Sometimes half is better than whole. That’s the idea behind a new multicenter study that Children’s Hospital of Philadelphia is participating in to compare a five-day (short) course of antibiotic therapy with a 10-day (standard) course of therapy to treat community-acquired pneumonia (CAP) in children. Pneumonia is a lung infection that is the leading infectious cause of death in children younger than 5 years old worldwide, according to the Centers for Disease Control and Prevention (CDC). Streptococcus pneumoniae is a common cause of bacterial pneumonia in preschool-age children, and usually physicians prescribe an oral beta-lactam antibiotic, such as amoxicillin, as a first-line treatment for 10 days. Researchers concerned about antibiotic resistance and adverse drug effects want to know if they can cut that treatment time in half without sacrificing effectiveness.
Antibiotic resistance, which is when microbes are able to resist the drugs created to destroy them, is a pressing problem. Each year in the U.S., at least 2 million people become infected with bacteria that are resistant to antibiotics, and at least 23,000 people die each year as a direct result of these infections, the CDC estimates.
Scientists and clinicians are aggressively tackling antibiotic resistance from multiple vantage points, explained Jeffrey Gerber, MD, PhD, an attending physician in the Division of Infectious Diseases at CHOP, medical director of its Antimicrobial Stewardship Program, and a principal investigator for the new study called SCOUT-CAP (Short Course vs. Standard Course Outpatient Therapy of CAP in Children).
“One strategy is to use antibiotics only when necessary,” Dr. Gerber said. “For example, for a cold or viral infection, treatment with antibiotics would not be effective. Another way is being careful to make the appropriate choice of antibiotics, to avoid using overly broad-spectrum drugs when narrower-spectrum drugs are equally effective. And the third is an area that is underexplored, which is the duration of antibiotics. Even in cases when antibiotics are necessary for known bacterial infections and correctly prescribed, we often continue administering them beyond the point when the infection is cured.”
Overuse of antibiotics can promote antibiotic resistance by leading to strains of bacteria that produce infections that are more difficult to treat, Dr. Gerber explained. Prolonged exposure to antibiotics also puts children at greater risk of adverse drug effects. And new research suggests that antibiotics can disrupt the human microbiome, which is the community of microorganisms that live on us and within our guts. Our microbial makeup provides many vital functions essential for human survival, and disturbing this commensal balance could potentially cause more harm than good.
SCOUT-CAP aims to find out if reducing children’s exposure to antibiotics prescribed for CAP can be done safely, which also would help to preserve the drugs’ long-term effectiveness. Physicians at five institutions, including CHOP, plan to enroll 400 children, ages 6 months to almost 6 years (71 months), in the clinical study. Two hundred participants will receive the standard 10-day course of antibiotics, and 200 children will receive the five-day course. An innovative aspect of the trial is that patients will be assigned to these groups after they’ve initially been diagnosed and prescribed the antibiotic by their primary care physician, emergency room physician, or urgent care physician.
“This is a comparative effectiveness clinical trial that is being done under real-world circumstances, which is important,” said Dr. Gerber, who is also associate director of CHOP’s Center for Pediatric Clinical Effectiveness (CPCE) and an assistant professor of Pediatrics and Epidemiology at Perelman School of Medicine at the University of Pennsylvania. “We need to create data that is generalizable to what is actually happening in practice.”
Another innovative part of the study is that the research team will use a new statistical analytic approach that has been specifically designed to assess the risks and benefits of new strategies to optimize antibiotic use. The new methodology will use response adjusted for duration of antibiotic risk (RADAR) and desirability of outcome ranking (DOOR), which will allow the researchers to categorize study participants and then create a hierarchy to determine if the shorter duration of therapy is advantageous. Study participants who have better overall clinical outcomes and shorter durations of antibiotic use receive higher rankings.
“If we do find that five days is as good as or better than 10 days, then we can significantly reduce the antibiotic exposure to kids with one of the most common indications of antibiotic use,” Dr. Gerber said. “It’s critical for us to start to chip away at potentially unnecessary antibiotic exposure for such common indications.”
CPCE’s clinical epidemiologists, including Director Theoklis Zaoutis, MD, MSCE, and core faculty member Kevin Downes, MD, are uniquely positioned to help accomplish this study, Dr. Gerber pointed out, because the study team will partner with CHOP’s Pediatric Research Consortium (PeRC). This group of primary care physicians and subspecialists within CHOP’s network all share the same electronic health record and have experience in conducting dozens of clinical trials that aim to improve children’s healthcare.
Other institutions participating in the study include Duke University, North Carolina; Cincinnati Children’s Hospital Medical Center; Children’s Hospital of Pittsburgh of UPMC; and Vanderbilt University, Nashville.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is sponsoring SCOUT-CAP. “Finding new strategies for treating bacterial infections and making better use of existing antibiotic medications are major areas of focus for researchers,” said NIAID Director Anthony Fauci, MD, in a press release about the new study.