Fears of a new bacterial threat
While infections with drug-resistant staph and E. coli have been grabbing headlines and public attention in recent months, a new bacterial threat has quietly emerged. Typically seen in elderly hospitalized patients, the illness has begun popping up in the community at large -- specifically among healthy younger people, including children and pregnant women.
The bacterium responsible, called Clostridium difficile, or C. difficile, has been blamed for recent outbreaks of intestinal infections in about 10 states, as well as Canada and Europe. Patients become ill with frequent bouts of watery diarrhea, fever and abdominal tenderness. In rare cases, the infection can progress to sepsis, colitis and even death.
“It’s something that is usually acquired in the hospital. But now the concern is that there is a new epidemic strain that is seen outside the hospital,” says Dr. Preeta Kutty, an investigator for the federal Centers for Disease Control and Prevention.
The strain, identified as NAP1, appears to be more virulent than its predecessor.
“There is a lot that is unknown, in particular, why we are seeing this shift from hospital cases to the community,” says Dr. Judith O’Donnell, an associate professor of medicine at Drexel University College of Medicine in Philadelphia.
C. difficile is found in feces and is one of the leading causes of hospital-acquired diarrhea. People become infected by touching items or surfaces contaminated with the bacterium and then transmitting it to their mouths. It gains ground when patients take antibiotics -- often broad-spectrum antibiotics, such as clindamycin, penicillin and increasingly the class of drugs called fluoroquinolones. The drugs upset the balance of normal bacteria in the colon, killing good types of bacteria that protect the body.
In doing so, they allow C. difficile to flourish and begin releasing toxins that damage the intestines, says Dr. L. Clifford McDonald, a medical epidemiologist with the CDC who has studied C. difficile trends. Two primary toxins, toxin A and toxin B, cause the diarrhea and inflammation.
The pattern of C. difficile illness began to change in the late ‘90s, according to data from the CDC. Cases almost doubled between 1996 and 2003, the most recent year for which data are available, rising from 31 per 100,000 to 61 per 100,000.
The emergence of the more toxic strain may be why doctors are seeing cases that are more severe and difficult to treat, McDonald says. The strain produces 16 times more toxin A and 23 times more toxin B.
The new strain may also explain why more cases are being identified outside of the hospital and in people who haven’t taken antibiotics. At the Infectious Diseases Society of America’s annual meeting this month, Kutty presented research showing that 18% of cases in one large sample of C. difficile patients from North Carolina were acquired outside the hospital.
“Almost half didn’t take antibiotics,” says McDonald. “I think that is one of the more perplexing things. That was the dogma -- that you had to take antibiotics to get the disease.”
The use of proton pump inhibitors for gastric reflux disease has been proposed as a possible cause of the C. difficile upsurge because the medications can have an antibiotic effect and can lower acid levels in the gastrointestinal tract. The acid would normally kill harmful bacteria. But the hypothesis is controversial, and Kutty’s study found no link to proton pump inhibitors.
Researchers are also stumped as to why children, and pregnant and postpartum women and other gynecological patients, seem particularly likely to be affected. A study in this month’s issue of the journal Clinical Infectious Diseases found a 6.7% rate of C. difficile in children admitted to an emergency room with severe diarrhea -- far above the 1.9% rate found in a previous study of diarrhea among children in a community.
Also, six healthy women ages 18 to 47 were diagnosed with the infection this year in Philadelphia, O’Donnell says. All developed the infection while outside the hospital.
The C. difficile emergence in this group of women “is sort of a mystery,” says O’Donnell, who presented the data at the IDSA meeting. “It warrants making sure that obstetricians and gynecologists and others caring for pregnant women are aware that this has now been seen. They should consider a diagnosis of C. difficile if a woman presents with diarrhea and fever.”
In rare, severe cases, the colon can bleed or become perforated and the patient can deteriorate rapidly. A post-hysterectomy patient in the Philadelphia cluster died of complications from the infection, and other deaths have been reported in healthy younger people. Among people with the more toxic strain, the death rate may be as high as 7% -- compared with the 1% death rate traditionally seen with C. difficile, says McDonald.
Though antibiotics can encourage C. difficile, other antibiotics are needed to curtail the infection. C. difficile is usually treated with an antibiotic called metronidazole, a drug that works particularly well in low-oxygen environments such as the colon. But some doctors recommend that severe cases be treated not with the standard treatment, but with vancomycin, an antibiotic that is usually considered the drug of last resort in curing infections.
Even people who appear successfully treated may not be cured. Up to 30% of C. difficile patients suffer a recurrence, says McDonald. And 10% to 20% of those experience a third bout.
“If you have a third bout, that is when you get into trouble,” he says. “Those people can have multiple recurrences. It can be totally life-disrupting.”
Lonna McDonald, 32, of Chino Hills (no relation to Dr. L. Clifford McDonald) took the antibiotic clindamycin for 10 days in June to treat a minor gynecological infection. She was eight weeks pregnant. Two weeks after finishing the antibiotic, the high school English teacher developed diarrhea and severe abdominal cramping. She was diagnosed with C. difficile in early July.
One week after finishing the standard metronidazole treatment, McDonald had a relapse. She also relapsed after a second round of treatment.
“I would get this sudden urge to go to the bathroom, and I had to run out of the room,” says McDonald, who had to leave her job for a period of time. “The abdominal cramping seemed to get worse and worse.”
In the meantime, she terminated her pregnancy after learning that the fetus had severe genetic defects. The defects are thought to be unrelated to the C. difficile infection, but McDonald says, “I wonder if it played a role in some way that is unknown.”
Now she is attempting to taper off a six-week course of vancomycin. “It’s frightening because I’ve read that after a couple of relapses, it’s more likely to be a resistant strain that will be with you for a while,” she says. “There is this fear of needing antibiotics again and again and what that will do to me.”
Infectious disease specialists are scurrying to study community outbreaks of C. difficile while hospitals are redoubling efforts to reduce transmission, epidemiologist McDonald says.
A vaccine for C. difficile is in the early stages of testing, and a drug treatment called tolevamer, which is designed to bind to and remove C. difficile toxins, is in phase-three clinical tests. Tolevamer, made by Genzyme Corp. of Cambridge, Mass., has been granted fast-track designation by the Food and Drug Administration.
Consumers can do their part too, says McDonald, by being aware of C. difficile symptoms. Anyone with diarrhea lasting more than three days and accompanied by a fever or blood in the stool should seek help. Proper hand washing is essential to reduce spread of the illness. And, says McDonald, antibiotics should be prescribed only when clearly necessary.
“We hope all clinicians and patients will think about antibiotic use,” he says. “They are important and save lives, but they are not without risk. If there is a silver lining in the C. difficile problem, it might be just that. It brings a little closer to home that antibiotics can have severe consequences.”
