Researchers Head to Botswana to Study Antibiotic Use in Hospitalized Children

The tide of antibiotic resistance continues to rise worldwide, and it is taking Eimear Kitt, MBBCh BAO (Hons), a third-year fellow in Infectious Diseases, and her study team to Botswana in sub-Saharan Africa this summer to prospectively collect information on antibiotic use in hospitalized children. When they return to Children’s Hospital of Philadelphia and analyze their data, their findings will help to inform strategies to improve antibiotic stewardship in low- and middle-income settings.

Antibiotic overuse is the key driver of antibiotic resistance, which has been described by the World Health Organization as “one of the three greatest threats to human health.” Infections with resistant bacteria increase patient morbidity and mortality and escalate healthcare costs.

“We know that in the U.S., the majority of children who are admitted to the hospital get an antibiotic, and the majority of them are potentially unnecessary,” Dr. Kitt said. “And we suspect, given data that is emerging, that there are a lot of resistant organisms in under resourced settings, which may in part be due to antibiotic overuse. Antibiotic resistance is a huge global problem.”

CHOP was one of the first pediatric hospitals in the U.S. to build and implement an antimicrobial stewardship program (ASP), which includes all departments and divisions, microbiology and virology laboratories, informatics, nursing, pharmacy, and infection prevention and control to optimize antimicrobial use across the institution. Directed by Jeffrey Gerber, MD, PhD, MSCE, the ASP has developed quality-improvement interventions to promote selection of the optimal antibiotic drug regimen for each patient, including dosing, duration of therapy, and route of administration. While ASP members have learned many lessons within CHOP over the last two decades, they know far less about antibiotic overuse and outbreaks of resistant organisms in under resourced countries where access to healthcare is reduced and the burden of disease is high.

“What is underlying the potential for serious outbreaks of resistant organisms?” Dr. Kitt asked. “When you encounter these multidrug-resistant bugs that need significant antibiotics, it perpetuates this ongoing cycle of drug resistance: more antibiotics, more drug resistance, more antibiotics. So to me, we need to figure out where to start. Let’s get to the root and see what factors could contribute to these problems, and then try and tackle it from there.”

When Dr. Kitt and her mentor Andrew Steenhoff, MBBCh, DCH, were brainstorming about research projects, they decided that the long-standing CHOP and Botswana-UPenn partnership (BUP) with Princess Marina Hospital, the major public hospital in the capital city, Gaborone, would be an ideal opportunity for Dr. Kitt to combine her interest in global health and her training in infectious diseases. Through clinical care, research, and medical education, the BUP is devoted to building capacity in sustainable and high-quality healthcare in Botswana through multi-cultural, multi-faceted efforts.

Dr. Steenhoff is medical director of CHOP’s Global Health Center and an attending physician in the Division of Infectious Diseases, an assistant professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and an adjunct senior lecturer in the Department of Paediatrics, Faculty of Health Sciences of the University of Botswana. He conducted a pilot study on the pediatric floor of Princess Marina Hospital 11 years ago that suggested potential interventions were needed to reduce antibiotic overuse. Since then, CHOP has helped Princess Marina Hospital and the University of Botswana to implement evidence-based clinical pathways in pediatrics. Dr. Kitt’s project will help to gain a better understanding of the best practices currently being used there to treat infections and help to identify any potential barriers to their success.

“We very much look forward to seeing the results of Dr. Kitt’s study,” said Dr. Dipesalema Joel, Academic Head of the Department of Paediatric and Adolescent Medicine, Faculty of Medicine, University of Botswana. “We believe that this study will help inform evidence-based care for children admitted to Princess Marina Hospital.”

One of the factors that Dr. Kitt’s study team will look at in their analysis is whether the presence of a clinical pathway is associated with improved antibiotic use.

“The success of pathways has been very well established in high-income countries, but in terms of low- and middle-income countries, we’re not really that sure,” Dr. Kitt said. “We don’t know if they are helpful or if there are other ways that we can help.”

Dr. Kitt described the three-month study as an “ear-to-the-ground” approach that will be carried out by a study team that will include a research nurse and two master’s in public health students and Tonya Arscott-Mills, MD, MPH, lead pediatrician in Botswana for CHOP’s Global Health Center. Dr. Kitt will stay in close contact with her home-based mentors, Dr. Steenhoff and Susan Coffin, MD, MPH, clinical director of the Division of Infectious Diseases at CHOP and professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. Drs. Steenhoff and Coffin also are core faculty members of Clinical Futures a CHOP Research Institute Center of Emphasis.

Every patient in the age range from birth to adolescence who is admitted to Princess Marina for infectious and non-infectious causes will prospectively enroll in the study with the caregiver’s consent. The study team will assess why they are being admitted, list the diagnosis, record when they came in, and note which antibiotics, if any, that they received. The investigators will review the patients’ paper charts every day and keep track of their drug regimens, as well as any clinical or laboratory test results. Once the patients are discharged, they’ll record the plan for antibiotic use outside of the inpatient setting. The study team will enter the data collected into a secure, online database called RedCap.

“Certainly, it’s a big undertaking, particularly for the neonatal population who often have rather prolonged hospital stays and receive multiple courses of antibiotics,” Dr. Kitt said. “It probably will be an eye-opener to see how we manage to collect such a vast amount of data with our team, but hopefully it will be very worthwhile. Depending on what we find, we’ll be able to define next steps so that we and our partners at the University of Botswana and Princess Marina Hospital can be more confident in future interventions focused on antibiotic stewardship and appropriate use in under resourced settings.”