UTIs in Small Animal Patients: Part 2: Diagnosis, Treatment, and Complications
There are multiple considerations when making a treatment plan for patients with urinary tract infections (UTIs). In part 2 of this review the authors discuss the clinical signs, diagnosis, treatment, and complications associated with bacterial UTIs in dogs and cats. Part 1 of this review summarized etiology and pathogenesis (see the Jan/Feb 2013 issue of the Journal of the American Animal Hospital Association).
Introduction
A urinary tract infection (UTI) is a common disorder in veterinary medicine. Diagnosis of a UTI incorporates findings from the history, physical examination, complete urinalysis, and urine culture. Proper classification and localization of the UTI are important when formulating a treatment regimen and evaluating treatment success and failure. Most UTIs can be successfully managed with appropriate antibiotic treatment; however, bacterial resistance and compromised host defense mechanisms can result in persistent/recurrent infections. In patients with recurrent UTIs, identification of underlying predisposing conditions will often improve treatment success. In patients where underlying causes cannot be identified or treated, therapies designed to prevent recurrent UTIs may be used.
Clinical Findings
History
Clinical signs associated with a urinary tract infection (UTI) depend on bacterial virulence, status of the host immune system, duration of the infection, and the site(s) of infection. The most common clinical signs associated with lower UTIs include pollakiuria, stranguria, dysuria, hematuria, inappropriate urination, or periuria. If a UTI occurs secondary to a micturition disorder, such as an ectopic ureter, urethral sphincter mechanism incompetence, or urine retention, clinical signs associated with the primary condition may predominate. Similarly, in dogs and cats with systemic disease and compromised host defense mechanisms, clinical signs associated with the underlying disease may predominate, and the UTI may be relatively asymptomatic.
Physical Examination
Dogs with uncomplicated UTIs often have unremarkable physical examination findings. Predisposing causes such as vulvar involution (Figure 1), severe perivulvular dermatitis, vaginal stenosis, cystic or urethral calculi, or urethral thickening may be identified in patients with complicated UTIs. Whenever possible, female dogs presenting with a UTI should have a digital vaginal examination performed to identify an anatomic abnormality that may alter normal host defense mechanisms. For example, palpation of a persistent paramesonephric remnant (Figure 2) may prompt further investigation for ectopic ureters, and palpation of vaginal strictures may prompt further investigation for urine retention. Rectal examinations may also identify abnormalities such as pelvic trauma, urethral stones, or urethral thickening associated with either neoplasia or granulomatous urethritis. Such findings can help the clinician determine the extent of the work-up required and may help with treatment recommendations by aiding in the identification of factors that may complicate treatment.
Citation: Journal of the American Animal Hospital Association 49, 2; 10.5326/JAAHA-MS-5944
Citation: Journal of the American Animal Hospital Association 49, 2; 10.5326/JAAHA-MS-5944
Localization
Acute bacterial pyelonephritis, prostatitis, and metritis are often associated with systemic signs such as fever, an inflammatory leukogram, lethargy, and anorexia. In contrast, patients with chronic prostatitis or pyelonephritis may not exhibit systemic signs; therefore, it may be more difficult to localize the infection. Localization of the UTI is important to optimize antimicrobial choices and duration of therapy (refer to Table 2 included in part 1 of this review published in the Jan/Feb 2013 issue of the Journal of the American Animal Hospital Association.
Diagnosis
Diagnosis of a UTI is made based on information obtained from history, physical examination, urinalysis (including method of collection), and (ideally) urine culture and sensitivity. Cystocentesis is the method of choice for collecting urine samples, especially if a urine culture is anticipated. Patients presenting with lower urinary tract signs (e.g., pollakiuria, stranguria) may make collection by cystocentesis difficult due to the small size of the urinary bladder. Alternative methods of urine collection may be acceptable if cystocentesis either cannot be performed or is contraindicated (e.g., suspected transitional cell carcinoma of the urinary bladder, pyoderma of the ventral abdomen). Urethral catheterization provides a superior sample than a free catch voided sample, but requires more technical skill, especially in female patients. Care should be taken during catheterization to prevent contamination from external structures by clipping surrounding hair and cleansing the external genitalia prior to the procedure. Based on current recommendations, free catch urine samples are not acceptable for culture.1 Urinalysis and urine culture results should always be interpreted in light of the urine collection method.2–4
Urinalysis
Urinalysis may be helpful in differentiating a UTI from other disorders causing lower urinary tract signs (e.g., bladder neoplasia), making initial antibiotic recommendations, and (in some cases) identifying potential predisposing disorders (e.g., glucosuria, crystalluria). Urine specific gravity can be variable in patients with a UTI. Dilute or minimally concentrated urine may be observed in patients with concurrent disease predisposing to UTI (e.g., diabetes mellitus, hyperadrenocorticism) or may be observed if the infection involves the upper urinary tract. With a UTI, hematuria and proteinuria are frequently observed on dipstick analysis. The dipstick analyses for nitrite (bacteria) and leukocyte esterase are designed for use in people and are not reliable tests for canine and feline patients.5,6 A urine sediment examination should be performed to identify pyuria and bacteriuria. If urine is dilute or if the patient is immunocompromised (e.g., suffers from hyperadrenocorticism or is receiving exogenous corticosteroids), it may be difficult to identify either WBCs or bacteria on urine sediment examination. According to one study, air-dried and stained sediment evaluations are more accurate than wet, unstained mounts for identifying bacteria when urine culture results are used as the gold standard (sensitivity is 82.8% and specificity is 98.6%).7 The air-dried and stained technique is easily performed in practice by placing one drop of sediment on a glass slide, allowing it to air dry without spreading, and then staining the sample with a commercially available modified Wright’s staina. It is important to remember that a culture is required for definitive diagnosis and will provide additional information (e.g., bacterial identification, number of organisms/mL of urine, antimicrobial susceptibility results).
Urine Culture
Although clinical signs and urinalysis findings may increase the index of suspicion for a UTI, a urine culture is the definitive diagnostic test. Ideally, the urine sample for culture should be obtained prior to starting treatment. In patients already receiving antimicrobial therapy, it may be necessary to discontinue treatment 3–5 days before collecting urine for culture. It is also important to consider storage and transport of samples for culture in practices where immediate culture processing is not possible.8,9 Sterile containers that do not contain additives or preservatives should be used. Commercially available urine collection kits may be acceptable for up to 72 hr if sample processing is delayedb.10,11 Bacterial counts can increase in urine stored at room temperature within a few hours. In refrigerated samples, quantitative bacterial counts differ after 6 hr of storage according to one study; however, this was not associated with a change in interpretation of the clinical significance. It is recommended that urine samples be cultured immediately; however, it is acceptable for urine to be refrigerated in a closed container for up to 6 hr prior to culture.8
Alternatives to sending a urine sample to a commercial laboratory for culture include using a calibrated bacterial loop (0.01 mL or 0.001 mL) to inoculate either blood or MacConkey’s agar plates in-house. Culture plates are then incubated for 24 hr and, if significant numbers of colonies are produced in light of the urine collection method, the plate can be sealed and shipped to a microbiology laboratory for bacterial identification and antimicrobial sensitivity testing. In most cases, a quantitative urine culture will help interpret results. In addition to bacterial numbers/mL of urine, knowledge of the normal flora may also be helpful in determining contamination versus infection when methods other than cystocentesis are used (refer to Table 1 in part 1 of this review, which was published in the Jan/Feb 2013 issue of the Journal of the American Animal Hospital Association).
Contamination
Bacteriuria is expected in patients with UTIs; however, bacteriuria may also be observed in healthy dogs and cats either if the urine sample has been contaminated with normal flora and/or pathogens from the distal urethra/urogenital tract or if the urine sample contacts a contaminated surface. Certain organisms are known to be commensal within the lower urinary tract; therefore, knowledge of the organism and urine collection method may help determine contamination versus a UTI. There is, however, overlap between normal flora and potential pathogens. Bacterial contamination of urine usually occurs when collecting a voided sample but it can also occur either during urethral catheterization or be associated with collection of urine from a contaminated surface (e.g., cage floor, examination table). It is important to differentiate urine contamination from a UTI because the former does not need to be treated. Contamination can be ruled out by either repeating a urinalysis with urine obtained via cystocentesis or by performing a quantitative urine culture on the voided or catheterized sample. Depending on the method of urine collection, the number of bacterial colony-forming units/mL of urine can vary between contamination and UTI (Table 1). As stated previously, free catch urine samples are not recommended for culture and sensitivity and should only be used when cystocentesis is neither possible nor recommended (e.g., transitional cell carcinoma, patients with bleeding disorders).
Values are in colony-forming units/mL of urine. Data represent generalities. Occasionally, bacterial urinary tract infections (UTIs) may be detected with fewer organisms (i.e., false-negative results).
For midstream voiding and manual expression, the contamination level may be 10,000 colony-forming units/mL or higher (i.e., false-positive result). Those samples should not be used for routine diagnostic culture.
Antimicrobial Susceptibility Testing
Ideally, antimicrobial administration should be based on results from culture and susceptibility. Unnecessary or inappropriate usage of antibiotics can either lead to antimicrobial resistance or delay the diagnosis of noninfectious causes of lower urinary tract signs.1 In addition to susceptibility results, the route and ease of administration, potential adverse effects, cost, and concentration in the urine (or other targeted tissues such as the prostate and kidney) should be considered when choosing an antibiotic.
Kirby-Bauer technique
Agar disk diffusion (Kirby-Bauer) is a form of antimicrobial susceptibility testing. This test requires inoculation of a Mueller-Hinton agar plate with a standardized suspension of a bacterial isolate. Paper disks impregnated with antibiotics are then placed on the plate, and the plate is allowed to incubate. Bacterial growth is inhibited around the disk, and the zone of inhibition is compared with a standard identified for that antibiotic. Results of the disk susceptibilities are usually listed as susceptible, resistant, and intermediate. Varying degrees of susceptibility or resistance are not described. In most laboratories, agar disk diffusion has been replaced by the microwell dilution technique (described below).
Minimum inhibitory concentration
Determining the minimum inhibitory concentration (MIC) involves using serial dilutions of an antibiotic to determine the lowest concentration that will inhibit bacterial growth (i.e., the MIC). Although results are reported as susceptible, intermediate, and resistant, they usually also include the actual MIC followed by the breakpoints used to determine susceptibility. The goal of the breakpoint is to predict clinical outcome for an individual patient. Breakpoints are determined by a combination of information including the species, bacteria, disease, antibiotic, dose, route, and frequency. It is important to keep in mind that there is limited data available in veterinary medicine; therefore, breakpoints are often determined by using information available from human breakpoints.
A result reported as susceptible indicates a high likelihood of treatment success (> 80%) with most antibiotics. Intermediate indicates possible treatment success with potential alterations in normal dosing. Finally, resistant indicates that a clinical cure is unlikely to occur with the selected antimicrobial agent. The result is considered susceptible if the MIC is in the breakpoint range or below, intermediate if it is at the high end of the breakpoint, and resistant if it is above the breakpoint.
Urine antibiotic concentrations are usually more important than plasma concentrations when treating a UTI. MICs and the anticipated urine antibiotic concentration may be used to guide treatment choices. Clinical efficacy is expected if urine concentration is maintained at > 4 × the MIC of the pathogen between doses (Table 2).13 For example, the MIC of ampicillin for a Staphylococcus spp. is approximately 10 μg/mL. The expected serum and tissue concentrations of ampicillin are 1–2 μg/mL, whereas the expected urine concentration of ampicillin is > 300 μg/mL. Because the expected urine concentration is > 4 × the MIC, sensitivity for a superficial UTI should exist. MIC testing based on anticipated urine concentrations is not appropriate for deeper tissue infections (e.g., pyelonephritis, thickened bladder wall) when serum and tissue antibiotic concentrations are needed.
Doses listed were used in the studies calculating mean urine concentrations and may not be consistent with current guidelines for treatment recommendations.
E. coli, Escherichia coli; SC, subcutaneous; PO, per os.
Result interpretation
The Clinical and Laboratory Standards Institute is a committee of experts that examines pharmacokinetics, microbiology, pharmacodynamics, bacterial population, MIC distribution, and clinical trial results. Recommendations from this committee are considered the gold standard for breakpoint determination. Veterinary laboratories (or a human laboratories with appropriate susceptibility panels for commonly used veterinary antibiotics) that follow the Clinical and Laboratory Standards Institute recommendations should be used for culture and sensitivity testing.
Depending on the laboratory, comparing antibiotics with similar susceptibility (e.g., cephalexin and cefazolin) may be necessary, but requires making assumptions. For example, when comparing cefazolin with cephalexin, cefazolin is typically administered IV q 6 hr, whereas cephalexin is typically administered per os q 8–12 hr. It is also important to remember that in vitro culture and sensitivity results may not correlate with in vivo efficacy. For example, regardless of the susceptibility results for Enterococcus spp., certain antibiotics, including cephalosporins, trimethoprim-sulfamethoxazole, clindamycin, and aminoglycosides should always be considered resistant because those are not effective clinically and do not correlate with in vitro results.14
In many cases, antibiotic sensitivity testing provides a clear direction for treatment with an antibiotic that is orally administered, has few potential adverse effects, and reasonable cost. In some cases, sensitivity results demonstrate a high degree of bacterial resistance. In those cases, route of administration, high cost of the antibiotic, and potential adverse effects of the potentially effective antibiotic may be concerning. Although MIC may be used as a guideline for antibiotic selection, veterinary breakpoints for most antibiotics in the urinary tract of dogs and cats have not been determined. When intermediate results are obtained, it may be possible to achieve a cure if no alternative antimicrobial exists. A cure would most likely be achieved by using a higher dose of an antimicrobial that is excreted in the urine. In resistant infections, requesting an expanded antimicrobial sensitivity profile (e.g., ceftazedime, carbenicillin) may suggest alternative treatment regimes. Most commercial bacteriology laboratories have a second and third tier of antibiotics for expanded sensitivity testing; however, high cost and parenteral administration may be trade-offs.
Classifying UTIs
Recurrent UTIs: Relapse versus Reinfection
The appropriate classification of a recurrent UTI can help the clinician modify therapy, identify predisposing factors, identify reasons for treatment failures, and identify the need for prophylactic therapies. Recurrent UTIs can be defined as either relapses or reinfections. A relapse is an infection cause by the same bacteria that caused the original infection that usually occurs within several days of cessation of treatment. Relapses are most frequently associated with ineffective antimicrobial treatment. This may be due to improper antibiotic usage (inappropriate selection, dose, duration, or poor owner compliance), emergence of drug-resistant pathogens, or failure to eliminate the predisposing causes that alter normal host defense mechanisms and allow the persistence of the bacteria. Relapses may be associated with a higher degree of antimicrobial resistance compared with the original infection.
The other type of recurrent UTI is reinfection. Reinfections occur when the initial infection was effectively treated (documented by negative culture after therapy and resolution of clinical signs) and repeat culture confirms another infection. Typically the time to reinfections is greater than the time between relapses. Reinfections usually indicate that host defense mechanisms are compromised.
Superinfection
Superinfections occur when a new bacteria colonizes the urinary tract during the course of antimicrobial treatment of either a UTI or another infection. Superinfections can be associated with urine diversion procedures (e.g., cystostomy, urethrostomy, indwelling urinary catheters) and are not common.
Hospital-acquired UTI
Urinary catheterization is often useful in the management of patients with urethral outflow obstructive disease, for monitoring urine production, or for patient cleanliness. Several patient risk factors need to be considered when weighing the risks and benefits of placing an indwelling urinary catheter. The risk of a hospital-acquired UTI increases by 27% for every day an indwelling urinary catheter is in place.3 In addition, the risk increases by 20% with every year of age and increases by 450% in patients receiving antibiotics.3 Gender does not correlate with increased risk of UTI for indwelling catheterization; however, male dogs may be at decreased risk following a single catheterization.15,16
The overall risk of nosocomial bacteriuria in catheterized patients is 10%.17,18 Attempts should be made to minimize iatrogenic UTIs by avoiding indiscriminate use of urinary catheters and using indwelling urinary catheters cautiously when pets are undergoing diuresis, are on immunosuppressive therapy, or are immunosuppressed. In addition, appropriately using antimicrobials and using diagnostic and therapeutic techniques that minimize trauma and microbial contamination of the urinary tract can help minimize the chance of infection.19 Whenever possible, intermittent catheterization is preferred to indwelling catheterization, especially in patients that are immunosuppressed and/or are already receiving antibiotic treatment. Previously used IV fluid bags can be used as part of a closed urinary system if sterile bags are not available because they are unlikely to be sources of bacterial contamination.20
Treatment
Treatment recommendations for bacterial UTIs are dependent on several factors and should be tailored to each individual patient. Factors to consider include classification of the UTI (e.g., complicated, uncomplicated, relapse, reinfection, superinfection), location of infection (e.g., bladder, kidney, prostate), and concurrent complicating factors (e.g., systemic disease causing predisposition, poor response to therapy, underlying disease affecting antimicrobial selection). Those factors affect both the duration of therapy and antimicrobial selection. Steps to follow for the ideal management of UTIs are listed in Table 3.
Steps 4 and 5 are especially important for recurrent UTIs.
UTI, urinary tract infection.
Antimicrobial Therapy
Antimicrobial selection
Inappropriate antibiotic dosages or unnecessary usage can lead to resistant organisms that impact not only the individual patient but other veterinary patients and owners.21 Antimicrobials that are excreted in the urine are the mainstay of UTI therapy. Initial antibiotic considerations can vary somewhat based on opinion. The authors of this report recommend amoxicillin and cephalexin as initial treatment options. Trimethoprim-sulfadiazine has been suggested as well; however, based on potential side effects (e.g., hypersensitivity, immune-mediated effects, keratoconjunctivitis sicca), trimethoprim-sulfadiazine should be chosen with care and owner education is important. When host defense mechanisms are compromised, sensitivity results (previous or current) indicate potential resistance, or when the infection involves the prostate or kidneys, second tier antibiotic choices should be considered, including potentiated β-lactams (e.g., amoxicillin trihydrate/clavulanate potassium), fluoroquinolones, or extended-release cephalosporins (e.g., cefovecin).22,23 Second tier antibiotics are not recommended as a first line treatment of an uncomplicated UTI without appropriate culture and sensitivity results. However, second tier antibiotics may be considered when rapid treatment is necessary to return to function, to prevent systemic spread of bacteria, or when penetration into a specific tissue (such as the prostate) is needed. For penetration into prostatic tissue, antibiotics should be lipid soluble, not highly protein bound, and ionize at the pH of the prostatic tissue. Good prostate gland penetration can usually be achieved with fluoroquinolones, trimethoprim-sulfas, and chloramphenicol.
Empirical antimicrobial therapy for uncomplicated UTIs
Dogs and cats with uncomplicated UTIs are typically treated with a 7–14 day course of antibiotics. It is reasonable to assume that shorter durations of appropriate antibiotics (≤ 7 days) may be effective; however, clinical trials are needed to further evaluate shorter treatment periods.1 It is always ideal to treat on the basis of urine culture and sensitivity results; however, economic constraints may preclude this in first time patients with a suspected uncomplicated UTI. In those cases, antimicrobial selection should be based on bacterial characteristics observed in the urine sediment (e.g., gram-positive versus gram-negative, cocci versus rods). For example, if a gram-negative rod is seen (e.g., Escherichia Coli [E. coli], Enterobacter spp., Klebsiella spp.), trimethoprim-sulfa and cephalosporins would be good options. If a gram-negative bacillus is seen (e.g., Mycoplasma spp., Proteus spp.), a cephalosporin or amoxicillin would be a good first line antibiotic. With gram-positive cocci (e.g., Staphylococcus spp., Streptococcus spp.), amoxicillin and cephalosporin would be options.
There are disadvantages to consider with empirical antibiotic therapy. For example, identification of gram-positive cocci could also be consistent with Enterococcus spp., which would be resistant to a cephalosporin. Clinical signs should resolve within 48 hr with appropriate treatment. Along with resolution of clinical signs, evidence of inflammation in urine sediment should also resolve in 3–5 days of antibiotic treatment.
When empirical antibiotic treatment is used, instructions to owners regarding what to expect and follow-up plans are critical. If presenting clinical signs do not resolve quickly, owners should be aware of the need for a follow-up urinalysis and culture and sensitivity. Owners should also be aware of the importance of completing the entire antibiotic regimen, even if signs resolve early in the course of treatment. Finally, owners should be instructed to observe their pets closely for signs of UTI recurrence after the treatment regimen is complete. Clear communication and understanding of the “game-plan” will result in an improved treatment outcome and an increased client willingness to return in cases of empirical treatment failures.
Short-course, high-dose protocols
Due to concerns with owner compliance during longer treatment protocols, short-course, high-dose protocols have been proposed for the treatment of uncomplicated UTIs in dogs. In a recent study in dogs, a short-course, high-dose of enrofloxacin (18–20 mg/kg q 24 hr for 3 days) was as effective as a traditional dose of amoxicillin trihydrate/clavulanate potassium (13.75–25 mg/kg q 12 hr for 14 days) in treating uncomplicated UTI.24 Preliminary evidence suggests this may be an effective option; however, additional research may be necessary to incorporate this into routine clinical practice.
Complicated UTIs
Antibiotic treatment of complicated UTIs should be prolonged (typically 4 wk) and always based on urine culture and sensitivity results. It is possible that shorter duration of therapy may be effective in either some or all clinical situations; however, further studies are needed to provide more specific recommendations.1 One wk into treatment and 1 wk prior to discontinuing antimicrobials, re-evaluation of the urine sediment can help evaluate response to therapy. When effective, neither bacteria nor WBCs should be observed on sediment exam. Re-evaluation of the urine culture is again recommended 5–7 days after completion of therapy to confirm successful resolution of the UTI. Prolonged treatment of a complicated UTI may be necessary to sterilize the urinary tract. Another important consideration is “buying time” for correction of host defense mechanism abnormalities. If host defense mechanism abnormalities are not corrected, it may be difficult to clear the current infection. More likely, the patient will experience reinfections.
Asymptomatic Bacteriuria
Identification of bacteria in the urine with an absence of clinical signs is defined as asymptomatic bacteriuria. Asymptomatic bacteriuria may be hospital-acquired in critically ill patients or patients with indwelling catheters, may be an incidental finding on culture, or may be associated with a disease that suppresses the normal inflammatory response. E. coli is most commonly isolated in patients with asymptomatic bacteriuria. Uropathogenic isolates from asymptomatic patients have been shown to express fewer virulence factors than those identified from patients with symptomatic UTIs.25 Asymptomatic bacteriuria should be treated when quantitative culture results suggest a UTI versus urine contamination. Treatment of asymptomatic bacteriuria associated with lower numbers of bacteria in urine (i.e., numbers associated with contamination) may contribute to antibiotic resistance and colonization of the bladder with more pathogenic strains of bacteria.26 Experimental colonization of less pathogenic strains of E. coli have even been evaluated in dogs as a potential treatment option for recurrent UTIs, further suggesting that asymptomatic bacteriuria does not require treatment.27
Treatment Failures
Treatment failures can involve the inability to either eradicate the current infection (including relapses) or reinfections. Relapses are most commonly associated with antibiotic treatment failures, whereas reinfections are most commonly associated with compromised host defense mechanisms (Table 4).
UTI, urinary tract infection.
Antimicrobial Resistance
Multidrug resistance (MDR) is becoming more common in veterinary medicine. The urinary tract is the most common extraintestinal source of MDR E. coli and Enterobacter spp. in dogs, accounting for 62% and 58% of the isolates, respectively.26 One report identified that 27% (10 of 37) of dogs had a urinary catheter, and all but one was given antimicrobials while a urinary catheter was in place.26 Risk factors for MDR were underlying illness contributing to immunosuppression (97%), hospitalization for ≥ 3 days (82%), and surgical intervention (57%).26 Several canine retrospective studies evaluating UTI isolates and resistance have been published. One study found a significant increase in recurrent E. coli infections and increased resistance with all antimicrobials tested, with the exception of tetracycline and trimethoprim-sulfamethoxazole.28 Another study found an increase in fluoroquinolone resistance.22 Evaluation of Staphylococcus spp. resistance found 100% of isolates to be resistant to at least one drug and 77% showed MDR.29 Increased incidence of multiresistant Enterococcus spp. has also been identified.30
Inability to Eradicate and/or Recognize Underlying Causes
Compromised local or systemic host defense mechanisms increase the risk of UTI and make treatment more difficult. Although a transient breach in host defenses can result in a simple uncomplicated UTI, it is of utmost importance to identify and resolve potential underlying causes whenever possible. Common systemic disorders known to predispose to UTI include chronic kidney disease, either endogenous or exogenous glucocorticoid excess, diabetes mellitus, and hyperthyroidism.31–34 Although some of those disorders may not be correctible, control of the underlying disease is often helpful. Local disorders of the lower urinary tract also increase the risk of UTIs. Examples include anatomic abnormalities like a “hooded” or recessed vulva, ectopic ureters, and urolithiasis.35 Systemic and local defense mechanism abnormalities are often ruled out with a complete minimum database and imaging, respectively.
Ancillary Prevention Therapies
Ancillary therapies designed to prevent recurrent UTIs are considered in patients either where breaches in host defenses are present but are not correctable or when an underlying cause for reinfection is not identified. Care should be taken to treat any underlying infection prior to starting any prevention measures. Owners should watch closely for clinical signs and be advised that frequent re-examinations will be necessary to detect and treat any breakthrough infections.
Prophylactic Antimicrobial Treatment (Low-dose Protocols)
Prophylactic antimicrobial treatment involves long-term daily administration of low-dose antimicrobials to either inhibit or minimize uropathogen growth, thereby decreasing the opportunity for bacterial adhesion and colonization of the uroepithelium. Unfortunately, there are no studies in dogs that have evaluated the efficacy and adverse effects of such protocols. Due to the risk of creating resistant infections, prophylactic low-dose antibiotic administration should be reserved for refractory cases and only after all attempts to resolve correctable problems have been exhausted.
Prophylactic low-dose antibiotic treatment should only be initiated after a standard-dose antibiotic treatment has been successful (negative urine culture). Best results are expected with drugs that are excreted in the urine. Other considerations should include potential side effects of the drug and previous culture and sensitivity results. Commonly used protocols include fluoroquinolones, cephalosporins, or β-lactam antimicrobials. The dose used should be one-half to one-third the therapeutic daily dose and should be administered immediately after the last voiding before bedtime. This protocol is typically recommended for a minimum of 6 mo, and urinalysis and culture should be performed q 4–8 wk. If at any point during the treatment a UTI occurs, it is treated as a complicated UTI. Prophylactic low-dose therapy can be restarted after the reinfection has been resolved.36
Cranberry Extract
Proanthocyanidins, specifically A-type isoforms, found in cranberry juice inhibit E. coli attachment by blocking interaction of bacterial P-fimbriae to the surface of uroepithelial cells.37,38 Canine studies evaluating the efficacy of cranberry extract are limited; however, some in vitro data shows promising results. One study demonstrated that E. coli in urine from dogs receiving oral cranberry extractc had a decreased ability to agglutinate to human red blood cells.39 Similarly, a second study demonstrated that E. coli in urine from dogs receiving an oral cranberry extract productd had a decreased ability to adhere to Madin-Darby Canine Kidney cells.40 Based on those in vitro studies, oral administration of cranberry extract may help reduce E. coli reinfections in patients with compromised host defense mechanisms. Due to large variations of the active compound in over-the-counter products, it may be of benefit to use the products evaluated for canine usec,d, dosed according to manufacturers’ recommendations.
Urinary Antiseptics
The most commonly used urinary antiseptic is methenamine, which is converted to formalin in an acidic environment. Methenamine may be considered in patients with either recurrent infections or patients with potentially untreatable/unresolved breaches in immunity. Just as with the use of cranberry extract, this prophylactic treatment is not recommended as a sole treatment of UTIs. Methenamine should only be used either in conjunction with antibiotics for the treatment of current infections or as a preventative once the previous UTI has been cleared.
Miscellaneous Treatments
Urinary acidifiers are not recommended as an adjunctive treatment of UTIs, with the possible exception of concurrent use with methenamine. Similarly, antimicrobial agents instilled directly into the urinary bladder are usually not recommended as they have not been shown to be effective. In addition, potential complications include bladder rupture and absorption of toxic concentrations of drugs through an inflamed bladder wall. Antibiotic administration via a urinary catheter would only be of use in patients with urine retention disorders that require intermittent urethral catheterization to empty the bladder (e.g., upper motor neuron bladder disorders).
Complications of UTIs
Polypoid Cystitis
Polypoid cystitis occurs when uroepithelial proliferation is severe, resulting in either mass-like lesions or diffuse thickening of the bladder wall associated with an intramural accumulation of inflammatory cells.41,42 Typically, lesions are identified by either ultrasound or contrast radiographs during evaluation for predisposing factors (Figure 3). If bladder wall thickening is present in the apex of the bladder and the lesion does not have prominent vascular flow on Doppler ultrasound, polypoid cystitis is likely; however, histopathology is required for definitive diagnosis. Proteus spp. are commonly associated with the development of polypoid cystitis.41,42 Polypoid lesions often contribute to patient discomfort and may also serve as a nidus for reinfection. Medical management involving treatment of the UTI with appropriate antimicrobials may resolve the lesions. Surgical excision and biopsy of localized lesions should be considered to decrease duration of medical therapy and to rule out transitional cell carcinoma as the possible cause.41 If cystoscopy is available, it may provide a less invasive option (i.e., for histopathology and culture).
Citation: Journal of the American Animal Hospital Association 49, 2; 10.5326/JAAHA-MS-5944
Emphysematous Cystitis and Pyelonephritis
Gas, which can be produced in the bladder wall, lumen, and/or renal pelvis as a consequence of bacterial infection, most commonly occurs in dogs and cats with diabetes mellitus because the presence of glucosuria provides a fermentable substrate (Figure 4).43 Emphysematous cystitis is usually caused by E. coli infections, but Proteus spp., Clostridium spp., and Aerobacter aerogenes infections have also been reported causes.43,44 Therapy should be similar to treatment of a complicated UTI, with additional treatment to resolve glucosuria (if present). Emphysematous pyelonephritis can occur for the same reasons as emphysematous cystitis, but appears to be a rare complication in veterinary medicine.
Citation: Journal of the American Animal Hospital Association 49, 2; 10.5326/JAAHA-MS-5944
Magnesium Ammonium Phosphate (Struvite) Urolithiasis
Urolithiasis can damage the uroepithelium and predispose dogs and cats to UTIs, but infections can also result in urolith formation. Struvite urolith formation most frequently occurs secondary to an infection involving a urease-producing bacteria such as Staphylococcus spp., Proteus spp., and, less commonly, Corynebacterium spp., Klebsiella spp., and Ureaplasma spp. Urease hydrolyzes urea to ammonia, which buffers urine hydrogen ions. In turn, ammonium ions are formed that increase urine pH, leading to an increased amount of dissolved ionic phosphate. The increased concentration of ammonia and phosphate, along with increased urine pH, sets the stage for struvite crystal formation, and inflammatory debris associated with the UTI may serve as a nidus for urolith formation. Differences exist between canine and feline patients with regard to struvite urolith pathophysiology. In canine patients, > 90% of uroliths occur secondary to a UTI; however, in feline patients, struvite uroliths are more likely to be sterile. If medical dissolution therapy is either not an option for struvite urolithiasis or if other complicating factors exist (such as other underlying host defense compromise or urinary obstruction), surgical removal may be indicated. Both the uroliths and a piece of bladder mucosa should be analyzed/cultured.45,46
Pyelonephritis
Most commonly, pyelonephritis (infection of the renal pelvis) occurs secondary to an ascending UTI. The kidneys are typically protected from ascending bacterial infection with long ureters that keep urine flowing (mostly) in one direction via peristalsis, the valve-like nature of the vesicoureteral junction preventing reflux of urine during voiding, and a relatively hypoxic environment in the renal medulla. Risk factors for pyelonephritis, similar to those for a lower UTI, include ectopic ureters, renoliths, obstructive uropathies, urine retention disorders, and systemic immunocompromise. In comparison with the presentation of a typical lower UTI, acute pyelonephritis can be associated with signs of systemic illness (e.g., lethargy, anorexia, fever, inflammatory leukogram, lumbar pain). In addition, renal azotemia and urine concentrating deficits may exist with bilateral pyelonephritis. Pyeloectasia is commonly observed on ultrasound, and a skilled ultrasonographer may be able to perform pyelocentesis for cytology and culture.47 If pyelonephritis is either suspected or confirmed, the UTI should be treated as a complicated UTI with a minimum of 6–8 wk of antibiotics and regular ultrasound monitoring.12 It has also been suggested that a treatment duration of 4–6 wk may be adequate.1 As with other suggested protocols, further research may help determine if a shorter duration of treatment may be effective.
Prostatitis
The prostate is exposed to commensal microorganisms from the distal urethra. With this constant exposure comes risk of infection. Bacterial prostatitis can occur as either a diffuse infection or as a prostatic abscess. A healthy prostate gland has local protective mechanisms that typically prevent colonization and infection, and it is likely that bacterial prostatitis occurs due to either a breakdown in the normal host defenses or secondary to other prostatic pathology (e.g., prostatic neoplasia, benign prostatic hyperplasia).48,49 In patients with suspected prostatic disease, catheterization for retrieval of prostatic fluid, washings with prostatic massage, and ejaculate or prostatic aspirates may be considered in addition to cystocentesis for culture evaluation.4 When treating chronic prostatitis, it is necessary to treat with antibiotics that penetrate the blood-prostate barrier such as fluoroquinolones, trimethoprim-sulfa combinations, and chloramphenicol. Treatment should be continued initially for 4 wk; however, extended therapy (6 wk) may be needed.1,50 In patients with acute prostatitis, disruption of the prostatic capsule should allow any antibiotic concentrated in the urine to penetrate into the prostatic tissue (however, as the inflammation subsides with treatment, antibiotic penetration may become an issue). In patients with abscessation of the prostate, either surgery or ultrasound-guided drainage should be considered.51,52 In intact male dogs, castration may be beneficial in resolving chronic bacterial prostatitis.53 Recurrence is possible, especially if underlying conditions are present.
Conclusion
Most UTIs are uncomplicated and appropriate antibiotic treatment rapidly clears the infection, resulting in a good prognosis. In contrast, the prognosis for a complicated UTI may be guarded. It is of utmost importance to correct underlying defects in host defenses whenever possible to achieve the best outcome with a complicated UTI. Following protocols for ideal UTI management and monitoring will improve treatment success and decrease the incidence of recurrent UTIs.
Photograph of an involuted or “hooded” vulva noticeable on physical examination.
Cystoscopic image of a dog with a paramesonephric remnant.
Ultrasound image of a mass-like lesion in the apex of the bladder consistent with polypoid cystitis.
Right lateral abdominal radiograph of a newly diagnosed diabetic cat with emphysematous nephritis and cystitis secondary to an Escherichia Coli (E. coli) and Streptococcus spp. urinary tract infection.
Contributor Notes
N. Smee’s updated credentials since article acceptance are DVM, MS.
N. Smee’s present affiliation is VCA Mission, Mission, KS.
K. Loyd’s present affiliation is Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO.
