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Kenneth Busby III, DO worked with experts at Kenya’s Moi Teaching and Referral Hospital to contextualize the clinical pathway for its children’s hospital.

headshot of Kenneth Busby III, DO
Kenneth Busby III, DO

When an infant or child with cancer spikes a fever, it can be deadly. Neutropenia is a condition often encountered following chemotherapy for children with blood cancer. As this reduces the patient’s ability to fight off an infection, a fever in the setting of neutropenia must prompt immediate action.

Starting patients on therapy quickly requires providers to make an informed guess on empiric antibiotics until culture results are available, hours or days later. In many scenarios, an infectious etiology is not identified; however, the patient may remain neutropenic for days to weeks following a single febrile episode. Historically, it was recommended to continue broad-spectrum antibiotics for the duration of neutropenia due to concerns of ongoing risk of infection. With the known threat of antibiotic resistance associated with overuse of these life-saving medications, clinicians have had to find ways of balancing this particularly difficult, and yet common, risk-benefit scenario.

According to the Institute for Health Evaluation and Metrics, antibiotic resistance was associated with more than 37,000 deaths in young children under age five in Kenya in 2019.

“Children with cancer are up to 25 times more likely to die from infections than in high-resource settings,” shared Ken Busby, a third-year pediatric hematology/oncology fellow at the University of North Carolina School of Medicine.

Busby participated in the development of the at UNC Children’s Hospital in 2022, under the leadership of Bill Wilson, PharmD, a pediatric infectious diseases pharmacist at UNC Children’s who spearheaded the work. The UNC guideline offers a clinical pathway for children with fever that is differentiated based on type of underlying malignancy and other variables.

The workgroup has also incorporated evidence-based practice to help combat antibiotic resistance in this high-risk patient population. One method that has been successfully implemented in various hematology and oncology patient populations is limiting the duration of broad-spectrum antibiotics in patients who experience fever and chemotherapy-induced neutropenia without a known infectious etiology identified. The guideline provides a uniform approach to safely de-escalating antibiotics in patients who meet criteria while ensuring adequate safety parameters are in place if there is a need to resume broad-spectrum antibiotics.

“A standardized approach to diagnosis and care is important as the clinical exam alone cannot reliably distinguish between children at low- and high-risk of infection,” said Wilson. “The guideline details the recommended approach for children in our hospital; however, treatment decisions may be individualized based on unique patient circumstances and should involve families in shared decision-making when appropriate.”

A conversation with Indiana University School of Medicine Professor Terry Vik, who is affiliated with the Childhood Cancer Treatment Program at Moi Teaching and Referral Hospital in Eldoret, Kenya, led Busby to UNC Oncology graduate Jenny Morgan, MD, the Academic Model Providing Access to Healthcare (AMPATH) Kenya Oncology lead, now associated with Indiana University. Then the idea crystalized to develop a pediatric febrile neutropenia guideline for use at the Moi children’s hospital to optimize and standardize how pediatric patients with cancer are treated for fever, as a part of an existing project on febrile neutropenia at the hospital with Nate Nessle, DO, a graduate of Michigan University’s Pediatric Hematology-Oncology fellowship and a National Institute of Health Fogarty fellow associated with the project.

The work is being carried out as a part of Busby’s practicum as part of his Master of Public Health degree program at UNC Gillings School of Global Public Health. Morgan serves as Busby’s practicum preceptor.

Shoe4Africa Children's Hospital
Shoe4Africa Children’s Hospital, a part of Moi Teaching and Referral Hospital in Eldoret, Kenya

“There is no pediatric guideline in place at Moi currently like there is for adults. Providers are doing all they can to provide quality care to children, and a guideline will be another tool in their tool kit,” Busby explained. “Moi serves children from Kenya and the East African region, drawing from a catchment area of more than 20 million people, so a small change could have a potentially large impact.”

Busby is drawing from several different febrile neutropenia guidelines in addition to UNC’s, peer-reviewed articles, and expert input from Moi’s physicians. Dr. Festus Njuguna, head of the Pediatric hemato-oncology unit at Moi, and Dr. Gilbert Olbara, another pediatric hematology-oncology physician, have led efforts to shepherd and guide the development of the clinical pathway.  The guideline will be expanded for use among an expanded range of providers, including nurses. Because it is anticipated that non-physician healthcare workers will also use the guideline, it will include definitions for fever, neutropenia, shock, and sepsis. It will also have an overview of the role of treatment guidelines, the importance of drawing cultures, and the importance of starting antibiotics within an hour of the fever episode. There will be details about what to do for non-neutropenic fever in children with cancer and information on de-escalation of antimicrobials to make it a more comprehensive clinical resource.

the guideline is drafted, Busby and Nessle will solicit additional feedback from the Moi team, which they will use to reiterate the guideline. Once completed, the Moi team plans to use it for a quality improvement project to improve outcomes for children with cancer.