Persistent Escherichia coli Urinary Tract Infection

Chapter 194

Persistent Escherichia coli Urinary Tract Infection

Bacteria account for the majority of urinary tract infections (UTIs), and Escherichia coli strains are isolated from 35% to 50% of cultures. The urogenital tract hosts an extensive array of commensal bacteria that can appear in urine because of ascension or sample contamination during voiding or urethral catheterization. The presence of bacteria in urine (bacteriuria) therefore is not equivalent to UTI, which specifically implies colonization of the bladder (or ureters, kidneys, or proximal urethra).

UTI develops when bacterial virulence factors overcome host defense mechanisms, which permits adhesion of bacteria to urothelium or renal cells and enables persistence and proliferation. UTI occurs frequently in dogs, with a lifetime incidence around 14%. UTI is less prevalent in cats, particularly young cats; however, common geriatric feline diseases (e.g., chronic kidney disease, diabetes mellitus, hyperthyroidism) dramatically increase UTI prevalence. Up to 30% of cats with stable chronic kidney disease are found to have a UTI. Most UTIs caused by E. coli represent easily curable episodes of uncomplicated cystitis, but animals in which rapid, durable cure is not easily achieved require additional assessment and targeted management.

Uropathogenic Escherichia coli

Medically significant E. coli strains can be grouped into three major categories: commensal strains (chiefly from phylogenetic groups A and B1), intestinal pathogenic strains (chiefly from groups A, B1, and D), and extraintestinal pathogenic strains (chiefly from groups B2 and D). Spontaneously occurring bacterial UTI in dogs and cats, as in humans, most often is caused by a subset of extraintestinal pathogenic strains termed uropathogenic E. coli (UPEC), which possess genes for one or more virulence factors (e.g., adhesins, iron acquisition systems, toxins, host defense avoidance mechanisms) that specifically capacitate colonization of and persistence within the urinary tract. Until recently, UPEC strains generally either have expressed virulence factors or have demonstrated significant drug resistance; however, UPEC strains that demonstrate both virulence and resistance now have been documented in companion animal populations.

Traditionally, pathogenic E. coli was classified as strictly extracellular, but recently the capacity for UPEC to invade urothelial cells has been demonstrated. This intracellular presence permits establishment of potentially long-lived reservoirs of organisms shielded from both host immunologic defenses and antimicrobial exposure, and likely plays a major role in persistence and relapse of UTI caused by UPEC. Cell entry is facilitated by several independent virulence factors that permit increased contact with host cells and easier penetration of cell membranes. Pili (or fimbriae) are several different types of filamentous organelles critical for bacterial adhesion to host cells; the most prevalent pili in UPEC are called type 1 pili. In many UPEC strains, type 1 pili have a tip adhesin, FimH, that binds monomannose molecules. This specific binding affinity increases the strength and duration of interaction with urothelial cells and thus also increases resistance to clearance from the bladder. Other virulence factors lead to cell membrane disruption and increased host cell mobilization, and thus facilitate easier entry of the bound UPEC first into the more superficial urothelial cells and then into deeper cell layers as well. As mentioned earlier, capacity for intracellular residence, particularly in deeper cell layers, permits bacterial persistence in the face of both physiologic defense and clearance mechanisms and also antimicrobial pressure.



A UTI is classified as a reinfection when, after one UTI is cured, another occurs due to a different isolate (although not necessarily a different bacterial species) and usually bespeaks an anatomic abnormality, physiologic dysfunction, or immunologic deficiency impairing host defenses against bacterial colonization (Box 194-1). Reinfection may occur shortly after an initial UTI is cured, or months may elapse between UTIs.


The term relapse is applied when, following effective treatment of one UTI, another occurs that is caused by the same isolate. Relapse often indicates a persistent nidus or reservoir that shields bacteria from contact with antimicrobials present in the urine, then permits recolonization of the urinary tract once antimicrobial pressure is removed. These sites may be host tissues (e.g., renal parenchyma, prostate, thickened bladder wall, bladder mass) or foreign objects (e.g., uroliths, intraluminal suture material). Relapse also commonly occurs without an obvious nidus; as described earlier, UPEC can behave as an opportunistic intracellular pathogen, and creation of intracellular reservoirs of bacteria likely plays a lead role in the pathogenesis of relapse. Distinguishing between reinfection and relapse when the same bacterial species is isolated can be challenging; using antimicrobial susceptibility profiles to discriminate between the two has been shown to be unreliable. Genetic sequencing techniques such as pulsed-field gel electrophoresis are required for accurate assessment of clonality or differences between strains, but these assays are not widely available for routine clinical use.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Persistent Escherichia coli Urinary Tract Infection

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