Last summer, a young pharmacy resident named Wei Wang began combing through the electronic charts of patients at St. Joseph’s Medical Center who had been diagnosed with Clostridium difficile, one of the nation’s most dangerous health care-associated infections.
Searching for common threads, Wang discovered that many of the infected patients at the Stockton hospital were on a type of antacid pill that is believed to make people more vulnerable to C. difficile, the infection’s nickname.
He dug deeper. The final tally was startling: Fully 76 percent of those patients, he found, were taking a kind of antacid drug sold under brand names such as Nexium, Prevacid and Prilosec.
Today, those antacids make up the third biggest-selling class of drugs in the United States.
Yet in a classic medical paradox, the very pills that are supposedly healing us can make us more susceptible to a dangerous infection marked by diarrhea, abdominal pain and even death.
Researchers have suspected for years that the antacids known as PPIs, or proton pump inhibitors, can increase patients’ vulnerability to C. difficile. For St. Joseph’s employees, seeing the hard numbers in the charts of their own patients brought the problem right home to Stockton.
“A lot of patients come into this hospital on these medications,” said Dr. William P. Yee, interim pharmacy director at the cream-walled hospital complex at Harding Way and California Street.
The St. Joseph’s study highlights one of the harsh realities of C. difficile, which spreads from a patient’s feces via long-living spores that can linger on equipment, bedrails and other surfaces or travel on the hands of health care workers. Other patients swallow the bacteria and can become infected, suffering severe diarrhea, inflamed intestines and bleeding ulcers. For some, it’s fatal.
C. difficile kills an estimated 14,000 to 30,000 people a year in the United States, federal reports show. It led to 330,000 hospitalizations in 2009 alone, and 9 percent of those cases proved fatal. In fact, the number of deaths skyrocketed in the past decade, driven in part by the emergence of a more deadly strain.issued an alert in February. The drugs may be causing a 65 percent increase in C. difficile-related diarrhea, reports a recent article in the American Journal of Gastroenterology that recommends more “prudent use” of PPIs.
Andy Sullivan, a spokesman for Prilosec OTC maker Procter & Gamble, wrote in an email,“to date, we have not identified any raised specific concerns which would connect Prilosec OTC and Clostridium difficile-Associated Diarrhea." He added, however, that the firm is following new FDA rules. “As in every aspect of our business, we intend to comply with FDA’s requirements and meet our own safety guidelines,” he said.
Introduced in the 1980s, these antacid drugs are widely prescribed for gastro-esophageal reflux disease, or GERD, and other acid-related diseases.
They work entirely differently than their antacid predecessors, such as Tums and Maalox, by blocking the production of gastric acid rather than neutralizing acid in the stomach.
Now many researchers believe that process can alter the stomach’s chemistry in a way that allows C. difficile to flourish.
Outside of medical circles, most people have never heard of the problem.
“I don’t think the public is really up on this. I haven’t seen any news media on this. I haven’t seen it coming through the Internet,” said Marcus C. Ravnan, an associate professor in the Department of Pharmacy Practice at the University of the Pacific’s pharmacy school.
Patients with prescriptions for the antacids can fall through the cracks, Ravnan added.
“People are staying on them, literally, for years,” he said. “Some patients are started appropriately in the hospital. Then they’re discharged on it, and the indications are gone, and then, it’s refill after refill after refill.”
That’s a syndrome that came to light at St. Joseph’s when Wang, 28, who got his doctor of pharmacy degree in 2011, began scrutinizing the charts of all patients on PPIs. Many were already on the antacids when they arrived at the hospital, but nothing in their charts explained why they were taking them, he found.
“That was the biggest surprise,” Wang said. “A very large number of patients were on PPIs as a home remedy, with no documented indication – nothing saying they had a history of GI disorders, or GERD.”
Some people may struggle to get off PPIs, especially if they’ve been popping the pills for years. Experts point to an upsurge in heartburn symptoms among some patients when they stop taking the pills.
“We don’t think people are going to go out and rob banks for them. But yes, there’s a physical dependence on them, and probably a behavioral dependence,” said Ravnan at UOP.
Now, in the wake of the FDA warning, some drug companies are changing the labels on over-the-counter PPIs to reflect the concerns about C. difficile.
Some of those labels had listed diarrhea and abdominal pain as side effects of the drugs, which could mean a patient with those symptoms might not contact a physician.
After talks with the FDA, the makers of Prevacid24HR, Prilosec OTC and two other firms are adding a new warning: “Stop use and ask a doctor if you get diarrhea,” according to FDA letters issued in September.
The FDA has issued other warnings about proton pump inhibitors, including their potential to lower magnesium levels—a condition that can cause muscle spasms, irregular heartbeat and seizures--and to increase the risk of hip, wrist and spine fractures. Warnings appear on labels for the drugs in prescription form but not the over-the-counter version.
“In contrast to prescription PPIs, (over-the-counter) PPIs are marketed in low doses and are only intended for a 14-day course of treatment up to three times a year,” FDA safety announcements explain.
Yet no one can guarantee that consumers will stop taking the pills after 14 days, said Dr. Sammy Amashat, a researcher with the Health Research Group at Public Citizen, a Washington-based public interest group.
“There’s just a trend of overuse, more so than just about any medication class that we know of,” Amashat said.
Public Citizen submitted a petition to FDA Commissioner Margaret Hamburg more than a year ago, requesting that her agency “immediately add black box warnings and other safety information concerning several severe risks to the product labels of all proton pump inhibitors (PPIs) presently on the market in the United States.” A black-box warning is a more visible alert on drug packaging and inserts.
The petition is still under review, FDA spokeswoman Stephanie Yao wrote in an email.
Researchers agree that the drugs do have a place in hospital care. For instance, doctors prescribe them to some patients in intensive care to ward off the chance that they may develop stress ulcers, said Yee at St. Joseph’s Medical Center.
“When you’re in an ICU, your body is put under stress,” Yee said. “This group of medicine actually has a protective effect.”
Some patients remained on the antacids after leaving intensive care, even if their charts did not give a reason. So Wang, the pharmacy resident, talked with doctors to find out why.
“A lot of times, when patients do get started on the PPIs, they are discharged on the PPIs. Some physicians forget they’re on them,” Wang said. When he talked to doctors, he said, “A majority decided to discontinue the PPIs or switch to a less potent acid suppressant therapy—although I did have one doctor who told me he didn’t believe in the studies.”
His residency completed, Wang is now a staff clinical pharmacist at Cedars Sinai Medical Center in Los Angeles. He said that he wants his research in Stockton to help educate people when and how PPIs should be used.
“Hopefully, they will be more aware and question their doctors about whether they really need to be on them” he said.
FDA Commissioner Margaret Hamburg’s name was misspelled in an earlier version of this story.