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Updated: Aug 9, 2026

An In Vitro Bladder Model of Catheter-Associated Urinary Tract Infection
Published on: June 24, 2025
Modulation of crystalline Proteus mirabilis biofilm development on urinary catheters
David J Stickler1, Sheridan D Morgan1
1Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3TL, UK.
Abstract:
The crystalline biofilms formed by Proteus mirabilis can seriously complicate the care of patients undergoing long-term bladder catheterization. The generation of alkaline urine by the bacterial urease causes calcium and magnesium phosphates to precipitate from urine and accumulate in the catheter biofilm, blocking the flow of urine from the bladder. The pH at which these salts crystallize from a urine sample, the nucleation pH (pH(n)), can be elevated by diluting the urine and by increasing its citrate content. The aim of this study was to examine whether manipulation of pH(n) in these ways modulated the rate at which crystalline biofilm developed. Experiments in laboratory models of the catheterized bladder infected with P. mirabilis showed that when the bladder was supplied with a concentrated urine (pH(n) 6.7) at a low fluid output (720 ml per 24 h), catheters blocked at 19-31 h. Diluting this urine 1:4 increased the pH(n) to 7.5 and models supplied with this urine at 2880 ml per 24 h took 110-137 h to block. When models were supplied with urine containing citrate at 1.5 mg ml(-1) or above (pH(n) 8.3-9.1), the catheters drained freely for the full 7 day experimental period. Scanning electron microscopy revealed that the catheter biofilms that developed in urine with high pH(n) values were devoid of crystalline formations. These observations should encourage a clinical trial to examine the effect of increasing a patient's fluid intake with citrate-containing drinks on the encrustation and blockage of catheters.
Insights
Manipulating urine
Area of Science:
- Urology
- Microbiology
- Biomaterials Science
Background:
- Proteus mirabilis crystalline biofilms complicate long-term bladder catheterization.
- Bacterial urease generates alkaline urine, causing phosphate salt precipitation and catheter blockage.
- Nucleation pH (pH(n)) influences salt crystallization and biofilm formation.
Purpose of the Study:
- To investigate if modifying urine's nucleation pH (pH(n)) affects crystalline biofilm development rate.
- To assess the impact of urine dilution and citrate content on catheter blockage.
Main Methods:
- Laboratory models of catheterized bladders infected with P. mirabilis.
- Manipulation of urine concentration, dilution (1:4), and citrate levels (≥1.5 mg ml⁻¹).
- Monitoring catheter blockage times and analyzing biofilm structure via scanning electron microscopy.
Main Results:
- Concentrated urine (pH(n) 6.7) led to blockage in 19-31 hours.
- Diluted urine (pH(n) 7.5) extended blockage time to 110-137 hours.
- Urine with citrate (pH(n) 8.3-9.1) prevented catheter blockage for 7 days; biofilms lacked crystalline formations.
Conclusions:
- Elevating urine nucleation pH (pH(n)) via dilution or citrate addition significantly inhibits crystalline biofilm formation.
- Citrate-rich fluids may prevent catheter encrustation and blockage in patients.
- Clinical trials are warranted to evaluate the efficacy of citrate supplementation in patients.
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