Urinary Infections: Report Offers Long-Needed Clarity

Larry Hand

November 13, 2013

Clinicians have long-needed clarity now in interpreting results of common urine culture tests for premenopausal women suspected of having a urinary tract infection, according to an article published in the November 14 issue of the New England Journal of Medicine.

Thomas M. Hooton, MD, from the University of Miami School of Medicine in Florida, and colleagues conducted an analysis of 236 episodes of cystitis in 226 women at the University of Miami Clinical Research Unit and at an outpatient clinic of the University of Washington in Seattle.

The customary urinary specimen used for cystitis testing is collected as midstream voided urine, the researchers write, but interpreting such cultures is complicated because of potential contamination by periurethral microorganisms. Although researchers in a 1982 study concluded that proven bladder bacteria had significant correlation with urinary colony-forming unit (CFU) counts as low as 102 per milliliter, no confirmatory studies have been done since then, and no studies have examined positive predictive value for bladder bacteriuria, the researchers write.

In the current study, the researchers performed microbiological analyses of midstream urine and urine collected by urethral catheter from women who had symptoms of cystitis for 7 days or less. The women, who were 73% white, ranged in age from 18 to 49 years, with a median age of 22 years; were in good general health; and were enrolled between 2002 and 2012. Paired culture specimens of midstream and catheter urine were available for 202 of 236 episodes.

In the Clinic Today

"The tests in the study are already used in the clinic, but people have had trouble interpreting them. This paper gives guidance to the laboratory that conducts them and also to clinicians who want to interpret those tests more reliably. I think it will be very helpful in the clinic," Linda Brubaker, MD, dean, Loyola University Chicago Stritch School of Medicine, and a urogynecologist in the Division of Female Pelvic Medicine and Reconstructive Surgery at Loyola University Health System, Maywood, Illinois, told Medscape Medical News.

The researchers found that at least 1 organism grew in 149 (74%) of catheter urine cultures and 200 (99%) of voided midstream urine cultures, and the uropathogens gram-negative rods, enterococci, group B streptococci, or Staphylococcus saprophyticus grew in 142 (70%) catheter urine cultures and 157 (78%) midstream urine cultures. Multiple organisms grew in 173 (86%) midstream cultures.

"The positive predictive values for [Escherichia coli] in midstream urine cultures were 93% for growth of at least 102 CFU per milliliter and 99% for growth of at least 104 CFU per milliliter, but for enterococci and group B streptococci, positive predictive values were low for all colony counts," the researchers write.

"These data suggest that enterococci and group B streptococci only rarely cause acute uncomplicated cystitis."

Instructive Suggestions

The researchers offer some instructive suggestions for better interpretation of cultures:

  • If clinical laboratories only test for growth for counts of 104 or higher, "cultures yielding low E. coli counts may be falsely reported as negative."

  • Enterococci and group B streptococci, commonly found in midstream urine cultures, rarely cause cystitis. Rather, E coli, commonly found in catheter urine cultures, "is the likely cause of many of these episodes."

  • "E. coli in mixed flora in midstream urine predicts bladder bacteriuria in 91% of episodes and should not be considered a contaminant."

They conclude, "For epidemiologic and research studies of healthy premenopausal women with cystitis, the use of 103 CFU per milliliter as a compromise threshold for a positive culture growing E. coli may be considered, given feasibility and cost constraints in the microbiology laboratory."

To determine how generalizable their results are, the researchers write, studies need to be conducted in other patients with urinary tract infections.

"This is a common area of clinical medicine that just doesn't get the [needed] scientific scrutiny," Dr. Brubaker, senior author for a related paper cited in the new study, explained. "Some of the new techniques, such as the DNA sequencing, coming online are going to be able to take this work...to the next level. We have some additional things that are soon to be published that will be very complementary to this work."

Long Time Coming

She concluded: "The significance of this paper is that it really updates some outdated clinical information and decision making for young premenopausal women with standard, garden-variety urinary tract infection.... It took them 10 years to get enough patients to do this study. It's been more than 50 years since the original studies about urine culture were done, so it was a much-needed study."

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hooton has reported receiving consulting fees from Merck and Pinnacle Pharmaceuticals and having an equity interest in Fimbrion Therapeutics. The other authors and Dr. Brubaker have disclosed no relevant financial relationships.

N Engl J Med. 2013;369:1883-1891.

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