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).