Treatment Failure and Chronic Management
UTI might be a frustrating disease to manage due to its high recurrence rate. Clinicians must always keep in mind that failure to identify and eliminate underlying causes is likely to result in failure to cure.
If the UTI is recurrent, potential underlying causes should be revisited. Often the pathology is limited to the urethra and can therefore not be documented using routine diagnostic workup. In such instances, other diagnostic modalities (e.g., cystoscopy) should be considered.In a subset of patients, where an underline disease either cannot be identified or eliminated, treatment is guided by culture and sensitivity testing. The selection of antibiotics might be challenging in some cases due the emergence of resistance (Couto et al. 2014; Delgado et al. 2007). When the isolated bacterium is resistant to all drugs available in the routine susceptibility panel, clinicians should communicate with the diagnostic laboratory to request an extended panel of antibiotics.
Both veterinarians and owners are often frustrated with the presence of repeated positive urine cultures despite a prolonged treatment using multiple medications. However, not every positive urine culture should be necessarily treated with the goal of achieving sterile urine. The results of a positive urine culture should be assessed in conjunction with the presence of clinical signs, presence of inflammation, and the risk for pyelonephritis. Asymptomatic bacteriuria is defined as the presence of bacteriuria (based on urine culture) in the absence of clinical signs or evidence of inflammation in the urine. Asymptomatic bacteriuria occurs commonly in human patients, and is documented in veterinary patients. Antimicrobial therapy in such patients is not indicated in the absence of clinical sings and inflammation, unless the risk of an ascending infection is considered high (e.g., given a previous history of pyelonephritis, predisposing anatomical abnormalities).
One needs to consider, however, that in veterinary medicine it is more difficult to define asymptomatic bacteriuria, as animals may experience and even demonstrate symptoms but owners might not interpret those as clinical signs. Therefore, both the presence of clinical signs and urinary inflammation should be used in conjunction. A long-standing infection, even if not accompanied by clinical signs but associated with inflammation, might result in epithelial proliferation, and, in dogs, when urease positive bacteria are involved, also with struvite urolithiasis.One of the common reasons for relapsing UTI and treatment failure is the presence of a deep-seated infection, in which the bacteria are not eliminated from tissues (e.g., bladder wall, kidney, prostate), despite their effective elimination from the urine, and therefore relapses occur days or weeks following cessation of antibiotic therapy. Deep-seated infections, infections in the upper urinary system, and those that involve the prostate, require longer treatment durations using antibiotics with good tissue penetration (e.g., fluoroquinolones).
In some cases, a long-standing infection induces epithelial proliferation in the urinary bladder or urethra, resulting in polypoid cystitis and proliferative urethritis, respectively (Crawford and Turk 1984; Martinez et al. 2003). These proliferations serve as a nidus for relapses and might intensify (or be the main cause of) clinical signs. Therefore, antibiotics should be used as described above for deep-seated infections, however, the addition of non-steroidal anti-inflammatory drugs should be considered in an attempt to relieve clinical signs and decrease epithelial proliferation. When only few urinary bladder polyps are present, resection using laser or a polypectomy snare under cystoscopic guidance can be attempted, but when diffuse and severe, surgical removal might be considered, depending on the nature of the polyps and their location.
A few ancillary therapies have been suggested in the management of recurrent and refractory UTI, including local instillation of antimicrobials and antiseptics into the urinary system, cranberry extracts, and urinary acidifiers. Currently, there is not enough evidence to support their use. However, sideeffects using these therapies are uncommon and their use is not associated with emerging resistance. Such therapies can be considered in specific circumstances (see later), but should not replace proper use of antibiotics to treat an existing infection.
Instillation of antimicrobials and antiseptics directly into the lower urinary system has been suggested as treatment for refractory cases. One of the major disadvantages of this approach is the need to introduce a urinary catheter to deliver the treatment, which, in and of itself might introduce infection, and the fact that this treatment, in most cases, cannot be delivered by owners on a routine basis. However, if persistent urine diversion
(e.g., a urine catheter or a cystostomy tube) is already in place, these therapies can be considered, as there is some evidence to suggest that the use of local antiseptics (e.g., chlo- rhexidine) decreases biofilm formation on urinary catheters (Segev et al. 2013).
Methenamine is a urinary antiseptic, which is converted in an acidic environment to formalin, and therefore interferes with bacterial growth (Lo et al. 2014). Concurrent administration of acidifying agents (ammonium chloride, vitamin C) is often required as the urine pH should acidic, however, caution should be used in animals that are already predisposed to metabolic acidosis (e.g., CKD).
Cranberry extract is known to inhibit attachment of particular uropathogens in people (Nowack 2007), but there is no solid evidence to suggest that these agents are effective in preventing UTI in dogs and cats. Cranberry extract should not be used to treat UTI. Rather, it might be considered as a preventative measure.