Dr Lee Riley has been studying antibiotic-resistant strains of E. coli, which can cause urinary tract infections. Photo / Brian L. Frank, The New York Times
As the infections become increasingly resistant to antibiotics, some standard treatments no longer work for an ailment that was once easily cured.
For generations, urinary tract infections, one of the world's most common ailments, have been easily and quickly cured with a simple course of antibiotics.
But there is growing evidence that the infections, which afflict millions of Americans a year, mostly women, are increasingly resistant to these medicines, turning a once-routine diagnosis into one that is leading to more hospitalisations, graver illnesses and prolonged discomfort from the excruciating burning sensation that the infection brings.
The New York City Department of Health has become so concerned about drug-resistant UTIs, as they are widely known, that it introduced a mobile phone app this month that gives doctors and nurses access to a list of strains of urinary tract infections and which drugs they are resistant to.
The department's research found that one-third of uncomplicated urinary tract infections caused by E. coli — the most common type now — were resistant to Bactrim, one of the most widely used drugs, and at least one-fifth of them were resistant to five other common treatments.
"This is crazy. This is shocking," said Lance Price, director of the Antibiotic Resistance Action Center at George Washington University, who was not involved in the research. The drug ampicillin, once a mainstay for treating the infections, has been abandoned as a gold standard because it is so often resistant to multiple strains of UTIs. Some urinary tract infections now require treatment with heavy-duty intravenous antibiotics. Researchers last year reported in a study that a third of all UTIs in Britain are resistant to "key antibiotics."
Certainly, the day-to-day experience of having a UTI is growing less routine for many women.
Carolina Barcelos, 38, a postdoctoral researcher in Berkeley, California, said she had several UTIs as a teenager, all successfully treated with Bactrim. When she got one in February, her doctor also prescribed Bactrim, but this time it didn't work.
Four days later, she returned and got a new prescription, for a drug called nitrofurantoin. It didn't work either. Her pain worsened, and several days later, there was blood in her urine.
Her doctor prescribed a third drug, ciprofloxacin, the last of the three major front-line medicines, and cultured her urine. The culture showed her infection was susceptible to the new drug, but not the other two.
"Next time," Barcelos said, "I'm going to ask them to do a culture right away. For eight days I was taking antibiotics that weren't working for me."
Usually, it is people with weakened immune systems or chronic medical conditions who are most vulnerable to drug-resistant infections, but UTIs have a dubious distinction: They are the single biggest risk to healthy people from drug-resistant germs.
Resistance to antibiotics has become one of the world's most pressing health issues. Overuse of the drugs in humans and livestock has caused germs to develop defences to survive, rendering a growing number of medicines ineffective in treating a wide range of illnesses — a phenomenon that is playing out worldwide with UTIs.
The World Health Organization, while noting that data on urinary tract infections and drug resistance is "scarce," said the fact the infections were so common strongly suggested that increasing resistance would lead to more severe illnesses and fatalities.
The solution, researchers and clinicians say, includes a continued push for more judicious use of antibiotics worldwide. But more immediately, a partial solution would be the development of quick, cheap diagnostic tools that would allow an instant urine culture so a doctor could prescribe the right drug for UTIs.
But whether to wait the several days it usually takes to get lab results before prescribing presents a tough dilemma for doctors and patients, who frequently are desperate for relief. Plus, depending on a person's insurance, getting a culture can be expensive.
Generally doctors still do not order a urine culture before prescribing an antibiotic.
"In the old days, the list of antibiotic options was short, but by and large they would all work," said Dr. James Johnson, an infectious-disease professor and leading researcher on urinary tract infections at the University of Minnesota.
Some women have UTIs that the body fights off on its own without using antibiotics, while other women may have a different low-level ailment that feels like a UTI, but isn't. The safest course is to see a doctor and make an informed decision that includes a judicious determination of whether antibiotics are warranted. The science does not support the efficacy of some popular remedies like cranberry juice or cranberry pills.
Officials from the federal Centers for Disease Control and Prevention said that UTIs acquired by otherwise healthy people were a growing concern and one poorly studied. They are not tracked nationally.
In older people, urinary tract infections can be deadly, but tracking in the United States is so weak that there are no reliable estimates on the numbers of deaths related to the infections. The CDC published an estimate of 13,000 per year, but that figure comes from a paper looking at 2002 data and refers only to UTIs acquired in hospitals.
Dr. Clifford McDonald, associate director for science in the division of health care quality promotion at the CDC, said the government planned to expand its research.
"If we don't do something soon," McDonald said, "it's going to push all our treatments to more advanced antibiotics that finally put a lot of pressure on the last-line treatments."
What makes these infections so dangerous, and commonplace, is human anatomy. In women, the urethra — the gateway to the urinary tract — is in proximity to the rectum. This can lead to easy transfer of bacteria in faecal residue that otherwise resides harmlessly in the gut.
In reproductive years, women are 50 times for likely than men to have a urinary tract infection; later in life, the ratio drops to 2 to 1, as men wind up having surgical procedures on their prostate, or catheters, that more easily expose their urinary tracts to infection.
There are multiple germs that cause UTIs, and their resistance levels to drugs vary both by strain and by where a patient lives. By far the most common cause of UTIs today is E. coli, and, in general, those infections have seen sharp rises in resistance to gold standard treatments over the past decade and a half.
New research shows that one crucial path of transfer of germs that cause UTIs is food, most often poultry. The consumed poultry winds up in a person's gut and can get transferred through faecal residue to the urethra.
A study published last year by the American Society of Microbiology, funded partly by the CDC, found 12 strains of E. coli in poultry that matched widely circulating urinary tract infection strains. One of the study's authors, Dr. Lee Riley, a professor of epidemiology and infectious diseases at the University of California, Berkeley, said he was working on a CDC-funded project to determine whether the urinary tract infection needs to be classified and reported as a food-borne illness.
Dr. Brad Frazee, an emergency room doctor at Highland Hospital in Oakland, California, has been a co-author of research that adds another troubling wrinkle: Increasingly, E. coli is proving resistant not just to individual antibiotics, but also to a broad group of drugs known as beta-lactam antibiotics. These drugs share a way of attacking infection, and when a germ develops resistance to this method of attack, it eliminates several key treatment options all at once.
Recently, a woman carrying such resistance showed up at Frazee's hospital, he said. She wound up with pyelonephritis, an infection in the kidney, and had to be treated in the hospital intravenously with a drug called ertapenem that can cost $1,000 a dose. A study found that around 5% of UTIs at the hospital carried this resistance.
Doctors are now confronting cases of resistant urinary tract infections in their practices. Dr. Eva Raphael, a primary care physician in San Francisco, recently received notice that one of her patients, a healthy woman in her mid-30s, was back in the emergency room with another UTI that was resistant to multiple antibiotics.
One of her prior UTIs had failed to respond to two commonly used treatments and had spread to her kidney, requiring hospitalisation to receive intravenous antibiotics. This time, Raphael consulted with infectious-disease specialists.
"It can be quite dangerous in this age where there is more and more resistance," she said, noting that without effective treatment, the infection can get into the blood. "It can be fatal."
Urinary tract infections, or UTIs, are one of the world's most common infections. Increasingly, they also are resistant to major drug treatments. Here's what you should know.
What is a drug-resistant urinary tract infection?
In the case of a resistant UTI, one or more standard antibiotics no longer work to cure the infection, but the bacteria is generally not resistant to all drugs.
What can I do to avoid getting a UTI in the first place?
Women are more susceptible to UTIs, owing to the way these germs infect: They often travel through faecal residue from the rectum to the urethra; this can happen through sex or poor bathroom hygiene. Even taking great care does not make them entirely avoidable.
Here are some steps that can help prevent urinary tract infections: Drink plenty of fluids, which helps flush out the bladder. Empty your bladder after sexual intercourse. Practice good bathroom hygiene, which, simply put, means wiping from front to back.
During the reproductive years, women are as much as 50 times more likely than men to get a UTI. However, those numbers even out significantly in an aging population because men wind up getting surgical procedures, or have bowel control issues, that might lead to the same spread of germs from gut and rectum to the urinary tract.
How often are UTIs resistant?
The majority of urinary tract infections are now resistant to one or more antibiotics. The drug ampicillin, once a common treatment, has been largely abandoned because most UTIs are now resistant to it.
The most important question isn't whether an infection is resistant to any drug, but whether it is resistant to the drugs that are commonly used to treat your particular infection.
When experts in the field think about resistant UTIs, they say that resistance "depends on the bug and the drug." What that means is that they try to figure out which particular germs are resistant to specific medications.
What drugs work?
The drugs that are used to treat urinary tract infections have changed over the years, in large part because of rising resistance. Currently, there are a few "front-line" drugs that are recommended by various expert organisations, such as the Infectious Disease Society of America.
Two drugs that are the most highly recommended for uncomplicated UTIs are nitrofurantoin, sold as Macrobid, and trimethoprim-sulfamethoxazole, sold as Bactrim or Septra. Both require a prescription, with doses and time courses that vary with the medication. But there has been growing resistance to Bactrim.
Nitrofurantoin seems to be more effective. Urinary tract infections caused by E. coli were susceptible to it 96 per cent of the time, the New York City health department found. But the nitrofurantoin tends not to work in more advanced UTIs where the infection reaches the kidneys, a condition known as pyelonephritis.
An older drug called fosfomycin has been revived as an alternative, but it is considered less effective than either nitrofurantoin or Bactrim. Other second-tier treatments tend to have either side effects or higher resistance rates.
What about other remedies, like cranberry juice?
Science doesn't back up the healing power of such remedies. However, they might appear to work because many UTIs will clear up over a few days as the body fights them off. In other cases, the symptoms may, in fact, be caused by another ailment that goes away on its own.
How do I know if my particular strain of UTI is resistant to a particular drug?
The only way is to get a urine culture. The lab results will identify the germ and what would be effective in treating the infection. But it can take several days to get the results.
Most patients want an immediate prescription so doctors usually make a best-guess determination of what drug will work given a patient's symptoms and history.
The importance of "history" cannot be overstated; if you have had a previous UTI, a previous resistant UTI, or have traveled outside the country, your history can help a doctor decide which drug to use.
Increasingly, experts tell us that you should ask for a culture when you go in for a UTI treatment, even if you get an immediate prescription. The culture will allow a doctor to change the drug if the first one does not work.
That said, there is an important catch about when to do a urine culture. Often, it will show bacteria in the bladder even when an infection is not present. Some amount of bacteria is normal. The Infectious Diseases Society of America cautions doctors against doing cultures when symptoms of a UTI are not present. The culture likely presence of bacteria can then lead to prescription of unnecessary antibiotics, contributing to the rise of resistance through overuse of the drugs.
Finally, some UTIs, even when there are symptoms, can clear up on their own. This is one of many reasons to seek the care of an informed professional.
Written by: Matt Richtel
Photographs by: Brian L. Frank
© 2019 THE NEW YORK TIMES
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