May 30, 2008 -- While bird flu and MRSA have been making headlines, a dangerous strain of C. diff has been making people sick in 38 U.S. states.
C. diff sickens about a half million Americans every year, and every year the epidemic gets about 10% bigger, CDC medical epidemiologist L. Clifford McDonald, MD, tells WebMD.
Bigger -- and more deadly. The death rate is soaring by 35% a year.
From 1999 to 2004, the bug became four times more lethal, with death rates increasing from 5.7 per million Americans to 23.7 per million Americans in 2004. During one hospital outbreak in Quebec, Canada, the one-year death rate hit 17%.
What's going on? WebMD has answers to these important questions:
- How bad is C. diff?
- Is C. diff a superbug?
- Why are C. diff cases rising so rapidly?
- Can you get C. diff from food?
- How do you get C. diff?
- Who is at risk?
- What are the symptoms?
- How is C. diff treated?
- How is C. diff prevented?
How bad is C. diff?
C. diff disease can range from mild diarrhea to life-threatening colitis. The bug produces toxins that destroy the mucosal lining of the gut.
There are many different C. diff strains circulating in the U.S. But since 2000, one of these strains has gone from a minor player to become the most frequently isolated C. diff strain. The strain has several names. Referring to its genetic fingerprint, the CDC calls it NAP1. In Europe and Canada, it's often called the 027 or BI strain.
The NAP1 strain of C. diff took off shortly after it acquired resistance to fluoroquinolone antibiotics. There's some evidence it may also have acquired some resistance to Flagyl, one of the two antimicrobial agents used to treat it (the other is vancomycin).
Antibiotic resistance isn't the only worrisome thing about NAP1. C. diff normally makes two toxins. The NAP1 strain makes 16 times more toxin A and 23 times more toxin B. And it also makes another toxin, called binary toxin, although it's not yet clear how this toxin affects humans.
To date, the NAP1 strain has been reported in 37 U.S. states and in the District of Columbia.
A recent report shows that adult C. diff hospitalizations doubled between 2000 and 2005 to about 300,000 hospitalizations a year. That's more hospitalizations than are seen with MRSA, which sends about 126,000 Americans to the hospital each year.
The CDC's C. diff expert, L. Clifford McDonald, MD, tells WebMD that if you count pediatric C. diff cases and cases in the community that do not enter the hospital, there are probably half a million U.S. cases of C. diff infection each year.
And yes, it is an epidemic: The infection rate is going up by about 10% a year. But the death rate is going up even faster, says Marya Zilberberg, MD, adjunct professor at the University of Massachusetts, Amherst, and president of the EviMed Research Group.
"The disease appears to be more likely to be fatal ... nearly doubling from a 1.2% to a 2.2% case fatality rate," Zilberberg tells WebMD.
During a hospital outbreak in Canada, the one-year mortality rate for C. diff infection was 17%.
"We're seeing increases both regionally and nationally in death certificates listing C. diff infection," McDonald says. "And hospitals are saying the same thing."
There are actually three ongoing C. diff epidemics. One is in hospitals. Another is in the community. And a third is in livestock.
Is C. diff a superbug?
"Superbug" is not a scientific term. The CDC's McDonald prefers to avoid it. The media originally coined the term to refer to germs that, like Superman, became bulletproof: That is, they became impervious to drugs that kill other germs. Dictionaries reserve the "superbug" designation for germs resistant to drugs that used to kill them.
"Superbug" has also been used to describe germs that, like many superheroes, once were normal but become super strong: That is, they became much more virulent than they used to be.
"I think if I were to use the word "superbug" I might use it to connote a particular strain or strains of a pathogen in which there has been a convergence of increased resistance to antibiotics ... and increased virulence," McDonald says.
All C. diff strains are resistant to many of the antibiotics normally used to treat other infections. In fact, that's the problem. C. diff most often strikes people whose intestinal flora have been disrupted by antibiotic treatment. But most C. diff strains remain sensitive to Flagyl and vancomycin, the drugs normally used to treat this infection.
The NAP1 strain of C. diff, however, is even more resistant to fluoroquinolone antibiotics than other C. diff strains. It makes 20 times more toxin than normal strains. And most importantly, there's evidence it causes more severe disease than other strains.
For these reasons, C. diff NAP1 is now being called a superbug, although you won't see the term in scientific reports.
Why are C. diff cases rising so rapidly?
The number of hospital patients with C. diff infection went up and down a bit from 1996 until 2000. But from 2000 to 2001 there was a steep increase -- and that increase continued at least through 2006. Preliminary data suggest the epidemic may have slowed a bit in 2007, but McDonald says it's too soon to say it's leveled off.
What happened in 2000? McDonald says that's when the NAP1 strain -- which has been around for at least 30 years -- developed fluoroquinolone resistance. This resistance, plus what McDonald calls the strain's "hypertoxin production," may explain why this strain has taken off.
Another reason for the epidemic is the rise of community-acquired C. diff infection. C. diff usually is thought of as a hospital infection, and community cases were thought to come from people who got C. diff during a hospital stay but who didn't develop symptoms until they got home.
A 2006 study in Connecticut showed that community-acquired C. diff disease struck seven people out of 100,000. One in four cases did not have the risk factors normally associated with C. diff. Moreover, a third of these cases had no exposure to antimicrobial drugs.
Where is the C. diff coming from? The vast majority of cases come from person-to-person transmission (see below).
Can you get C. diff from food?
There's troubling evidence that at least a few cases come from food. There are two reasons to think this might happen:
- In 2005, Canadian researchers bought 53 packages of beef and seven packages of veal from five grocery stores in Ontario and in Quebec. One out of five packages carried C. diff. Two-thirds of the C. diff isolates were similar to the NAP1 strain.
- C. diff isolates from human patients are quite similar to isolates found in pigs and cattle. Some of the pig isolates are almost indistinguishable from human isolates.
The CDC's McDonald says there is "at least the appearance" of "migration" of strains epidemic in food-producing animals to humans. That's because the animal epidemics occurred before the human epidemic.
"We think that direct transmission from animals to humans via the food supply, IF it occurs at all -- no one has proven this -- would account for a very small proportion of overall human C. diff infection," McDonald writes in an email to WebMD.
The CDC, together with academic researchers, is culturing samples of retail meats; results of these studies are expected soon. Eventually the CDC will look at dietary risk factors associated with community-acquired C. diff infection.
Even if you can get C. diff from food, the vast majority of infections come from person-to-person transmission (see below).
How do you get C. diff?
Even many health care professionals wrongly think everyone carries C. diff in their intestines and that the bug only overgrows when antibiotic therapy or illness disrupts the normal gut ecology and gives it room to grow.
That's not the case. Only 5% of the population is "colonized" by C. diff. And because population studies have only looked at one point in time, even most of these people may only be having a temporary infection.
Even so, more than half of Americans show evidence of a previous C. diff infection some time in their lives. This often happens soon after birth. But infants only rarely get C. diff disease. The reason for this isn't clear, but there's evidence from animal models that C. diff toxins have trouble binding to the immature gut.
C. diff bacteria are very sensitive to oxygen. But C. diff spores are another matter. They are nearly indestructible and can survive for months on dry surfaces. The CDC recommends disinfecting surfaces with bleach, because the usual hospital disinfectants don't affect it.
People with C. diff infection have millions of C. diff spores in their feces. These spores carry the infection to others via what experts indelicately call fecal-oral contact. Careful hand washing rinses the spores from contaminated hands, but alcohol gels won't do the trick.
Two things have to happen for you to get C. diff disease:
- You have to ingest C. diff spores.
- Something has to disturb the ecological balance of the normal bacteria living in your colon.
Who is at risk?
More than nine out of 10 hospital infections with C. diff occur in people who have received antibiotic treatment.
But community-acquired C. diff does not depend on antibiotics. The CDC's McDonald says there's evidence that 30% to 40% of community-acquired cases are in people not suffering a current or recent medical problem.
Fluoroquinolone antibiotics are most strongly linked to C. diff disease. Risk is also higher for patients who receive multiple antibiotics and for patients who receive longer courses of antibiotic treatment.
Other risk factors include:
- Age over 65
- Severe illness
- Nasogastric intubation
- Anti-ulcer medications. There is conflicting evidence on this.
- Long hospital stays, particularly in long-term-care facilities
It's not at all clear how long it takes to get C. diff disease after you've ingested the spores. One study that performed a series of cultures in hospital patients showed that patients who had C. diff disease were not infected the week before.
This suggests incubation can occur in less than seven days. But another study found an increased risk of C. diff disease throughout the first four weeks after leaving the hospital.
What are the symptoms of C. diff disease?
Mild C. diff disease starts with mild to moderate diarrhea with no blood in the stool. Sometimes there's cramping in the lower abdomen, too. Other than mild abdominal tenderness, there aren't any other symptoms.
Severe C. diff disease is another matter. It starts with profuse watery diarrhea and abdominal pain. Patients often have fever, nausea, and dehydration. There may be a little blood in the stool, but very bloody stool is rare.
These symptoms usually signal colitis, a serious bowel infection. If the diarrhea stops after severe colitis, it does not necessarily mean you're getting better. It could be a sign of bowl paralysis and a life-threatening condition called toxic megacolon. Most patients with toxic megacolon need surgery -- and 32% to 50% of patients who undergo surgery for C. diff disease die.
Patients with symptoms of C. diff infection should seek immediate medical attention. Mild C. diff disease can progress quickly to severe disease.
Relapse is common after C. diff infection. There's an ongoing debate over whether this is a true relapse or reinfection.
Whatever the cause, 12% to 24% of patients develop a second episode of C. diff disease within two months. Patients who have two or more relapses have a 50% to 65% chance of yet another recurrence.
How is C. diff treated?
Several different stool tests detect C. diff.
Before starting treatment, stopping treatment with whatever antibiotic you've been taking could be enough. Before effective treatments were developed, one study of 20 patients with C. diff colitis eventually recovered after stopping their antibiotic treatment.
However, doctors will almost always treat C. diff infection with antibiotics. Flagyl is the first-line treatment of choice for mild disease, although patients must be followed closely to be sure this treatment works. Vancomycin is an option for treatment for moderate or severe disease.
There is evidence that treatment with probiotics -- good bacteria that repopulate the gut -- makes antibiotic treatment more effective and prevents relapse. Saccharomyces boulardii appears to be particularly effective, although good results have been seen with Lactobacillus species as well.
How is C. diff prevented?
C. diff is a preventable disease. There are two main means of prevention:
- Wash your hands. Frequent and careful hand washing keeps you from getting C. diff spores on your hands and carrying them to your mouth.
- Use antibiotics only when absolutely necessary. Most respiratory infections are caused by viruses, so don't demand antibiotics from your doctor every time you get the sniffles or a cough.