April 2014

Study Will Compare Broad, Narrow-Spectrum Antibiotics

Story2_Antibiotics

The Children’s Hospital of Philadelphia’s Jeffrey S. Gerber, MD, PhD, recently received an approximately $1.8 million contract from the Patient-Centered Outcomes Research Institute (PCORI) to compare the effectiveness of broad and narrow-spectrum antibiotics in treating acute respiratory infections. An infectious diseases specialist and a Center for Pediatric Clinical Effectiveness (CPCE) faculty member, Dr. Gerber investigates the epidemiology and outcomes of antibiotic use in children.

PCORI was established by the Affordable Care Act to fund and carry out comparative effectiveness research. Last year PCORI awarded the CPCE’s Ron Keren, MD, MPH, more than $2 million to study the effectiveness of oral and intravenous antibiotics. Since PCORI began funding research projects in 2012, the organization has awarded a staggering $464 million to support 279 projects. Dr. Gerber’s award was one of 71 announced during the fourth quarter of 2013.

Dr. Gerber’s three-year investigation will be focused on the use of antibiotics to treat acute respiratory tract infections (ARTI), such as ear and sinus infections. Despite the fact that guidelines frequently recommend clinicians use narrow-spectrum antibiotics to treat ARTI, many doctors often prescribe broad-spectrum antibiotics.

According to a 2011 Pediatrics study led by the University of Utah’s Adam L. Hersh, MD, PhD, between 2006 and 2008 there were approximately 65.6 million doctor’s visits for respiratory conditions, comprising 29.9 million visits for ARTI for which antibiotics are indicated, 19.5 million visits for ARTI for which antibiotics are not indicated, and 16.2 million for other “respiratory conditions for which antibiotics are not definitely indicated.”

During those 65.6 million visits, there were 31.7 million antibiotic prescriptions made (or during 48.4 percent of visits), including 5.8 million prescriptions to treat ARTI for which antibiotics are not indicated. Overall, broad-spectrum antibiotics were prescribed more than half the time. Dr. Gerber said roughly 80 percent of outpatient pediatric antibiotic prescriptions are intended to treat four conditions: ear infections, strep throat, sinus infections, and pneumonia.

While prescribing antibiotics can be challenging for general practitioners because there are so many different types of drugs — and within those types different classes, as well as new drugs being approved all of the time — “guidelines for antibiotic prescribing for the most common conditions that affect kids are relatively straightforward,” Dr. Gerber said. For example, the CDC’s prescription guidelines for pharyngitis recommend using a penicillin (a narrow-spectrum drug) to treat group A strep, reserving broader-spectrum agents for patients allergic to penicillin.

Because pediatric antibiotic prescription rates have been documented, with this project Dr. Gerber and his team will seek to learn more about the safety and efficacy of those drugs. “Using parent- and patient-centered outcomes, this study is designed to identity which antibiotic choices best optimize clinical outcomes while minimizing side effects,” said Dr. Gerber.

Using Qualitative Research to Inform Quantitative Research

Dr. Gerber’s project will be conducted in two parts: first the researchers will conduct in-person qualitative interviews with parents and children who visit the pediatrician’s office with ARTI symptoms. The goal of this interview study is to allow parents and children to express, in their own words, the outcomes related to antibiotics that are most important to them. The investigators will then use the data gleaned from these interviews to generate outcomes that will be assessed the study’s second arm.

To oversee the interviews, Dr. Gerber has teamed with a medical sociologist, Julia Szymczak, PhD. Dr. Szymczak, a postdoctoral fellow in the Division of Infectious Diseases, designed the interviews to “help generate outcomes that can then be tested quantitatively,” she said. The strength of qualitative research “lies in its open-endedness and ability to generate insights that you hadn’t previously considered.” This first arm of the study is already underway, and the researchers are ultimately looking to recruit 100 parents and children across the CHOP network.

In the second half of the project — tentatively scheduled to begin in the fall — the researchers will conduct phone interviews with a much larger patient population, approximately 3000 families. They will follow the patients prospectively, calling 10 and 30 days following an antibiotic prescription. In addition to assessing traditional medical outcomes, the investigators are seeking to gauge “outcomes that aren’t typically on a medical chart” — like diarrhea, sleeplessness, absence from school, and missed days of work, which may not require a visit to the hospital but can be disruptive for patients and families, Dr. Gerber said.

 Project’s Possible Implications

The possible implications of the project are wide-ranging, as antibiotic prescribing, and ARTI, are so widespread. “This project was selected for PCORI funding not only for its scientific merit but also for its potential to fill an important gap in our health knowledge and ultimately help patients and those who care for them make more fully informed decisions about their care,” said PCORI Executive Director Joe Selby, MD, MPH.

There are a number of side effects and adverse events associated with antibiotic use. Side effects associated with penicillin, for instance, include upset stomach and diarrhea, and in serious cases rash, fever, and facial swelling. Erythromycin is also associated with upset stomach and diarrhea, as well as vomiting, stomach cramps, and mild skin rash. In rare cases it can cause hives, difficulty breathing, jaundice, and vaginal infections.

Additionally, there is a concern that overuse of antibiotics in general can lead to drug-resistant infections. Calling antibiotic resistance “a quickly growing, extremely dangerous health problem,” the CDC notes that 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. Many more people die from other conditions that were complicated by an antibiotic-resistant infection.”

Dr. Gerber’s hope is that his project helps to empower families to ask the correct questions about their children’s care, and that it helps clinicians design better interventions.

“Given that these four conditions account for 80 percent of antibiotic prescribing, and given that outpatient antibiotic prescribing accounts for 80 percent of all antibiotic prescribing, even a small difference in efficacy can have huge implications,” Dr. Gerber said.

And for her part, Dr. Szymczak said the study is “a very comprehensive effort to be patient-centered,” adding that it is “exciting because it makes our science more relevant to people in the real world.”

In addition to Drs. Gerber and Szymczak, Children’s Hospital’s Theoklis Zaoutis, MD, MSCE, Alex Fiks, MD, and Louis M. Bell, MD, have all contributed to Dr. Gerber’s investigation.

To read more about Dr. Gerber’s project, see its PCORI page or the CPCE website.

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