When antibiotic works too well

Elimination of friendly bacteria in the stomach

paves the way to fatal ones, writes Jane E. Brody.

MARK SHULMAN OF Woodstock , New York , had a scary medical problem: a tumour on his neck. Although a biopsy indicated it was benign, it was growing and had to be removed surgically under general anaesthesia.

But that turned out to be a much smaller ordeal than the one after Shulman left the hospital. The doctors thought the unusual growth might have been caused by an infection, so they gave Shulman large doses of antibiotics. His neck wound was healing, nicely, but that’s when his troubles really began.

Within a week, he developed diarrhoea – not the ordinary kind you might experience with an intestinal virus or after eating tainted food, but unrelenting, watery stools and severe cramps that kept him glued to the bedroom and adjacent bathroom for days.

Soon he was losing more water than he could consume and had to be taken to the emergency room. There the cause of his devastating problem was soon identified : Clostridium difficile, a spore-forming, toxin-producing bacterium that can flourish in the large intestine when antibiotics kill off the competition, the healthful bacteria that normally inhabit the gut and suppress the growth of such noxious organisms.

In recent years, C. difficile, has emerged as one of the world’s most common hospital-acquired infections. In the US alone, it is estimated to cause about three million cases of diarrhoea and colitis (colonic inflammation) and 5,000 to 20,000 deaths each year, and the incidence is rising.

Experts attribute the rise to the use and abuse of antibiotics as well as inadequate hygienic practices by hospital and nursing home personnel, at-home care providers and unsuspecting carriers of C. difficile who have no symptoms.

Furthermore, studies indicate that C. difficile, so named in the 1930s because it was difficult to isolate and grow in the laboratory, has become more virulent in recent years, perhaps because potent antibiotics killed off less noxious variants of the organism. Superstrains of the organism produce about 20 times as many colon-damaging toxins as typical strains.

C. difficile is believed to be responsible for nearly all intestinal infections, from mild diarrhoea to severe or even fatal colitis, that occur after antibiotic therapy.

So far, this bacterium remains susceptible to one or both of two oral antibiotics: Flagyl (metronidazole) and Vancocin (vancomycin), which were used to treat Shulman successfully. But it may be only a matter of time before C. difficile evolves a way around these drugs and becomes an even deadlier scourge.

C. difficile is a surprisingly ubiquitous inhabitant of the environment and people. It forms heat-resistant spores that can survive for months to years. These spores can be found in marine sediment; sand; the dung of camels, horses and donkeys; the feces of dogs, cats and birds; and the human genital tract, as well as the intestinal tract and feces of people. The organism spreads by the fecal-oral route, often by hands contaminated through environmental objects like toilet seats or doorknobs.

As many as 70 per cent of healthy infants are born with C. difficile inhabiting their colons. For unknown reasons, possibly because the infant gut lacks receptors for the bacterium’s two toxins, it does not make these babies sick. But by about age of two years, when a child’s gut is better developed and well stocked with friendly bacteria, the presence of C. difficile fades, dropping to two to three per cent of children.

But if a healthy carrier is treated with antibiotics that destroy the beneficial bacteria. C. difficile can emerge as a threat. And if medical personnel are not assiduous about hand washing, the organism can spread readily in health care settings. This does not mean, however, that everyone who becomes infected will become ill. About 20 per cent of patients acquire C. difficile during their stay in hospital, but only about a third of these develop diarrhoea as a result. The rest remain as asymptomatic carriers.

The longer a person is hospitalized, the greater the risk of acquiring C. difficile, increasing to half of patients in for four weeks or more. The organism and its spores have been found throughout the hospital – on toilets, telephones, stethoscopes and the hands of workers.

The illness this bacterium causes can occur during a patient’s hospital stay or within days, weeks or even months after discharge. It can also afflict people taking antibiotics outside the hospital. The resulting diarrhoea can be mild, ending within a week without treatment, or it can become severe, as happened to Shulman.

The elderly and people sick with other serious illnesses are especially at risk of developing severe, even life-threatening infections. Dehydration can occur quckly in severe cases and cause the kidneys to shut down.

Toxins produced by C. difficile attack the gut lining and can cause the formation of telltale pseudomembrances – small patches of cell debris, inflammatory cells and clotted serum on the colon’s surface. In the severest cases, the colon can perforate, resulting in often-fatal sepsis.

C. difficile infections are most rapidly identified by an immunoenzymatic assay that detects bacterial toxins in the stool. Experts suggest that a C. difficile infection should be suspected in anyone with diarrhoea who has been given antibiotics in the previous two months or when diarrhoea occurs 72 hours or more after hospitalization.

Most important to preventing a C. difficile infection is to reserve the use of antibiotics for situations when they are truly needed. Mostly, this means first identifying a bacterium or fungus as the cause of a patient’s illness, not just taking antibiotics “just in case”. When antibiotics are needed, drugs with a narrow range of activity given for only three to five days are preferable to longer courses with broad-spectrum antibiotics. NYTNS.