Complicated UTIs

Confronting the Complicated Urinary Tract Infection
Lauren Devine, DVM, DACVIM

In this time of increasing antibiotic resistance, the World Health Organization named November 14-20, 2016 as World Antibiotic Awareness week. Complicated urinary tract infections have become an increasing issue in veterinary medicine as more pets are managed for long-term diseases. Repeated use of antibiotics in dogs and cats with recurrent urinary tract infections can result in development of antibiotic resistance. How can we control the spread of resistance and improve our patient’s quality of life? Understanding the root of the problem, the cause of the infection, is often key to appropriate treatment.

Urinary tract infections develop when the host defense mechanisms are overcome by bacterial virulence factors to allow adhesion of bacteria to the urothelium, which in turn promotes persistence and proliferation of the bacteria. The lifetime incidence of UTIs in dogs is around 14%, and the incidence in cats much lower, especially young cats. Most of these infections are caused by Escherichia coli and easily curable. Cases in which rapid, durable cures are not achieved through a standard short course of antibiotics require more diagnostics and management. Determining the type of complicated urinary tract infection may be helpful for management, but is often challenging.

Reinfection occurs when one UTI is cleared and another occurs due to a different isolate. This isolate may or may not be a different bacterial species. These infections are most commonly observed shortly after curing the initial infection. Common anatomic abnormalities resulting in reinfection include vulvar recession/hooding, ectopic ureters, vaginal bands (vestibulovaginal remnants) or prostatic cysts/abscesses. Urine retention and/or incontinence may also contribute to re-infection. Urinary tract infections have been frequently associated with systemic diseases such as hyperadrenocortism, diabetes mellitus, the use of immunosuppressive medications and cancer.

A relapsed UTI occurs when the same bacterial isolate is identified following effective treatment of one UTI. It is often indicative of a persistent nidus that protects bacteria from antibiotic exposure and permits recolonization once the pressure is removed (discontinuation of the antibiotic). The site of nidus may be host tissue such as renal parenchyma, prostate, thickened urinary bladder wall, urinary bladder mass (neoplasia vs polypoid cystitis), or the uroepithelium itself. Alternatively, foreign objects can be the site of nidus such as uroliths or intraluminal suture.

Persistent UTIs occur when the infection has failed to clear despite appropriate therapy. These infections are documented through a positive urine culture during or within 1 week of discontinuation of antibiotics. These infections may be caused by medication factors (dose, duration or noncompliance), bacterial factors (sequestration, resistance) or host factors (impaired host defenses, anatomic or physiologic abnormalities).

Strains of uropathogenic E.coli (UPEC) have recently emerged to possess both virulence factors and significant drug resistance. Additionally, UPEC has been demonstrated to invade urothelial cells, which permits the development of long-lived reservoirs protected from host immunologic defenses and antimicrobial exposures. This in turn plays a significant role in persistent and relapsing infections.

Since differentiating reinfection, relapse and persistent urinary tract infections can be challenging; a thorough physical examination and systemic evaluation is warranted in most cases. This includes full blood work (CBC, serum chemistry) and urine evaluation (urinalysis and urine culture). If the presence of a urinary bladder mass is suspected, a midstream urine culture may be obtained and interpreted in light of the collection method. Imaging of the urinary tract is often necessary to ensure there are no overt anatomic abnormalities. Radiography and ultrasonography provide complimentary information. Abdominal radiographs, in general, are better at determining the number and location of urinary stones. On the other hand, ultrasound is a more useful diagnostic technique to evaluate renal, urinary bladder and prostate structure. Additional diagnostics such as cystoscopy may be necessary to evaluate for ectopic ureter and/or vaginal bands. Urinary bladder wall biopsies may also be collected at the time of cystoscopy for culture and histopathology.

While uncomplicated urinary tract infections are curable with a 7-14 day course of antimicrobial therapy, complicated urinary tract infections often require a longer duration (4-6 weeks). UTIs in cats and intact male dogs should be treated as complicated urinary tract infections. Special consideration of antimicrobial penetration into the prostate for intact male dogs is warranted (trimethoprim/sulfa, chloramphenicol and enrofloxacin). Culture-directed antimicrobial therapy is essential for the treatment of all complicated urinary tract infections. A urine culture performed 1 week into antimicrobial therapy and 1 week after discontinuation of therapy is recommended to ensure complete clearance of the organism. Management or treatment of the underlying disorder, if present, is critical to prevent recurrence and complete clearance of the organism. A good recommendation is to check a urinalysis and urine culture every 3-4 months in most chronic diseases (hyperadrenocortism, diabetes mellitus, CKD, etc.).

Due to the pervasiveness of complicated urinary tract infections both in human and veterinary medicine, a number of alternative and nonantibiotic therapies has been proposed. The most promising therapy both in women and our canine patients is cranberry extract (proanthocyanidins). Cranberry proanthocyanidins has been shown to be effective at preventing pillous adhesion of Escherichia coli to the urothelial cells in several studies of women with recurrent UTIs. A 2016 study from the “American Journal of Veterinary Research” showed a reduced recurrence of urinary tract infections in a small population of dogs treated with oral cranberry extract. Not all cranberry supplements have adequate amounts of pranthocyandins. Therefore, try to prescribe products with at least 93 mg of cranberry extract. Other alternative therapies have been proposed to reduce recurrence of complicated urinary tract infections; however, evidence for recommending these therapies is lacking.

Complicated urinary tract infections will continue to pose a treatment challenge. However, by identifying the root of the problem we may obtain better treatment and management strategies. With time, we may be able to decrease the threat of rising antibiotic resistance.