Introduction

Urinary tract disease is commonly in dogs and cats, and a leading reason for antimicrobial use. Proper diagnostic and treatment plans are critical for optimal patient care and prudent (and effective) antimicrobial use. In human medicine, detailed guidelines are available and provide excellent guidance to physicians on management of various infectious diseases, including urinary tract infection. Practice guideline development is a relatively new phenomenon in veterinary medicine and is hampered by a relative lack of adequate research.

However, a combination of available data, general principles of infectious diseases and antimicrobial therapy and expert opinion have been used to develop preliminary guidelines for urinary tract infections.¹¹ All urinary tract infections are not alike, and the approach to diagnosis and management can be different.

Sporadic Bacteriuria Cystitis

Previously often referred to as ‘simple uncomplicated urinary tract infection’ sporadic bacterial cystitis is a more accurate term that highlights the presence of inflammation (as opposed to subclinical bacteriuria) and acknowledges that our understanding of complicating factors may be limited.

This category has been previously used to only describe patients that a) that are otherwise healthy non-pregnant females or neutered males; b) with no known urinary tract anatomical and functional abnormalities or relevant comorbidities (e.g., endocrinopathy, spinal disease); and, c) that have had fewer than 3 episodes of known or suspected urinary tract infection in the preceding year. However, patients with urinary tract abnormalities or co-morbidities can develop sporadic cystitis and not necessarily be at substantially increased risk for complications or recurrence or have infections that are more difficult to treat. Initial or rare (<3 episodes of cystitis in the preceding year) sporadic cystitis in individuals with urinary tract abnormalities or comorbidities should be approached as is described here. Sporadic cystitis is rare in intact male dogs but should be approached as described here if there is no evidence of concurrent prostatitis.

Diagnosis is based on the presence of clinical signs of lower urinary tract disease and urinalysis, ideally with bacterial culture results. Urine culture is preferred for all cases but empirical therapy in lieu of culture can be justified in dogs with sporadic disease, particularly in animals with limited previous antimicrobial exposure and in situations where the likely pathogens and susceptibility patterns are well known. Diagnosis in cats should be confirmed by aerobic bacterial culture in all cases due to the low likelihood of bacterial disease in cats with clinical signs of lower urinary tract disease.

Ideally, specimens for culture should be collected by cystocentesis unless there is a contraindication (which would rarely be present in animals with sporadic bacterial cystitis) or significant difficulties in sample collection (e.g., large morbidly obese dog) are anticipated. Samples should be refrigerated and processed by the diagnostic laboratory within 24 hours of collection. Culture of voided samples should only be performed when cystocentesis is not possible because of the potential for both false positive and false negative cultures. Voided samples should only be cultured if they are refrigerated and processed by the diagnostic laboratory within a few hours.¹² The level of growth (>100,000 CFU/ml), bacterial species and whether mixed growth is present are important factors to assess when evaluating any culture results from voided samples.

Clinical signs are a result of inflammation. In dogs, a decision to start antimicrobial therapy while awaiting culture results (if samples are submitted) is reasonable. However, there is evidence from humans that analgesics alone may be as effective as antimicrobials in uncomplicated cases.^13,14 Consideration can be given to prescribing an initial course of analgesics and adding antimicrobials 3–4 days later if clinical signs persist or worsen. Regardless, analgesics should be considered during the initial treatment period to help ameliorate clinical signs. To avoid overtreatment in cats, withholding antimicrobial treatment pending the result of aerobic culture is reasonable, unless there is clear evidence on urine sediment analyses to support bacterial infection.

Optimal empirical choices vary based on the pathogen and resistance patterns in the region. However, amoxicillin is a reasonable first choice in most areas. If amoxicillin without clavulanic acid is not readily available, use of amoxicillin/clavulanic acid is reasonable. Evidence of a need for clavulanic acid is lacking and it may not be necessary, even in infections with beta-lactamase producing bacteria, because of the high amoxicillin concentrations that are achieved in urine. Trimethoprim-sulfonamide is another first tier option but may be associated with greater adverse event concerns and is difficult to recommend over amoxicillin or amoxicillin/clavulanic acid. The recommended duration of therapy is 3–5 days. The short end of that dosing period may be optimal, but veterinary research is currently limited.

There is no indication for measures beyond monitoring of clinical signs. Provided the full course of antimicrobials is administered correctly, there is no evidence that intra- or post-treatment urinalysis or urine culture is indicated in the absence of ongoing clinical signs of cystitis.

Recurrent Bacterial Cystitis

In human medicine, recurrent bacterial cystitis implies a diagnosis of ≥3 episodes of recurrent bacterial cystitis in the previous 12 months or 2 or more bladder infections in six months.^15-17 This definition has also been adopted in veterinary medicine. Recurrent cystitis may result from relapsing or persistent infection, or reinfection. Refractory infections are defined when there is no response or incomplete clinical response to a course of treatment.

Since recurrent cystitis is almost always associated with an underlying cause, identification and management of relevant risk factors and comorbidities is critical for long-term success. Repeated antimicrobial administration is unlikely to provide long-term cure and can be associated with antimicrobial resistance, treatment costs and risks of adverse effects of antimicrobials. Contrast imaging or cystoscopy may be considered for refractory clinical recurrent bacterial cystitis cases if biopsy of the bladder mucosa is warranted or to investigate further to underlying comorbidities.

Urine culture, ideally from a sample collected via cystocentesis, should be performed. If the pathogen isolated from a patient with recurrent infections is different from previous organisms isolated, reinfection is likely and efforts should be undertaken to identify and address any predisposing factors. If the same bacterial species (e.g., E. coli) is isolated again from a patient with clinical signs of lower urinary tract disease but the isolate has a different antibiogram than a previous isolate, advanced molecular studies would be required to conclusively determine if the patient had a new infection, as opposed to selection of a resistant subpopulation of the initial infection that was never fully eradicated.¹⁸ However, re-infection is likely or at least possible. If the isolate has the same antibiogram as a previous isolate, it is likely that relapsing or persistent infection is present, but advanced molecular studies would still be required to conclusively determine if bacterial species present is identical to that previously isolated.

Recurrent cystitis encompasses a broad patient range, some that develop repeated and relatively uncomplicated infections that likely respond quickly to antimicrobials and others that have marked bladder pathology that complicates treatment.

In human medicine, several studies support short-course therapy for acute and recurrent bacterial cystitis.¹⁵ Long-term therapy is not automatically warranted for recurrent bacterial cystitis. Short (3–5 d) durations should be considered for cases where re-infection seems to be occurring. Longer courses (7–14 d) may be reasonable in persistent, and potentially relapsing, infections, if factors that inhibit response to antimicrobials, such as bladder wall invasion, are suspected to be present.

Upper Urinary Tract Infections (Pyelonephritis)

Given the potential severity, accurate and prompt diagnosis is required to institute effective treatment as soon as possible. Whenever pyelonephritis is suspected, culture and susceptibility testing should always be performed. Immediate treatment is indicated, using an antimicrobial with good activity against gram-negative Enterobacteriaceae. Fluoroquinolones are the main recommendation based on their spectrum and efficacy for tissue-associated infections. Knowing resistance trends in urinary E. coli isolates in the practice can be helpful to guide initial therapy. Combination therapy can be considered initially, with changes potentially made based on culture results. If combination therapy was initiated and the isolate is susceptible to both drugs, one might be discontinued if supported by evidence of clinical response. If resistance is reported to one of the drugs, that antimicrobial should be discontinued. A second drug to which the isolate is susceptible should be substituted if the patient has not responded sufficiently; substitution is not necessary if patient response has been sufficient. There is little evidence to guide duration of treatment. Treatment of 4–6 weeks is often recommended and that is reasonable, although a shorter duration of therapy might be effective. Treatment of 4–6 weeks has previously been recommended for veterinary patients.¹¹ However, the recommended duration of therapy for acute bacterial pyelonephritis in children is 7–14 days.³¹ For adult humans, 10–14 days for beta-lactams or trimethoprim-sulfamethoxazole and 7 days for ciprofloxacin are recommended.³² There is no reason to suspect that a longer duration would be necessary for dogs and cats. In the absence of veterinary-specific data, the 10 to 14 days of treatment has now been recommended.

References

References available upon request.