— A nasty bug that appears to be disarming the top drugs used to treat bladder infections is raising concerns for the 6 million to 8 million sufferers, mostly women, who develop the painful, annoying conditions each year.
A rare but aggressive strain of multi-drug-resistant E. coli bacteria, dubbed E. coli ST131, could be responsible for up to 1 million bladder infections and for more than 3,000 deaths a year from infections that started out in the urinary tract, estimated Dr. James R. Johnson, an infectious disease expert at the Veterans Affairs Medical Center in Minneapolis.
“I think it’s high time to worry,” said Johnson, who adds that the new strain is one resistance gene away from being untreatable. “Before, resistant strains were wimpy. Now, we have a winner.”
Most people think of E. coli as a diarrhea-causing gut bug that harms people who eat tainted hamburger or spinach. But E. coli that occurs outside the intestine is far more common — and causes far more infection and death, Johnson said.
Extra-intestinal E. coli is responsible for about 80 percent to 90 percent of the urinary tract infections that occur annually. Most respond to common treatments: guzzling gallons of water, swilling quarts of cranberry juice, and, if all else fails, heading to the doctor for a quick course of antibiotics.
But in a recent study based on a national sample, Johnson found that although the E. coli ST131 strain accounted for only about 17 percent of E. coli isolates overall, it accounted for more than 50 percent of bacteria resistant to more than one antibiotic, including the top two types used to treat most urinary tract infections, or UTIs.
It also was responsible for nearly 70 percent of resistance to the biggest guns of mainline UTI treatment, fluoroquinolones and extended-spectrum cephalosporins.
“ST131 looks like the Grinch that stole Christmas,” said Johnson, a professor of medicine whose work was published in the journal Clinical Infectious Diseases.
Bladder infection kills Maine woman
The bug’s virulence was evident in the 2007 death of an otherwise healthy Portland, Maine, woman, who developed a bladder infection that quickly outgunned the usual course of antibiotics. (The woman’s family declined to be interviewed, but they agreed to allow medical personnel to discuss her case.)
The woman had gone to care for her sister, who had suffered serious, recurrent urinary tract infections for five years. The women were in their late 40s and early 50s. When the first sister returned home, she developed the typical symptoms of a UTI — burning, pain and an urgent need to urinate.
A week later, sick and feverish, the woman was admitted to a Maine hospital, where doctors gave her Ciprofloxacin, a fluoroquinolone. Three days later, she developed septic shock, and doctors switched her to one set of more powerful drugs, and then another. On the fifth day, despite aggressive treatment, the woman died. Laboratory cultures showed that the organism responsible was E. coli ST131.
“There was really nothing wrong with this lady a week before,” said Rob Owens, a clinical pharmacy specialist and co-director of the antibiotic stewardship program at the Maine Medical Center Research Institute, where the woman was treated. “Within a two-week time span, she was dead.”
The woman’s sister also was infected with E. coli ST131, tests showed, raising the likelihood it was transmitted between the siblings, Owens said. That's different than many E. coli UTIs, which often are caused by bacteria transmitted during sexual activity or toileting, for instance. That sister survived, but she continues to struggle with UTIs and with the trauma of her loss, Owens said.
E. coli ST131 probably caused the most significant multi-drug resistant E. coli infections in the U.S. in 2007, the year Johnson studied, constituting a serious public health threat.
"What's new about our research is, we're seeing, gee, there's more resistance out there," Johnson said. "What we've found is an explanation for that rising resistance: It's this one strain."
Bugs that disable antibiotics
E. coli ST131 is included in a category of E. coli bacteria that produces enzymes that disable antibiotics, known as extended-spectrum beta-lactamase, or ESBL, bugs thought to cause the hardest-to-treat infections. A few years ago, ESBLs were rare, noted Dr. Thomas “Mac” Hooton, a professor of medicine and infectious disease expert at the University of Miami.
“Now, ESBL is like a second-language,” Hooton said. “I guarantee you that this will be something we’re seeing in five or 10 years and it will be all over the place.”
The E. coli ST131 findings add to the growing concerns about drug-resistance in common infections such as UTIs. For nearly two decades, doctors and scientists have watched — and worried as resistance mounted.
First came the trimethoprim-sulfamethoxazole or TMP/SMX drugs, brands such as Septra and Bactrim, which fell out of favor when they started developing resistance, now gauged to be about 20 percent, doctors say. Then came the fluoroquinolones, the stronger, widely prescribed drugs such as Cipro and Floxin, which were once invincible, but now show overall resistance in perhaps 10 percent of cases in some places, though the level can vary widely.
In fact, Cipro, a top fluoroquinolone, is known as “Vitamin C” because it’s so ubiquitously prescribed for bladder and other infections, said Owens.
New UTI guidelines expected to be issued by the Infectious Diseases Society of America this fall are aimed at tackling the wide use of fluoroquinolones, said Hooton.
“They’re going to say, ‘We’ve got a big problem with resistance, let’s reserve our fluoroquinolones for big infections,” he said. “We’re advocating it be approached like a public health problem.”
First drugs might not work
The vast majority of those who get urinary tract infections — typically young, healthy women who’ve become sexually active — will continue to be treated as they always have. They’ll likely receive a TMP/SMX antibiotic such as Septra or Bactrim or a prescription for nitrofurantoin, an old-line UTI drug, known as Macrobid or Macrodantin, which is back in favor because resistance remains very low.
But more young women — perhaps 1 in 10, Owens estimated — might find that the first drug they take doesn’t work. And maybe the second drug won’t work, either.
In some of those cases, or for patients who’ve taken antibiotics previously, or those who have other health problems, the situation could get serious. Their infections may become chronic, or they may worsen markedly, requiring hospitalization and aggressive treatment. In very rare cases, the infections could become life-threatening or even deadly.
“Overall, I think these bad resistant bugs are uncommon,” Hooton said. “But it's the canary in the coal mine type of thing."
The rising levels of resistance overall and the appearance of new highly resistant bugs should prompt more attention — and more action, said Johnson, who has has received grants or served as a consultant for several top drug companies and has had contracts with many others.
“Part of the reason that now is the time to worry is that you need to worry in advance to do something about it,” he said. “The lead time to coming up with any fixes is pretty long.”