Managing complicated urinary tract infections (Proceedings)
Most bacterial infections of the lower urinary tract respond quickly to antimicrobial treatment; however, urinary tract infections (UTI) associated with defects in the host immune system (complicated UTI) often fail to respond or recur after antibiotic withdrawal and can be a therapeutic challenge.
The most common bacterial pathogens associated with UTI in the dog include Escherichia coli, Klebsiella, Staphylococcus, Enterococcus, Proteus, Pseudomonas, Enterobacter, and Streptococcus. These are dermal or intestinal floras that ascend the urethra and then adhere to the mucosa of the bladder and multiply. Although many enteric organisms are anaerobes, the oxygen tension in urine probably inhibits growth of strict anaerobic bacteria and therefore, anaerobic UTI is rare. A recent study of recurrent and persistent UTI in dogs showed that 25% of culture positive urine specimens had two or more bacterial species isolated. Mycoplasmal infections are relatively rare but have been associated with recurrent or persistent UTI in dogs. Mycoplasma should be considered in dogs with persistent pyuria and negative urine culture, dogs with persistently alkaline urine and negative urine cultures, and dogs with persistent or recurrent UTI that don't respond to appropriate conventional antibiotic treatment.Normal Host Defense Mechanisms
The status of host defense mechanisms appears to be the most important factor influencing the pathogenesis of UTI. Normal voiding is an efficient natural defense mechanism against UTI. Mechanical washout as a result of complete voiding is responsible for removing greater than 95% of non-adherent bacteria that gain entrance into the urinary bladder. Increased urine production and frequency of voiding enhance washout of bacteria. Disorders that decrease the frequency and/or volume of voided urine, or that result in an increased urine residual volume may predispose animals to UTI. Normal urine residual volume for dogs is less than 0.2 to 0.4 ml/kg body weight.
Bacteria are normally present in increasing numbers from the mid to distal urethra, but seldom do these organisms cause UTI in normal dogs. The high-pressure zone in the mid urethra and spontaneous urethral contractions help prevent ascension of bacteria. Differences in epithelial morphology (decreased epithelial receptor sites) also help decrease bacterial colonization in the proximal and mid urethra. The length of the urethra and bactericidal prostatic secretions in male dogs are thought to decrease the incidence of UTI compared with female dogs, however, nearly equal gender distribution in recurrent/persistent UTI has recently been reported. In both sexes, the valve-like nature of the vesicoureteral junction helps protect against bacterial ascension to the upper urinary tract.
Colonization of vulval and preputial luminal mucous membranes by nonpathogenic flora serves to decrease colonization by uropathogens. Normal flora occupy most of the epithelial receptor sites, produce bacteriocins that interfere with uropathogen metabolism, and have a high affinity but low requirement for essential nutrients required by uropathogens. Mucosal secretions also help prevent adherence of uropathogens to epithelium; immunoglobulins coat pathogenic bacteria and glycosaminoglycans form a protective barrier over the mucosal surface.
The antibacterial property of urine is an additional important host defense mechanism against UTI. Urine is frequently bacteriostatic and sometimes can be bactericidal depending on its composition. Low pH and high concentrations of urea and weak organic acids in concentrated urine inhibit bacterial growth. Although polyuric disorders may increase washout of non-adhered bacteria from the bladder, UTI may occur due to decreased antibacterial properties of urine.
Complicated vs. Uncomplicated Urinary tract Infections
Uncomplicated UTI are infections without detectable underlying structural or functional abnormalities in the host's defense mechanisms. This form of infection is easiest to treat and is usually cleared soon after appropriate antibiotic treatment is initiated. Complicated UTI are associated with a defect in the host's defense mechanisms; i.e., interference with normal micturition, anatomic defects, damage to mucosal barriers, alterations in urine volume or composition, or systemic immunocompromise. In almost all cases, the underlying defect must be corrected in order to eliminate the UTI.
Abnormal micturition often results in incomplete voiding and retention of urine, which allows for multiplication of bacteria within the urinary tract. Damage to mucosal barriers may result in UTI, depending on the extent of the lesion and concurrent introduction of uropathogens. It is interesting to note that pathogenic bacterial inoculation of the urinary bladder in experimental animals usually fails to establish a UTI unless the uroepithelium is first damaged by a chemical or mechanical insult. Any time the urinary bladder is catheterized; bacteria are carried up the urethra to the bladder. If the catheter is inserted too far and damages the bladder mucosa, the chance of infection increases. Anatomic defects may allow ascending migration of bacteria (e.g., indwelling urinary catheters or an ectopic ureter) or may damage mucosal barriers (e.g., urolithiasis, neoplasia, urachal remnant, thickened bladder wall due to chronic inflammation). Altered urine composition (glucosuria or excretion of irritating drugs like cyclophosphamide) can enhance the environment for bacterial growth. In addition to the above local factors, systemic disorders such as renal failure, hyperadrenocorticism, prolonged steroid administration, neoplasia, and diabetes mellitus can result in complicated UTI. In a recent retrospective study, aerobic urine cultures from 159 dogs with diabetes mellitus yielded bacterial growth in 34 cases (21%).
Elimination of clinical and laboratory signs of complicated UTI with antibiotic treatment is usually not possible; signs either persist during antibiotic treatment or recur shortly after antibiotic withdrawal. Although antibiotic treatment is the cornerstone of management, the status of host defense mechanisms is thought to be the single most important determinant of the outcome of UTI treatment. In complicated UTI, antibiotic treatment should control the pathogenic bacterial growth for a period sufficient to allow host defense mechanisms to prevent colonization of the urinary tract without further antibiotic administration.
Recurrent Urinary Tract Infections
Recurrence of clinical and laboratory signs of UTI can be classified into two groups: relapses and reinfections. Relapses are infections caused by the same species of bacteria usually within several days of cessation of treatment. In this case the previous antimicrobial treatment failed to eliminate the infection. Relapses may be due to use of improper antibiotic or dose, emergence of drug-resistant pathogens, or failure to eliminate predisposing causes that alter normal host defense mechanisms and allow the persistence of the bacteria. Urinary tract infections that relapse are frequently associated with a higher degree of antimicrobial resistance compared to the original infection. Relapses in male dogs may be caused by chronic prostatic infections.
On the other hand, recurrent UTI may be reinfections. In this case, the previous antibacterial treatment cleared the first infection and the urinary tract has subsequently become infected with another bacteria. In most cases the time between reinfections is greater than the time between relapses. Reinfections often indicate failure to eliminate predisposing causes that alter normal host defense mechanisms. Alternatively, reinfections may be iatrogenic (follow-up catheterization) or spontaneous. Reinfections with less invasive bacteria (e.g., Pseudomonas aeruginosa) generally suggest the host's immune system is compromised.
Superinfections occur when additional bacteria colonize the urinary tract during the course of treatment. Superinfections are often associated with urine diversion techniques (e.g., cystostomy, urethrostomy, and indwelling urinary catheters) and can appear to be persistent or recurrent UTI.