Home >> ALL ISSUES >> 2016 Issues >> Missed UTIs? ‘Enhanced cultures’ suggest so

Missed UTIs? ‘Enhanced cultures’ suggest so

image_pdfCreate PDF

Kevin B. O’Reilly

August 2016—The long-held belief that urine is sterile is facing a serious challenge from new research combining sequencing techniques and an enhanced urine culturing protocol to uncover an array of uropathogens hitherto unseen in microbiology laboratories.

The notion that urine, indeed the entire bladder, is sterile is one medical students are still taught and “it’s a pretty deeply entrenched dogma,” says Linda Brubaker, MD, a urogynecologist and professor of obstetrics and gynecology and urology at Loyola University Chicago Stritch School of Medicine. She and a team of Loyola colleagues have worked for years to learn more about urinary microbiota and in the process demonstrated that currently standard urine culturing techniques fail to spot an alarmingly high proportion of uropathogens that may well be clinically relevant. Their findings were presented in June at the American Society for Microbiology’s Microbe meeting.

Dr. Brubaker

Dr. Brubaker

“What we’re going to do is replace the dogma that clinical care is based on,” Dr. Brubaker says. “There is a great deal of excitement because this is a vast unknown. It’s like discovering a tribe in the middle of the Amazon. We never knew these people were here, or how they eat, or how they live. We have to understand this [bacterial] community now—how it maintains health, how it deals with perturbations, like when patients are catheterized and a certain number of patients will get infections. Not all of them do. We may learn why some do and some don’t.”

The longer-term research and clinical implications of the finding that urine is not sterile could be profound, leading to a better understanding of what causes myriad urologic conditions. Most immediately striking are the implications for clinical microbiology laboratories and clinicians struggling to help patients with recurrent urinary tract infections.

A protocol developed at Loyola and dubbed the enhanced quantitative urine culture, or EQUC, tests a much larger volume of urine in a CO2-enriched environment over two days, twice as long as the standard 24-hour urine culture. What EQUC uncovers that the standard urine culture misses comes as a bracing affront to the sterile-urine hypothesis.

In a study involving 150 female patients who were asked, “Do you feel you have a UTI?” those enrolled were split evenly between patients who answered yes and those who answered no. Urine specimens from the patients were tested using the standard urine culture (1 µL of urine, blood agar plate, MacConkey agar, incubated 24 hours in aerobic conditions at 35°C) and a variety of other culturing approaches. The latter included what the Loyola team calls the “streamlined EQUC” (100 µL of urine, BAP, MacConkey agar, CNA agar, incubated 48 hours in five percent CO2 air at 35°C).

The standard urine culture detected just 33 percent of 182 uropathogens, while the streamlined EQUC protocol spotted 84 percent of the uropathogens. But how many of those uropathogens make a clinical difference in patients? This is why patients were asked about their symptoms. In the group reporting UTI symptoms, the standard urine culture detected only 57 percent of uropathogens, while the EQUC spotted 91 percent (Price TK, et al. J Clin Microbiol. 2016;54[5]:1216–1222).

Dr. Sautter

Dr. Sautter

This finding is “very significant,” says Robert Sautter, PhD, the recently retired director of microbiology for the Carolinas Pathology Group that serves the massive Carolinas HealthCare System.

“It’s one of the biggest things I’ve seen in urine cultures in the last 20 years, and the reason is that we now think we’re missing all these infections, the causative agents—67 percent by their numbers. That’s amazing. That’s worse than flipping a coin. And if we can close that gap a little bit, that’s an enormous thing,” says Dr. Sautter, who now works as a clinical microbiology consultant in Lancaster, SC, and presented an unrelated talk on direct detection methods for diagnosing UTIs at the ASM meeting.

The Loyola team “is showing things we did not know in the past,” adds Dr. Sautter, who was not involved in their research. “We’ve known about breakpoints in colony counts, that for certain diseases were different, for 50 years. Some people followed it and some people didn’t. But now we’ve got an indication that maybe we’ve missed the boat over these 50 years and we are missing some clinically important infections with these organisms that are not being detected.”

The false-negatives with the standard urine culture appear to have an impact on patient outcomes, Alan J. Wolfe, PhD, said in his presentation at the ASM Microbe meeting. Dr. Wolfe is a professor of microbiology and immunology at Loyola and co-director, with Dr. Brubaker, of the Loyola Urinary Education and Research Collaborative.

Following up with patients after treatment, researchers discovered that 61.5 percent of those found positive for a UTI by both standard urine culture and EQUC—and thus treated with antibiotics under the prevailing standard of care—saw their symptoms improve. Another 30.8 percent said their UTI symptoms stayed about the same, while 7.7 percent said they felt worse.

By contrast, among patients who were negative by the standard urine culture but positive by EQUC—and thus received no antibiotics—only one-third reported UTI symptom improvement. The other two-thirds of these patients said their symptoms stayed the same or grew worse with time.

“So the question, of course, is would they have improved if they were treated?” Dr. Wolfe said. “Another question would be this. Here you have some individuals that were standard urine culture-positive and they were treated, but they didn’t improve. Is that because there were uropathogens underlying the suspected broad uropathogen that was treated?”

These and other questions about the patient impact of the EQUC protocol are ones the Loyola team hopes to answer with a clinical trial for which enrollment will begin later this year. The researchers have developed a different treatment algorithm for patients whose urine tests positive by EQUC (but negative by the standard urine culture) to see what, if any, improvement can be seen in the course of their UTIs.

CAP TODAY
X