METHODS
We conducted a single-centre prospective cohort study including all
children (0-18 years) receiving chemotherapy for haematological
malignancy or undergoing HSCT from 1st November 2016
until 31st January 2020 at Perth Children’s Hospital
in Western Australia. As per institutional guidelines, addition of
empiric vancomycin to standard febrile neutropaenia therapy
(piperacillin-tazobactam) is recommended in all patients at highest-risk
of VGS-BSI (those with AML, relapsed ALL, infant ALL or undergoing
HSCT), and any patient with clinical signs of shock. Shock was defined
as inadequate cardiac output with hypotension requiring intravascular
volume expansion (fluid bolus ≥20ml/kg) and/or inotropic support.
Neutropaenia was defined as an absolute neutrophil count of
<0.5x109/L. Fever was defined as core body
temperature ≥38.5°C on a single occasion or ≥38.0°C on two sequential
occasions within a 24-hour period.
All VGS-BSI episodes were identified from the laboratory information
database of blood culture isolates. A VGS-BSI episode was defined as
isolation of Viridans group Streptococcus spp. from a
blood culture. Episodes with concomitant growth of a gram-positive
commensal (e.g. Micrococcus spp. or coagulase negativeStaphylococcus ) were excluded as contaminants.
For each VGS-BSI episode, demographic and clinical data were collected
from patient medical records including the presence of shock,
requirement for mechanical ventilation, admission to the intensive care
unit (ICU), and survival at day 7 and day 30. Laboratory data included
blood culture time-to-positivity and antibiotic susceptibility.
Susceptibility testing was carried out using an E-test (Biomerieux,
France) as per manufacturer specifications.16Susceptibility to empiric B-lactam antibiotic (piperacillin-tazobactam)
was inferred from penicillin minimum inhibitory concentration, with
breakpoints defined as per the Clinical & Laboratory Standards
Institute.17
Statistical analysis was performed using GraphPad QuickCalcs (GraphPad
Software, Inc., CA, US). Fisher’s exact test was used to compare the
characteristics of high-risk and non-high-risk patients for categorical
data, and the Mann-Whitney U test for continuous variables. P
values of <0.05 were considered statistically significant.
National ethics approval was granted by the Western Sydney Local Health
District Human Research Ethics Committee (HREC/16/WMEAD/281).