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This article originally appeared in the February 2007 Harvard Health Letter and is provided courtesy of Harvard Health Publications.
C. difficile–associated disease on the rise
A newly recognized strain of a bacterium found mostly in hospitals is causing more illness.
The day after she started taking an antibiotic for a respiratory problem, 69-year-old Ellen Cornwall (not her real name) developed diarrhea. At first, she wasn’t worried; antibiotics are known to upset the gut. But this was no ordinary upset. A few days later, she was admitted to a hospital suffering from round-the-clock diarrhea, severe abdominal pain and bloating, dehydration, and declining kidney function. She was too weak to stand. Tests showed that her white blood cell count had skyrocketed and her colon (large intestine) was inflamed. The cause? The common bacterium Clostridium difficile, also called C. difficile (or just “C diff”). Had she gone much longer without medical attention, Ellen might have needed emergency surgery to remove her colon — a procedure with a mortality rate in such cases as high as 50%.
C. difficile–related diarrhea and inflammation of the colon (colitis) have been recognized since the 1970s as a complication of antibiotic use — usually in people ages 65 and over, and mostly in hospitals and long-term care facilities. Until recently, clinicians have been able to manage the bug through infection-control measures, care in choosing antibiotics, and proven treatments. But C. difficile–related illness has become more common, more severe, and harder to treat. It’s also occurring more often outside the usual risk groups. Some experts believe that a new, more virulent strain of the bacterium is to blame.
Most people exposed to C. difficile will not get sick from it, nor will most people who take antibiotics. But you can help limit the spread of this emerging troublemaker if you learn the risk factors and take some simple precautions to protect yourself and others.
How does C. difficile cause illness?
C. difficile is a spore-forming bacterium found widely in the environment. It doesn’t always cause disease; in fact, it lives in the gut of 3% of healthy adults. But under the right circumstances, some strains of the organism can produce toxins that attack the cells lining the colon and cause symptoms that range from mild diarrhea to severe colitis. These illnesses are collectively referred to as CDAD, for C. difficile–associated disease. In extreme cases, life-threatening complications may occur, including toxic megacolon (a greatly distended colon, vulnerable to rupture), bowel perforation, and even death. Rarely, surgery to remove the colon (colectomy) is needed.
Fortunately, contracting CDAD isn’t as simple as being exposed to C. difficile.
Dr. David Hooper, an infectious disease expert at Boston’s Massachusetts General Hospital, explains that you won’t get sick from C. difficile unless at least two conditions are met: “You have to get the toxin-producing version into the gastrointestinal tract, and you have to be exposed to antibiotics that disrupt the normal flora.” (See illustration.) Antibiotics, of course, kill off harmful bacteria, but they can also wipe out the good bugs in the large intestine that keep the harmful ones in check. That, in turn, gives C. difficile a chance to get a foothold.
| C. difficile–associated disease C. difficile bacteria is most often transmitted in hospitals and other health care facilities. In order to cause illness, two steps must occur: Bacteria enters body C. difficile enters the body orally, but doesn’t cause illness on its own. A mixture of organisms that inhabit the colon, called normal flora, help ward off dangerous bugs like C. difficile. Antibiotics disrupt flora Treatment with antibiotics reduces normal flora. This allows C. difficile to reproduce and release toxins that damage the cells lining the colon, causing diarrhea and sometimes colitis. |
All antibiotics have the potential to disrupt normal gut flora, but those most commonly associated with CDAD are broad-spectrum antibiotics, which have the greatest impact on normal intestinal flora. These include clindamycin, amoxicillin, ampicillin, and cephalosporin drugs (for example, cephalexin, cefaclor, and cefixime). There are signs that fluoroquinolones (for example, Cipro, Levaquin, and Floxin) have joined this group and may cause even more trouble than the others. (See “Why experts are worried.”)
Why experts are worried |
| Reports of C. difficile–associated disease (CDAD) outbreaks and deaths in the United States, Canada, and England are raising concern that the bacterium is changing and becoming more virulent. Researchers studied an outbreak of CDAD at a Pittsburgh hospital in 1999–2001 that required an unusually high number of surgeries to remove the colon (colectomies) and caused an unusually high number of deaths. The C. difficile strains involved were found to have mutations that made them overproduce toxins. This outbreak was linked to the use of fluoroquinolones, antibiotics to which C. difficile has evidently acquired resistance. Researchers investigating hospital outbreaks in eastern Quebec concluded that from 2002 to 2004, the incidence of CDAD in that region increased fourfold overall and tenfold in people over age 65. Moreover, a higher proportion of patients were developing serious complications, including toxic megacolon, colectomy, and death. Again, fluoroquinolones were involved. Laboratory analyses showed that most of the cases were caused by a single strain, called NAP1/027, which has been found to produce 16 to 23 times more toxin than other variants of the bacterium (Lancet, Sept. 24, 2005). Around the same time, the Centers for Disease Control and Prevention (CDC) received reports of higher-than-normal rates of CDAD in the United States. The agency studied outbreaks at eight hospitals in six states and found NAP1/027 at all of the institutions. The strain has also been reported in Great Britain and other parts of Western Europe. Another concern is that C. difficile has begun to appear in the community and affect people once thought to be at low risk. In December 2005, the CDC reported on 33 cases of CDAD, including 11 in children and 10 in women who were either pregnant or had recently given birth. Of the 33, 23 had not been hospitalized for any reason and eight had no documented exposure to antibiotics in the preceding three months. Also, in December 2005, researchers reported in the Journal of the American Medical Association that CDAD was identified in 1,233 British patients who hadn’t been hospitalized in the previous year; of those whose diagnoses were confirmed with toxin testing, 34% had not used antibiotics in the three months preceding their CDAD diagnosis. There’s some speculation that alcohol-based hand gels contribute to the spread of C. difficile. Staff in many hospitals are required to use these products because they help prevent the spread of many multi-drug-resistant organisms. But they don’t kill C. difficile spores. Soap and water does. The CDC recommends that health care workers use both soap and water and an alcohol-based hand gel after contact with patients suffering from CDAD. |
C. difficile is found in soil, in water, and even on pets, but you are most likely to encounter it in the hospital, where 20% to 40% of patients are colonized with the organism. Excreted in the feces of infected people, including healthy C. difficile carriers hospitalized for unrelated reasons, the spores can survive for months on surfaces such as floors, furniture, sinks, bedpans, toilet seats, and stethoscopes. Patients and visitors may pick up the spores on their hands and inadvertently transfer them to their mouths. Spores can also be spread on the hands and clothing of health care workers. The risk of developing the disease, which occurs only when the spores are ingested, is higher for patients who are older, spend more time in the hospital, and are treated for a longer period with antibiotics. Other risk factors include abdominal surgery, serious underlying illness, and immune system problems.
Some people, including healthy carriers, may be protected from CDAD by antibodies against the C. difficile toxins. Interestingly, as many as 70% of newborns harbor C. difficile in the intestine, but they don’t get CDAD, possibly because they haven’t yet developed receptors for the toxins.
Clinicians have a number of tests for C. difficile toxins in the stool, but when they need an immediate diagnosis, they may use endoscopy to view the colon directly. In about 20% of patients, CDAD goes away when the antibiotic that sparked the illness is discontinued; this usually takes two or three days for diarrhea and 10 to 12 days for uncomplicated colitis. But most people need medical treatment, usually a 10-day course of an antibiotic that can kill C. difficile. The ones used most often are metronidazole (Flagyl) and vancomycin (Vancocin), usually taken by mouth.
As many as 20% of patients who have been successfully treated for CDAD relapse shortly after completing antibiotic therapy. The reasons aren’t entirely clear. Maybe the antibiotic didn’t completely eliminate the bug, or perhaps the body’s immune response was inadequate. To treat a relapse, doctors may prescribe vancomycin or metronidazole again for a longer period and then taper the dose. Probiotics (beneficial bacteria) supplements may also be given to help replenish intestinal flora.
What to do
CDAD isn’t a reportable disease in most states, so we don’t know exactly how many cases there are; estimates range from 300,000 to 3 million annually in the United States. We do know that the number of reported cases has doubled since 2002, with a higher proportion of severe illness. The risk of becoming sick from C. difficile is still extremely low, but here are some points to keep in mind:
Handwashing with soap and water is one of the best ways to stop the spread of C. difficile (and many other dangerous organisms). If you or a loved one is in the hospital, insist on careful hand hygiene from hospital staff.
If you visit a hospital or other health care facility, be sure to wash your hands thoroughly with soap and water for at least 15 to 20 seconds as soon as possible after your visit.
Most antibiotic-associated diarrhea isn’t caused by C. difficile, but rather by the antibiotic’s impact on carbohydrate digestion. Symptoms usually aren’t severe and subside shortly after the drug is stopped. But C. difficile is responsible for most cases of antibiotic-associated colitis. If you develop watery diarrhea and abdominal pain, see your clinician right away.
CDAD is yet another reason to be circumspect about seeking or prescribing antibiotics. In particular, don’t ask your clinician for antibiotics to treat a cold or respiratory illness. Antibiotics are of no use in treating most such diseases anyway. When taking an antibiotic, take it exactly as prescribed.
Sometimes you need to be in the hospital. But as soon as you feel well enough, find out if home health care is an option for you. The shorter your hospital stay, the lower your risk of coming in contact with C. difficile spores.
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