First, bacterial density in the urine may not correlate with the numbers of bacteria in the bladder wall. Significant numbers of bacteria can remain within the tissue even in the absence of bacteriuria.
Second, a single exfoliated urothelial cell can contain ∼105 CFU of bacteria but would only be enumerated as a single colony by traditional culture-based methods unless the sample were properly homogenized to release the bacteria within the IBC.
Lastly, culture-based methods underestimate the bacterial burden when filamentous populations are present. A single filament of 70 μm has the CGP 3466B and the genetic content of 35 bacteria but would translate to only 1 CFU. These confounding issues underscore the need for new diagnostic approaches.
The Role of Urothelial Invasion in UTI
Recent research in animal models has shown that UPEC, which accounts for 70%-90% of human UTIs, is capable of forming biofilm-like communities within superficial bladder epithelial cells in the setting of cystitis (Fig. 1).5 and 29 These IBCs are difficult to detect in urine specimens, can remain quiescent for extended periods despite antibacterial therapy, and can re-emerge to cause recurrent infection.30 and 31 In this scenario, the bladder wall itself may serve as a reservoir for infection of the urinary tract lumen. There is evidence that other organisms, such as Enterococcus faecalis and Klebsiella pneumonia, can also form IBCs in experimental models of UTI. 32 and 33