Not long ago, a friend phoned. He sounded cheerful until I asked about his wife and their summer vacation. Suddenly the energy drained from his voice. “Actually, we were grounded,” he confided. “Candy has had diarrhea for weeks. Her doctor is finally running some stool tests.”

“I’m so sorry,” I said, adding—almost by rote—“I hope C. difficile is on the list.”

The following night, my friend rang again, this time both ebullient and relieved. “Guess what? You were right!” he began. “Candy’s C. diff toxin was positive. We think the doxycycline she’s been taking for her skin set it off. Wow, great diagnosis, Doc.”


By all rights, I should have blushed. In 2010, no special brainwork is needed to think of Clostridium difficile; it is everywhere. But each time I hear about another once-unlikely sufferer like Candy, it takes me back.

Years ago, by pure luck, I witnessed the dawn of knowledge concerning this now-ubiquitous blight: a toxin-producing bacterium that thrives in the guts of patients whose healthy bacteria have been depleted by treatment with antibiotics. The toxin that C. difficile pumps out is a protein that attacks the lining of the bowel. This can bring on watery diarrhea, and in some people the toxin can also transform a previously sturdy intestinal lining into a dangerously inflamed rag. Which brings me to the most dramatic case of the disease that I ever saw.

Clostridium difficile, seen in a colorized micrograph,
produces a toxin that can cause intestinal disease.

Dr Kari Lounatmaa/Photo Researchers

Back in 1980 I was an infectious diseases fellow at Tufts–New England Medical Center in Boston. Over the preceding five years, Tufts researchers had painstakingly chipped away at the mystery of C. difficile infection. In particular, they had treated lab hamsters with an antibiotic called clindamycin; the experiment led to the isolation of the disruptive toxin that C. difficile produces and helped bring about a diagnostic stool test. After that, apprentice specialists like me were often charged with collecting and transporting fecal specimens from patients whose diarrhea might be linked to antibiotic use.

One weekend, I was called to the bedside of a man in his seventies who was completing a monthlong course of IV antibiotics for an infected heart valve. No one specifically mentioned C. difficile. All I knew was that diarrhea had plagued the patient for days. I expected that I would complete a history and physical, then take the usual handoff: a container of brownish fluid destined for our laboratory fridge. To my surprise, a nurse with a worried expression stopped me at the patient’s door. “Sorry, no stool specimen on this one. And if you need to do an exam, you’d better be quick. Mr. Murphy’s about to go downstairs for an X-ray.”

“Why?” I asked. All of a sudden, events weren’t going as anticipated.

“You didn’t hear? This morning he spiked a fever to 103 and his blood pressure crashed. Now his abdomen is tender. The surgeons are on their way.”

I entered the room and introduced myself to a frail, motionless man who barely nodded in reply. His pulse was thready and fast, his belly distended, his bowel ominously silent. The next thing I knew, I was walking alongside the patient’s gurney as an orderly wheeled him to radiology. Twenty minutes later, a surgical resident and I both gazed in dismay at the film on the backlit view box. Mr. Murphy’s cecum—the pouchlike segment that marks the beginning of the large intestine—was massively dilated, and crescents of air lined the underside of his diaphragm.

“He’s perforated his bowel, all right,” the resident said grimly. “We’ll take him to the OR, but it doesn’t look good. I wonder what the heck caused this.”

That’s when I remembered the animals in the lab. Cecitis! Although the syndrome had not yet been widely reported in humans, a florid inflammation of the cecum almost always developed in the clindamycin-treated hamsters just before they died. In fact, it was the injection of filtered cecal contents from moribund hamsters into the intestines of new, healthy ones that first proved a toxin was to blame for the disease later credited to C. difficile. (At that stage in the research, the causative organism had not yet been identified.)