Management of Urinary Tract Infection
World Small Animal Veterinary Association World Congress Proceedings, 2005
David F. Senior
Louisiana State University

Urinary tract infection (UTI) is most commonly a consequence of ascending migration of bacteria through the genital tract and urethra to the bladder with further extension to the ureters and kidneys. While the proximal urethra, bladder, ureters, and kidneys are normally sterile, the distal urethra and external genitalia have a normal flora and are constantly exposed to potential colonization by enteric organisms. Cultures of the vaginal and preputial flora usually grow a wide variety of bacteria, some of which may be potential uropathogens. Occurrence of UTI is determined by the balance between two opposing forces: bacterial invasiveness and host defenses.

Host defense mechanisms

A wide range of host defense mechanisms to prevent bacterial colonization have been identified or hypothesized.

Host Defense Mechanisms

 Normal Micturition

 Adequate urine flow

 Frequent voiding

 Complete voiding

 Anatomic Structures

 Urethral high pressure zone

 Surface characteristics of urethral urothelium

 Urethral peristalsis

 Prostatic antibacterial fraction

 Length of urethra

 Ureterovesical flap valves and ureteral peristalsis

 Mucosal Defense Barriers

 Antibody production

 Surface glycosaminoglycan layer

 Intrinsic mucosal antimicrobial properties

 Bacterial interference

 Exfoliation of cells

 Antimicrobial Properties of Urine

 Extremes (high or low) of urine pH

 Hyperosmolality

 High concentration of urea

 Organic acids

 Renal Defenses

 Glomerular mesangial cells?

 Extensive blood supply and large blood flow

Causative organisms

E.coli is the most common isolate with Staphylococcus spp., Streptococcus/Enterococcus spp., Proteus spp. and Klebsiella spp. less common.

Bacterial Isolates in Canine Urinary Tract infection:

n = 8,354

% age of
total isolates

Escherichia coli

44.1

Staphylococcus spp.

11.6

Proteus spp.

9.3

Streptococcus spp.

5.4

Klebsiella spp.

9.1

Enterococcus spp.

8.0

From: Ling GV, Norris CR, Franti CE, Eisele PH, Johnson DL, Ruby AL, Jang SS. Interrelations of organism prevalence, specimen collection method, and host age, sex, and breed among 8,354 canine urinary tract infections (1969-1995). J Vet Intern Med. 2001 Jul-Aug;15(4):341-7.

Management of simple UTI

Diagnosis

When an active infection causes irritation, animals exhibit urgency to urinate, pollakiuria, unproductive straining to urinate at the end of urination and hematuria. A strong urine stream may not be developed. Owners can also report urinary incontinence between urinations and an offensive odor to the urine. However, in sub-acute, long-standing infections and in dogs with hyperadrenocorticism, clinical signs may be present but attenuated. A large proportion of canine patients with UTI exhibit minimal clinical signs.

On physical examination, there may be increased sensitivity to abdominal palpation of the bladder and the animal may be febrile if there is significant acute renal or prostatic involvement or the inflammation of the bladder is massive. When inflammation is confined to the lower urinary tract, fever does not generally occur. The bladder is often painful on palpation in acute cystitis and in both acute and chronic cystitis, the bladder tends to feel thickened.

The interpretation of urinalysis and bacterial culture results depends upon the method of collection. Urine samples for urinalysis and culture are best obtained by cystocentesis because results are much easier to interpret. However, this procedure can be difficult to perform in patients with UTI because the bladder may remain small and not readily palpable. Catheterization is acceptable but not ideal and mid-stream voided samples are not recommended for urine culture.

On urinalysis, bacteria, white blood cells, red blood cells, proteinuria, strands of mucus, and increased numbers of epithelial cells may be seen. If the inflammation involves the kidney, white blood cell casts and granular casts may be observed but this is an inconsistent finding. The identification of bacteria in the urine sediment is more accurate if the urine sediment is stained with modified-Wright's stain. Urine culture should still be performed even when bacteria are not obvious in the urine sediment. Definitive diagnosis by urine culture, and sensitivity testing is highly recommended. Urine should be cultured within four hours of collection. With cystocentesis samples, any bacterial growth is considered significant, but with catheterization, greater than 105 colonies per ml must be present to be considered significant. Voided specimens are not satisfactory for urine culture.

Sensitivity testing and selection of antimicrobials

Antimicrobial sensitivity tests using the Kirby-Bauer disc-diffusion method are based on antimicrobial concentrations achievable in tissue and serum. When an isolate appears sensitive to an antimicrobial, the result is most likely reliable. However, when an isolate appears resistant, the result may be erroneous because the antimicrobial concentration attainable in urine may be up to 100 times the serum level. Thus, the minimum inhibitory concentration (MIC) antimicrobial sensitivity technique is preferred when selecting the appropriate antimicrobial in lower urinary tract infection. The mean urinary concentration (MUC) of commonly used antimicrobials is shown below. This data can predict the likelihood of success with various drugs once MIC values for the isolated bacteria are known. The "breakpoint" is the maximum MIC for which the drug shown is likely to be effective. MIC levels above the "breakpoint" usually indicate that the microorganism will be resistant to that particular drug. Note that patients forming dilute urine may not achieve these levels.


Mean urinary concentration of commonly used antimicrobial drugs

Antimicrobial

Dose and route
of administration

Mean (+/- 1 SD)
urine concentration
(μg/ml)

Breakpoint
(MUC/4)
(μg/ml)

Amoxicillin

11 mg/kg tid PO

202 +/- 93

50

Ampicillin

25 mg/kg tid PO

309 +/- 55

75

Cephalexin

10 mg/kg tid PO

805 +/- 421

200

Enrofloxacin

2.5 mg/kg bid PO

40

10

Gentamicin

2 mg/kg tid SC

107 +/- 33

25

Marbofloxacin

2 mg/kg sid PO

41 +/- 9.3

10

Nitrofurantoin

4.4 mg/kg tid PO

100

25

Sulfisoxazole

22 mg/kg tid PO

1466 +/- 832

350

Tetracycline

18 mg/kg tid PO

137 +/- 64

35

Trimethoprim- Sulphadiazine

15 mg/kg bid PO

55 +/- 19

*14

* = based on the trimethoprim fraction


Antimicrobial sensitivity results for infections that involve the kidney and prostate must be based on plasma achievable antimicrobial levels because antimicrobials diffuse into the parenchyma of these tissues from plasma, not urine. Antimicrobials that are weak bases (high pKa), lipid soluble, and/or poorly bound to plasma protein tend to be the most effective because of high prostatic penetration. Acidic antimicrobials such as penicillins and cephalosporins penetrate the prostate poorly.

Localization of infection

Pyelonephritis causes production of dilute urine, intermittent WBC casts in the urine sediment and peripheral leukocytosis in acute cases, none of which are observed in infection confined to the lower urinary tract. Radiographically in chronic pyelonephritis, the kidneys may appear small and irregular with pelvic dilation, and the renal diverticula are widened, divergent and have irregular borders. In intact male dogs with UTI the prostate is almost always colonized and treatment must be designed to address the unique antimicrobial diffusion characteristics of this organ.

Treatment

Treatment is usually started prior to knowledge of the antimicrobial sensitivity test results. Fortunately some bacterial species have predictable sensitivity patterns that may be applied to empirical antimicrobial treatment. If cocci (Staphylococcus spp., Enterococcus spp., Streptococcus spp.) or rods in very alkaline urine (Proteus spp.) are observed in the urine sediment, the sensitivity of the infecting organisms is likely to be more predictable. However, if rods are seen in the urine sediment of neutral or acidic urine (E coli, Klebsiella spp., Enterobacter spp., Pseudomonas spp.), the antimicrobial sensitivity of the infecting organism is likely to be less predictable.


Sensitivity of frequent isolates from dogs with previously untreated UTI

 

Ampicillin

Cephalexin

Potentiated Sulfa

Chlorum- phenicol

Gentamicin

Unpredictable

E. coli

         

X

Staphylococcus spp.

X*

X

X

X

X

 

Streptococcus spp.

X

X

X

X

X

 

Enterococcus spp.

X

X

X

 

 

 

Proteus spp.

X

X

X

X

X

 

Klebsiella spp.

         

X

Pseudomonas spp.

       

X

X

Enterobacter spp.

         

X

*X = 90 % or more of isolates will be sensitive to standard doses


Antimicrobial treatment should continue for 10-14 days in acute infections and 4 to 6 weeks in chronic infections and where prostatic or renal involvement appears likely. Follow-up urinalysis and urine culture should be performed several days after the end of treatment to ensure that the medication was successful.

Treatment of intact male dogs requires antimicrobials that penetrate the prostate gland, e.g., fluoroquinolones, trimethoprim, doxycycline, and chloramphenicol. Penicillins and cephalosporins do not penetrate well and should not be used.

For both prostatic and renal infections, the interpretation of antimicrobial sensitivity tests should be based on plasma achievable concentrations of antimicrobial rather than urinary achievable concentrations because drugs penetrate these tissues from plasma, not from urine.

Diagnosis of recurrent UTI

Failure of an antimicrobial agent to sterilize the urine should alert the clinician to one or more of the following possibilities:

1.  Inappropriate drug, dose, or duration of therapy. Owner compliance is very important in this respect.

2.  Failure of the drug to reach sufficient concentrations in urine despite drug administration. e.g., Intestinal malabsorption of the drug, impaired renal concentrating capacity and therefore failure to concentrate the drug in urine to inhibitory concentrations, and development of antimicrobial resistance.

3.  The presence of a nidus of infection which is capable of colonizing the urinary tract as soon as antimicrobial therapy is withdrawn. e.g., Pyelonephritis, prostatitis, neoplasia, infected urachal remnant and urolithiasis.

4.  The presence of some defect in the anatomical or functional characteristics of the urinary tract that lowers resistance to bacterial colonization, but is undetectable by presently available clinical methods of diagnosis.

In male dogs a routine workup for prostatic disease should be performed including cytology and culture of a prostatic wash or ejaculate, ultrasonic examination and possibly prostatic aspiration or biopsy. Plain and contrast radiographic studies including IVP, double contrast cystography and retrograde and voiding urethrography should be sufficient to diagnose or rule out the presence of major anatomical defects. Urolithiasis is a frequent cause of recurrent signs of lower urinary tract inflammation in dogs and cats of any age while neoplasia of the bladder, urethra or prostate is often the underlying problem in older dogs.

Treatment of recurrent UTI

Identification of a specific anatomical abnormality should be addressed. Vulval involution should be corrected by episioplasty, vulvo-vaginal stricture should be resected. Infected urachal remnants should be resected. Uroliths should be eliminated either medically or surgically. Bladder polyps and tumors should be resected if possible. Hyperadrenocorticism and diabetes mellitus should be controlled. Intact male dogs should be treated for at least 30 days with antimicrobials that penetrate the prostate.

When an animal suffers frequent recurrences of UTI despite adequate treatment and in the absence of detectable or correctable anatomic and functional disturbances, long term management with antimicrobials may be necessary to prevent additional recurrences. A potentiated sulfa or amoxicillin-clavulanic acid given for 6 months at 25-30% of the total daily dose at night after the last void prevents recurrence. By giving the treatment after the last void at night, the urine concentration of antimicrobial will be high enough during the 8 to 10 hour period of sleeping to kill ascending susceptible pathogenic bacteria. A full course of antimicrobial treatment should be used first to eliminate the infection. Patients undergoing long-term low-dose antimicrobial treatment should always have urine culture and sensitivity tests repeated monthly throughout treatment. Follow-up specimens of urine taken from patients with a history of recurrent UTI should always be collected by cystocentesis. Urethral catheterization should be avoided in this circumstance because trauma to the urethral mucosa may facilitate re-infection.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

David F. Senior
Louisiana State University


MAIN : Nephrology and Urology : Pathogenesis/Management of UTI
Powered By VIN

Friendly Reminder to Our Colleagues: Use of VIN content is limited to personal reference by VIN members. No portion of any VIN content may be copied or distributed without the expressed written permission of VIN.

Clinicians are reminded that you are ultimately responsible for the care of your patients. Any content that concerns treatment of your cases should be deemed recommendations by colleagues for you to consider in your case management decisions. Dosages should be confirmed prior to dispensing medications unfamiliar to you. To better understand the origins and logic behind these policies, and to discuss them with your colleagues, click here.

Images posted by VIN community members and displayed via VIN should not be considered of diagnostic quality and the ultimate interpretation of the images lies with the attending clinician. Suggestions, discussions and interpretation related to posted images are only that -- suggestions and recommendations which may be based upon less than diagnostic quality information.

CONTACT US

777 W. Covell Blvd., Davis, CA 95616

vingram@vin.com

PHONE

  • Toll Free: 800-700-4636
  • From UK: 01-45-222-6154
  • From anywhere: (1)-530-756-4881
  • From Australia: 02-6145-2357
SAID=27