DISCUSSION
VGS-BSI can cause life-threatening complications in children with cancer and early initiation of appropriate antibiotic therapy is essential. With increasing penicillin-resistance amongst VGS isolates,12 febrile neutropaenia monotherapy with an extended spectrum B-lactam agent may be suboptimal in patients at high risk of VGS-BSI.13 However, the universal addition of vancomycin to empiric febrile neutropaenia therapy has not shown benefit, increases nephrotoxicity,18 and the emergence of resistance,19 and is not routinely recommended.15,20 A risk-stratified approach limits the addition of empiric vancomycin to febrile neutropaenia therapy for high-risk and clinically unstable patients, maximising utility and minimising the potential for harm. This report demonstrates that this approach is safe and effective, guiding appropriate therapy and supporting good clinical outcomes in VGS-BSI.
The proportion of non-penicillin susceptible VGS isolates (57.9%) was comparable to previous paediatric studies (29.6% to 67.5%).6,9,21 Reassuringly, there were no VGS-BSI related deaths and all VGS isolates in high-risk patients were susceptible to the recommended empiric antibiotics. Whilst four non-high-risk patients had a non-penicillin susceptible VGS-BSI, vancomycin was added within 24 hours and all recovered without incident. The clinical stability observed in these patients, despite the slight delay in vancomycin therapy, may attest to the lower pathogenicity of VGS in lower risk populations.
Modern laboratory methods allow continuous assessment of blood culture samples, allowing early notification and time-to-positivity assessment. In this study, all blood cultures were detected as positive for VGS-BSI within 17 hours, indicating that empiric vancomycin targeting VGS can be safely discontinued in stable patients at 24 hours if cultures remain negative.
This study is limited by the single-centre design and small sample size but given the limited data assessing such a risk-stratified approach, the findings remain important. Secondly, we employed a pragmatic definition of BSI including all single VGS isolates, which may have led to an overestimation of VGS-BSI episodes. The definition of VGS-BSI is not standardised and whilst some previous surveillance studies required isolation of VGS from two samples,7,9 several other studies have defined VGS-BSI as any single isolation of VGS6,8,22 as this would result in treatment initiation from a clinical perspective. Notably, all VGS-BSI episodes in this study were associated with fever and were treated as true episodes of bacteremia.22
In conclusion, this data demonstrates the safety of a risk-stratified approach targeting the addition of empiric vancomycin to febrile neutropaenia therapy in children with cancer at high-risk of VGS-BSI. The majority of patients received appropriate antibiotic cover for VGS-BSI and no episodes progressed to VGS-BSI related shock requiring ICU admission; there were no VGS-BSI associated deaths. All VGS isolates flagged positive within 24 hours indicating empiric vancomycin can be discontinued after 24 hours in clinically stable patients. Broader assessment of this risk-stratified approach is warranted.