IF YOU are unfortunate enough to catch it, you will suffer from intractable diarrhoea with gut-searing pain and fever. If you are frail, you may die. Should you survive, you may be stricken by repeated bouts of sickness. The disease is so debilitating that some turn to a treatment that is stomach-churning in its own right: enemas containing the faeces of a healthy donor, often a spouse. Although methicillin-resistant Staphylococcus aureus (MRSA) is more famous, Clostridium difficile is a superbug to be reckoned with. Like many other infections caught in hospital, it is increasingly becoming resistant to treatment with antibiotics.
Ordinarily, the human colon harbours very few of the rod-shaped bacteria that cause Clostridium difficile associated disease or CDAD. But the guts of those people who are given antibiotics to prevent or treat infection during a stay in hospital are different. Antibiotics may rid the colon not only of harmful bacteria, but also of the beneficial ones that normally live there. This, in turn, can give C. difficile the chance to take hold.
Rates of the disease among patients in, or recently discharged from, American short-stay hospitals seem to have doubled between 2000 and 2003 and risen another 25% in 2004, the most recent year for which estimates are available. That translates into at least 225,000 new cases a year, according to the Centres for Disease Control, a government agency based in Atlanta, Georgia. As this number does not capture all of America's hospitals and ignores its nursing homes, the real figure is probably at least 500,000 cases a year.
What lies beneath
The full extent of the illness is unclear because American hospitals are not required to report it. Even when someone with the disease dies, his death certificate may not say he had it. Whatever the true numbers, about 20% of people infected have repeated bouts of the illness and some 1-2% of the stricken die; chiefly, but not exclusively, the victims are elderly people who are already in frail health.
Worryingly, the disorder is now being found in people who have not stayed in hospital. This new sort of case includes 48 pregnant women, one of whom died along with her fetus; others miscarried. Some of the people who seem to have caught the disease outside hospital had recently been on antibiotics; early studies suggest that others may have picked up the disease from eating infected animals or by taking medicines to combat heartburn and indigestion.
Australia, Belgium, Britain, Canada and Japan have been grappling with the problem, too. In Britain since January 2004, all health-care facilities in National Health Service trusts—not just hospitals—have to report every case in a person aged 65 and older. Acute-care hospitals in Quebec, in Canada, must report every case that strikes within a month of a patient's being discharged, regardless of his age.
Three American federal agencies—the National Institutes of Health, the Food and Drug Administration and the Centres for Disease Control—are so alarmed that they recently convened a workshop in Atlanta to determine what research is needed to tackle the disease.
Unlike many bacteria, C. difficile makes poison-forming spores. These spores are, in effect, reservoirs for infection. Only when they hatch in the intestines do they produce their toxins. About half the hospital patients infected after taking antibiotics have no symptoms of CDAD. But they still shed spores and so are carriers.
The spores can survive for months on virtually everything they touch: toilets, bedpans, bathroom floors, sheets, bed rails, call buttons, telephones and door-knobs. The spores cling to the hands of hospital staff, lurking under fingernails and rings. A good defence is for doctors and nurses to wash their hands meticulously with soap and water between seeing each patient, but that is not easy to enforce. Alcohol-gel hand-cleaners are more convenient than hand-washing, but are less effective. Household bleach is the most efficient killer of C. difficile spores, but most hospitals do not routinely apply it to every patient's room, let alone to communal areas.
What else can be done to combat C. difficile? Dale Gerding of the Loyola Stritch Medical School in Maywood, Illinois, wants a sensitive, rapid and affordable test for the diagnosis of CDAD and the prompt identification of carriers. Such a test could rely on a technique known as “polymerase chain reaction” to magnify a small sample to the point where testing becomes relatively easy. Several companies are developing such tests but none is ready for widespread use.
Moreover, there is a problem: C. difficile grows poorly in the laboratory—which is why it was named “difficile” when it was discovered in the 1930s. The name is still well deserved. Molecular biologists are still struggling to pin down the bacteria's genes and their behaviour—in order, among other things, to verify the apparent emergence of more virulent strains of the bacterium. Fortunately, there are other kinds of bacteria that form spores in much the same way as C. difficile does. These are being used to understand exactly how the genes responsible for making spores work, which in turn may make it possible to switch them off.
Can you get better?
Patients also need treatments to cure sudden, severe cases of the disease. Two drugs, metronidazole and vancomycin, are commonly prescribed for C. difficile, but both are antibiotics that can themselves predispose patients to relapses. Ciaran Kelly, a Harvard Medical School researcher, says that broad-spectrum antibiotics—used to treat many different kinds of bacteria—tend to make many species of bacteria resistant to them, and limit the treatments available for CDAD. Antibiotics designed especially to act against C. difficile would be far less likely to affect other bacteria: some in late-stage clinical trials give cause for hope.
Another advance could come from inactivating the spores. Two drugs that could have been useful—cholestyramine and colestipol—are already on the market. Unfortunately, their effects have, to date, been modest. Neither was developed for C. difficile, and they do not bind well to its spores. At least one newer candidate—tolevamer—could, in principle, do a better job by binding not to the spores but to the toxins they produce. It, too, is in late-stage clinical trials. Because it is a synthetic polymer, not an antibiotic, it should not destroy the good, protective bacteria along with the bad ones in the gut. At the very least it would be more pleasant than some of the treatments patients turn to today.