Three tips for paediatric cancer infection management

Marking International Childhood Cancer Day on 15 February, Adam Esbenshade of Vanderbilt University Medical Center offers his view on how to improve quality of care and antimicrobial stewardship, in particular for children with cancer. 

Facing cancer treatment, families often contemplate with trepidation the risk of severe infection that can accompany chemotherapy. Paediatric cancer care providers place a priority on infection prevention and early, aggressive treatment; however, how an infection is managed greatly varies across centres. Furthermore, a “more is better” approach to the use of additional antibiotics and other antimicrobials is common, even though many are guided in their decision-making by published evidence that contradicts this approach.

Antimicrobial sensitivity refers to how effectively a specific antibiotic eliminates an infection. Resistance occurs when the bacteria can evade the antibiotic. The overuse of antibiotics is leading to a significant resistance problem that could set up situations where there are untreatable infections. It is therefore paramount for providers to be responsible stewards in their prescribing, thoughtfully using antibiotics in situations only where they are needed and stopping them when they are not justified.

There are three ways providers can make management changes that both encourage good stewardship and improve patient care. The research supporting these changes were largely done in countries where resources are available, such as where patients are seen expediently, complete blood count results are available within two hours, and antibiotics can be given quickly. Thus, I would recommend caution in implementing these measures in areas where these prerequisites are not met.

1) Use published clinical practice guidelines

Researchers have created clinical practice guidelines (CPGs) by closely evaluating the published literature and determining the optimal care for many aspects of paediatric cancer infection management. The Children’s Oncology Group has officially endorsed some of these guidelines, available online (https://childrensoncologygroup.org/cog-supportive-care-guidelines). The internationally formed international Pediatric Oncology Guidelines in supportive care (iPOG) Network has also assembled a large repository of them (https://ipognetwork.org/guidance/supportive-care-guidance-library/). The guidelines don’t address every topic, but if followed, can ensure that patients are getting best standard of care.  

2) Use a risk prediction tool to stop giving antibiotics to low-risk paediatric cancer patients with a good neutrophil count

New infections are usually initially attacked by a type of white blood cell called the neutrophil, and these cells are measured as an absolute count (ANC; count/microliter). If the neutrophil count falls below 500, it is necessary to cover these patients with antibiotics. However, when this number is above 500, many centres will still give antibiotics, even without evidence to show this is needed. The actual risk of a bacterial infection to paediatric cancer patients with a good ANC and fever is around 4% overall, and it is possible to use clinical information at the time of new fever to predict the likelihood of a bacterial infection requiring antibiotics immediately.

With my research team, I designed a web-based model (EsVan) that makes these predictions (https://cqs.app.vumc.org/shiny/RiskPrediction/). We have used this at Vanderbilt to eliminate initial antibiotic use in over 70% of cases, without any patients experiencing harm (link). We also recently completed a study at 18 additional hospitals to show that this model creates reliable predictions across locations. The key to success of using these tools is that anyone who appears severely ill-immediately receives antibiotics, but for those who have a predicted low risk of a blood stream infection, it is safe to wait on the culture results.

3) Instead of worrying about the time to antibiotic delivery, focus on delivering thoughtful care to each patient

There has never been consistent evidence showing the benefit of giving antibiotics to all paediatric cancer patients presenting with low ANC and fever within 60 minutes of medical centre arrival. Until recently, however, US medical centres have spent considerable resources to accomplish this as it was upheld as a required metric by US News and World Report paediatric cancer programme rankings. Although it is important to deliver antibiotics quickly to those who are ill, all patients were required to receive antibiotics within 60 minutes to be compliant with the rankings metric; this led some centres to give antibiotics before running a full clinical/laboratory evaluation. At times, they would even resort to painful intramuscular injections without a pre-treated blood culture.

My recently published study of over 2,300 fever episodes showed that giving antibiotics in under 60minutes did not improve any clinical outcomes. Based partially on these data, the metric requirement has been dropped, which should now allow centres to fully evaluate and give appropriate care to each patient.

Effective antimicrobial stewardship is critically important to addressing the growing resistance of microbes to the drugs designed to kill them – with serious consequences for cancer care. The more providers apply its principles and advocate for its role in their own practice settings, the better the chance for our antibiotics and other medicines to work when we need them to. Patients and caregivers would also be reassured to know they are receiving the care that is appropriate for them, without unwanted extras that can be painful and complicate their treatment.