Cystitis and Urethritis: Urinary Tract Infection

Chapter 8 Cystitis and Urethritis


Urinary Tract Infection



Introduction




A. Urinary tract infection (UTI) is defined as bacterial colonization of portions of the urinary tract that normally are sterile (i.e., kidneys, ureters, bladder, proximal urethra).
1. UTI can occur superficially on luminal surfaces, deeper within the parenchyma, or in both locations.

2. Infection with fungal or chlamydial organisms is rare. Viral infections have not been conclusively identified as a cause of lower urinary tract clinical signs.

B. UTI most commonly is discovered when animals are presented with clinical signs of lower urinary tract distress (i.e., symptomatic bacteriuria) such as hematuria, pollakiuria, and increased frequency of urination.
1. UTI may exist without clinical signs (i.e., asymptomatic bacteriuria). In these instances, infection is diagnosed fortuitously.


image UTI may be asymptomatic.




2. As many as 10% of hospitalized dogs (with a variety of illnesses) have asymptomatic UTI.

C. UTI is common in dogs, but not in cats.
1. UTI may be the most common infectious disease of dogs.
a. An estimated 10% of dogs presented to veterinarians for any reason have UTI.

b. Approximately 14% of dogs will have at least one UTI during their lifetime.


image UTI may be the most common infectious disease in dogs.





c. Female dogs have a higher risk of developing UTI than do male dogs.

d. UTI occurs as a single episode in 75% of affected dogs.

e. Multiple episodes of UTI occur in some dogs, with predisposing factors favoring recurrence. Of all dogs presented to a referral hospital, 0.3% were estimated to have recurrent UTI.

2. UTI occurs in only 0.1% to 1% of all cats.


image UTI is uncommon in cats.





a. Geriatric cats are more commonly affected.

b. Siamese cats may have a higher risk for developing UTI than other breeds.

c. Increased incidence of UTI in male cats is related to the increased use of urinary catheters to relieve urinary obstructions in males. When it does occur, UTI is a single episode in 85% of affected cats.

d. In cats older than 10 years of age presenting with signs of lower urinary tract irritation, more than 50% are expected to have UTI. Most of these cats have underlying chronic renal disease with submaximal ability to concentrate urine.

D. The term cystitis often is used to refer to bacterial UTI. The urinary bladder primarily is involved in these disorders, but the urethra may also be part of the process. Cystourethritis may be a better term.
1. It is difficult to assess the involvement of the urethra in UTI because of limitations of the commonly used diagnostic tests.

2. Urethroscopy provides a method to determine the extent of urethral involvement.


Pathogenesis and Pathophysiology



Bacteria Associated with Urinary Tract Infection





1. Bacteria commonly associated with urinary tract infection in dogs and cats are shown in Figures 8-1 and 8-2.
a. Most UTIs are caused by a single organism (monomicrobic). A single organism is isolated in 75% of cases, two organisms are isolated in 20%, and three organisms are isolated in 5% of UTI.

b. Gram-negative bacteria cause UTI in 75% of cases.
(1) Escherichia coli is the most common uropathogen in dogs and cats.

image

FIGURE 8-1 Bacteria associated with urinary tract infection in dogs. Organisms isolated in significant quantitative growth from cystocentesis samples in dogs. 5,060 urine samples were cultured yielding growth in 28% and no growth in 72%. Organisms listed as <1% each (<5% total) included Acinetobacter, Citrobacter, Clostridium, coagulase-negative Staphylococcus, Corynebacterium sp, Klebsiella oxytoca, Lactobacillus, Malassezia, Mycoplasma, Pasteurella multocida, Pasteurella sp, Pseudomonas sp, Serratia, and yeast.


(Courtesy of The Ohio State University Microbiology Laboratory, January 2000-April 2007.)


image

FIGURE 8-2 Bacteria associated with urinary tract infection in cats. Organisms isolated in significant quantitative growth from cystocentesis samples in cats. 1429 urine samples were cultured yielding growth in 15% and no growth in 85%. Organisms listed as <1% each (<5% total) included Corynebacterium, Enterobacter, Klebsiella, lactose-negative E. coli, Pasteurella sp, Moganella, Serratia, and yeast.


(Courtesy of The Ohio State University Microbiology Laboratory, January 2000-April 2007.)



image Escherichia coli is the most common uropathogen in dogs and cats.







(a) Coagulase-negative Staphylococcus species can be pathogenic in the urinary tract of cats, accounting for about 20% of isolates in recent reports (Staphylococcus felis).
(i) Traditionally, coagulase-negative staphylococci have been considered contaminants. S. felis is a normal commensal organism of the skin, conjunctiva, and saliva of cats.

(ii) Most laboratories report staphylococci as “coagulase-negative” and do not further characterize as to species (which requires ribosomal RNA gene sequencing technology).

(iii) S. felis UTI is associated with a higher urinary specific gravity than that encountered with other causes of UTI. All S. felis isolates are urease-positive, which is associated with alkaline urinary pH and struvite crystalluria.

(2) Pasteurella is an occasional pathogen in cats.

c. Sex differences.
(1) Multiple organism (i.e., polymicrobic) infections are more common in female dogs.

(2) Male dogs have a higher incidence of Klebsiella infections than females.

(3) Female dogs have a higher incidence of Proteus and Enterococcus infections than males.

d. Breed differences.
(1) German shepherd dogs, miniature and toy poodles, Labrador retrievers, dachshunds, Doberman pinschers, and miniature Schnauzers may have increased incidence of UTI.

(2) In Labrador retrievers and Dalmatians, more males are affected than females.

(3) In dachshunds and English Springer spaniels, more females are affected than males.

(4) In dachshunds, males are unlikely to have UTI caused by Staphylococcus.

(5) Origin of bacteria (route of entry).

e. Ascent of bacteria.
(1) Ascension of fecal flora is the most common pathogenesis of UTI.
(a) Fecal flora contaminate the perineum, ascend the urethra, and enter the bladder.


image Ascent of fecal bacteria is the most common route of infection.







(b) Organisms that successfully gain entry into the bladder then have the potential to ascend the ureters, cross the renal pelvic epithelium, and enter renal parenchymal tissue.

(c) Fecal flora is the most common source of organisms for UTI though they can also arise from the skin.

(2) Ascending organisms can originate from the environment (e.g., hospital flora).

(3) Ascending organisms can arise from the vagina, prepuce, and distal urethra.

f. Hematogenous and lymphogenous.
(1) These routes of infection occasionally are encountered, especially during septicemia.

(2) Organisms can localize in the kidney initially, with the potential to inoculate the lower urinary tract.

g. Direct extension from an infected site near the urinary tract.
(1) Uterine stump abscess.

(2) Laparotomy sponge infection.

(3) Osteomyelitis.

(4) Perirenal abscess.

h. Urinary catheterization.
(1) Introduction of normal flora during catheterization; contamination with fecal or hospital flora is also possible.

(2) Indwelling catheter (i.e., migration of bacteria between the catheter and urethral mucosa or through the lumen of the catheter).


Normal Host Defenses Against Establishment of Urinary Tract Infection





1. Abrogation of some aspect of the normal host defense system may allow UTI to be established.

2. Normal flora of the distal urethra, vagina, and prepuce may be protective. Normal flora may occupy uroepithelial receptors and consume micronutrients, preventing pathogenic bacteria from establishing an infection.

3. Urine from healthy animals inhibits the growth of bacteria.
a. Urea in urine has antibacterial properties.

b. High urine osmolality inhibits bacterial growth. This mechanism may be particularly important in cats.

c. Highly acidic urine can be bacteriostatic or bactericidal.

d. Ammonia in urine may contribute antibacterial effects.

4. Host defense mechanisms exist for the perineum, vagina, prepuce, urethra, bladder, ureters, renal pelvis, and renal parenchyma.
a. Very little is known about perineal host defense mechanisms.

b. Urethral host defense mechanisms.
(1) Epithelial cells lining the urethra (i.e., urothelium) can physically trap bacteria and bar their ascent.

(2) The mid-urethra has a functionally important high-pressure zone that helps prevent bacterial ascension.

(3) Urethral length, width, and distance from anus.
(a) The female urethra is wider and shorter than the male urethra, conceivably making it easier for bacteria to ascend into the bladder. Since the anus is closer to the urethral orifice of female dogs than males, there is a greater chance of fecal contamination and inoculation of organisms for female dogs. Male dogs may have additional protective mechanisms due to antibacterial prostatic secretions.

(4) Timely, forceful, and complete emptying of bladder urine mechanically flushes out low numbers of bacteria that may have ascended the urethra (so-called hydrokinetic washout).

c. Urinary bladder.


image Host defense mechanisms must be decreased for UTI to occur.






(1) Hydrokinetic washout of small numbers of bacteria from the bladder may be important.

(2) Normal glycosaminoglycans (GAG) on the uroepithelium inhibit attachment of bacteria (antiadherence properties).

(3) Bladder urothelium has some inherent bactericidal properties, but bacteria must be in close apposition for this effect to be valuable.

(4) Some poorly characterized secretions of the normal bladder are antibacterial.

(5) Local secretion of immunoglobulin can occur, but is not of major importance. A systemic immunoglobulin response also can occur, but is not protective.

d. Ureters.
(1) The distal movement of urine (i.e., from kidney to bladder) inhibits ascent of bacteria. However bacteria in the ureters can ascend by Brownian motion against the flow of urine.

(2) The normal oblique intramural passage of the ureters into the bladder provides functional closure of the ureters as the bladder fills.

e. Kidneys.
(1) Renal pelvic epithelium.

(2) Renal medulla.
(a) The renal medulla is much more susceptible to bacterial colonization after ascending or hematogenous infection than is the renal cortex.

(b) Low medullary blood flow and high interstitial osmolality impair the inflammatory response.


Requirements for Development of Urinary Tract Infection





1. Exposure to sufficient numbers of uropathogenic bacteria (Figure 8-3).

2. Presence of epithelial receptors for uropathogens.

3. Failure of normal urinary defenses.
a. Reduced anti-adherence properties of the uroepithelium.

b. Decreased antibacterial properties of urine.

c. Abnormal patterns of voiding.

d. Reduced integrity of intrinsic mucosal defenses.

e. Presence of anatomic abnormalities.

image

FIGURE 8-3 Uropathogenic Escherichia coli and uorepithelial cell. Structure with pili, adhesions, and virulence factors. In order for a UTI to become established it is necessary for adhesins on the end of fimbria to interact with specific receptors on the uroepithelial cells. 1, Supercoiled bacterial DNA; 2, Lipopolysaccharide (LPS) of bacterial wall; 3, 4, and 6, show fimbria without adhesins that fit into uroepithelial receptors; 5, Shows fimbria with adhesins that specifically fit into the uroepithelial receptors—binding with these receptors is pivotal in allowing the establishment of UTI; 7, Flagellum; 8, Various virulence factors produced by the organisms that favor pathogenicity. (Drawn by Tim Vojt.)



Increased Risk for Development of Urinary Tract Infection





1. Anatomic abnormalities of the genitourinary system (Boxes 8-1 and 8-2).
a. Urachal remnants may provide a reservoir of stagnant urine, have decreased GAG, and be associated with microabscesses.

b. Ectopic ureters.
(1) Most common in female dogs.

(2) Higher incidence in Siberian huskies, toy and miniature poodles, golden retrievers, Labrador retrievers, fox terriers, West Highland white terriers, collies, soft coated Wheaten terriers, and Welsh corgis.

(3) Low incidence in cats, but males are more commonly affected.

(4) Most ectopic ureters terminate in the urethra of females and may allow vaginal bacteria to ascend the ureter into the kidney.

(5) Incontinence is the most common sign.

(6) UTI may be present without clinical signs.


BOX 8-1 ANATOMIC AND FUNCTIONAL ABNORMALITIES PREDISPOSING TO OR PRERPETUATING URINARY TRACT INFECTION



Bladder atony (high residual urine volume)

Deep-seated cystitis (chronic bladder wall changes)

Ectopic ureters (developmental)

Emphysematous cystitis

Encrusting cystitis

Metritis or pyometra

Neoplasia of the bladder or urethra

Peri-urachal microabscesses

Polypoid cystitis

Poor vulvar conformation (developmental)

Prostatitis (sexually intact male dogs)

Pyelonephritis

Small urinary calculi that have been previously missed

Urachal remnant (developmental)

Ureterocoele

Urethral fistula

Urethral sphincter incompetence with urinary incontinence

Urethral stricture

Vestibulovaginal stenosis (developmental)


BOX 8-2 METABOLIC CONDITIONS PREDISPOSING TO URINARY TRACT INFECTION



Chemotherapy

Diabetes mellitus

Exogenous corticosteroid administration

Hyperadrenocorticism

Hyperthyroidism (cats)

Immunosuppression

Renal failure (especially cats)


image Animals receiving long-term exogenous corticosteroids and those with hyperadrenocorticism or diabetes mellitus are at increased risk for developing UTI, with or without clinical signs. Cats with CRF are also at high risk for developing UTI.


2. Exogenous corticosteroid use in dogs.


a. About 40% of dogs receiving long-term corticosteroid therapy (6 months or longer) for chronic skin disease have UTI.

b. Greater risk in females, and castrated male dogs.

c. Many do not have clinical signs of UTI, and urinalysis can be normal. Pyuria often is absent.

d. Urine culture is necessary for diagnosis.

3. Endogenous corticosteroids in dogs (i.e., hyperadrenocorticism).
a. UTI occurs in 46% of dogs with hyperadrenocorticism.

b. Many do not have clinical signs of UTI, and urinalysis can be normal.

c. Urine culture is necessary to identify UTI in dogs with hyperadrenocorticism.

4. Diabetes mellitus.
a. UTI occurs in 37% of dogs and 12% of cats with diabetes mellitus.

b. Many do not have clinical signs of UTI, and urinalysis can be normal.

c. Urine culture is necessary to identify UTI in dogs and cats with diabetes mellitus.

5. Decreased systemic immunity.

6. Abnormal mucosal defenses.

7. Abnormal micturition.

8. Clitoral hyperplasia, especially in greyhounds.

9. Urolithiasis.
a. Urine culture obtained by cystocentesis may be negative in animals with urolithiasis.

b. Bacteria may adhere to bladder mucosa or uroliths, and the bladder biopsy specimen and uroliths should be cultured at surgery.

10. Perineal urethrostomy in dogs and cats.

11. Indwelling urinary catheter in dogs and cats.


image Urinary catheterization increases the risk of UTI.





a. Persistent UTI often develops even when using a closed system of urine drainage.

b. In dogs and cats with indwelling catheters, 50% develop UTI within days, even if receiving antimicrobials.

c. Bacterial organisms migrate along the outside of the catheter in the periurethral space.

d. Normal bacterial flora are carried into the urinary bladder during catheterization.

12. Single episode of urinary catheterization in female dogs.
a. UTI develops in 20% of female dogs within 3 days after passage of a urinary catheter.

13. Cats with chronic renal failure (CRF).
a. UTI occurs in approximately 30% of cats with CRF, often within 1 year of diagnosis.

b. Females with CRF are more likely to have UTI.

c. E. coli typically is isolated.

d. UTI may be a factor in the progression of CRF in cats.

14. Cats with hyperthyroidism.
a. UTI occurs in approximately 12% of cats with hyperthyroidism.

b. Urine culture is recommended, because many cats have no clinical signs of UTI.

15. Incontinence.
a. Urine scalding may change the resident perineal bacterial population.

b. Wicking action of urine may allow ascent of organisms.

c. Excessive perivulvar skin folds and pyoderma (especially in recurrent UTI).
(1) Episioplasty or vulvoplasty increases exposure of external genitalia to air and eliminates excessive skin folds.

(2) The bacterial population in the perivulvar region is reduced, thus decreasing the likelihood of bacterial ascent.

f. Vestibulovaginal stenosis.
(1) So-called vestibulovaginal stenosis is unlikely to be a major predisposing factor in development of UTI.

(2) What has been called stenosis most likely is a normal variant of the junction of the vestibule with the vagina in the area of the cingulum.


History




Dogs





1. Age at presentation with first UTI ranges from 0.3 to 16 years, with a median of 7 years.


Cats





1. Affected males have a mean age of 6.3 years at presentation, and females have a mean age of 10.6 years.

2. Cats older than 10 years of age that present for irritative voiding and signs of lower urinary tract disease (LUTD) commonly have bacterial UTI, unlike young cats presented with similar signs.


image Older cats with lower urinary tract disease (LUTD) signs commonly have bacterial UTI whereas young cats with LUTD signs typically do not have bacterial UTI.




3. Many affected cats have a history of dilute urine, perineal urethrostomy, or previous urinary catheterization.


Clinical Signs




A. Most animals with UTI present with clinical signs of lower urinary tract distress (i.e., symptomatic bacteriuria).
1. Hematuria.

2. Pollakiuria.

3. Stranguria or dysuria.

4. Urination in inappropriate locations.

5. Incontinence.

6. Decreased volume of urine voided also may occur in animals with partial obstruction of the urethra (e.g., granulomatous urethritis).

B. Animals with UTI may have no clinical signs (i.e., asymptomatic bacteriuria).
1. Eighty percent of all dogs with UTI have no clinical signs.

2. As many as 10% of hospitalized dogs with a variety of illnesses have UTI without clinical signs.


Physical Examination




A. A thickened or painful urinary bladder may be palpated.

B. Thickening or induration of the urethra sometimes is detected during rectal examination when the urethra is involved.

C. The prostate gland may be palpably abnormal in sexually intact male dogs.


Diagnosis



Hematology and Serum Biochemistry





1. Complete blood count (CBC) and routine serum biochemistry are normal if UTI is limited to the lower urinary tract.


image Complete blood count (CBC) and serum biochemistry are normal if UTI is limited to the lower urinary tract.



Urinalysis



Urine Specific Gravity (USG)






a. Urine usually is concentrated if UTI is limited to the lower urinary tract.

b. Dilute urine may occur in the presence of pyelonephritis or when lower UTI is associated with systemic absorption of bacterial endotoxin, which impairs the responsiveness of the collecting ducts to antidiuretic hormone.

c. UTI caused by E. coli tends to be associated with USG of <1.025.

d. UTI caused by staphylococci or streptococci tends to be associated with USG of more than 1.025.

e. Varying combinations of hematuria, pyuria, proteinuria, and bacteriuria usually are identified on urinalysis.

f. UTI caused by E. coli is associated with pyuria but not hematuria.

g. UTI caused by streptococci is associated with hematuria.


Pyuria






a. The combination of pyuria in association with bacteriuria increases the likelihood that bacteria actually are present in the urine sample. Clumps of white blood cells (WBCs) also add credence to the presence of bacteria.
(1) Dipsticks designed to detect neutrophils in urine do not work well in the urine of dogs or cats (false negatives are common in dogs and false positives are common in cats). The urine sediment must be evaluated microscopically to determine if pyuria is present.


image Dipsticks to detect WBCs in the urine are not accurate in dogs and cats. Urinary sediment examination must be performed microscopically.






(2) The WBC response (i.e., severity of pyuria) may vary among individuals and over time.

(3) Decreased WBC numbers are seen in animals with UTI that also have diabetes mellitus, hyperadrenocorticism, Pseudomonas UTI, or very dilute urine and in those that have received exogenous corticosteroids or antineoplastic drugs.


Urine pH






a. Consistently alkaline urine pH (>7.0) can be supportive of UTI associated with urease-producing organisms such as Staphylococcus aureus and Proteus spp.

b. Many UTI occur in acidic urine, however.


Urine Sediment






a. Failure to observe bacteria in wet mounts of urine sediment does not exclude their presence (i.e., false negative).


image Failure to visualize bacteria in urine sediment does not rule out UTI, and presence of bacteria does not necessarily mean UTI is present.





b. Bacteria also can be reported in wet mounts of urine sediment when they are not present (i.e., false-positive). False-positive results are especially common in the urine of cats, which may contain artifacts that resemble bacteria (pseudobacteria).


Direct Examination of Urine






a. Place one drop of well-mixed, fresh urine on a slide. Do not smear. Allow to air dry

b. Gram stain and examine under oil immersion (1000×).

c. Visualization of 2 bacteria or more per oil immersion field is indicative of bacterial UTI. This method is very specific and sensitive for diagnosis of UTI.


Modified Wright Stain of Urine Sediment






a. One drop of urine sediment applied to a slide. Air dry and stain with modified Wright’s stain.

b. Evaluate 20 fields at 1000× (oil immersion).

c. Enumerate as none, occasional (1-4), few (5-9), moderate (10-20), many (>20).

d. Good correlation with quantitative culture results—superior to that estimated by routine wetmount of urine sediment. Less false-positive and false-negative results.


Urine Culture






a. Collect urine for culture by cystocentesis (highly preferred) or urinary catheterization.

(1) Do not culture voided urine due to the high likelihood of growth of bacterial contaminants.


image Do not culture voided urine.






(2) Culture of urine obtained by urinary catheterization is not recommended for routine purposes.

b. Plate collected urine on blood agar and MacConkey media within 15 minutes of collection.
(1) Most bacteria will grow within 18 to 24 hours at 37° C. Most veterinary isolates of Mycoplasma grow within 3 days on routine blood agar plates (unusual strains can require 7 days or longer) and special media. Corynebacterium can require up to 4 days to grow following inoculation.
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Related posts:

  1. Familial Renal Diseases of Dogs and Cats
  2. Diseases of the Glomerulus
  3. Acute Renal Failure
  4. Disorders of Micturition and Urinary Incontinence

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Jul 10, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on Cystitis and Urethritis: Urinary Tract Infection

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