Abstract

Two recent reports suggested that the less common, less virulent enterococcal species, Enterococcus gallinarum and E. casseliflavus, with low-level vancomycin resistance due to chromosomally encoded vanC1 and vanC2/3, may influence host immunity. We reported that peri-transplant gut colonization with E. gallinarum and E. casseliflavus is associated with lower mortality after allogeneic hematopoietic cell transplantation (HCT). Because most acute leukemia patients undergoing HCT have received intensive chemotherapy (usually requiring prolonged hospitalization) for their underlying disease before HCT, we hypothesized that some may have acquired vanC-positive enterococci during chemotherapy. Therefore, we evaluated the presence of the vanC gene cluster using vanC1 and vanC2/3 qPCR in thrice-weekly collected stool samples from 20 acute leukemia patients undergoing intensive chemotherapy. We found that an unexpectedly large proportion of patients have detectable vanC1 and vanC2/3 (15% and 35%, respectively) in at least one stool sample. Comparing qPCR results with 16S rRNA gene sequencing results suggested that E. gallinarum may reach high abundances, potentially persisting into HCT and influencing transplant outcomes.

Highlights

  • Hematopoietic cell transplantation (HCT) is a potentially curative approach for many patients with high-risk hematologic malignancies. After their initial anti-neoplastic treatment, often including intensive chemotherapy, such patients are referred for HCT

  • We recently reported that colonization with E. casseliflavus or E. gallinarum is associated with lower transplant-related mortality and better survival [10]

  • The mechanisms underlying this association are unknown, but alterations in host immunity have been reported [11]. It is not known whether patients acquire E. casseliflavus and E. gallinarum during HCT or before HCT during the treatment of their underlying hematologic disorder. To determine when these species are acquired, we investigated the presence of vanC genes in the stool of acute leukemia patients undergoing intensive chemotherapy

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Summary

Introduction

Hematopoietic cell transplantation (HCT) is a potentially curative approach for many patients with high-risk hematologic malignancies. After their initial anti-neoplastic treatment, often including intensive chemotherapy, such patients are referred for HCT. Gut colonization with antibiotic-resistant organisms is common during HCT [1,2,3]. The genus Enterococcus, frequently harboring antibiotic resistance genes (ARGs), is one of the most common gut colonizers in HCT patients [4,5]. The plasmid-encoded vanA gene is the most common enterococcal.

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