Is it time to rethink midstream urine culture for UTI diagnosis?

Midstream urine culture (MSU) is currently seen as the gold standard test for diagnosing a urinary-tract infection (UTI) in adults.
 
However, a recent study published in the Journal of Clinical Microbiology is questioning whether it should remain in top position.
 
The study looked at urine specimens from 33 patients with chronic lower-urinary-tract symptoms (LUTS) attending their first appointment, 30 LUTS patients on treatment whose symptoms had relapsed, and 29 asymptomatic controls.
 
Researchers compared the bacterial enrichment capabilities of the MSU culture with those of a 50 µl uncentrifuged culture, a 30 ml centrifuged sediment culture, and 16S rRNA gene sequencing.
 
‘We showed that the routine MSU culture, adopting the UK interpretation criteria tailored to acute UTI, failed to detect a variety of bacterial species, including recognised uropathogens,’ the authors wrote.
 
They concluded the diagnostic MSU was unable to discriminate between patients and controls.
 
‘This work put the MSU head-to-head with modern DNA analysis methods – and it failed spectacularly,’ researcher Dr Jennifer Rohn, head of Urological Biology at University College London’s Department of Renal Medicine in the Division of Medicine at the Royal Free Hospital, said.
 
‘On the other hand, genomic sequencing using enriched urine specimens easily managed to pick out people who were genuinely ill.’
 
As part of the study, researchers found that fewer than 10% of patients with a clinically suspected UTI had a positive MSU, with only four of 33 new patient cultures producing non-microbial growth at 10⁵ CFU/ml.
 
In contrast, bacterial DNA sequencing revealed bacteria, including recognised uropathogens, in 32 new patients. These included symptomatic patients who were reported to have a negative MSU.
 
In conclusion, the study found that the MSU protocol ‘misses a significant proportion of bacteria’.
 
The researchers therefore state that an MSU ‘may be unsuitable for excluding UTI in patients with LUTS’ and advise that those responsible for UTI detection, diagnosis and patient care ‘may wish to use caution when interpreting a negative or mixed-growth MSU in symptomatic patients’.
 
Dr Rohn said MSUs have been under suspicion as a diagnostic test for some time.
 
‘We’ve had inklings of this for years,’ she said. ‘This really proves it for the first time.’
 
Dr Rohn said embarrassment and stigma about UTIs, as well as with conservative thinking in medicine, may be among the reasons this issue has remained in the background.
 
‘I feel like it’s been neglected in medicine because these people have been neglected,’ she said.
 
‘It’s really sad. People tell these same stories, “I’m begging for antibiotics, I’ve had symptoms for 10 years but the computer says no. The test is negative”.
 
‘I feel it’s a moral issue in a way, that patients are getting a bad deal.’
 
This is not the first study to question the usefulness of the MSU in detecting UTIs.
 
Research published in the Journal of Clinical Microbiology in May 2016 found that, compared to the expanded-spectrum enhanced quantitative urine culture (EQUC), the standard urine culture missed 67% of all detected uropathogens and 88% of non-E.coli uropathogens.
 
Professor James Malone-Lee is a world leader in the study of chronic UTIs who worked on the most recent research. He is also critical of the diagnostic abilities of the MSU.
 
‘The test we currently use for urinary-tract infections is primitive and has never been properly validated,’ he said.
 
‘We’re still using the same test we were using 70 years ago.’
 
Along with questioning the idea of whether MSU is the best test to detect UTIs, Professor Malone-Lee also believes UTIs can be chronic. He said patients with chronic UTI may have bacteria that get inside the lining of the bladder and therefore cannot be detected in urine, making MSU obsolete as a diagnostic tool.
 
In such cases, Professor Malone-Lee said long-term (even up to six years’ worth) maximum dose of first-generation urinary antibiotics may be needed.
 
Many factors dictate what test to use in diagnosing UTIs, including cost, effectiveness, ease of access, and more.
 
So what should GPs do if they suspect a patient has a UTI, but the MSU comes back negative?
 
‘We should be looking harder if people get a negative result but present with UTI symptoms,’ Alexandra Mowat from the UroGynaecological Society of Australia said.
 
‘In highly resourced clinics, we can ask the microbiologists to look for the DNA of certain bacteria which are hard to cultivate but that are known to cause bladder symptoms, such as gonorrhoea, chlamydia and mycoplasma.’
 
Meanwhile, Dr Rohn believes that when it comes to MSUs, ‘We urgently need to develop alternative rapid diagnostic tests to take its place’.
 
According to Kidney Health Australia, around one in two women and one in 20 men will get a UTI in their lifetime.

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