More than 450,000 Americans get infected with the deadly bug Clostridium difficile each year, according to a new report. And almost all cases are caused by the overuse of antibiotics.

“C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011,” the team of researchers reported Wednesday in the New England Journal of Medicine.

That’s almost twice as many deaths as any other survey has shown before for the infection, usually called C. diff for short. “This national estimate of C. difficile infection is higher than previous U.S. estimates (240,000 to 333,000),” they wrote.

The number’s probably been undercounted for so long because many people get sick after they leave the hospital. And the study showed people are not just getting infected in hospitals. They are getting infected in doctors’ offices, the dentist’s chair, and in other healthcare settings.

“This is the first study that really highlights the important burden of this infection,” said Dr. Ghinwa Dumyati of the University of Rochester Medical Center, who helped conduct the study with the Centers for Disease Control and Prevention.

“The driver of this is antibiotic use.”

Clostridium difficile bacteria are very hard to fight for two reasons. One, they release a toxin that, once in the body, cannot be cleared up by drugs. Second, they release spores that are not killed by hand sanitizer or antibiotics and that can lurk in hospital nooks and crannies, or inside the body.

Worse, there’s a new strain that emerged in 2000 and that causes 30 percent of cases. “It is more easily transmitted than other strains,” said the CDC’s Dr. Cliff McDonald, who worked on the study. “It also does seem to cause more severe disease.”

C. diff causes severe diarrhea, inflammation and sepsis. Even before this new data, it was known to be the No. 1 cause of deadly hospital infections.

“Because hand sanitizers don’t kill the spores, it is essential to use soap and water to remove them,” Dr. Michael Bell, deputy director of CDC’s Division of Healthcare Quality Promotion, told reporters in a teleconference. There is, he says, no room for error.

The toxin damages the lining of the intestines. It creates inflammation and allows the germs and the toxins they make to get into the bloodstream.

People with C. diff infections have an imbalance in the normal population of microbes that keep us healthy, and it’s very difficult to recover from a C. diff infection. This also explains why it’s not usually best to use antibiotics to treat a C. diff infection — the drugs are what helped cause the infection in the first place, by killing the “good” bacteria in the bowel, allowing C. diff to take over.

“Once somebody gets C. diff, it usually means your normal bacteria in the bowel are so damaged that returning to normal can be very difficult,” Bell said. The new study found that C. diff came back in 20 percent of patients, and that one out of every nine patients 65 or older died within 30 days of a C. diff diagnosis.

“If we can improve antibiotic prescribing, we can expect to see better C. diff rates,” Bell said.

“Antibiotics are clearly driving this whole epidemic.”

Fighting C. diff. costs hospitals up to $4.8 billion each year, CDC says. More than 100,000 nursing home patients get a C. difficile infection every year.

Previous research showed C. difficile killed about 14,000 Americans a year, causing 12 percent of all healthcare-associated infections. Researchers funded by the CDC found last year that about 650,000 people developed hospital-associated infections in 2011 and that 75,000 died. Other data showed an estimated 107,700 C. difficile infections in hospitals.

For the new C. diff study, the CDC-led team did an actual count of C. diff cases in 2011. They found 15,461 cases in 10 regions of the country. About two-thirds were associated with some sort of health care, but only 24 percent of people actually got sick while in the hospital.

From this, they extrapolated across the whole population to come up with 453,000 cases.

The good news is that cases are going down. CDC has documented a 10 percent decrease in hospital-onset C. difficile infections between 2011 and 2013. The Health and Human Services Department will start penalizing hospitals that do not reduce such cases in 2017.

One possible treatment is fecal transplant, which may help a patient infected with C. diff get a healthy batch of gut bacteria from someone else.