Defining and managing canine urinary infections

Introduction

Urinary tract disease is a common problem in dogs and a leading reason for antimicrobial use. In addition to patient welfare issues, infections can be problematic because of cost, owner frustration and the potential for complications (e.g., struvite urolithiasis). These problems are compounded in dogs with recurrent or poorly responsive infections.

Because of the importance of urinary tract disease in dogs, clinical guidelines have been produced by the International Society for Companion Animal Infectious Diseases (ISCAID), describing diagnosis, treatment and prevention recommendations 1. The size and scope of the guidelines demonstrate the potential complexity of urinary tract disease in dogs and offer valuable advice to clinicians.

What’s in a name?

Terminology can be important, as it facilitates clear understanding and communication of the disease process. This can play a role in decision-making regarding diagnosis or treatment. A variety of different classifications or descriptions can be used (Table 1). 

Urinary tract infection vs. bacterial cystitis

“Urinary tract infection” or “UTI” is common nomenclature; however, this term is used variably in the veterinary literature, including situations where lower urinary tract disease is present 2 3, as well as cases where there are no overt signs of disease but bacteria are detected by culture or cytological examination of the sediment 4 5 6 7. This can cause confusion regarding the clinical relevance of results if cystitis is not differentiated from subclinical bacteriuria, as discussed below.

Because of the potential confusion revolving around “urinary tract infection”, the variability in how the term is used, and a need to focus on the disease process (e.g., cystitis), it has been recommended to use the term “bacterial cystitis” when referring to bacterial infection of the lower urinary tract that results in evidence of disease 1.

Subclinical bacteriuria

Traditionally, the urinary bladder has been considered to be essentially a sterile site. However, it is now apparent that this is not the case. Bacteria likely cycle in and out of the bladder on a routine basis, with this being more common in female dogs (because of the short urethra) and in certain diseased populations (e.g., animals that are immunosuppressed, have spinal cord disease, or are morbidly obese). Apart from movement of single organisms in and out of the bladder, there is increasing information suggesting that a “urine microbiota” is present. This has not been reported in dogs, but human studies using advanced techniques have identified a variable microbial population in the urine of healthy individuals, as well as people with medical conditions such as spinal cord disease and renal disease 8 9 10. While much less abundant and diverse than sites such as the gastrointestinal tract, a large number of different bacteria can be identified. The dynamics of the microbiota, its role in disease and even whether viable bacteria (rather than just DNA) are present remain to be elucidated.

Irrespective of whether bacteria are in the bladder as a sporadic transient event or as part of an overlooked resident microbiota, it is clear that bacteria are commonly found in the canine bladder without evidence of lower urinary tract disease. Prevalence varies by study and dog population, but can be high (Table 2).

One shift in the approach to urinary tract disease in dogs has been recognition that subclinical bacteriuria does not usually need to be treated 1. In humans, substantial efforts are undertaken to reduce treatment of subclinical bacteriuria because of a lack of evidence of need and concerns about antimicrobial resistance 11 12 13 14 15. Treatment of subclinical bacteriuria has been associated with increased risk of subsequent UTI in healthy women, when compared to untreated controls 16. Concern is sometimes expressed about the potential for subclinical bacteriuria to progress to cystitis, pyelonephritis or urosepsis. However, data indicating a risk are lacking in dogs. Study has been limited, but bacteriuria was not associated with outcome in paralyzed dogs 17 or otherwise healthy female dogs 18. 

Further, when one considers the potentially high prevalence of subclinical bacteriuria in some dog populations (e.g., diabetics, obese dogs, dogs on immunosuppressive medications) and the low incidence of urinary tract disease or urosepsis in those populations, the notion that subclinical bacteriuria is typically a benign state becomes apparent. Therefore, treatment of subclinical bacteriuria is not usually recommended 26.

Complicated or uncomplicated, or does it matter?

Classification of bacterial cystitis in dogs has often used human terminology; “simple uncomplicated” or “complicated”. However, it is unclear whether those definitions are applicable. At best, they are an over-simplification of the range of infections that occur. At worst, they are inaccurate and potentially misleading. In humans, “simple uncomplicated” UTI typically refers to sporadic infections in otherwise healthy women with no apparent risk factors apart from sexual activity and no underlying factors that would increase the risk of treatment failure. Most of these infections are in healthy, sexually active young women, a population without a direct analogy to most dogs. That does not mean that uncomplicated infections do not occur in dogs. Rather, what actually constitutes an uncomplicated infection and how (or if) that alters management is unclear. Defining a dog as having a “complicated” infection often leads to automatic recommendation of longer durations (e.g., 28 days) of antimicrobials, something that may not always (or often) be warranted. Even within complicated cases, the approach to cases must vary. For example, a dog with recurrent infections caused by an anatomical abnormality may be more akin to having a series of “uncomplicated” infections that respond to short duration treatment. Therefore, in the author’s opinion, “complicated” and “uncomplicated” terminology is best avoided as it may lead to unnecessary assumptions or approaches.

Does persistent infection vs. re-infection matter?

In a word, yes. Patients with recurrent disease can be difficult and frustrating to manage. When infections recur, determining the reason is critical to have any potential for long-term clinical success. Repeated antimicrobial treatment in lieu of determining the root of the problem is a suboptimal approach that can result in repeated disease and increasingly resistant infections from repeated antimicrobial exposure. Ultimately, a cause cannot be identified in all patients with repeated infections, and when a cause is identified, it is not always treatable. However, it is worthwhile to attempt to identify the underlying cause.

Determining whether infections are likely because of a failure to eliminate the offending organism (persistent infection) or because of repeated entry of new organisms into the bladder (re-infection) will alter the approach to diagnosis and management.

Can we differentiate persistent vs. repeated new infections?

The short answer is – sometimes. If different bacterial species are identified each time, then re-infection is obvious. If the same bacterial species is present but it has a markedly different susceptibility profile (especially differences in resistance that are based on acquisition or loss of a gene, such as beta-lactam resistance), then re-infection is likely. If the same bacterial species with the antimicrobial susceptibility is identified, this could represent persistent infection or it could be re-infection with a similar strain, something that can only be discerned through molecular typing. Determining which of these scenarios is most likely can refine the list of leading differential diagnoses and streamline the diagnostic plan (Table 3). 

Diagnosis of bacterial cystitis

In dogs, strong suspicion of bacterial cystitis can be generated based on history and physical examination. In contrast to cats, where most cases of lower urinary tract disease do not have an infectious cause, bacterial cystitis can reasonably be suspected in dogs with typical clinical signs (e.g., pollakiuria, stranguria, hematuria and/or dysuria in the absence of extra-urinary signs). Urinalysis should be performed since it is an easy, cost-effective and useful diagnostic step (Figure 1). Urine specific gravity (USG) can provide information about renal function. Dipstick analysis can identify or confirm hematuria, provide information about urine pH and identify potentially relevant abnormalities such as glucosuria. Cytology can help confirm a diagnosis through detection of white blood cells, red blood cells and bacteria, and may identify crystals, casts or abnormal cells that might indicate concerns about urolithiasis, renal disease or bladder neoplasia, respectively (Figure 2). 

Whilst urine culture is preferred, empirical therapy is justifiable in dogs with a first episode of bacterial cystitis. Culture is not usually needed to confirm the diagnosis, so it is most relevant for choosing the antimicrobial. In situations where resistance to first-line options is unlikely (e.g., a dog has not had recent antibiotic treatment and the prevalence of resistance in the area is low), there is a high chance of success with empirical therapy. When the likelihood that a resistant pathogen is present increases, either because of dog or population factors, culture becomes more important. Free-flow samples are fine for cytology but cystocentesis is preferred for culture. It has been shown that cleanly collected free-flow samples can provide similar results to cystocentesis when samples can be processed by the laboratory within hours and when a cut-off of 100,000 CFU/mL is used 27. The inherent delay from sample collection to processing by the laboratory precludes this as a viable option in most clinical situations, unless in-house culture is performed. Therefore cystocentesis should be considered the default technique when culture is desired.

It is important to critically interpret culture results, even when cystocentesis samples are used. Contamination and colonization can result in isolation of bacteria that are not clinically relevant. Whenever multiple organisms are identified, thought should be put into which is the most likely offending agent, as targeting of all of the bacteria may not be required. When bacteria that are not usually uropathogens are identified (e.g., Bacillus, coagulase negative Staphylococci, various environmental organisms), it is important to consider whether they might be contaminants. Pure growth of an uncommon organism might truly indicate infection by that organism, so it cannot be completely dismissed. However, this is not guaranteed, and use of higher tier drugs for multidrug resistant but clinically questionable bacteria may not be required, and empirical treatment with typical first-line options may be preferable, despite contradictory culture results.

There should be some consideration of underlying causes, as most cases probably have some inciting (if not elusive) cause. Detailed investigation after a single episode is hard to justify, but investigation is never contraindicated, and is certainly indicated when recurrent disease is present (Figure 3). 

Treatment of bacterial cystitis

There has been a marked shift in the approach to bacterial cystitis in dogs in the past decade. While long (e.g., 14 day) durations were widely used, this was done without evidence of optimal durations. In humans, shorter periods (e.g., 3-5 days) are typically recommended 28 29, with little reason to believe that there should be a difference for dogs. The 2011 ISCAID guidelines recommended 7-10 days of treatment, with a comment that shorter durations are probably effective, but evidence is lacking 26. Subsequently, studies have reported comparable efficacy of shorter durations as compared to typical longer durations in dogs, such as clinical equivalency of three days of trimethoprim-sulfa compared to 10 days of cephalexin 3, or three days of enrofloxacin compared to 14 days of amoxicillin/clavulanic acid 2. Randomized controlled studies comparing outcomes after use of the same drug for different durations are still lacking, but evidence to date supports use of shorter treatment regimens than in the past. As such, the revised 2019 ISCAID guidelines recommend 3-5 days of treatment for sporadic cystitis 1. First-line antimicrobial options are presented in Table 4. Other antimicrobials may be indicated in some cases based on antimicrobial susceptibility, disease aspects (e.g., concern about involvement of tissue, not just urine and uroepithelium), patient drug tolerance and owner compliance with dosing regimens.

Case studies

Many of the above points can be covered by illustration of a few cases studies. 

Case study 1 – Subclinical bacteriuria

Meg is an 8-year-old Golden Retriever who was identified as bacteriuric from culture of a cystocentesis sample collected at an annual wellness visit. She did not have signs of lower urinary tract disease. She has a history of inflammatory bowel disease that has been controlled on a low dose (5 mg q24h) of prednisone. Bacteriuria (> 40/hpf) was evident microscopically, with mild pyuria (5-10 WBC/hpf) but no hematuria. USG was 1.044. Hematology was unremarkable. She was diagnosed with subclinical bacteriuria and treatment was not recommended.

While routine clinical testing of dogs without evidence of lower urinary tract disease is not typically recommended 1, Meg has been followed with serial urinalyses to better understand this disease. Urine samples have been collected, typically on a monthly basis. Cystocentesis has been performed when possible; otherwise, free-flow samples have been collected and processed within hours and using a cut-off of > 100,000 CFU/mL 27. E. coli has been isolated from every urine sample over the past 8 months. An inflammatory sediment has been identified, with white blood cells but no gross or microscopic hematuria. No signs of urinary tract disease (or any other disease) have been noted. Since she has had no evidence of disease, treatment has not been recommended and no problems have been encountered. The reason for subclinical bacteriuria has not been identified, and cystoscopy would be the next diagnostic step.

Meg is an example of persistent subclinical bacteriuria. In the past, each of these episodes where E. coli was isolated would likely have led to antimicrobial treatment. However, in humans, abundant data indicate that treatment of people with bacteriuria in the absence of clinical signs is not rewarding. Widespread efforts are ongoing in human medicine to reduce testing and treatment of people with subclinical bacteriuria. This includes patients with complex medical histories (e.g., renal transplant recipients and people that cannot report clinical signs, such as paralyzed individuals and those with dementia). Therefore, since Meg is not suffering any apparent problems from this bacterium, she is not being treated.

Case study 2 – Sporadic bacterial cystitis

Molly is a 4-year-old Labradoodle who is presented with pollakiuria and dysuria of 24 hours duration. Molly is otherwise healthy, with an unremarkable medical history and physical examination. A free-flow urine sample is collected which is grossly abnormal; cloudy and red-tinged with flocculent material. Dipstick results indicate hematuria but no other abnormalities. USG is 1.030, and cytology is consistent with cystitis, with 50 RBC and 20-30 WBC/hpf. Numerous rod-shaped bacteria are evident, and bacterial cystitis is the most likely cause. Furthermore, in a dog with no recent antimicrobial exposure or hospitalization, the odds of a resistant infection are deemed very low. Given those factors, cystocentesis and culture are discussed with the owner but are not strongly recommended. The owner elects to forego culture. Amoxicillin (20 mg/kg PO q12h for 4 days) is prescribed. A single dose of meloxicam (0.2 mg/kg PO) is also administered to help control pain. Clinical signs improve within 24h. A follow-up telephone call a few days after cessation of antimicrobials is performed and the owner reports no problems. No further signs of lower urinary tract disease are reported at Molly’s next wellness visit, six months later.

While rather simplistic, this case shows a typical scenario. Culture is a useful tool but is less rewarding when it is of little use for making the diagnosis (bacterial cystitis) and when the odds of resistance to typical empirical antimicrobials are low. This is the case in most dogs with sporadic bacterial cystitis and no history of antimicrobial exposure or hospitalization. However, culture is never contraindicated and would have been desirable had treatment failed, so discussion of the cost-benefit of culture is warranted in any dog with suspected bacterial cystitis.

Case study 3 – Struvite urolithiasis

Frankie is an 8-year-old mixed breed neutered male dog that is presented for pollakiuria and stranguria of at least 14 days duration. Physical examination is unremarkable and he has no history of previous urinary tract infections.

Because sporadic bacterial cystitis is less common in adult male dogs, a cystocentesis sample is collected for urinalysis and culture. Urine pH is 8 and USG is 1.028. Hematuria (100 RBC/hpf) is evident, with mild pyuria (10 WBC/hpf). Sporadic cocci are noted, along with moderate numbers of struvite crystals. Because of concern about struvite urolithiasis, based on the crystalluria, cocci and high urine pH, abdominal radiographs are taken. A urolith consistent with struvite urolithiasis is identified. Options are discussed and the owner elects to attempt medical treatment.

Empirical treatment with amoxicillin (20 mg/kg PO q12h) is chosen, for a duration of 7 days. The longer duration compared to Meg is because of the complicating factor of the urolith, which could potentially result in more inflammation of the bladder wall and a more complicated local environment. However, once the active cystitis is controlled, there is no evidence that antimicrobials are needed if medical dissolution of the urolith is being pursued 1. While some clinicians use antimicrobials throughout the dissolution period, supporting data are not available. Data indicating efficacy without antimicrobials are similarly lacking; however, anecdotal information from clinicians that do not use antimicrobials during dissolution, with good success, supports a conservative approach to antimicrobials. Once the active infection is eliminated, it is difficult to justify ongoing treatment since no clinically relevant bacteria should be present. The potential for liberation of bacteria embedded in the urolith as it dissolves is often discussed; however, while bacteria can be found within uroliths, there is no evidence that adequate numbers of viable bacteria are eliminated to cause subsequent infections.

Culture results are obtained on day 4 and Staphylococcus pseudintermedius, > 100,000 CFU/mL, is reported. The bacterium is susceptible to amoxicillin and the lower urinary tract signs resolve quickly. A dissolution diet is prescribed and the urolith is no longer evident radiographically 8 weeks later. No further episodes of urinary tract disease are encountered over the next year.

The terminology employed when classifying urinary tract disease is important, because it allows better understanding of the disease process and assists communication, both between the owner and the clinician, and between members of the veterinary care team. When the correct terminology is used it can, in turn, play a useful part in decision-making regarding diagnosis or treatment for dogs with urinary tract signs. Further research into the role of urinary bacteria will allow better understanding of canine bladder disease pathophysiology.