'Fecal transplant' procedure pioneered by Lawrence doctor in 1959 makes comeback to treat antibiotic-resistant illnesses

Dr. Noel Kleppel in his Lawrence home. (Oct.

Dr. Noel Kleppel in his Lawrence home. (Oct. 22, 2013) (Credit: Newsday / John Paraskevas)

Dr. Noel Kleppel knew extraordinary steps would have to be taken to save his patient.

Within days of surgery to remove 12 cancerous polyps, a 65-year-old man had become overwhelmingly infected in his intestinal tract.

"It was Staphylococcus aureus," said Kleppel, 82, a clinical associate professor of surgery at SUNY Downstate Health Sciences Center in Brooklyn. "Staph had gotten smart and had become drug resistant" -- and there was nothing doctors at the time could do to contain it.


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Uncontrollable, antibiotic-resistant staph aureus infections were sweeping through hospitals causing killer bouts of diarrhea. The term "superbug" had yet to be coined. The year was 1959.

 

Doctor's theory proved rightWhat Kleppel, of Lawrence, did next earned his research a page in medical history linking him with doctors today dealing with other resistant strains. He proposed a "fecal feeding," sending a stream of the matter in saline solution through a tube threaded from nose to gut.

It would restore normal intestinal flora without bombarding infectious microbes with antibiotics, which weren't working anyway, Kleppel theorized. He proved himself right.

Today, the procedure -- called a "fecal transplant" -- is making a comeback as antibiotic overuse threatens a return to an era in which even simple infections could become lethal.

The transplants are still done via the nasal-gastric route, but some doctors perform them through colonoscopy.

Dr. Bruce Hirsch of North Shore University Hospital in Manhasset said patients there have undergone fecal transplants in recent years, primarily for C. difficile -- C. diff -- which has become a nationwide emergency.

"C. diff is a desperate problem and a major issue," said Hirsch, describing it as one of the most serious threats facing hospitals.

Federal health authorities recently put C. diff, a spore- and toxin-forming bacterium, at the top of their list of hypervirulent pathogens. One strain, NAP-1, is multidrug resistant, producing more toxins than other C. diff variants.

An estimated 335,000 cases of C. diff infections involving all strains occur annually in the United States, killing 14,000 people.

Most infections are contracted in health care settings.

Hirsch said he's very much aware that fecal transplants are a revival of midcentury medicine. He and his colleagues are also producing "poop pills" in a North Shore lab for some patients encumbered by relapsing C. diff. The fecal matter is processed until only the bacteria remain, which then is put in gel capsules for patients to swallow.

As with the transplants, poop pills repopulate the intestine with healthy flora.

The Food and Drug Administration considers the pills and transplants experimental, requiring patients' informed consent.

Kleppel, a surgical resident at Long Island College Hospital in Brooklyn in 1959, said consent forms weren't required.

Resistant staph had evolved because of antibiotic misuse, which included overexposure to everything from penicillin to the tetracyclines, a potent class developed after World War II. Kleppel said doctors couldn't up the ante and wipe out resistant staph with other antibiotics because newer ones were still under development.

Scant options led to method

Today, by comparison, doctors have reached the end of the Miracle Drug run.

"We didn't have methicillin at that point," Kleppel said, referring to the drug staph aureus would learn to repel in the 1960s, leading to methicillin-resistant staph aureus -- MRSA.

Methicillin was developed in 1959 to specifically address resistant staph aureus.

"We did have penicillin -- the old penicillin -- which didn't help. We had the old sulfa drugs, which were like a Model T Ford."

With so few options and mindful that death is swift with proliferating staph, Kleppel decided to pull out all the stops.

He said he chose feces from hospitalized orthopedic patients because they were generally quite healthy.

"We mashed it up. Yeah, it was gross, but dying isn't so great, either," said Kleppel, noting he carried out the process in the hospital's old bacteriology laboratory.

In addition to saline -- sodium chloride and distilled water -- Kleppel and his colleague, Dr. Louis Cutolo, who died last year, added Lactobacillus acidophilus. This microbe is naturally occurring in the human gastrointestinal tract. Indeed, many L. acidophilus strains are considered probiotic, a term that wasn't in vogue at the time.

By definition, probiotic refers to beneficial bacteria that help maintain the balance of natural flora in the colon.

Kleppel's patient, whose name he recalls was Robert Kelleher, survived the infection, but later died of colon cancer.

Dozens of other patients at the hospital infected with staph became candidates for the "feedings." Kleppel wrote about his first case in an October 1959 edition of the New York State Journal of Medicine.

Kleppel said he's among the first physicians to develop the concept and publish on it. A Denver team, however, preceded him into print in 1958, calling its procedure a "fecal microbiota transplantation." It was performed via enema, which doctors now say is not as effective as other techniques.

Dr. Stuart B. Levy, founder of the Alliance for the Prudent Use of Antibiotics, a Boston-based nonprofit at Tufts University, commends Kleppel and other visionary investigators who figured out ways to outwit bacteria.

"This was remarkable, and especially during that time," said Levy, also a Tufts professor of medicine.

Kleppel, meanwhile, said he's not surprised the procedure has been revived.

"The more things change," he said, "the more they stay the same."

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