E. coli in mid-stream urine highly sensitive for cystitis

Image: PD

1. Detection of E. coli at concentrations as low as 10 CFU/ml in mid-stream urine specimens was strongly predictive of E. coli detection in catheter specimens.

2. Enterococci and group B streptococci were commonly found in midstream urine but rarely caused cystitis.

Evidence Rating Level: 2 (Good)

Study Rundown: Given the frequency of urinary tract infections and the sizable cost of antibiotics prescribed for these infections in the US, the authors sought to investigate the utility of the commonly ordered clean-catch midstream urine specimen in diagnosing urinary tract infection (UTI). This diagnostic test is a convenient, non-invasive test that can aid in the diagnosis of UTI, but these cultures do not perfectly reflect the microbiology of the bladder. The results showed a strong correlation between the concentration of gram negative Escherichia coli and Klebsiella pneuomniae in the midstream urine culture and bladder microbiology; the same was found in 6 cases of Staphylococcus saprophyticus. Additionally, E. coli detected in the midstream urine culture at concentrations as low as 10 colony forming units (CFU) per milliliter was predictive of E. coli in the bladder. On the other hand, when enterococcus or group B streptococcus were grown in cultures from the midstream urine sample, they were rarely found in corresponding bladder samples.

Taken together, these results detract from the utility of the midstream voided urine sample in the diagnosis of UTIs, especially since outcomes in patients have been shown not to improve with the information from this test. First, clinical laboratories not reporting E. coli at low concentrations (as low as 10 CFU per milliliter) or E. coli with mixed flora as a positive result may be reporting false negative results. Second, laboratories that report high concentrations of enterococci or group B streptococci as positive may be presenting clinicians with false positive results. The strengths of the study include the simple study design with matched samples in a well-defined population. However, the results pertain to a population with a median age of 22 years that was predominantly white, and caution should be exercised in interpreting these results among other groups. Further studies must address this question in patients excluded from the analysis (e.g. those with diabetes or CVA tenderness).

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Click to read the study, published today in NEJM

Click to read an accompanying editorial in NEJM

Relevant Reading: Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial

Study author, Dr. Thomas M. Hooton, MD, talks to 2 Minute Medicine: Professor of Medicine, University of Miami Miller School of Medicine; Associate Chief of Staff, Miami VA Healthcare System

“These data reinforce the opinion of many that the voided urine culture for diagnosis of cystitis in healthy women has limited value. For the clinician who feels that a voided urine culture is warranted in the evaluation of a symptomatic woman, it is important to know:

that E. coli in voided urine even in very low counts or in mixed flora is predictive of bladder urine growth and, thus, the likely cause of the woman’s UTI symptoms – and should not be ignored by the clinician.
that the laboratory should be asked to quantify Gram negative rods to low levels in voided urine specimens (most laboratories do not quantify to low levels unless asked to do so).
that enterococci and Group B streptococci, when grown in voided urine in a woman with UTI symptoms, are not likely to be the cause of such symptoms.”

In-Depth: This study involved 202 women diagnosed with typical symptoms of cystitis (dysuria and urinary frequency or urgency), who contributed paired samples of clean-catch midstream urine specimens followed by bladder urine specimens obtained by urethral catheter. The median age of the participants was 22 years and 73% were white. Exclusion criteria included (but were not limited to) temperature over 38ºC, costovertebral angle tenderness, and diabetes mellitus. The primary study outcome was a comparison of the positive and negative predictive values of organisms grown in midstream urine, using the presence or absence of the organism in urine obtained by catheter as a reference and careful quantitative culture methods.

At least one organism grew in 74% of catheter urine and 99% of voided midstream urine. Uropathogens (gram negative rods, enterococci, group B streptococci and S. saprophyticus) grew in 70% of the catheter urine samples and 78% of mid-stream urine samples. Notably, among 114 midstream cultures in which E. coli grew along with any other organism as part of mixed flora, 104 episodes (91%) showed E. coli growth in catheter specimens. Colony counts of E. coli were strongly correlated (Spearman’s r=0.944) with colony counts in catheter urine; the same was found for Klebsiella pneumoniae (Speaman’s r=0.999). Gram positive bacteria showed weaker correlations (Spearman’s r’=0.322 and 0.272 for enterococci and group B streptococci, respectively).

The positive predictive value of E. coli in midstream urine cultures was 93% for growth of at least 10² CFU per milliliter and 99% for growth of at least 10⁴ CFU per milliliter, compared to 10% for enterococcus colony counts of at least 10² CFU per milliliter and 8% for group B streptococci of at least 10² CFU per milliliter.

By Matthew Growdon and Adrienne Cheung

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