Urine Culture in Cystitis
Voided midstream urine culture and acute cystitis in premenopausal women.
Hooton TM, Roberts PL, Cox ME, Stapleton AE.
N Engl J Med. 2013 Nov 14;369(20):1883-91. [Full text]
What is the “true” cutoff for a positive urine culture? Much of the literature establishing the common >105 CFU/mL in common use today was published in the 1950-60s; however, a 1982 prospective study of dysuric women found that >105 CFU/mL was only 51% sensitive, though it was 99% specific. In contrast, >102 CFU/mL was 95% sensitive and 85% specific [1].
Given a sizable time gap had passed since that publication, the authors of this 2013 study aimed to performed a detailed microbiologic analyses of both midstream urine and urine collected by catheter from women with confirmed cystitis.
Patient population and Design
Patients were recruited from two outpatient centers in Seattle and Miami. Women between 18 and 49 years that were in good general health, and had had typical cystitis symptoms (dysuria and urinary frequency or urgency) for 7 days or less were eligible. Women were excluded with fever (>38°C), costovertebral angle tenderness, diabetes mellitus, known anatomical abnormalities of the urinary tract, recent antibiotic use (<2 weeks), a diagnosis of urinary tract infection (UTI) in the month prior, or if they were pregnant. Women that participated provided both a clean catch and catheterized urine specimen.
The primary outcome was if bacteria in the midstream urine matched that of the catheter urine culture, as measured by its PPV and NPV. Enterococcal and group B streptococci (GBS) were of particular interes. Secondary outcomes included the prevalence of atypical organisms (not usually considered uropathogens), the frequency of polymicrobial cystitis, and the presence of pyuria.
Results
Between 2002 and 2012, a total of 236 episodes of acute cystitis were evaluated which included recurrent epsodes from nine women. Paired midstream urine and catheter urine were available for 202 episodes. The median participant age was 22 and all had a chief complaint of dysuria or frequency.
The midstream urine cultures grew at least one organism in 200 (99%) of samples, while only 149 (74%) of catheter urine had at least one organism. When considering organisms that are typical uropathogens, grew in and in 35 cultures (17%) of midstream urine was polymicrobial with only 4 (2%) in catheter urine cultures.
Gram-negative rods (GNRs) where seen in grew in 145 episodes of cystitis (72%), with Escherichia coli growing in 132 of those (65% of total). Among 114 episodes in which E. coli grew in midstream urine cultures, 104 episodes (91%) showed E. coli growth in the catheter urine culture. The operating characteristic of a midstream urine culture showing E.coli compared to the catheter urine culture are as follows:
| E. coli | Sens | Spec | PPV | NPV | LR+ | LR- |
| >102 CFU/mL | 94% | 89% | 93% | 91% | 8.6 | 0.07 |
| >105 CFU/mL | 60% | 99% | 99% | 62% | 60 | 0.4 |
Enterococci, a gram positive organism, was isolated from 20 episodes (10%) midstream, but only 2 catheter urine cultures. Similarly, GBS was isolated in 25 episodes (12%) midstream but only 2 from catheter urine. Operating characteristics for midstream urine culture showing Enterococci and GBS are as follows:
| Enterococci | Sens | Spec | PPV | NPV | LR+ | LR- |
| >102 CFU/mL | 100% | 91% | 10% | 100% | 11 | 0 |
| >105 CFU/mL | 50% | 98% | 25% | 99% | 25 | 0.5 |
| GBS | Sens | Spec | PPV | NPV | LR+ | LR- |
| >102 CFU/mL | 100% | 88% | 8% | 100% | 8.3 | 0 |
| >105 CFU/mL | 50% | >99% | 50% | >99% | >50 | 0.5 |
Seven cultures showed lactobacilli, three G. vaginalis and S. aureus in in five cultures.
Discussion
This 2013 study of over 200 healthy women outpatients with uncomplicated cystitis demonstrated similar results to a 1982 study. While >105 CFU/mL on a midstream urine culture is highly specific, when compared to a catheter urine culture, it is only about 50-60% sensitive, depending on the organism.
When looking at GNRs, specifically E.coli, >102 CFU/mL on a midstream urine culture is 94% sensitive, maintains a 89% specificity for a 93 PPV and 91% NPV, when compared to a catheter urine culture. These operating characteristics would be generally considered excellent for most diagnostic tests. While the equivalent >102 CFU/mL of Enterococcus and GBS each had a similar sensitivity and specificity, because the incidences were low, the associated PPVs may limit the application of this threshold.
In this population of outpatients with new dysuria and frequency but without systemic symptoms, the pre-test probability is high enough that a urinalysis is often not necessary, let alone a urine culture. Therefore, populations that would require urine culture are more of interest, for example in those that fail antibiotics, or those with pyelonephritis. Whether similar results to this study apply in those cases is not known. In 1956 patients with pyelonephritis mostly had >105 CFU/mL , though there were many with 102 – 105 CFU/mL also [2, 3]. There does not appear to be an update to this work. We are thus left to extrapolate from the current study: in those with a high pre-test probability, a midstream urine culture with >102 CFU/mL can be consistent with infection, especially in the case of E.coli.
| F: Follow up | N/A, index visit |
| R: Randomization | N/A |
| I: Intention to treat | N/A |
| S: Similar at baseline | N/A |
| B: Blinding | N/A |
| E: Equal treatment | N/A |
| S: Source (funding) | National Institute of Diabetes and Digestive and Kidney Diseases |
- Stamm WE, Counts GW, Running KR, Fihn S, Turck M, Holmes KK. Diagnosis of coliform infection in acutely dysuric women. N Engl J Med. 1982 Aug 19;307(8):463-8.
- Kass EH. Asymptomatic infections of the urinary tract. 1956. J Urol. 2002 Feb;167(2 Pt 2):1016-9; discussion 1019-21.
- Breu, Tony, @tony_breu, “Why do we use 100,000 CFU/mL as our cut-off for true bacteriuria?” January 30, 2022.
