Bacterial Urinary Tract Infections

In context of surgery, conceptual understanding of alterations in interactions between host defenses and pathogenic microbes that result in bacterial urinary tract infections (UTI) are important for at least two reasons. First, many surgical procedures designed to correct noninfectious disorders of the urinary tract may partially or totally interfere with local host defenses that normally prevent or impair development of UTI. Second, surgical correction of abnormalities that affect host defense mechanisms may be a prerequisite to preventing recurrent or persistent bacterial UTI.

Why is it Important to Recognize that Bacterial Urinary Tract Infection is not a Primary Diagnostic Entity?

Although the urinary tract communicates with an external environment loaded with bacteria and other potentially pathogenic agents, most of it is normally sterile and all of it is normally resistant to infection. As with all systems of the body, resistance to urinary tract infection is dependent on the interaction of several host defense mechanisms [1]. The pathogenesis of UTIs is related to the relationship between the virulence of uropathogenic infectious agents (analogous to seeds) and the functional status of host defense mechanisms (analogous to soil; Table 65-1). Growth of bacteria (seeds) usually will not occur unless abnormalities of host defenses (suitable soil) are present. Therefore, in context of diagnosis, prognosis, and therapy, a bacterial urinary tract infection (UTI) may be viewed as a secondary (or complicating) rather than a primary (or definitive) diagnostic entity.

CAVEAT - In addition to focusing on antimicrobial treatment of bacterial pathogens (which are usually secondary causes of urinary tract disease), it is also important to consider detection and treatment of abnormalities in host defenses that allow bacteria to colonize and invade tissues of the urinary tract (Table 65-1 and Table 65-2). If UTIs are managed inappropriately, one or more sequelae may occur (Table 65-3). Early detection followed by proper treatment and follow-up evaluation will minimize the occurrence and severity of these sequelae.

What Diagnostic Classification will Facilitate Treatment of Bacterial Utis?

Bacterial UTI encompass a wide variety of clinical entities whose common denominator is microbial invasion of any of its components. Urinary tract infections may be classified on the basis of 1) anatomic location (i.e., kidney, ureter, bladder, and/or urethra), 2) etiology (Escherichia coli, Staphylococcus intermedius, etc.), 3) complexity (uncomplicated or complicated), and/or 4) response to therapy (persistent, relapse, reinfection, or superinfection) [1-3].

Anatomic localization of infections within the urinary tract should be considered because it may influence the prognosis; type, dosage, and dose interval of antimicrobial agent selected; and duration of therapy. Classification of UTIs based on complexity is also of prognostic and therapeutic significance because it allows differentiation of uncomplicated (or simple) urinary tract infections from complicated urinary tract infections (Table 65-1 and Table 65-2).

Uncomplicated UTI

An uncomplicated UTI is defined as an infection in which an underlying structural, neurologic, immunologic, or functional abnormality cannot be identified. Although useful, this classification may be misleading in that it implies that bacterial infection is the primary rather than a secondary abnormality. However, most bacteria survive and multiply only when host defenses are compromised. Many simple UTIs encompass transient and potentially reversible defects in the patient's innate defense mechanisms, even though the underlying cause may escape detection. Others occur when normal host defenses are overwhelmed by virulent uropathogens. For example, nosocomial UTI could occur as a result of improper transurethral catheterization in a hospital intensive care unit harboring resistant uropathogens. Uncomplicated UTIs might also be caused by replacement of the normal microbial flora (so-called good bacteria) of the distal urethra and genital tract with uropathogenic microbes that have emerged as a consequence of prior treatment of the patient with antibiotics. Uncomplicated UTIs are usually associated with a better prognosis for recovery.

Complicated UTI

Complicated UTIs occur as a result of bacterial invasion of the urinary system secondary to an identifiable disease that interferes with one or more defense mechanisms (Table 65-2) [1,2,4]. A relationship exists between the severity of host defense abnormality and the frequency and severity of UTI. In general, the abnormality in host defenses must be corrected or removed if secondary bacterial infection is to be completely eradicated and prevented from recurring. Failure or inability to do so is a common cause of persistent or recurrent UTI (relapse or reinfection).

CAVEAT -Differentiation of uncomplicated from complicated UTIs and anatomic localization of UTI require appropriate diagnostic evaluation, which may include transrectal palpation of the genitourinary tract, ultrasonography, survey and contrast radiography, cystoscopy, and aspiration, punch, or surgical biopsy.

Why is it Important to Differentiate UTIs According to whether they are Persistent, Relapses, Reinfections, or Superinfections?

Relapses

Recurrent bacterial UTIs that occur following withdrawal of therapy may be classified as relapses or reinfections (Table 65-4). Relapses (i.e., relapse of a persistent pathogen) are defined as recurrences of clinical signs caused by the same species (and serologic strain) of microbe. In this situation, remission of clinical signs and eradication of bacteria from the urine are not associated with eradication of pathogenic bacteria from tissues of the urinary tract. Although viable bacteria remain sequestered in sites inaccessible to bacteriocidal concentrations of antimicrobics, results of the culture of urine samples obtained by cystocentesis during antimicrobic therapy are likely to be negative if the drug is eliminated in high concentration in urine. Relapses of clinical signs usually occur within several days to a few weeks after interruption of antimicrobic therapy. The bacteria may become more resistant to antimicrobial agents than prior to therapy. The pathogenesis of relapsing UTI likely involves failure to completely eliminate pathogenic bacteria before antimicrobic therapy is withdrawn. Relapses represent antimicrobial treatment failures associated with one or more causes, and affect both male and female dogs throughout their lifespan (Table 65-5). Relapses have the potential to cause significant morbidity if mismanaged (Table 65-3).

Reinfections

Reinfections are defined as recurrent UTI caused by one or more different pathogens (Table 65-4). In this situation, bacteria have been eradicated from urine and surrounding tissue, but persistent dysfunction of one or more host defense mechanisms predisposes to reinfection with different uropathogens (Table 65-2 and Table 65-6). If superficial damage to tissues of the urinary tract induced by bacteria by the initial infection have time to heal, recurrence of clinical manifestations of reinfections often occur at a longer interval following cessation of therapy than relapses. Reinfections appear to be more common in female dogs and young to middle-aged cats with lower urinary tract disease.

Superinfections

Superinfections are defined as infections with one or more additional pathogens during the course of antimicrobial therapy [1]. They are most likely to occur in association with in-dwelling transurethral catheters; as a sequela to urinary diversion techniques (i.e., antepubic urethrostomy, tube cystostomy, percutaneous nephropyelostomy); and because of anatomic abnormalities that promote ascending migration of bacteria into the urinary tract.

CAVEAT -The therapeutic plan for relapses often differs from the therapeutic plan for reinfections. Therefore, it is important to compare results of bacterial culture of urine obtained prior to initiation of therapy to bacterial cultures of urine obtained during and/or after withdrawal of therapy.

Why is Diagnostic Urine Culture the Gold Standard of Diagnosis of Bacterial UTI?

Because UTI encompasses a spectrum of underlying abnormalities in host defense mechanisms in addition to bacterial pathogens, diagnostic and therapeutic requirements vary from case to case. No pathognomonic history, physical examination, radiographic, or ultrasonographic findings are associated with bacterial UTI.

In addition to bacterial infection, many diverse noninfectious disease processes, including neoplasia and urolithiasis, result in inflammatory lesions of the urinary tract characterized by exudation of RBC, WBC, and protein into urine. The resultant hematuria, pyuria, and proteinuria suggest inflammatory urinary tract disease, but do not indicate its cause or location within the urinary tract. Diagnosis of bacterial UTI solely on the basis of urinalysis and detection of inflammatory cells in urine sediment will result in over-diagnosis. Therefore, it is essential to distinguish between inflammation and infection related to urinary tract disease. Although detection of bacteria in fresh urine sediment should prompt consideration of UTI, it should be verified by urine culture. Non-bacterial "look-alikes" in urine sediment are often confused with bacteria [4].

Quantitative urine culture is considered to be the gold standard for diagnosis of bacterial UTI [8]. In addition to facilitating differentiation of bacterial contaminants from bacterial pathogens, accurate identification of specific bacterial species aids in selection of antimicrobial drugs. Also recall that recurrent UTIs owing to relapses cannot be distinguished from recurrent UTIs owing to reinfections without comparison of pretreatment bacterial culture results to follow-up culture results.

CAVEAT -Failure to perform bacterial urine cultures or failure to correctly interpret the results of urine cultures may lead not only to diagnostic errors but therapeutic failures as well. Although detection of bacteria in properly collected urine samples is highly indicative of bacterial UTI, further information is required to confirm and localize the site(s) of infection.

How should Urine Samples be collected for Diagnostic Culture?

We prefer to collect urine samples for bacterial culture by cystocentesis to eliminate problems of differentiating contaminants from pathogens [3]. Detection of bacteria, even in low numbers, in urine aseptically collected by cystocentesis is indicative of UTI. However, false positive results may occur if the needle penetrates a loop of intestine during cystocentesis, or if the sample is contaminated during transfer to culture media. For this reason, quantitative urine culture is routinely recommended, even for samples collected by cystocentesis. Urine culture results should be interpreted in context of other clinical findings (Table 65-7) [5].

CAVEAT -Catheter-induced UTIs (nosocomial infections) are common in patients with urinary tract diseases, and could even result in iatrogenic pyelonephritis, renal failure, and septicemia. Therefore, transurethral catheterization of patients at increased risk for UTI should be evaluated in context of risks and benefits.

How should Urine Samples be Preserved Prior to Culture?

If diagnostic bacterial cultures are to be performed, urine should be collected for culture before antibacterial therapy is initiated. If the patient is currently being treated with an antimicrobic, it should be discontinued for approximately 3 to 5 days prior to diagnostic urine culture in order to minimize inhibition of in vivo and in vitro bacterial growth.

Because urine may be a good culture medium at room temperature (bacterial counts may double every 20 to 45 minutes), it should be cultured within 15 to 30 minutes from the time of collection [6]. Another indication for culture of fresh urine samples is that destruction of some fastidious bacteria may be detectable within an hour of collection. If for any reason culture of freshly collected urine samples is not possible, the samples should be kept in a sealed sterile container and immediately refrigerated following collection. Refrigerated samples may be stored for 6 to 12 hours without significant additional growth of bacteria [6]. However, it is emphasized that fastidious organisms may be killed in the urine environment if refrigeration storage time is prolonged.

Alternatively, commercially manufactured collection tubes combined with refrigeration may be used to preserve samples for up to 72 hours. Commercially manufactured urine culture and susceptibility test kits are also available (IndicatoRx, Idexx Laboratories, Westbrook, Maine).

CAVEAT -Transport of urine specimens to a commercial microbiology laboratory results in increased time between urine collection and aerobic culture and, therefore, adds a potential source of error, especially if the samples are not properly preserved. Freezing urine samples may also destroy bacteria.

Why are Quantitative Bacterial Urine Cultures a Standard of Practice in the Management of Utis?

The gold standard for diagnosis of UTI is isolation of bacteria in a properly collected urine sample. However, the presence of bacteria in urine per se is not synonymous with UTI because urine may be contaminated with bacteria as it flows through the urethra, and after it is removed from the patient, but before it is cultured. Quantitative urine culture includes determination of the number of bacteria (colony-forming units) per milliliter of urine in addition to isolation and identification of bacteria. Because it facilitates differentiation of bacteria that have contaminated the urine sample from bacteria that are likely to be causing UTI, quantitative culture is the preferred method of diagnostic culture for urine samples obtained by any collection method.

The concept of significant bacteriuria was introduced to aid differentiation between harmless bacterial contaminants of urine and pathogenic bacteria causing infectious disease of the urinary system [1,2,7]. A high bacterial count in a properly collected and cultured urine sample indicates the high probability of UTI (Table 65-8). Small numbers of bacteria obtained from untreated patients usually indicate contamination.

The lower limit of numbers of bacteria isolated from feline urine that indicate infection (so-called cutoff values) has not been precisely determined. However, it is usually less than that in dogs because feline urine appears to be less conducive to bacterial growth than urine of dogs (Table 65-8) [8].

CAVEAT -When interpreting bacterial cultures, several variables should be considered (Table 65-7). In up to 20% of canine patients, bacterial UTI may be present with less than 10,000 colony-forming units per milliliter of urine [2]. In this circumstance, samples collected by catheterization or during voiding might erroneously be interpreted as contaminants (Table 65-8). This observation emphasizes the importance of cystocentesis as the preferred method of collection for diagnostic urine culture.

How can Routine Quantitative Aerobic Cultures of Urine be Adapted to a Primary Care Veterinary Practice?

Many veterinarians do not routinely perform urine cultures because of the time and expertise required to specifically identify bacteria. However, all individuals can recognize lack of growth of bacteria on culture plates. Therefore, we recommend that veterinarians quantitatively culture urine on microbiology plates (such as blood agar and MacConkey agar) utilizing calibrated microbiologic loops [9]. If no growth occurs after incubation of the culture plates at 37° for approximately 24 hours, or if only small numbers of bacteria grow (contaminants), further efforts to identify bacterial species is unnecessary, and treatment with an antimicrobial drug is usually not warranted (Table 65-8). If significant numbers of bacteria (colony-forming units) are isolated, the microbiologic plates, or swab cultures from the plates, can then be sent to commercial laboratories for species identification and antimicrobial susceptibility tests. Therapy with an appropriate antimicrobial drug (refer to next section on empirical choices of antimicrobics) may be initiated pending results from the commercial laboratory.

We routinely use calibrated bacteriologic inoculating loops (available from Veterinary Lab Supply, 120 S. 1st Ave., Winterset Iowa 50237) or microliter mechanical pipettes that deliver exactly 0.01 or 0.001 milliliters of urine to culture plates. To facilitate culture, urine is streaked over the surface of agar plates with the inoculating loops by conventional methods. The plates are placed in an incubator upside down at 37°C for 18 to 24 hours, and then examined for bacterial growth. Blood agar will support growth of most aerobic organisms encountered in patients with UTI. MacConkey agar provides information that aids in tentative identification of bacteria and prevents "swarming" of microbes.

This strategy of in-hospital bacterial culture of urine not only fosters appropriate diagnosis and therapy, it is also financially sound. The fee normally paid to the diagnostic laboratory for a sterile urine culture can be rightfully earned by the veterinary hospital. This strategy also enhances use of urine cultures to monitor the effectiveness of therapy (so-called "test of effectiveness").

CAVEAT -Before culture, urine should not be kept at room temperature or frozen. Also, urine should not be placed in enrichment broth immediately following collection to enhance bacterial growth, as this will invalidate the results of quantitative culture.