Baylor College of Medicine and Texas Children’s Hospital have received a five-year, $7.5 million grant from the National Institute of Allergy and Infectious Diseases, part of the NIH, that will accelerate efforts to combat Clostridium difficile (C. diff), the most common and potentially deadly bacterial infection impacting children and adults in the U.S.
C. diff, a bacterium that causes diarrhea and severe inflammation of the colon, is a hospital-acquired infection often associated with inappropriate antibiotic use. While antibiotics are used to treat infections in children and adults, they also can disrupt the natural communities of healthy bacteria in the gut, allowing C. diff to colonize and cause disease.
“This grant will accelerate our existing work in C. diff as it relates to the human microbiome,” said Dr. Tor Savidge, associate professor of pathology & immunology at Baylor, associate director of Texas Children’s Microbiome Center and principal investigator of this study. “Our long-term goal is to achieve a better understanding of why certain patients fail antibiotic treatment and which patients are more susceptible to recurrences in order to help us develop new methods to treat C. diff infection.”
The microbiome refers to the communities of bacteria, viruses, fungi and organisms that inhabit the body. Studying the microbiome can provide important information about human disease. Researchers in this project will apply the study of the microbiome of the gut to the understanding of susceptibility to C. diff infection with a focus on how antibiotics affect the intestinal ecosystem.
The multi-institutional project will draw on the strengths of Baylor’s Alkek Center for Metagenomics and Microbiome Research, the Texas Children’s Microbiome Center and the Gulf Coast C. diff Collaborative, an initiative that was launched in 2012 that includes Baylor, Texas Children’s, Texas A&M University, The University of Texas, the University of Houston and UCLA.
“C. diff is a disorder of microbial ecology,” said Dr. James Versalovic, the Milton J. Finegold Professor of Pathology at Baylor, pathologist-in-chief at Texas Children’s and director of Texas Children’s Microbiome Center. “Some patients are more susceptible to C. diff recurrence following treatment with antibiotics while other patients may struggle with infections due to drug-resistant bacteria, including C. diff. These issues can pose enormous challenges to successfully treating these patients.”
Discovery of an intestinal ecosystem that may predict treatment failure in patients with C. diff would be a significant advance in the field and is a major goal of the project. Using a systems biology approach and the latest state-of-the-art technologies, Savidge and his research team will analyze the stool specimens of C. diff patients in the Texas Medical Center and compare them to specimens of healthy subjects. Researchers will also examine the common threads and differences between adults and children with C. diff infection. A unique aspect of this study is the inclusion of infants who are not susceptible to this pathogen.
“Babies in their first year of life may be colonized during infancy by C. diff,” Versalovic said. “Their microbiome develops very early in life but infants may or may not respond to the toxins produced by C. diff. We have much to learn about the susceptibility of young children to C. diff disease. We know that the numbers of children infected with C. diff have expanded greatly in the past 15 years.”
Developing a greater understanding of how antibiotics effect the microbiome may also help the medical community be smarter about antibiotic use. Novel technology for rapid antimicrobial resistance detection developed by co-investigator Antony Haag in the Texas Children’s Microbiome Center will facilitate physicians’ ability to prescribe the right antibiotics.
“I think some fundamental lessons will emerge in this study that will help us understand childhood infections and lifetime risk of serious infections further down the road,” Savidge said.
This collaborative study is a direct result of the Precision Medicine Initiative led by President Barack Obama designed to equip clinicians with the necessary resources to determine which treatments will work best for which patients based on specific characteristics like human genetic makeup, or in this case, the bacterial composition of a patient’s microbiome.
The NIH-funded Texas Medical Center Digestive Diseases Center provided strong seedling support to facilitate the big science proposed in this project, Savidge said. In addition, several faculty played key roles, notably Drs. Robert Britton, Anthony Haag, Joseph Petrosino and Margaret Conner, all of Baylor; Julian Hurdle, Texas A&M; and Kevin Garey, University of Houston.