DNA to identify antibiotic resistance genes using the MEGARes database.
• Statistical analysis using univariate and Inverse Probability of Treatment Weighting (IPTW) linear regression to assess associations between ESBL gene abundance and antibiotic exposure.

Main Results:

• Pre-existing gut microbiome disruption at HCT showed a stronger correlation with ESBL gene expansion than post-transplant antibiotic exposure.
• Patients with a higher baseline resistome distance from healthy children exhibited increased ESBL genes during neutropenia.
• While post-transplant beta-lactam exposure did not increase ESBL genes in colonized patients, aminoglycosides and anaerobic antibiotics were linked to new ESBL organism acquisition.

Conclusions:

• Antibiotic stewardship before HCT is critical for preventing ESBL-related infections.
• Minimizing the use of anaerobic active antibiotics during early transplant may also help reduce ESBL acquisition.
• Addressing pre-existing gut microbiome disruption is key to controlling resistant bacteria selection post-HCT.