This article is part one of a two-part series on bacterial urinary tract infection.
Over the past few years, it has been evidenced the urinary tract is not a sterile environment and is instead inhabited by a unique microbiota.1,2 The concept of subclinical bacteriuria (SB) (i.e. the presence of bacteria in urine determined by quantitative urine culture [QUC] without obvious clinical signs of lower urinary tract disease [LUTD]) has also been recognized, revealing the presence of bacteriuria is not necessarily synonymous with bacterial infection.3,4 As a result, it can be unclear to the clinician when to diagnose and treat a urinary tract infection (UTI). This article is a comprehensive review of the current literature and guidelines for the diagnosis and management of bacterial urinary tract infection and subclinical bacteriuria in dogs and cats.
Definition, pathogenesis, and classification
A UTI develops when an infectious agent adheres, multiplies, and persists within the urogenital system.3,4 As such, UTIs occur most commonly secondary to bacterial infections, although viruses and fungi have been involved, too.5,6 The bacteria primarily originate from the gastrointestinal (GI) tract, the perineal skin, or the genital area, and ascend the genitourinary tract to the urinary bladder.5-7 Colonization and adherence of bacteria to the vesical uroepithelium engenders bacterial cystitis. Uropathogenic bacteria can invade the uroepithelial cells facilitating bacterial spread within the urinary tract. Internalized bacteria are protected from the host’s immune system and antimicrobial treatments, creating bacterial reservoirs for relapsing UTIs.6,8 In some cases, further bacterial ascension may lead to upper urinary tract infection and pyelonephritis.6,9 Less commonly, UTI is caused by hematogenous spread from a systemic infection.5,6 Establishment of a UTI depends on the integrity of host defense mechanisms and the virulence of the infectious agent factors.6,10 Host defense mechanisms that prevent the colonization of the urinary tract by microorganisms include anatomic and physiologic constituents (see Table 1 below).6,11 Any breach in the defense system may predispose an animal to UTIs, hence the necessity to search for underlying disorders in case of recurrent infections.
UTIs can be classified into different categories, especially based on their localization (upper versus lower urinary tract), frequency (sporadic versus recurrent), and clinical expression (clinical versus subclinical) (Table 1, below). This classification is very useful clinically, as it guides the clinician toward appropriate diagnosis and management of the urinary tract affection.3,4,12
Studies have shown 10 to 14 percent of dogs suffer from a UTI at some point in their lifetime13,14 and 4.5 percent of dogs with a UTI have recurrent or persistent UTI,15 while 0.4 to 1.3 percent of the canine hospital population has pyelonephritis.9 Another study reported 17.5 percent of positive culture among 5,923 urine samples submitted for QUC and sensitivity.16 Unfortunately, these figures cannot be used as a surrogate to evaluate the prevalence of the disease in dogs in the entire population. Indeed, the various study designs and differing patient selections criteria (dogs selected at euthanasia/necropsy, dogs selected based on submission of a urine sample for QUC, referral hospital canine patient population) invariably introduced bias. In addition, some of these studies included dogs without clinical signs of UTI, which, considering the emerging concept of subclinical bacteriuria, raises the question whether all these dogs truly had a UTI. For example, in one retrospective study assessing persistent UTI and reinfections in dogs, 87 percent had no historic or physical evidence of a UTI.11 Recent studies have reported a prevalence of SB of 2.1 to 8.9 percent in healthy dogs.17,18 Up to 92 percent of UTIs in dogs with underlying disease are subclinical.11, 19-21
Healthy cats have traditionally been considered more resistant to UTI than dogs, owing to their high urine concentration and high urine osmolality.22 The majority of studies have evaluated the prevalence of bacterial UTI in cats with clinical signs of LUTD. The estimated frequency varies from one to 4.9 percent23-25 to eight to 33 percent.26-29 These differences have been attributed to the large number of cases and/or the feline patient referral population in the studies reporting lower frequencies. Interestingly, one of these studies reported UTI was diagnosed in 12 percent (2,789/22,908) of cats with LUTD among which three percent (784/22,908) of cats had bacterial UTI; 0.1 percent (13/22,908) of cats had viral UTI; and 72 percent (1,993/22,908) of cats had an unspecified cause of UTI. These findings raise questions about the diagnostic criteria of a UTI used in this study, especially since the data were retrieved from medical records for all cats evaluated at veterinary teaching hospitals in the U.S. and Canada that submitted data to the Veterinary Medical Databases (VMDB) between 1980 and 1997. In addition, most studies used various methods of urine collection (catheterization, cystocentesis, etc.), while others did not document the urine sampling technique, obscuring the assessment of the study methods and preventing comparisons between studies.
One recent study evaluated SB in healthy cats and documented a frequency of one percent.28 Additional studies reported SB in 6.1 to 56 percent of UTIs in cats with underlying disease.25,30-35 Disparities have been suspected to reflect study design, patient population (young versus older cats, healthy versus ill cats), and sample handling or analysis differences.
The most prevalent bacteria involved in UTIs in dogs and cats is E. coli.11,15,19,25,36,37 In two large retrospective studies of dogs with persistent or recurrent UTIs, the most common bacteria were E. coli, Klebsiella spp., Staphylococcus spp., Enterococcus spp., Proteus spp. Pseudomonas spp., and Streptococcus spp.11,15 Two retrospective studies identified E. coli, Enterococcus spp., and Staphylococcus spp. as the three most common bacteria in dogs with pyelonephritis.9,37
Enterococcus and Staphylococcus spp. are frequently reported in UTIs in cats.30,33,35 In particular, S. felis was reported with a high prevalence in one study in cats.30 The majority of the urine culture yield a single microbial isolate (56 to 79 percent).15,25,32,36,37 Polymicrobial infections are less frequent, with approximately 20 percent and five percent of UTIs being caused by two and three isolates, respectively.9,36
Underlying disorders were identified in 64.7 to 71 percent of dogs with persistent and recurrent UTIs11,37 and 75 to 87 percent of cats with a UTI or SB.38 It is clinically important to recognize these concurrent diseases, as they may predispose patients to recurrent UTIs and their correction (if possible) may improve response to treatment.11 Indeed, one study showed an apparent disease-free interval superior to 24 weeks was seen in 41.7 percent of the dogs whose predisposing diseases were corrected compared to 5.4 percent of the dogs who did not have correction of their predisposing disease and were treated only with antibiotic therapy.11
When evaluating a patient with bacteriuria, it is important to classify and localize the UTI, as this will determine treatment options and help evaluate the possibilities for treatment failure in case of persistent or recurrent UTIs.12 It may be particularly challenging to differentiate cats with bacterial UTIs from those with idiopathic cystitis and concurrent SB as clinical presentation and urinalysis findings are similar.38 Therefore, a UTI diagnosis should be based on complete history, physical examination, urinalysis, and QUC results.4,12 Additional testing (complete blood count [CBC] and biochemistry, abdominal radiographs/ultrasonography, etc.) may be necessary to help localize the UTI and assess for concurrent disorders or complications.
A thorough history is required in patients with bacteriuria. It is important to determine whether the bacteriuria is subclinical or associated with clinical signs of LUTD, which may be overlooked or predominated by signs of concurrent disorders. Classic clinical signs of LUTD include pollakiuria, stranguria, dysuria, hematuria, and inappropriate urination.4,7,10,12 It can be challenging to distinguish pollakiuria from behavioral marking (Figure 1).7 Additional signs such as urinary incontinence (Figure 2), nocturia, and polyuria and polydipsia (PU/PD) may reflect concurrent disorders (e.g. ectopic ureters, urethral sphincter mechanism incompetence, chronic kidney disease [CKD]). In some cases, PU/PD may be associated with pyelonephritis, although in one canine study, this was reported to occur in only 17 percent of cases.9 Altered urine odor and cloudy appearance to urine may be detected and raise suspicion of a UTI. Overgrooming of the genital area may promote a UTI and may initially be related to urinary incontinence, dermatitis, urinary tract pain, or vaginal/penile discharge (Figure 3, page 40).7 The clinician must bear in mind that in feline patients under the age of 10 years, signs of LUTD are more frequently associated with feline idiopathic cystitis or urolithiasis than UTI.4 One study in dogs with diabetes mellitus (DM), hyperadrenocorticism (HAC), or both did not show any association between the presence of clinical signs of LUTD and UTIs.19 Conversely, studies in cats with DM, CKD, or hyperthyroidism (HT) showed an association between the presence of clinical signs of LUTD and UTIs, particularly in older cats.31,39 In these studies, only five percent of dogs with UTI had clinical signs of LUTD (stranguria, pollakiuria, or discolored urine) and a limited number of cats had recorded signs attributable to the LUTD (6.9 to 37.5 percent). Clinical signs of LUTD could be overlooked by the owners, especially in animals suffering from concurrent disease when other signs may predominate. However, these studies were performed over the last two decades and may have included dogs and cats with what would now be classified as SB. Hence, the presence or lack of associations between UTIs and the presence of clinical signs of LUTD should be interpreted cautiously.
Physical examination is generally unremarkable in patients with sporadic cystitis.12 Fever and abdominal or back pain may be consistent with pyelonephritis, prostatitis, or pyometra.7,12 These signs were present in less than a quarter of dogs with pyelonephritis.9 Therefore, the absence of these signs should not deter the clinician from investigating this eventuality if pyelonephritis is clinically suspected. Lethargy, anorexia, vomiting, and dehydration were the most frequent clinical signs in dogs with pyelonephritis and were often associated with concurrent diseases.9 Rectal examination should be performed, as it may reveal narrowing of the pelvis canal associated with pelvic trauma; urethral thickening secondary to chronic urethritis or neoplasia; urethrolithiasis;12 or prostatic pain and enlargement consistent with prostatitis or other protastic disease (e.g. abscess, neoplasia).40 The perineal and genital area should be carefully evaluated for evidence of cutaneous lesions (e.g. perivulvar dermatitis, urine scalding) and genital conformation abnormalities (e.g. recessed vulva), which could predispose the patient to UTIs.41,42 Additional anatomic abnormalities, such as vaginal stenosis or vaginal septa (also called persistent paramesonephric remnant) may be detected with direct digital examination of the vestibule and vagina.12 Although these malformations may be incidental in some dogs, they have been associated with persistent urinary incontinence, vaginal pooling of urine, ectopic ureters, chronic recurrent UTIs. Thus, their finding may direct further testing.43-45
Blood work is usually unremarkable in patients with a lower UTI.10,12,31 However, blood work is indicated if systemic signs, such as lethargy, fever, or PU/PD are present, or in patients where a concurrent disease is suspected. Results are often nonspecific, with one study reporting 18 percent of dogs had a normal CBC and only 29 percent of dogs had renal azotemia.9 The low proportion of azotemic dogs with pyelonephritis likely reflects the fact azotemia develops only with decreased renal perfusion or when three quarters of the renal functional mass is impaired.9 Additional changes may be present if there is concurrent disease.
Abdominal radiographs and ultrasound are useful to detect urinary tract anomalies and help localize the UTI (upper versus lower UTI, prostatic involvement, etc.).4,12 Survey abdominal radiographs may reveal uroliths, gas in the lumen and urinary bladder wall (emphysematous cystitis), and allow evaluation of kidney size, shape, and opacity, as well as other anomalies that predispose to UTI.10,46 Excretory urogram or intravenous pyelogram is indicated in patients with hematuria and allow ureter evaluation (ectopic or ruptured ureters), although computed tomographic urography is now considered the method of choice to investigate ectopic ureters.46 Retrograde double-contrast cystography is useful to investigate suspect radiolucent cystic calculi, bladder tumor/polyps, and chronic cystitis, while positive contrast retrograde urethrography is the method of choice to evaluate the urethra (obstruction, urethrolith, urethritis, urethral neoplasia).46 Ultrasonography is the method of choice to evaluate the urinary tract.46 Abdominal ultrasound can assess pyelectasia, hydroureter, and hydronephrosis, which, in one retrospective study of dogs with pyelonephritis, were the most common findings.9,46 These findings are not specific for pyelonephritis and can be related to neoplasia of the urogenital tract, ectopic ureter, obstructive urolithiasis, and CKD, which can also be assessed by ultrasonography.47 In addition, ultrasound can help identify bladder pathology, as well as assess much of the genital tract and part of the urethra.46
Urinalysis is recommended as part of a minimum database.10 It is particularly indicated in patients with PU/PD, signs of LUTD, discolored urine, or systemic illness.48 Urinalysis is a rapid, readily available, inexpensive, and informative test clinicians should use to full advantage.
What is the appropriate handling and storage of urine for dipstick and sediment analysis after? Fresh urine samples should be evaluated within 30 minutes of collection, as biochemical compounds, cell morphology, bacterial count, and crystal type may change.48,49 If this is not possible, it may be refrigerated for up to 24 hours and rewarmed to room temperature prior analysis.48,49
If urine needs to be shipped to a laboratory for analysis of the sediment or crystal identification, the sediment should be resuspended in 0.5 mL of urine in a small, sealed container that should be refrigerated immediately until shipping with a cold pack.48 Stained and unstained slides prepared shortly after sample collection can also be submitted, particularly for cytologic evaluation of suspected neoplastic cells.48