‘UTI’ an overused diagnosis in the era of the microbiome

For Thomas E. Finucane, MD, FACP, the concept of urinary tract infections (UTIs) is so mythical, ambiguous, and harmful that he uses quotation marks around the term.

At Johns Hopkins Bayview Medical Center in Baltimore, he even encourages housestaff and colleagues to make air-quotes when they say it out loud. “A lot of people have a very resilient idea that if somebody has a ‘UTI,’ they must get antibiotics, and I want to try to undermine the whole construct,” said Dr. Finucane, emeritus professor of medicine in the division of geriatric medicine and gerontology.

In a special article published online in May 2017 by the Journal of the American Geriatrics Society, he describes UTI as an “ambiguous, expansive, overused diagnosis” that can lead to the myriad harms of antibiotic overtreatment. Dr. Finucane has also explored the relationship between UTIs and the microbiome (2017) and bacteriuria and delirium (2014) in articles published by the American Journal of Medicine.

He recently spoke with ACP Internist about medicine's evolving understanding of UTIs, specifically in nonpregnant patients who do not have catheters and do have anatomically and functionally normal urinary tracts.

Q: What got you thinking about UTIs in this way?

A: For years, it's been obvious that antibiotic overtreatment of bacteriuria is a very serious problem in geriatrics, and the elderly are particularly subject to overtreatment and particularly at risk to be harmed by the overtreatment. In one study, of all the cultures sent to check for a UTI, change in the smell or appearance of the urine was the reason in about 10%, and there's no evidence, of course, that improving the appearance or the smell of urine by antibiotic treatment benefits the patient in any way. But people see a dirty look in urine or a smell in urine and they say, “Oh, I think there's a UTI. Let's give antibiotics.”

For a young woman with painful urination, it's standard of care to give antibiotics. But the true data show that the pain improves, and it improves a little bit faster than [with] placebo. The bacteria go away a little bit faster if you take the antibiotic, but nothing bad happens to you if you don't take it except that it hurts for a few more days. It's essentially a benign, self-limited condition except for the pain that it causes. And about half the time, there is no bacteriuria.

Q: But what about serious sequelae of UTIs, such as pyelonephritis?

A: There are several randomized controlled trials of young, healthy women who have painful urination, and they're randomized to antibiotic treatment or placebo. There's another couple where they're randomized to antibiotic treatment or ibuprofen. There is a low rate of pyelonephritis in the women who received placebo or ibuprofen, but it's the same rate in the women who receive antibiotics. “UTI” is associated with pyelonephritis; antibiotic treatment does not reduce the risk of pyelonephritis in any of those trials that have been done, or if you sum all of the evidence.

For patients who have asymptomatic bacteriuria, which is often defined as a UTI, there are randomized controlled trials in ambulatory elderly men and women, institutionalized elderly men and women, diabetic women, young women … where treating asymptomatic bacteriuria with antibiotics leads to no benefit and to some harm. There's an important trial of women who've had recurrent “UTIs” in the past, meaning acute uncomplicated cystitis (bacteriuria and painful urination), where they come in and they have asymptomatic bacteriuria, and they're randomized either to antibiotic treatment or no treatment at all. … It turns out, if you use antibiotics to get rid of the asymptomatic bacteriuria, they get more symptomatic infections in the next year than if you just leave it alone. And that is, by the way, highly understandable, in light of the microbiome.

Q: It seems like in the past few years, we've gotten a greater understanding of the microbiome. How long have we known, for example, that the old thinking that urine is sterile is false?

A: Scientists have demonstrated it several years ago using genetic techniques, where instead of using what we've been using for 135 years and seeing if something will grow on an agar plate, they examine what the genetic material is in the urine. Expanded culture techniques have now confirmed these findings. [These] new diagnostic techniques have shown that everybody has bacteriuria all the time, and basically always, there are several different bacterial species living in the bladder and probably in the kidneys of completely asymptomatic people, and a virome has been demonstrated, as well. … In this trial of women who had previous recurrent UTIs, the authors felt that getting rid of the bacteria with antibiotics destabilized what was a stable, beneficial microbiome in the bladder, and the untreated women retained that stable protective microbiome and had fewer symptomatic infections than the women treated with antibiotics.

Q: Did you anticipate this discovery?

A: I don't think I did. To me, the microbiome is the most powerful, important, and astonishing thing that's come to medicine since I got an MD in 1978. It completely revolutionized the way you have to think about people and the world.

Q: What feedback do you get from physicians regarding your way of thinking about UTIs?

A: People are usually vaguely amused and resolved to be more vigilant about it. But a lot of docs know that the rates of treatment of asymptomatic bacteriuria, where it can only be harmful, are pretty high. Asymptomatic bacteriuria is frequently treated, even though the data have been unequivocal for over a decade.

Many symptoms, including dysuria and delirium, but so many more, are attributed to “UTI” when bacteriuria is found. This way of thinking ignores the fact that bacteriuria is always present if you use modern diagnostic techniques. So if you say, for example, that delirium is caused by bacteriuria, you're saying it's caused by a bacterial species that happens to grow on agar. And that it is safe to ignore all the other species that are in the bladder but are more difficult to identify.

Q: What should an internist do if a patient calls reporting symptoms of a UTI?

A: I often ask them to come in in the hopes that things will blow over before they get there. A lot of times, dysuria is just a matter of a few days, and there's a couple of papers on delayed prescriptions. … A good chunk of the patients never fill the prescription and just get better on their own before they feel that drugs are necessary. But there are true believers who say “Yes, doctor,” and then they go straight to the pharmacy and get the antibiotics.

Q: When is treating UTIs with antibiotics indicated?

A: The biggest category is if a patient is medically unstable with signs of infection, especially signs of sepsis, you have to give antibiotics and you need to do it right away. And that's completely without regard to any findings in the urine. Then, No. 2, if you have bacteremia and it's also in the urine, then you've got to treat the blood infection, and it's reasonable to call that a UTI and assume that it arose in the bladder, although we don't know that to be the case. That has a bunch of names: bacteremic bacteriuria, urosepsis, and there are other names for it.

Let me give you two more: There's pretty good evidence that if you have asymptomatic bacteriuria and you're pregnant, probably you should take antibiotics. That is the recommendation from the Infectious Diseases Society of America (IDSA). And then, in people who are about to have invasive procedures on the urinary tract, if they have asymptomatic bacteriuria, the [IDSA] recommendation is to give them antibiotics just before the procedure.

Q: Looking ahead, what do you anticipate happening in this area?

A: Glacial change. The antibiotic treatment of self-limited conditions is uniformly gratifying. It's very deeply embedded in the psyche of the docs, and the patients, and the patients' families. So all of those factors add up against any radical change.

Q: How would you like to see internists change their approach to UTIs?

A: In a randomized trial in Scandinavia of several hundred women with acute uncomplicated cystitis, they either got placebo or an antibiotic. And a large majority of the women who were asked said, “Yes, I would be willing to delay the antibiotics for a day or two to see if I'm assigned to the placebo arm.” What I have been doing is to say, “Let's try some [ibuprofen], let's try some fluids, let's wait and see what Mother Nature has in mind. Here's a prescription. If you must, fill it, but remember that it has the following 10 harmful consequences.”