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Are You Using the Best Diagnostic Tests for Infectious Diseases?

Brillman, Judith C. MD

doi: 10.1097/01.EEM.0000359176.52736.5b
ID Rounds

Dr. Brillman is a professor of emergency medicine, the dean of graduate medical education, and the co-director of emergency medicine research at the University of New Mexico, and the medical coordinator of bio-surveillance at Los Alamos National Laboratory.

Part 1 in a Two-Part Series

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From urine dipsticks to fecal screenings, the tests commonly ordered by emergency physicians are right on the money. Confirmation of that came in meta-analyses relating to infectious diseases in the June issue of Infectious Disease Clinics of North America. (2009;23[2]:225.)

One chapter reviews diagnostic tests; others examine treatment of various infectious disease syndromes, but all confirm our current use of tests in the ED. Sensitivity, specificity, summary receiver operating characteristic (SROC) curves, positive and negative predictive values, and diagnostic odds ratios (DOR) are all measures used to assess diagnostic efficacy.

Acute sinusitis: In 13 studies of acute sinusitis confirmed by sinus puncture, clinical risk scores and radiography provided useful information, but ultrasound did not. Sinus opacity or fluid had a sensitivity of 0.73 and a specificity of 0.80 (SROC=0.83). Clinical risk scores had an SROC of 0.74 in identifying patients with positive radiographs. (J Clin Epidemiol 2000;53[8]:852.) In another nine studies, clinical examination was unreliable while radiography (Q*=0.82) was more sensitive than ultrasound (Q*=0.80) in identifying patients with a positive sinus puncture. (J Clin Epidemiol 2000;53[9]:940.) The Q* is where sensitivity equals specificity, the most rightward, upward point of the ROC.

Urine dipsticks for UTI: In an analysis of 72 studies, negative results for leukocyte esterase and nitrite rule out disease in all populations, but positive results require confirmation (BMC Urol 2004;Jun 2[4]:4.) In 26 studies in children, dipstick analyses for nitrite and leukocyte esterase performed similarly, and were superior to microscopic analyses for pyuria. For five white blood cells per high-power field in a centrifuged urine sample, the true positive rate (TPR) was 0.67, and the false positive rate (FPR) was 0.21. For fewer than 10 white blood cells per mm3 in uncentrifuged urine, the TPR was 0.77, and the FPR was 0.11. (Pediatrics 1999;104[5]:e54.)

Procalcitonin use for identifying sepsis or bacteremia: In 17 studies of procalcitonin (PCT) in ED patients of all ages, PCT was moderately effective in identifying bacteremia. The unweighted SROC curve provided the best overall estimate of test performance, with an area under the curve of 0.84 (95% confidence interval [CI] 0.75–0.90). Sensitivity analysis based on study quality did not significantly change the results. Subgroup analysis including only studies that used a test threshold of 0.5 or 0.4 ng/mL yielded pooled estimates for sensitivity and specificity of 76% (95% CI 0.66–0.84) and 70% (95% CI 0.60–0.79), respectively. (Ann Emerg Med 2007;50[1]:34.) In 18 studies of ED and ICU patients, the diagnostic performance of PCT showed mean values of sensitivity and specificity as 71% (95% CI 67–76) and an area under the SROC curve of 0·78 (95% CI 0.73–0.83). (Lancet Infect Dis 2007;7[3]:210.)

C-reactive protein in meningitis: Thirty-five studies addressed the benefits of using CRP to discriminate between patients who had bacterial meningitis and patients with other diseases, particularly aseptic meningitis. The odds ratio for bacterial meningitis versus aseptic meningitis for a positive cerebrospinal fluid CRP test was estimated at 241 (95% CI 59–980), and the sensitivity and the false-positive fraction (1-specificity) were estimated at 0.94 and 0.06, respectively. The corresponding figures for a serum CRP were 150 (95% CI 44–509), 0.92 and 0.08, respectively. If the pretest probability of bacterial meningitis is 10% to 30% a negative CRP results in a post-test probability of 97% of not having bacterial meningitis. (Scand J Clin Lab Invest 1998; 58[5]:383.)

Imaging tests of osteomyelitis: In 16 studies of all patients suspected of foot osteomyelitis, MRI was the best test. DOR for MRI was 42.1 (95% CI 14.8–119.9), and the specificity at a 90% sensitivity cutoff point was 82.5%. In studies in which a direct comparison could be made with other technologies, the DOR for MRI was consistently better than that for Technetium 99m bone scanning (seven studies: 149.9 vs. 3.6), plain radiography (nine studies: 81.5 vs. 3.3), and indium-labeled leukocyte scans (three studies: 120.3 vs. 3.4). (Arch Intern Med 2007;167[2]:125.)

For patients with diabetic foot ulcers, nine studies showed similar results. Exposed bone or probe-to-bone test had a sensitivity of 0.60% and a specificity of 0.91%. Plain radiography had a sensitivity of 0.54% and a specificity of 0.68%. MRI had a sensitivity of 0.90% and a specificity of 0.79%. Bone scan was found to have a sensitivity of 0.81% and a specificity of 0.28%. Leukocyte scan was found to have a sensitivity of 0.74% and a specificity of 0.68%. The DOR for clinical examination, radiography, MRI, bone scan, and leukocyte scan were 49.45, 2.84, 24.36, 2.10, and 10.07, respectively. (Clin Infect Dis 2008;47 [4]:519.)

Fecal screening tests: Fecal ferritin (lactoferrin) was more accurate than fecal leukocytes when compared with culture. Fecal leukocytes alone had the lowest area under the ROC curve; a combination of occult blood, fecal leukocytes, and clinical data had an intermediate ROC; ferritin had the best combination of sensitivity and specificity. Although the test is not specific for a particular pathogen, it seems highly sensitive for inflammatory bowel process. (Pediatr Infect Dis J 1996;15[6]:486.)

Intravascular device-related bloodstream infections: In 22 studies comparing qualitative, semi-quantitative, and quantitative blood cultures, quantitative catheter segment culture demonstrated the greatest accuracy in diagnosing catheter-related infections. Sensitivity increased with rising level of quantization. Quantitative blood cultures had a pooled sensitivity and specificity of greater than 90%. (J Clin Microbiol 1997;35[4]:928.) In 51 studies of intravascular device infection, the most accurate test was paired quantitative blood culture (Q*=0.94 [95% CI 0.88 to 1.0]). The most accurate catheter segment culture test was quantitative culture (Q*=0.87 [CI 0.81–0.93]) followed by semi-quantitative culture (Q*=0.84 [CI 0.80–0.88]; Ann Intern Med 2005;142[6]:451).

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Next Month in ID Rounds

In Part 2 of this series on diagnostic tests, Dr. Judith Brillman reviews the meta-analyses of treatments for common ED conditions.

© 2009 Lippincott Williams & Wilkins, Inc.