The outbreak of the antibiotic-resistant bacteria known as Klebsiella pneumoniae was not made public until Wednesday, when NIH researchers published a scientific paper describing the advanced genetic technology they deployed to trace the outbreak.
This was “the proverbial superbug that we’ve all worried about for a long time,” said Tara Palmore, an infection control specialist at the Bethesda hospital.
With some 99,000 U.S. deaths attributed to hospital-borne infections annually, the NIH outbreak provides a stark case study of the dangers of the latest wave of hospital-bred bacteria and the extreme measures hospitals must adopt to stem the rising superbug tide.
The NIH Clinical Center now screens every patient transferring from another facility for superbugs, tests every patient in the intensive care unit twice a week and screens every patient monthly.
“This was our introduction to [antibiotic-resistant] Klebsiella,” Palmore said. “We hoped we would never see it.”
Clinical Center spokeswoman Maggie McGuire said the hospital did not alert the public earlier because Klebsiella infections do not trigger mandated reports to the Centers for Disease Control and Prevention like other infectious diseases do, such as HIV.
She also downplayed such outbreaks as too common to be newsworthy.
“There are . . . hospital-
acquired infections in almost every hospital in the country,” she said. “It’s happening everywhere.”
Nationwide, about 6 percent of hospitals are battling outbreaks of the class of superbugs known as carbapenem-resistant bacteria, which includes Klebsiella, said Alexander Kallen of the CDC. These bacteria usually live harmlessly in our intestinal tracts, and they pose little or no threat to patients with healthy immune systems. But in patients with compromised immune systems, the bacteria can turn dangerous, gaining an enzyme that defeats even the most powerful antibiotics. That’s what happened at NIH.
The six patients who died of bloodstream Klebsiella infections had immune systems weakened by cancer, anti-rejection drugs given after organ transplants, and genetic disorders.
The CDC detected this type of antibiotic-resistant bacteria in 2000. “Since then, we’ve seen it spread across the country,” Kallen said, to 41 states.
Later this year, the CDC is launching a program in 10 cities, including Baltimore, to watch for hospital-borne outbreaks of Klebsiella and related superbugs. CDC staff will review hospital records, Kallen said, and hospital labs will be asked to report any antibiotic-resistant bacteria to the CDC.
At NIH, the superbug arrived in June 2011. Hours before a 43-year-old female lung transplant patient arrived from New York City, NIH nurses noted something startling in her chart: She was carrying an antibiotic-resistant infection.
Desperately wanting to contain the superbug, the NIH staff isolated the woman in the ICU. Staff members donned gowns and gloves before entering her room. Her nurses cared for no other patients.
After the patient was discharged the next month, Palmore and her staff thought these measures had worked. There were no signs that the bacteria had spread.
But a few weeks later, Palmore was “horrified,” she said, when a second patient tested positive for the bacteria. A third and fourth soon followed. Those three patients died as the bacteria grew impervious to every known antibiotic — even experimental new drugs.
The pattern baffled Palmore. If the superbug had jumped from the New York patient, it should have showed up sooner in three new patients.
But by reading the bacteria’s DNA, scientists at the NIH’s National Human Genome Research Institute saw that the organisms from patients No. 2 and 3 were so closely related — differing at just one or two genetic letters out of 6 million — they had to have come from the New York patient.
That meant two unsettling things, said Julie Segre, the scientist at NHGRI who led the DNA analysis. The bacteria had lingered for weeks unnoticed, either in the hospital or in the new patients; and the hospital’s infection control measures for the New York patient had failed. Details of the genetic analysis and the outbreak were published Thursday in the journal Science Translational Medicine.
“It still got out, after only two 24-hour periods in the ICU,” Palmore said. “During that time, the bacteria were transmitted to three people.”
With genetic evidence of a single-source outbreak, in mid-August the Palmore-led staff quickly rolled out strict new measures. They built a wall in the ICU and moved the Klebsiella-positive patients into a new, six-bed unit. Blood pressure cuffs and other reusable gear were tossed after one use.
The hospital hired monitors to ensure doctors and nurses were donning gowns, gloves and masks and scrubbing their hands. If monitors fell asleep or otherwise shirked, Palmore fired them and found new ones. At one point, nine monitors were on duty.
“It was an enormous effort on a daily basis,” Palmore said.
Staff members took throat and rectal swabs from every ICU patient. When the bacteria were found in two patients outside the ICU, the sweep was broadened to every patient in the hospital.
Staff swabbed rolling carts, sinks, toilets and furniture. They hired a contractor to flood patient rooms with vaporized hydrogen peroxide — a potent disinfectant.
Still, they found Klebsiella on a ventilator that had been bleached twice. They found it in a sink drain in a patient’s room, so they tore out the plumbing. And they kept finding it in patients, at a rate of about one per week.
“Every single time a new patient, a new case came to light, it felt like a failure,” Palmore said. “It felt like a string of failures.”
As hospital staff desperately raced to stanch the outbreak, they also struggled to treat the infected. They infused patients with colistin, a decades-old antibiotic that fell out of favor after it became apparent it can severely damage the kidneys. While colistin defeated the superbug in a few NIH patients, in at least four, the bacteria evolved so rapidly it outran colistin, too. Those four died.
“This is the moment that my professors talked about when we would run out of antibiotics,” said Palmore, recalling 20-year-old medical school lectures that warned of a new era of nasty superbugs.
The strict infection-control measures eventually paid off. The last new case was found in January, and no new cases have occurred since, she said. However, two Klebsiella-positive patients remain at the hospital.
“I would say we controlled the outbreak, but we’re in constant danger of transmission from patients still here,” she said. “We’re not out of the woods yet.”
To slow the spread of superbugs, hospitals and long-term care facilities such as nursing homes must be ever-vigilant, the CDC’s Kallen said. Although most hospitals can’t afford the extreme measures the NIH implemented, the CDC encourages hospitals to adhere to the basics, such as constant hand-scrubbing and isolation of infected patients.
Surveillance is key to stemming hospital-borne outbreaks, he said, especially in light of the lack of new superbug-fighting drugs in the pharmaceutical industry’s pipeline.
“We’re talking in the range of a decade before we have new antibiotics that might be able to help,” Kallen said.