Thread by @tony_breu

1/16
Why do we use 100,000 CFU/mL as our cut-off for true bacteriuria?

This question was posed to me by @BryanCiccarelli. The answer has an interesting history so I thought I'd share it here.

2/
Much of the reliance on urine cultures grew out of the observation that many patients found to have pyelonephritis on autopsy were never diagnosed before death.

It seemed that using clinical findings alone wasn’t good enough.

t.ly/wEWg

3/
Enter the urine culture!

Maybe bacteria identified in voided urine could be used as a surrogate for bladder bacteriuria/infection and/or pyelonephritis.

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There is a problem, of course.

False-positive urine cultures (i.e., “contamination”), particularly with these voided urine samples.

It wasn’t enough to have bacteriuria. We needed a value above which contamination became less likely and infection became more likely.

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In the 1950s, Edward Kass performed a series of studies with the goal of determining what number of bacteria - in voided urine - provided a clue to the diagnosis of pyelonephritis.

Kass used clinical features as the “gold standard” for diagnosis.

t.ly/ACIO

6/
In 1956 Kass published a report in which he noted that:

➤ 95% of those in whom pyelonephritis was made or suspected had >10⁵ CFU per mL of urine

But notice:

➤ Some patients with pyelonephritis have counts as low as 10² CFU/mL.

t.ly/ACIO

7/
Nonetheless, the studies by Kass led to the practice of defining true bacteriuria as >10⁵ CFU/mL, both for pyelonephritis and cystitis.

Over the next few decades, additional evidence emerged that using >10⁵ CFU/mL is too insensitive.

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In 1982, Stamm et al published a study in which they compared urine obtained via suprapubic aspiration or a catheter to a voided sample.

The two former methods were used to represent a gold standard for true bladder bacteriuria.

t.ly/s5zc

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Stamm et al found that >10⁵ CFU/mL has a sensitivity of just 51%. When the value was lowered to 10², the sensitivity increased to 95%.

Important note: this study only assessed coliform bacteria (e.g., E. coli, the most common cause of UTI).

t.ly/s5zc

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Despite these results, in the intervening decades >10⁵ CFU/mL continued to be used by many as the cutoff for UTI.

I certainly did.

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More than 3 decades passed. In 2013 Hooton et al. looked at the question again.

They examined 236 episodes of cystitis and compared urine obtained via a catheter to a midstream voided sample.

t.ly/qcnv

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As with prior studies, a cut-off of >10⁵ CFU/mL missed many infections (sensitivity 60%).

This may lead to undertreatment of symptomatic patients.

And as with Stamm, when the value was lowered to 10², the sensitivity increased, this time to 94%.

t.ly/qcnv

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So the original studies by Kass and follow-up studies by Stamm then Hooton all agree:

Using >10⁵ CFU/mL leads to missed cases of true bacteriuria in symptomatic patients.

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One place you continue to see reference to >10⁵ CFU/mL?

Asymptomtic bacteriuria. And the original studies by Kass are used as support for this cut-off.

t.ly/9x7M

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It's worth noting that most guidance doesn't require urine culture in women with typical symptoms.

And if cultures are obtained resources such as UpToDate suggest 10³ CFU/mL as the cut-off.

t.ly/vGRvA

16/16
📌The search for a level of bacteriuria consistent with UTI emerged from a desire to avoid missed pyelonephritis
📌Though >10⁵ CFU/mL has long been associated with true positive bacteriuria, in those who are symptomatic this value has low sensitivity