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Antimicrobial therapy will vary depending on whether a urinary tract infection involves the kidney or is confined to the bladder. Hence, the clinician must localize the site of infection as reliably as possible. Many clinical clues are helpful in distinguishing pyelonephritis from cystitis, although none is completely reliable. The symptoms of infection confined to the bladder are dysuria, urgency, and frequency. Symptoms of fever, nausea, rigors, and back pain suggest upper urinary tract infection. On physical examination, suprapubic tenderness occurs in cystitis; costovertebral angle tenderness may be present in pyelonephritis. The peripheral WBC count is normal in bladder infection but is usually elevated in renal infection. In the elderly patient with pyelonephritis, fever and leukocytosis are often absent. Pyuria is almost always present in both upper and lower tract infection. WBC casts occur only in pyelonephritis.
A variety of invasive and noninvasive methods have been employed to distinguish cystitis from pyelonephritis. Two invasive methods, the Stamey test and the Fairley test, are among the most reliable. The Stamey test employs a ureteral catheter to carry out quantitative urine cultures of the bladder. Cultures can be taken from both ureters, and renal infection can be determined to be unilateral or bilateral. The test can even be modified so that percutaneous puncture of the renal pelvis can be performed. The test carries some risk in that patients are instrumented during active infection without antimicrobial therapy. False-positive test results can occur as a consequence of vesicoureteral reflux, especially in children. The Fairley bladder washout test also uses quantitative cultures to localize infection. An indwelling Foley catheter is inserted. Saline solution and an antimicrobial agent are instilled into the bladder. The catheter is clamped for 45 minutes and then rinsed with saline solution periodically in 100-mL samples. The catheter is again clamped and samples are taken at 10, 20, 30, and 60 minutes. In pyelonephritis, infected urine travels from the kidney to the bladder, and a 10% rise in colony count will occur as additional samples are obtained. In cystitis, colony counts remain relatively low because the bladder bacteria have been inhibited by the antimicrobial bladder rinse. This test is very sensitive but is not popular because it requires placing a Foley catheter in an already infected urinary tract.
In 1974, a direct immunofluorescence method for the detection of antibody-coated bacteria (ACB) was reported to differentiate kidney from bladder infection. The test, relatively simple and noninvasive, was based on the premise that bacteria invading kidney parenchyma will stimulate production of specific antibody. This antibody will be present on the bacterial surface and can be detected by a fluorescent antibody against human antibody proteins. Initial studies were very promising, but experience with this test over time uncovered many theoretical and technical problems. The definition of a positive test result has varied among investigators. For example, the percentage of fluorescing organisms for a test result to be considered positive has varied from 1% to 25%. The concentration of the urine evaluated will affect the sensitivity of the test. Cocci can be difficult to distinguish from artifact.
It appears that early in the course of pyelonephritis, the ACB test result may be negative. A direct correlation between a positive ACB test result and duration of upper tract symptoms has been reported in one study. In addition, certain mucoid Pseudomonas organisms produce a false-negative test result because they do not bind to specific antibody. An ACB test result can be positive in patients with lower urinary tract infection. Urine can be contaminated with vaginal bacteria that are antibody-coated. Patients with prostatitis or hemorrhagic cystitis are often ACB-positive. Patients with proteinuria, ileal conduit, and bladder tumors also can have false-positive test results.
Excretion of b2-microglobulin has also been used as a test for distinguishing upper from lower urinary tract infection. This protein is synthesized by nucleated cells and secreted in serum and other body fluids at a constant daily rate. It passes through glomerular membrane but is almost completely reabsorbed in proximal tubules. When tubular damage is present, as in upper urinary tract infection, urine excretion of b2-microglobulin increases. One study showed essentially no overlap in levels of urinary b2-microglobulin in 24-hour collection in cystitis versus pyelonephritis. Among patients who have both lower urinary tract infection and tubular renal disease, false-positive tests will certainly occur.
A similar type of test in theory is the urinary lactate dehydrogenase assay. Large quantities of lactate dehydrogenase 4 and 5 are present in the renal medulla and can be detected in urine when the medulla is damaged by pyelonephritis. Considerably more overlap in values has been reported for this test than for urinary microglobulin. A b-glucuronidase assay is the least discriminating urinary enzyme measurement.
An elevated level of C-reactive protein commonly accompanies acute pyelonephritis. It is rarely elevated in cystitis. However, the test is nonspecific and elevated levels are detectable in many other types of infection.
Maximal urinary concentrating ability has long been considered a useful adjunct in the assessment of urinary tract infection, as upper tract infection can cause loss of concentrating ability. Intrarenal deamino–D–arginine vasopressin has been studied to assess concentrating ability and localize infection in children.
Radiologic methods are rarely used to localize acute urinary tract infection in the United States. Intravenous urograms are used to define structural abnormalities that predispose patients to this infection and to rule out complications such as perinephric abscess. Although signs such as poor concentration of dye and delayed calyceal appearance can suggest upper tract infection, most investigators find the IV pyelogram insensitive and nonspecific for this purpose. Radioisotopic imaging shows some promise in distinguishing upper and lower disease. Schardijn et al. (1984) noted uptake of gallium 67 in all patients with acute pyelonephritis and no uptake in those with lower tract infection. Contrast-enhanced helical computed tomography has also been used in the diagnosis of upper urinary tract infection. The speed of helical scanning allows for better tissue contrast. It has been successful in identifying perinephric fluid collections and small stones and is more sensitive in identifying parenchymal abnormalities.
A practical therapeutic test is highly recommended by most investigators in this field. The cultures of patients with cystitis who are given a short course of oral antimicrobials quickly become negative. Those whose cultures remain positive can then be evaluated further for upper tract infection and treated with more aggressive antimicrobial regimens. (S.L.B.)
Clark H, Ronald AR, Turck M. Serum antibody response in renal versus bladder bacteriuria. J Infect Dis 1971;123:539.
Determination of hemagglutinating antibody activity is of only limited use in predicting the site of infection in individual patients with bacteriuria.
Eykyn S, et al. The localization of urinary tract infection by ureteric catheterization. Invest Urol 1972;9:271.
Early study showing that ureteral catheterization will yield infected urine in patients with upper tract infection.
Fairley KF, et al. Simple test to determine the site of urinary tract infection. Lancet 1967;2:427.
Initial description of the antimicrobial bladder washout method for localizing infection.
Hooton TM, et al. Localization of urinary tract infection in patients with spinal cord injury. J Infect Dis 1984;150:85.
Investigators localized site of urinary tract infection in asymptomatic bacteriuria patients with spinal cord injury. Study compares bladder washout, ACB, and urinary leukocyte count.
Hulter HN, et al. Localization of catheter-induced urinary tract infections. Interpretation of bladder washout and ACB tests. Nephron 1984;38:48.
ACB test may not be of value in chronically catheterized patients.
Kaplan DM, Rosenfield RT, Smith RC. Advances in the imaging of renal infection. Helical CT and modern coordinated imaging. Infect Dis Clin North Am 1997;11:681.
Describes newer imaging techniques in the diagnosis of pyelonephritis, particularly the value of helical computed tomography.
Komaroff AL. Urinalysis and urine culture in women with dysuria. Ann Intern Med 1986;104:212.
Describes value of urine analysis in assessing type of infection.
Menon EB, Tan ES. Pyuria: index of infection in patients with spinal cord injuries. Br J Urol 1992;69:144.
Patients with a WBC count of more than 100 per high-power field are more likely to have morbidity from urinary tract infection.
Montplaisier S, et al. Limitations of the direct immunofluorescence test for antibody-coated bacteria in determining the site of urinary tract infections in children. Can Med Assoc J 1981;125:993.
The ACB test is unreliable in localizing urinary tract infection in children.
Pappas PG. Laboratory in the diagnosis and management of urinary tract infections. Med Clin North Am 1991;75:313.
A good update on methods to localize urinary tract infection, particularly noninvasive methods, such as the ACB test and b2-microglobulin.
Poirier KP, Jackson GG. Characteristics of leucocytes in urine sediment in pyelone-phritis. Am J Med 1957;23:579.
An attempt at a histologic correlation of renal biopsy findings and the detection of glitter cells in the urine by the technique of Sternheimer and Malbin.
Pollock HM. Laboratory techniques for detection of urinary tract infection and assessment of value. Am J Med 1983;75:79.
Describes laboratory tests used to define urinary tract infection, particularly with respect to specimen collection and localization to upper or lower tract.
Ronald AR, Boutros P, Mourtada H. Bacteriuria localization and response to single-dose therapy in women. JAMA 1976;235:1854.
Uses single-dose therapy to differentiate upper and lower tract infection.
Ronald AR, Cutler RE, Turck M. Effect of bacteriuria on renal concentrating mechanisms. Ann Intern Med 1969;70:123.
Provides some evidence that upper tract infection is more likely to cause defect in renal concentrating ability.
Rumans LW, Vosti KL. The relationship of antibody-coated bacteria to clinical syndromes. As found in unselected populations with bacteriuria. Arch Intern Med 1978;138:1077.
Describes limitations of ACB test in an unselected population with bacteriuria.
Sanford JP. Urinary tract symptoms and infections. Annu Rev Med 1975;26:485.
Shows that clinical symptoms are often unreliable in distinguishing upper from lower tract infection.
Schardijn G, Statius van Eps LW, Swaak AJG. Urinary b2-microglobulin in upper and lower urinary tract infections. Lancet 1979;1:805.
Urinary microglobulin 24-hour excretion was elevated in all pyelonephritis patients and normal in all patients with lower urinary tract infection.
Schardijn GH, et al. Comparison of reliability of tests to distinguish upper from lower urinary tract infection. Br Med J 1984;289:284.
Reports excellent results with both b2-microglobulin and scintiphotography with gallium 67 in localizing urinary tract infection.
Seng OB, Kincaid-Smith P. Urine concentration after pitressin administration in upper and lower urinary tract infection. Med J Aust 1969;1:982.
One third of patients with a renal source of infection had a concentrating defect; no patients with bladder infection had a comparable concentrating defect.
Sheldon CA, Gonzalez R. Differentiation of upper and lower urinary tract infections: how and when? Med Clin North Am 1984;68:321.
Review article on methods to differentiate upper and lower tract infection, including symptomatology, biochemical tests, and radiology.
Stamm WE. Measurement of pyuria and its relation to bacteriuria. Am J Med 1983; 75:53.
Only 4% to 5% of cases of pyelonephritis do not have pyuria.
Thomas VL, Forland M, Shelkov A. Antibody-coated bacteria in urinary tract infection. Kidney Int 1975;8:520.
Shows that chronic prostatitis will give a positive ACB test result.
Thomas V, Shelokov A, Forland M. Antibody-coated bacteria in the urine and the site of urinary tract infection. N Engl J Med 1974;290:588.
Early study suggested that ACB test could distinguish upper from lower urinary tract infection. Later studies showed problems with this test.
Turck M. Localization of the site of recurrent urinary tract infection in women. Urol Clin North Am 1975;2:433.
A review of the correlation between the indirect techniques of localization and ureteral catheterization in a homogeneous population of women with urinary tract infections but without structural abnormalities.
Turck M, Ronald AR, Petersdorf RG. Relapse and reinfection in chronic bacteriuria. The correlation between site of infection and pattern of recurrence in chronic bacteriuria. N Engl J Med 1968;278:422.
In women, relapse after antimicrobial therapy suggests upper tract infection.


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