Metagenomics vs. $10 Billion Problem: Hospital Infections 
by Nick Miller

Hospital infections make very sick people even sicker—or worse. 

Despite extensive infection control programs, hospital-based infections number more than 720,000 a year and account for around 70,000 deaths, according to the U.S. Centers for Disease Control and Prevention (CDC). A study in JAMA Internal Medicine by Harvard Medical School estimates the cost to the U.S. healthcare system at close to $10 billion a year.

One problem:  current blood tests generally do a poor job of detecting multidrug-resistant bacteria. But Cincinnati Children’s is developing—and is close to clinically testing—a new early detection system, according to David Haslam, MD, Director of the Antimicrobial Stewardship Program here.

David Haslam.

David Haslam, MD, (shown) worked closely with clinical fellow Heidi Anderson, MD, to compare whole genome sequencing information from patient samples to known DNA information about dangerous pathogens.

Haslam and colleagues have learned that some highly vulnerable children—such as children with cancer and children waiting for organ transplants—enter the hospital already carrying dangerous, resistant forms of Escherichia coli, Enterococcus faecalis or other organisms. 

The new system seeks to use emerging technology to detect the organisms before a full-blown infection can develop in these children and possibly spread to others. 

“Knowing that a child is carrying a resistant or potentially dangerous organism before getting the infection would be an indication to put the child in isolation,” explains Haslam. “It’s not just about one patient. It’s also an infection prevention methodology for the entire institution.”

The importance of the initiative is underscored by the fact that it is funded by grants from the CDC and the Center for Pediatric Genomics at Cincinnati Children’s.

Precision Metagenomics

Working closely with clinical fellow Heidi Anderson, MD, Haslam and his research team are combining the latest biology and computer technologies to advance the concept of precision metagenomics—the study of genetic material recovered from individual environmental samples.

In this case, clinicians collect fecal samples, cheek swabs or skin scrapes from seriously ill children admitted to the hospital. The team compares whole genome sequencing information from the patient samples to known DNA information about dangerous pathogens.

This allows caregivers to confirm the presence of antimicrobial-resistant genes. It also lets researchers to detect similarities in the genetic signatures of drug-resistant organisms among different patients—information that could be vital to detecting and preventing an outbreak.

But the potential advantages go even further. By looking at changes to an organism’s DNA structure, researchers can even tell how long a resistant pathogen has lived in or on a particular patient.

This information can be plugged into electronic medical records to determine which rooms, floors and hospital areas were occupied by affected kids. Tracking this information, along with seeing how organisms in different patients are related genetically, can give care staff a powerful tool for detecting and shutting down paths of infection, Haslam and Anderson say.

“This work allows us to dig into the question of whether these infections are picked up inside an institution or whether an organism was already on a patient when they came in,” Anderson says. “Infections get classified as hospital-acquired, or not, based on whether the child was in the hospital, but that doesn’t determine where the pathogen came from. Was it already in the hospital or did it come in with the child?”

How the Initiative Works

Haslam and Anderson boil down the precision metagenomics initiative into four basic steps: 

Isolating patients colonized with harmful organisms to prevent transmission 
Identifying how prevalent a multidrug-resistant pathogen is in patients (and possibly the environment) and preventing inappropriate exposures 
Eliminating pathogenic organisms with targeted probiotics or fecal transplantation
Choosing the correct antimicrobial treatment for a patient colonized with a multidrug-resistant pathogen who develops an infection.

The problem of hospital infections is serious enough that other hospitals and other groups within Cincinnati Children’s are interested in the project and asking when they can use the technology, Anderson and Haslam say.

So far, the metagenomics analysis has been performed using samples from more than 150 severely ill hospitalized children. Haslam says the approach “works very well and we’ve done all the research in humans.”

The research team is expanding testing to other patient populations, including healthier children, to assess which patients may benefit most from metagenomic screening.