A Non‐Surgical Rat Model of Foreign Body‐Associated Urinary Tract Infection with Pseudomonas aeruginosa

Abstract

This study established a rat model of foreign body-associated urinary tract infection. A spiral polyethylene tube (PT) was placed transurethrally into the bladder without surgical manipulation, followed by transurethral inoculation with Pseudomonas aeruginosa. The persistence of P. aeruginosa in the kidneys and bladder was significantly enhanced by placement of the PT, whereas the bacteria were eliminated rapidly from the urinary tract in the animals without the PT. Scanning electron microscopy revealed a thick biofilm on the surface of the PT from the early stage of infection. Histopathologically, acute pyelonephritis was followed by chronic renal inflammation as well as continuous and sporadic polymorphonuclear leukocyte accumulation and hemorrhage in the pelvis and adjacent tissues, suggesting continuous ascending introduction of the bacteria from the biofilm adhering to the PT. We believe our model simulates the pathophysiology of foreign body-associated urinary tract infection characterized by biofilm formation on the surface of a foreign body.Key words: Rat model, Pseudomonas aeruginosa, Urinary tract infection, Foreign body-associated UTI Urinary tract infections (UTI) associated with foreign bodies including urinary catheters and/or stents are some of the most common and problematic of hospitalacquired infections (3, 16). Typically, the biofilm mode of bacterial growth on the surface of the urinary catheter and adjacent mucosa accounts for the pathophysiology of foreign body-associated UTI (6-8). The role of bacterial biofilms on the surface of urinary catheters in UTI has been studied in rabbit models (5, 13). To determine the pathogenesis of foreign body-associated UTI in terms of its immunological and bacteriological aspects, numerous efforts have been made to establish rodent models of foreign body-associated UTI. These include models in which UTI was induced by placement of foreign bodies, such as glass beads (I), zinc rings (10, 12, 15), catheter segments (4), sutures (11), and polyurethane sponges, into the bladder (9). These models, however, have had few clinical parallels mainly because surgical manipulation to implant the foreign body into the bladder could not be avoided. Surgical incision of the bladder

Bladder catheterization increases susceptibility to infection that can be prevented by prophylactic antibiotic treatment

“…Our findings are in line with previous reports demonstrating that CFU recovered from experimental E. faecalis and Pseudomonas aeruginosa infections are higher in catheterized animals as compared with noncatheterized animals (14,35,37). Indeed, that the ID 90 for E. faecalis and UPEC are greatly reduced in catheter-bearing animals compared with noncatheterized mice highlights the truly vulnerable host state induced by catheter implantation.…”

“…Catheterization induces physical changes in the bladder and provides a structural surface permitting colonization by uropathogens. In animal studies, infected and noninfected catheterized bladders show profound tissue damage, including disruption of the epithelial barrier, as compared with noncatheterized infected rodents (14,35). Our studies have revealed that the initial inflammatory host response to catheterization is sustained for at least 1 week, as evidenced by continuous neutrophil recruitment to the catheterized bladder.…”

Role of biofilm in catheter-associated urinary tract infection☆

“…21 The catheter also damages the bladder mucosa by triggering an inflammatory response and by mechanical erosion. 18,22 Once organisms gain access to the catheterized urinary tract, low-level bacteriuria usually progresses to >10 5 colony-forming units/mL within 24 to 48 hours in the absence of antimicrobial therapy. 23 For patients with an indwelling urethral catheter, the daily rate of acquisition of bacteriuria is 3% to 10%.…”

Enterococcus faecalis Overcomes Foreign Body-Mediated Inflammation To Establish Urinary Tract Infections

“…The insertion and presence of indwelling urinary catheters disrupt the normal mechanical and host defenses of the urinary tract, allow extracellular microbes access to the sterile environment of the bladder by ascending through the catheter lumen or from the urethral meatus along the catheter, and provide an additional surface for biofilm formation and the establishment of antibioticrecalcitrant chronic or recurrent infections (2)(3)(4)(5)(6)(7)(8)(9). Even in the absence of microbial colonization, urinary catheterization was shown to be associated with histological and immunological alterations in the bladder, including urothelial damage and exfoliation, bladder wall edema, inflammatory cytokine production, immune cell infiltration, and mucosal lesions of the bladders and kidneys (7,(10)(11)(12)(13) which can lead to bladder cancers (14,15). However, there remains a need to uncover molecular details and the functional role of the catheter-induced host responses during bacterial colonization and catheter-associated UTIs (CAUTIs).…”