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Pittsburgh: C. diff's ground zero
Source: http://www.thespec.com/article/371828
Out of Control - Part IV: Pittsburgh: C. diff's ground zero
September 17, 2008
Naomi Powell
The Hamilton Spectator
Over and over, patients were wheeled into the operating room of the University of Pittsburgh, Presbyterian hospital, their colons grossly inflamed.
Surgeons cut the infected organs out, often to no avail. Most patients died shortly after they were wheeled out.
Dr. Ramsey Dallal, then a young surgical trainee, started digging through the hospital records. Sixteen colons removed in 2000, all riddled with the same bacteria, Clostridium difficile.
C. diff? For decades, the bug had been in every hospital, the pest behind painful diarrhea and sometimes worse. But not normally a serial killer -- until now.
C. diff had morphed into a deadly new strain, one resistant to antibiotics, targeting the elderly and capable of wreaking havoc in hospitals.
An old bug, with a frightening new identity.
"You're seeing these patients come up over and over again, people dying of C. difficile colitis," said Dallal, now a bariatric surgeon at Philadelphia's Albert Einstein Healthcare Network.
"It was strange ... You've never been taught that this is C. diff."
The 2000 Pittsburgh outbreak was the epidemic strain's first known appearance in North America. It wouldn't be its last.
The superbug has become the most widespread C. diff strain, causing outbreaks in hospitals across the United States, Canada and Europe.
Each time, it has left doctors puzzled by how it passes through some patients quietly, without causing any damage, and rips through others, killing them within days and sometimes hours of its appearance.
At the peak of the Pittsburgh outbreak, the number of C. diff cases in the hospital tripled. The number of patients facing life-threatening symptoms doubled.
"Our patient-safety people were freaked out by the fact that we were having deaths related to C. diff," said Dr. Carlene Muto, medical director of infection control at the hospital. "We believed this to be a nuisance disease before this happened."
Muto expected studies on the Pittsburgh outbreak to send shock waves through the medical community. But though it would forever change Pittsburgh's understanding of C. difficile, the outbreak caused barely a ripple outside the city.
"The interesting thing is for quite a while, no one believed there was anything new or novel with C. difficile disease," Muto said. "It took us a long time to get our case control study paper published because nobody was that interested."
Pittsburgh's story grabbed the attention of at least one expert.
When Dr. Dale Gerding heard about the 16 C. diff colectomies in the hospital, he "just about fell over."
"I couldn't believe it. I had probably seen two or three patients in 20 years undergo a colectomy for C. diff and they had 16 in one year?"
A professor of medicine at Chicago's Loyola University, Gerding had collected C. diff samples since the early 1980s, when a test was first developed for the bug.
The strain that attacked in Pittsburgh -- called NAP1, BI or 027, depending on the system used to identify it -- matched a sample Gerding had collected in 1984. Both produced a pair of toxins (labelled A and B) and both had a genetic mutation that prevented a "repressor gene" from limiting the amount of toxins produced.
There was one crucial difference: The Pittsburgh strain had acquired a stubborn resistance to a class of antibiotics known as fluoroquinolones.
Among the most common hospital antibiotics, fluoroquinolones came into broad use in the 1990s as a treatment for respiratory illness.
NAP1's new armour against them made it enormously powerful. While the fluoroquinolones swept aside protective bacteria in the gut, NAP1's resistance allowed it to stay and thrive.
It could grow and release its toxins -- the bug was later found to produce 16 times more toxin A and 23 times more toxin B than other strains. It could inflame the bowel and eventually pass on more spores through diarrhea, further contaminating the hospital environment.
Outside the body -- where the bacteria struggles to survive in oxygen -- the spores provide an ideal shelter. They allow the bacteria to hide, dormant, inside a tiny indestructible vessel that can withstand most hospital-grade cleaners.
The bug only comes to life as active bacteria inside the colon, where it is believed to feed on the carbohydrates in our bodies. It grows rapidly as long as it has enough to eat, then hits a stationary phase, when it releases toxins and more spores.
Exactly how and when the bug evolved to outsmart fluoroquinolones remains a mystery that experts chalk up to the constant, spontaneous genetic evolution of an ancient organism.
"It's got different armour," said John Bartlett, an expert on infectious disease at Baltimore's Johns Hopkins University.
"It causes disease differently and now it's an epidemic in the U.S. and in Europe and all over the place.
"A roaring epidemic. But it's an old bug. That's what's interesting."
If Pittsburgh was a wake-up call to C. diff's heightened potential to kill, Quebec was a screaming alarm bell. The bug's deadly attack on that province, which began in 2002, would eventually kill at least 2,000 people.
For Dr. Mark Miller, it began in April of that year, with a scenario eerily similar to Dallal's in Pittsburgh.
"One of the colorectal surgeons called me and said, 'I just took out my second colon for C. diff in a month,' " said the director of infection prevention and control at Montreal's Jewish General Hospital. "He asked me if there was something going on."
Miller asked around. His colleagues at other Montreal hospitals were all experiencing the same thing: higher infection rates and deaths.
That fall, the doctors called an emergency meeting. Over pizza, they mapped out an ad hoc system to track the number of patients dying of C. difficile.
"We met again in December and put our numbers down on the table," Miller said. "We were absolutely horrified."
At the height of the Quebec epidemic, 15 per cent of all patients infected with C. diff died. In Miller's hospital alone, there was an average of 40 cases of the disease and seven deaths every month.
And everywhere in the region, doctors were finding that traditional outbreak remedies such as handwashing and isolating patients weren't enough, according to Dr. Michael Libman, director of the infectious disease division at McGill University Health Centre.
"The total failure of our initial infection control measures was a shock," he said. "Essentially, our getting together as a group was a bit of a panic reaction. We were getting together because we didn't know what to do."
Controlling the new strain and removing its spores from the environment required a previously unseen level of vigilance.
Visitors and staff draped in gowns and gloves became a common sight in the hallways of Montreal hospitals. A new set of rules governing handwashing and cleaning techniques was enforced. And the Quebec government sent teams of professionals into hospitals to ensure proper cleaning, isolation and antibiotic management.
"What we've learned in Quebec is this bug is extremely unforgiving," Miller said. "You make one or two slip-ups in infection control and it comes back with a vengeance. It just doesn't stay put."
Around the same time that hospitals were fighting NAP1 in Quebec, the superbug was launching attacks in Georgia, Illinois, Maine, New Jersey, Oregon and Pennsylvania. Though some of the bugs had slightly different DNA fingerprints -- indeed, Pittsburgh's bug bore a slightly different DNA pattern than the one in Quebec -- all were versions of NAP1.
The damage in Quebec was severe enough to earn the bug a new nickname: the Quebec strain.
C. diff has since made its mark in Ontario, attacking first at the Peterborough Regional Health Centre in 2002. Though researchers never tested for NAP1 in the outbreak, in which 17 patients died either directly or indirectly because of C. diff, the strain was later found at the hospital.
The bug's more widely publicized assaults in Ontario came later. Burlington's Joseph Brant Memorial Hospital remains the site of the deadliest Ontario attack on record. There, 91 patients infected with C. difficile died in a 20-month outbreak that started in May 2006.
Other episodes occurred at the Sault Area Hospital in Sault Ste. Marie and Barrie's Royal Victoria Hospital in 2006, followed by Oakville-Trafalgar Memorial Hospital, Mississauga's Trillium Health Centre and Simcoe's Norfolk General Hospital in 2007.
These are only the incidents that the public knows about.
A tally by The Spectator shows at least 460 patients infected with C. diff have died at just 22 of Ontario's 157 hospitals since 2006. The newspaper is the only reporting source to date for Ontario C. diff fatalities.
Fighting the bug remains a struggle. Some say stricter cleaning regimes and updated hospital designs are necessary to minimize the number of C. diff spores. Others believe the best way to combat the bug is in hospital pharmacies, through the restriction of fluoroquinolones and other high-risk antibiotics.
Even then, it may be only a matter of time before the bug learns to outsmart the next drug thrown in its way.
"The expression some people have used is squeezing the balloon," Libman said. "You can squeeze off quinolone use, but the reality is some other antibiotic is going to have to pick up the slack. And then most likely the bug will just evolve to develop resistance to that one."
Few believe C. diff infection or death rates have peaked in Ontario, where the extent of the bug's presence will remain unknown until mandatory reporting begins on Sept. 26.
"It's not like the war against bacteria and infections is something we're going to win," Libman said. "It's going to go on forever."
Out of Control is a three-month investigation by Spectator reporters Carmela Fragomeni, Naomi Powell and Joan Walters into killer superbug C. difficile. It examines the crisis in patient safety in hospitals, the response by government and hospital administrators and the impact on victims and their families. In May, Joseph Brant Memorial Hospital revealed 91 patients died of the virulent superbug C. difficile between May 2006 and December 2007 in the worst recorded outbreak in Ontario's history. Other C. diff outbreaks have killed hundreds of patients in Ontario hospitals since 2006. JOAN WALTERS can be reached at 905-526-3302 or jwalters@thespec.com. NAOMI POWELL can be reached at 905-526-4620 or npowell@thespec.com. CARMELA FRAGOMENI can be reached at 905-526-3392 or cfragomeni@thespec.co
Inset:
C. difficile in North America
Clostridium difficile was first identified in 1935 when researchers discovered the rod-shaped bacterium in the stool of a healthy infant. They initially named it Bacillus difficilis, "the difficult bacteria," because it was tough to grow in the lab. It was later renamed Clostridium difficile, placing it in a separate class of oxygen-resistant bacteria. Though the organism was shown to produce a lethal toxin in experiments with mice, its discovery got little attention because it was not found to cause problems in humans. In 1974, researchers at Barnes-Jewish Hospital in St. Louis found a link between the antibiotic Clindamycin and pseudomembranous colitis -- an infection of the colon that causes inflammation, diarrhea, abdominal cramps and fever. C. diff's role in colitis wasn't uncovered until 1977, when Dr. John Bartlett at Baltimore's Johns Hopkins University fingered it as the true cause of the disease. Though many strains of C. diff can be deadly, the NAP1 strain's rapid spread and ability to cause severe disease has stunned experts.
* 2000: The first known outbreak of the deadly NAP1 strain strikes the University of Pittsburgh, Presbyterian hospital.
* 2000-2003: The NAP1 strain of C. diff pops up in outbreaks at health care institutions in Georgia, Illinois, Maine, New Jersey, Oregon and Pennsylvania.
* 2002: A massive outbreak of the superbug hits hospitals across Montreal and Sherbrooke, Que. At least 2,000 infected patients die.
* 2002: The Atlanta Veterans Affairs Medical Center has an outbreak of C. difficile in its long-term care facility. Though the death rate does not increase, researchers tie the outbreak to the use of new fluoroquinolone antibiotics.
* 2002: A cluster of deaths directly or indirectly caused by C. difficile occurs at the Peterborough Regional Health Centre. A Ministry of Health epidemiologist and others do not test to see if NAP1 is responsible, though the bug is later found at the hospital.
In the years that follow, NAP1's assault on North America is relentless. It is identified in 37 states and most Canadian provinces.
* 2006: NAP1 moves full-force into Ontario. It causes or contributes to deaths at the Sault Area Hospital, Barrie's Royal Victoria Hospital, Oakville-Trafalgar Memorial Hospital, Norfolk General Hospital and Quinte Health Care.
In 2007, the bug is linked to deaths at Mississauga's Trillium Health Centre. In the deadliest Ontario outbreak on record, 91 infected patients die at Joseph Brant Memorial Hospital in Burlington.
A tally by The Spectator shows at least 460 patients infected with C. diff have died at just 22 of Ontario's 157 hospitals since 2006.
That outbreak in 2000 marked the fatal NAP1 strain's arrival in North America. Its rapid spread and the severe toll it took on its victims shocked experts.
Out of Control - Part IV: Pittsburgh: C. diff's ground zero
September 17, 2008
Naomi Powell
The Hamilton Spectator
Over and over, patients were wheeled into the operating room of the University of Pittsburgh, Presbyterian hospital, their colons grossly inflamed.
Surgeons cut the infected organs out, often to no avail. Most patients died shortly after they were wheeled out.
Dr. Ramsey Dallal, then a young surgical trainee, started digging through the hospital records. Sixteen colons removed in 2000, all riddled with the same bacteria, Clostridium difficile.
C. diff? For decades, the bug had been in every hospital, the pest behind painful diarrhea and sometimes worse. But not normally a serial killer -- until now.
C. diff had morphed into a deadly new strain, one resistant to antibiotics, targeting the elderly and capable of wreaking havoc in hospitals.
An old bug, with a frightening new identity.
"You're seeing these patients come up over and over again, people dying of C. difficile colitis," said Dallal, now a bariatric surgeon at Philadelphia's Albert Einstein Healthcare Network.
"It was strange ... You've never been taught that this is C. diff."
The 2000 Pittsburgh outbreak was the epidemic strain's first known appearance in North America. It wouldn't be its last.
The superbug has become the most widespread C. diff strain, causing outbreaks in hospitals across the United States, Canada and Europe.
Each time, it has left doctors puzzled by how it passes through some patients quietly, without causing any damage, and rips through others, killing them within days and sometimes hours of its appearance.
At the peak of the Pittsburgh outbreak, the number of C. diff cases in the hospital tripled. The number of patients facing life-threatening symptoms doubled.
"Our patient-safety people were freaked out by the fact that we were having deaths related to C. diff," said Dr. Carlene Muto, medical director of infection control at the hospital. "We believed this to be a nuisance disease before this happened."
Muto expected studies on the Pittsburgh outbreak to send shock waves through the medical community. But though it would forever change Pittsburgh's understanding of C. difficile, the outbreak caused barely a ripple outside the city.
"The interesting thing is for quite a while, no one believed there was anything new or novel with C. difficile disease," Muto said. "It took us a long time to get our case control study paper published because nobody was that interested."
Pittsburgh's story grabbed the attention of at least one expert.
When Dr. Dale Gerding heard about the 16 C. diff colectomies in the hospital, he "just about fell over."
"I couldn't believe it. I had probably seen two or three patients in 20 years undergo a colectomy for C. diff and they had 16 in one year?"
A professor of medicine at Chicago's Loyola University, Gerding had collected C. diff samples since the early 1980s, when a test was first developed for the bug.
The strain that attacked in Pittsburgh -- called NAP1, BI or 027, depending on the system used to identify it -- matched a sample Gerding had collected in 1984. Both produced a pair of toxins (labelled A and B) and both had a genetic mutation that prevented a "repressor gene" from limiting the amount of toxins produced.
There was one crucial difference: The Pittsburgh strain had acquired a stubborn resistance to a class of antibiotics known as fluoroquinolones.
Among the most common hospital antibiotics, fluoroquinolones came into broad use in the 1990s as a treatment for respiratory illness.
NAP1's new armour against them made it enormously powerful. While the fluoroquinolones swept aside protective bacteria in the gut, NAP1's resistance allowed it to stay and thrive.
It could grow and release its toxins -- the bug was later found to produce 16 times more toxin A and 23 times more toxin B than other strains. It could inflame the bowel and eventually pass on more spores through diarrhea, further contaminating the hospital environment.
Outside the body -- where the bacteria struggles to survive in oxygen -- the spores provide an ideal shelter. They allow the bacteria to hide, dormant, inside a tiny indestructible vessel that can withstand most hospital-grade cleaners.
The bug only comes to life as active bacteria inside the colon, where it is believed to feed on the carbohydrates in our bodies. It grows rapidly as long as it has enough to eat, then hits a stationary phase, when it releases toxins and more spores.
Exactly how and when the bug evolved to outsmart fluoroquinolones remains a mystery that experts chalk up to the constant, spontaneous genetic evolution of an ancient organism.
"It's got different armour," said John Bartlett, an expert on infectious disease at Baltimore's Johns Hopkins University.
"It causes disease differently and now it's an epidemic in the U.S. and in Europe and all over the place.
"A roaring epidemic. But it's an old bug. That's what's interesting."
If Pittsburgh was a wake-up call to C. diff's heightened potential to kill, Quebec was a screaming alarm bell. The bug's deadly attack on that province, which began in 2002, would eventually kill at least 2,000 people.
For Dr. Mark Miller, it began in April of that year, with a scenario eerily similar to Dallal's in Pittsburgh.
"One of the colorectal surgeons called me and said, 'I just took out my second colon for C. diff in a month,' " said the director of infection prevention and control at Montreal's Jewish General Hospital. "He asked me if there was something going on."
Miller asked around. His colleagues at other Montreal hospitals were all experiencing the same thing: higher infection rates and deaths.
That fall, the doctors called an emergency meeting. Over pizza, they mapped out an ad hoc system to track the number of patients dying of C. difficile.
"We met again in December and put our numbers down on the table," Miller said. "We were absolutely horrified."
At the height of the Quebec epidemic, 15 per cent of all patients infected with C. diff died. In Miller's hospital alone, there was an average of 40 cases of the disease and seven deaths every month.
And everywhere in the region, doctors were finding that traditional outbreak remedies such as handwashing and isolating patients weren't enough, according to Dr. Michael Libman, director of the infectious disease division at McGill University Health Centre.
"The total failure of our initial infection control measures was a shock," he said. "Essentially, our getting together as a group was a bit of a panic reaction. We were getting together because we didn't know what to do."
Controlling the new strain and removing its spores from the environment required a previously unseen level of vigilance.
Visitors and staff draped in gowns and gloves became a common sight in the hallways of Montreal hospitals. A new set of rules governing handwashing and cleaning techniques was enforced. And the Quebec government sent teams of professionals into hospitals to ensure proper cleaning, isolation and antibiotic management.
"What we've learned in Quebec is this bug is extremely unforgiving," Miller said. "You make one or two slip-ups in infection control and it comes back with a vengeance. It just doesn't stay put."
Around the same time that hospitals were fighting NAP1 in Quebec, the superbug was launching attacks in Georgia, Illinois, Maine, New Jersey, Oregon and Pennsylvania. Though some of the bugs had slightly different DNA fingerprints -- indeed, Pittsburgh's bug bore a slightly different DNA pattern than the one in Quebec -- all were versions of NAP1.
The damage in Quebec was severe enough to earn the bug a new nickname: the Quebec strain.
C. diff has since made its mark in Ontario, attacking first at the Peterborough Regional Health Centre in 2002. Though researchers never tested for NAP1 in the outbreak, in which 17 patients died either directly or indirectly because of C. diff, the strain was later found at the hospital.
The bug's more widely publicized assaults in Ontario came later. Burlington's Joseph Brant Memorial Hospital remains the site of the deadliest Ontario attack on record. There, 91 patients infected with C. difficile died in a 20-month outbreak that started in May 2006.
Other episodes occurred at the Sault Area Hospital in Sault Ste. Marie and Barrie's Royal Victoria Hospital in 2006, followed by Oakville-Trafalgar Memorial Hospital, Mississauga's Trillium Health Centre and Simcoe's Norfolk General Hospital in 2007.
These are only the incidents that the public knows about.
A tally by The Spectator shows at least 460 patients infected with C. diff have died at just 22 of Ontario's 157 hospitals since 2006. The newspaper is the only reporting source to date for Ontario C. diff fatalities.
Fighting the bug remains a struggle. Some say stricter cleaning regimes and updated hospital designs are necessary to minimize the number of C. diff spores. Others believe the best way to combat the bug is in hospital pharmacies, through the restriction of fluoroquinolones and other high-risk antibiotics.
Even then, it may be only a matter of time before the bug learns to outsmart the next drug thrown in its way.
"The expression some people have used is squeezing the balloon," Libman said. "You can squeeze off quinolone use, but the reality is some other antibiotic is going to have to pick up the slack. And then most likely the bug will just evolve to develop resistance to that one."
Few believe C. diff infection or death rates have peaked in Ontario, where the extent of the bug's presence will remain unknown until mandatory reporting begins on Sept. 26.
"It's not like the war against bacteria and infections is something we're going to win," Libman said. "It's going to go on forever."
Out of Control is a three-month investigation by Spectator reporters Carmela Fragomeni, Naomi Powell and Joan Walters into killer superbug C. difficile. It examines the crisis in patient safety in hospitals, the response by government and hospital administrators and the impact on victims and their families. In May, Joseph Brant Memorial Hospital revealed 91 patients died of the virulent superbug C. difficile between May 2006 and December 2007 in the worst recorded outbreak in Ontario's history. Other C. diff outbreaks have killed hundreds of patients in Ontario hospitals since 2006. JOAN WALTERS can be reached at 905-526-3302 or jwalters@thespec.com. NAOMI POWELL can be reached at 905-526-4620 or npowell@thespec.com. CARMELA FRAGOMENI can be reached at 905-526-3392 or cfragomeni@thespec.co
Inset:
C. difficile in North America
Clostridium difficile was first identified in 1935 when researchers discovered the rod-shaped bacterium in the stool of a healthy infant. They initially named it Bacillus difficilis, "the difficult bacteria," because it was tough to grow in the lab. It was later renamed Clostridium difficile, placing it in a separate class of oxygen-resistant bacteria. Though the organism was shown to produce a lethal toxin in experiments with mice, its discovery got little attention because it was not found to cause problems in humans. In 1974, researchers at Barnes-Jewish Hospital in St. Louis found a link between the antibiotic Clindamycin and pseudomembranous colitis -- an infection of the colon that causes inflammation, diarrhea, abdominal cramps and fever. C. diff's role in colitis wasn't uncovered until 1977, when Dr. John Bartlett at Baltimore's Johns Hopkins University fingered it as the true cause of the disease. Though many strains of C. diff can be deadly, the NAP1 strain's rapid spread and ability to cause severe disease has stunned experts.
* 2000: The first known outbreak of the deadly NAP1 strain strikes the University of Pittsburgh, Presbyterian hospital.
* 2000-2003: The NAP1 strain of C. diff pops up in outbreaks at health care institutions in Georgia, Illinois, Maine, New Jersey, Oregon and Pennsylvania.
* 2002: A massive outbreak of the superbug hits hospitals across Montreal and Sherbrooke, Que. At least 2,000 infected patients die.
* 2002: The Atlanta Veterans Affairs Medical Center has an outbreak of C. difficile in its long-term care facility. Though the death rate does not increase, researchers tie the outbreak to the use of new fluoroquinolone antibiotics.
* 2002: A cluster of deaths directly or indirectly caused by C. difficile occurs at the Peterborough Regional Health Centre. A Ministry of Health epidemiologist and others do not test to see if NAP1 is responsible, though the bug is later found at the hospital.
In the years that follow, NAP1's assault on North America is relentless. It is identified in 37 states and most Canadian provinces.
* 2006: NAP1 moves full-force into Ontario. It causes or contributes to deaths at the Sault Area Hospital, Barrie's Royal Victoria Hospital, Oakville-Trafalgar Memorial Hospital, Norfolk General Hospital and Quinte Health Care.
In 2007, the bug is linked to deaths at Mississauga's Trillium Health Centre. In the deadliest Ontario outbreak on record, 91 infected patients die at Joseph Brant Memorial Hospital in Burlington.
A tally by The Spectator shows at least 460 patients infected with C. diff have died at just 22 of Ontario's 157 hospitals since 2006.
That outbreak in 2000 marked the fatal NAP1 strain's arrival in North America. Its rapid spread and the severe toll it took on its victims shocked experts.