Researchers unraveled a medical mystery that left six patients dead last year at the National Institutes of Health’s elite research hospital, demonstrating that gene sequencing can help in the fight against hospital-acquired infections.
The NIH researchers’ sleuth work—they stalked a deadly strain of antibiotic-resistant Klebsiella pneumonia through 18 patients at the agency’s 243-bed Clinical Center in Bethesda, Md.—was detailed in a study published online Wednesday by Science Translational Medicine. The scientists sequenced the genes of the microbial invader to reveal its exact path from patient to patient until the deadly outbreak was contained in December.
“Our standard shoe-leather methods [of tracking disease] really could not elucidate the transmission in anywhere near the precision we got,” said Tara Palmore, a hospital epidemiologist at the Clinical Center.
Lessons from the episode could help hospitals that have struggled to reduce the spread of difficult-to-treat infections, including drug-resistant bacteria that have evolved to survive most antibiotics. There are more than one million health-care-associated infections each year, according to the U.S. Centers for Disease Control and Prevention. The CDC estimates that one in 20 hospitalized patients has one of these infections.
Hospitals generally disclose bursts of infections to the CDC, patients and other authorities. The Clinical Center did not publicly disclose the outbreak until now. In addition to the six patients who died from the infection, the deaths of five other infected patients at the center were attributed to their underlying diseases.
The outbreak began on June 13, 2011, when a 43-year-old female patient with a history of multiple drug-resistant infections was transferred from a New York City hospital. Although the patient was admitted into an isolation area, the Klebsiella colony she had brought with her into the hospital soon leapt to at least three other patients. The NIH did not identify the New York hospital.
After two other patients became infected, researchers began sequencing the bacteria’s genes and determined the bug matched the one in the initial New York patient, meaning the new infections had been acquired in the NIH hospital. The study demonstrates that health-care facilities can be more definitively linked to hard-to-trace infections, a broad problem that experts say leaves as many as 100,000 Americans dead each year.
The fact that the outbreak happened at the center, which is in the vanguard of infection-prevention efforts, underscores the need for hospitals to improve those efforts, said Peter Pronovost, senior vice president for patient safety at Johns Hopkins Medicine. “In many places, this outbreak would never have been identified,” he said, because hospitals might not recognize a pneumonia death as a preventable, hospital-acquired infection.
Klebsiella bacteria are a leading cause of health-care-associated infections, including pneumonia. Patients breathing with the help of ventilators, hooked up to catheters and taking long courses of certain antibiotics are at the highest risk for the infections, the CDC said.
The research showed that “what we did to isolate [the first patient] was insufficient, and what we did to do surveillance to see if any other patient was exposed was insufficient,” said Julie Segre, a senior investigator at the NIH’s National Human Genome Research Institute. But sequencing the bug as the outbreak spread—a novel effort facilitated by new genomic tools that can decode genes in almost real time—helped focus efforts to contain it. The last patient died in December, and the hospital has seen no additional cases tied to the outbreak.
While traditional tests can identify infections such as Klebsiella, “genomic sequencing provides a higher-powered microscope,” Dr. Segre said. The team compared six million base pairs of genetic material in the bacteria collected from 18 infected patients, and charted the mutations as the bug spread through the facility.
Researchers estimated when a patient picked up the bacteria by determining the number of mutations the fast-evolving bugs underwent each week. By comparing such mutations, they could also tell whether an infection had leapt from a bacterial colony in a patient’s throat or lungs, a potential indication of how it spread, such as from ventilator tubes.
The sequencing work also allowed the hospital to track the exact route of the infections as they ping-ponged around the hospital. Without such sequencing, it can be hard to determine whether patients arrive with infections or contract them from other patients.
Hospitals have resisted efforts to require mandatory reporting of infection rates, in part because of the longstanding difficulties of establishing whether patients arrive with infections.
At community hospitals, patients routinely arrive from nursing homes, emergency rooms and other facilities with health-care-acquired infections—or they pick up bugs bred within the hospital.
“Sometimes, we don’t know,” said Linda R. Greene, director of infection prevention at Rochester General Health System in New York. Knowing definitively when the hospital is responsible could help push doctors and nurses to work harder to prevent infections, she said.
The researchers expect their work to force hospitals to take on infections more directly. “This level of certainty is going to change the concept of hospitals’ responsibility,” said Dr. Segre. But, she added, many hospitals may not have the resources to incorporate genomics into their infection-control departments.
The NIH team used sequencing devices made by drug and diagnostics maker Roche Holding AG ROG.VX -0.69% and Illumina Inc., ILMN -0.24% a gene-sequencing company, that cost between $125,000 and $500,000 each, Dr. Segre said. She said the team spent an additional $2,000 a specimen to sequence 18 samples for the study.
Until the technique is proven effective in more outbreaks, it will not be clear the benefits outweigh the time and costs that come with the genetic tools, said William Jarvis, a hospital-infection consultant and former CDC official. It’s “hard to predict the value of this technology,” he said.
At the NIH’s Clinical Center, researchers began sequencing the bacteria specimens in mid-August after three patients displayed symptoms. They determined that the third patient to become infected had actually acquired the bacteria from the original New York patient while both were being treated in the ICU, before passing it on to the second patient who showed symptoms.
The first patient survived, after being treated with a toxic antibiotic called colistin, but the infections began leaping to a new patient each week. Hospital workers cordoned off a portion of the hospital to contain the outbreak, instituted strict hand-washing policies and other measures, and banned traffic between the quarantined portion of the hospital and other wards.
The researchers determined that the bug was also spreading from sink drains, based on the genetic trail, possibly by splashing upward as people washed their hands. “We didn’t test this possibility—we just had the plumbers take out the drain pipes,” Dr. Segre said in an email.