PROJECT SUMMARY/ABSTRACT
Viridans group streptococci (VGS) are the most common causes of bacteremia in neutropenic patients with
hematologic malignancies and cause substantial morbidity and mortality. Fluoroquinolone (FQ) prophylaxis is
recommended to prevent bacterial infections in neutropenic patients, but VGS that cause bacteremia despite FQ
prophylaxis are FQ-resistant. There is an urgent need for novel approaches to prevent VGS infections in neutro-
penic patients. The objective of this proposal is to determine how screening for colonization with FQ-resistant
VGS could identify patients at high risk of developing VGS bacteremia despite FQ prophylaxis. An alternative
approach to prophylaxis could then be pursued in these high-risk patients. The hypothesis is that neutropenic
patients who develop VGS bacteremia despite FQ prophylaxis are colonized with FQ-resistant VGS prior to
neutropenia and that microbial factors, such as the species of VGS and expansion of VGS in the oral microbiome,
increase the risk of bacteremia in colonized patients. The specific aims of this project are: 1) Determine the
optimal screening method to detect colonization with FQ-resistant VGS; 2) Determine the prevalence and clinical
significance of colonization with FQ-resistant VGS in neutropenic patients and identify alternative prophylactic
antimicrobial agents; 3) Identify risk factors for VGS bacteremia despite FQ prophylaxis in FQ-resistant VGS-
colonized neutropenic patients. In this study, oral (buccal), oropharyngeal, and perianal swab specimens will be
collected from 135 participants prior to hematopoietic cell transplantation (HCT). Specimens will undergo selec-
tive culture to identify FQ-resistant VGS by direct plating and with a broth enrichment step to identify the optimal
body sites to screen and the need for broth enrichment to detect colonization. The prevalence of and risk factors
for colonization will also be identified. Study participants will be followed to determine how pre-transplant coloni-
zation with FQ-resistant VGS increases the risk of VGS bacteremia during neutropenia. Colonizing and blood-
stream FQ-resistant VGS isolates will undergo sequencing to determine whether patients develop bacteremia
from their colonizing strain and antimicrobial susceptibility testing to identify alternative prophylactic agents with
activity against these bacteria. Clinical and microbial risk factors for VGS bacteremia among colonized patients
will then be identified, using 16S rRNA gene sequencing to assess the impact of the oral microbiome on this risk.
The contributions of this proposal are that we will identify the optimal screening test to detect colonization with
FQ-resistant VGS, determine the prevalence of colonization prior to HCT and the risk of VGS bacteremia in
colonized neutropenic patients, and identify which colonized patients are at highest risk of VGS bacteremia.
These contributions are significant and innovative because, if confirmed and expanded upon in a larger multi-
center study, they could lead to a novel individualized approach to prevent VGS bacteremia where patients are
screened for colonization with FQ-resistant VGS prior to neutropenia and their prophylactic approach is modified
if colonization is detected, as opposed to the current “one-size-fits-all” approach of universal FQ prophylaxis.
