Those Stubborn UTIs: Diagnostic and Therapeutic Techniques

Melissa S. Wallace, DVM, Dipl. ACVIM


Overview

Urinary Tract Infection (UTI) is the presence of bacteria in the urine. Since we obtain the urine typically from the urinary bladder in the dog and cat, or sometimes from a midstream catch of a voided sample, localization of the UTI is based predominantly on clinical signs. The urine sediment examination may occasionally suggest that the kidney is the site of infection, and radiography and ultrasonography also may be helpful. In many dogs and cats, localization will be difficult with any degree of certainty, because clinical signs may be lacking or nonspecific, or because the infection involves multiple sites. Localization to the upper urinary tract, however, may have clinical significance, as renal impairment and/or struvite renoliths may result from untreated or poorly controlled renal infections.

Pyelonephritis

Pyelonephritis refers to infection within the renal pelvis. The route of infection is usually ascending from the lower urinary tract, and the risk factors are lower urinary tract infection, vesicoureteral reflux, decreased immune response, poor urine flow in the renal pelvis and/or ureter, dilute urine, and abnormalities of local defense mechanisms in the urinary epithelium. In addition, the bacteria themselves may possess special attachment structures and secrete specific substances that enhance their ability to adhere to and colonize the urothelium (i.e. virulence factors).

Clinical signs of pyelonephritis often go unrecognized in dogs and cats until renal failure ensues. If signs are present, they are polyuria, polydipsia, and lumbar or flank pain. Some animals will exhibit fever or malaise, especially if the infection is acute. Pyelonephritis is sometimes seen as a cause of acute renal failure, but is more commonly associated with chronic renal failure. On the urinalysis, the presence of inadequate urine concentrating ability, hematuria, pyuria, proteinuria, and/or white blood cell casts are all helpful. Because casts come from the tubular lumen, they are the most localizing sign, but are not reliably present and are often affected by poor handling of the urine sample.

Radiographic techniques that are helpful in diagnosis of pyelonephritis include ultrasonography and intravenous pyelography. Dilation of the renal pelvis and proximal ureter are common signs, and the dilation may be asymmetrical. Lack of these changes does not completely exclude pyelonephritis. The presence of staghorn calculi within the renal pelvis is usually from infection-induced struvite renolithiasis.

Lower Urinary Tract Infection

Bacterial infection of the lower urinary tract is usually cystitis. Prostatitis is also considered a lower UTI, but is covered in a separate lecture. Since the urethra has normal bacterial flora, it is difficult to diagnose bacterial urethritis, although it probably occurs. The same defense mechanism problems and virulence factors that predispose animals to pyelonephritis also contribute to cystitis. In addition, decreased frequency of voiding (lack of access to the outdoors in housebroken or crate-trained dogs), retention of urine due anatomic abnormalities of the lower urinary tract, urocystoliths, vaginitis, urine pooling, etc. are all additional risk factors.

Clinical signs of lower urinary tract infection are pollakiuria, hematuria, and dysuria or stranguria. Other signs might include urinating in inappropriate places, licking the vulva or prepuce, a painful caudal abdomen, or gross pyuria. Occasional animals will also exhibit urinary incontinence, although true incontinence is an uncommon sign of lower UTI. The same urinalysis findings associated with pyelonephritis are seen, except the urine will not have casts and is usually not isosthenuric. Polyuria and polydipsia are not typical of lower UTI.

Radiographs are indispensable in the diagnostic evaluation of lower urinary tract infections, because many cases of chronic or recurrent UTI will be associated with urolithiasis. Radiographic contrast studies will reveal radiolucent calculi, and will diagnose anatomical defects such as vesicourachal diverticuli. Ultrasound will also be extremely helpful in the diagnosis of stones, thickening of the bladder wall (usually cranioventral in lower UTI), and tumors.

Laboratory Diagnosis of UTI

Urinalysis

This is the most important test in evaluation of urinary tract infection, followed closely by the urine culture. Urinalysis may be collected by cystocentesis, midstream voided catch, or by urinary catheterization. Samples obtained at home by the client are fraught with problems, which may cause spurious results and diagnostic confusion. The rule of thumb is that the cleanest urine collection and the timeliest analysis will give the most reliable results. Cystocentesis is the only urine collection method that results in an uncontaminated specimen with respect to urethral and vaginal or preputial bacteria and WBCs.

The most important indicators of UTI in the urinalysis are increased numbers of WBCs (> 3-5/hpf) and bacteria in the urine sediment. Other suggestive signs include hematuria and proteinuria. The urine pH may be helpful if urolithiasis is diagnosed, or if infection with urease-producing bacteria is diagnosed (i.e. Staph. sp or Proteus sp.).

Urine Culture

The above comments about urine collection are even more critical with respect to urine culture. If possible, culture a sample collected by cystocentesis. If a cystocentesis sample cannot be obtained on an outpatient basis, it may be helpful to keep the animal in the clinic for the day to try again later. Ultrasound may also facilitate cystocentesis in difficult cases. It is sometimes next to impossible to obtain a cystocentesis sample from an animal with pollakiuria from cystitis. Obtaining a urine culture from an animal with pyelonephritis is more easily accomplished because the patient may be both polyuric and less urgent than the lower UTI patient.

Any bacterial growth in urine collected by cystocentesis and handled sterilely before culture is abnormal. If a cystocentesis cannot be accomplished, passing a sterile urinary catheter in a male dog or cat can by done; growth of > 10,000 colonies/mL is considered significant. In a female dog or cat, or in a male dog or cat where catheterization is not desired, a midstream voided sample may be cultured, provided it is collected in a sterile container. Growth of > 100,000 colonies/mL is considered significant. Growth of three or more different bacteria is likely to be from a contaminated sample regardless of collection method.

All positive urine cultures should have antimicrobial susceptibility testing. The best method is an agar or broth dilution method that directly determines the Minimum Inhibitory Concentration (MIC) from a series of dilutions. The MIC is the least amount of the antimicrobial drug that will inhibit the growth of an inoculum containing a standard number of bacteria that were isolated from the patient.

Therapeutic Principles for UTI

•  Select the antimicrobial agent based on bacterial susceptibility testing and concentration achievable in the urine. The concentration of the antibiotic achievable in the urine should be at least 4x the MIC.

•  Keep safety in mind, and don't use an antibiotic that should be reserved for serious infections unless the infection is serious (e.g. chronic pyelonephritis).

•  For simple or first time infections, or while pending the culture result, use broad-spectrum antibiotics such as first generation cephalosporins, amoxicillin, or trimethoprim-methoxazole.

•  If dosing frequencies are flexible, use the more frequent dosing interval in treating UTIs to maintain high urine concentrations of the drug.

•  Do follow-up urinalysis and urine culture during therapy (in difficult or recurrent cases) and ~ one week after therapy (in all cases).

•  Treat cystitis for two weeks, unless it is chronic or recurrent, in which case it may be treated for 4 weeks. Follow-up cultures should be repeated monthly for three months in difficult or recurrent cases.

•  Pyelonephritis is usually treated for a minimum of four weeks. Follow-up cultures should be performed during and after therapy, and then monthly for three months, and then every 3 - 4 months for two years.

Therapeutic Failures

If treatment was based on urine cultures collected by appropriate methods, and if client compliance was good, then treatment failures may indicate that the animal has an underlying disease process or nidus of infection which should be evaluated further, or that the bacteria are developing resistance to antimicrobials during therapy. Start by evaluating the urinary system for anatomic defects, urinary retention, and stones. Ultrasound, IVP, cystourethrogram and/or vaginourethrogram are all considerations, depending on the case. Also, evaluate the patient for systemic diseases that depress the immune response (e.g. hyperadrenocorticism, neoplasia, FIV). If no underlying cause can be found, continue to treat aggressively based on frequent urine cultures and antimicrobial susceptibility testing. Try to educate the client that even if the problem can not be cured, lifelong control can be achieved in many cases, preventing complications such as recurrent uroliths and/or renal failure.

If infections respond to therapy but reoccur frequently, and no predisposing cause can be found, they may sometimes be prevented (after cure) with prophylactic low-dose antibiotics. Typically 1/3 of the usual daily dose of a broad-spectrum antibiotic is given at bedtime. Good antibiotic choices are amoxicillin, cefadroxil, or trimethoprim-sulfamethoxazole (watch for KCS). It is a good idea to reserve certain antibiotics (e.g. fluoroquinolones) for serious infections that are resistant to the 'older' antibiotics. If a fluoroquinolone is used for prophylaxis, the patient may develop an infection anyway, because she has some underlying defense mechanism failure. However, the infection will be resistant to the fluoroquinolones, leaving only injectable, expensive, and/or nephrotoxic antimicrobials with which to treat the recurrence. Animals on prophylactic antibiotics should have routine urine cultures done, and conventional antibiotic therapy based on culture and sensitivity testing should be administered whenever a recurrent infection is diagnosed. Urinary acidifying agents or acidifying diets are useful in preventing recurrence of struvite urolithiasis in cases of chronic or recurrent urinary tract infections caused by urease-producing bacteria.