A High Throughput, Minimally Invasive, Ultrasound Guided Model for the Study of Catheter Associated Urinary Tract Infections and Device Encrustation in Mice

Abstract

Catheter associated urinary tract infections are one of the most common health care associated infections. The condition is frequently complicated by encrustation, which blocks the catheter lumen. Preclinical research is limited by the lack of relevant high throughput and cost-effective animal models. Current models are restricted to female mice, associated with major transurethral loss of catheter materials during micturition, highly invasive and complex. We present an ultrasound guided, minimally invasive model that enables catheter associated urinary tract infection and catheter encrustation studies in each mouse gender. Catheter segments (4 mm) were implanted in murine bladders percutaneously in 15 males and 5 females, and transurethrally in 15 females using the Seldinger technique under ultrasound guidance. Proteus mirabilis was instilled intraluminally. Catheter encrustation was monitored by ultrasound. Bacteria were quantified in urine, and catheters and encrustation were analyzed on day 6 or 21. Percutaneous and transurethral catheter implantations were performed in a mean ± SE 3.6 ± 0.8 vs 2.5 ± 0.5 minutes in all mice. Ultrasound confirmed that 100% and 66% of implanted catheters, respectively, remained indwelling during the study period. Catheter encrustation developed in P. mirabilis infected urine 48 hours after instillation and an increase with time was detected by ultrasound. Fourier transform spectroscopy of the encrustation confirmed a typical struvite spectrum. Control catheters remained sterile during 21 days. Our minimally invasive, reproducible percutaneous technique is suitable for studying catheter associated urinary tract infection in each gender. Infecting urine with P. mirabilis generates a preclinical model of catheter encrustation within 3 days. The progression of encrustation can be monitored invivo by ultrasound, making this image based model suitable for assessing novel antibacterial and anti-encrustation therapies.