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Abstract & Commentary
Source: Galetto-Lacour A, et al. Bedside procalcitonin and C-reactive protein tests in children with fever without localizing signs of infection seen in a referral center. Pediatrics 2003; 112:1054-1060.
Pediatric fever is worrisome, especially in young children. White blood cell (WBC) and band counts traditionally influence clinical decisions, but with broad variability. C-reactive protein (CRP) has assumed prominence in some centers, as well. Since 1993, measurement of procalcitonin (PCT), a proinflammatory peptide akin to interleukin-6 and tumor necrosis factor-alpha, has proven to be of value in detecting serious infections such as sepsis or meningitis. PCT reaches peak levels more rapidly than CRP (6 hours vs 12) after onset of illness and may herald invasive infection at an earlier stage. To evaluate the utility of rapid (20 minutes by bedside technique) PCT determination in pediatric practice, Galetto-Lacour and colleagues analyzed a cohort of ill children seen at an academic emergency department in Switzerland.
Ninety-nine patients ages 7 days to 36 months with rectal temperatures exceeding 38°C with no identifiable focus of infection were studied at University Children’s Hospital, Geneva. Those on antibiotics with fever lasting more than seven days or with immunodeficiencies were excluded. All cases were tested with WBC and differential, CRP, PCT, and cultures of blood and urine. Toxic children (n = 17) underwent lumbar puncture. Patients with positive urine cultures greater than 105 colony forming units underwent renal scanning with technetium-99 dimercaptosuccinic acid (DMSA) for cortical defects consistent with pyelonephritis. Of all cases, 40 (40%) were admitted for intravenous antibiotics. Of the 60 sent home, 36 (61%) received antibiotics. Average temperature for each group was 39.5°C (38-41°C).
Serious bacterial infections (SBI) were documented in 29 (29%) patients — four had bacteremia (three Streptococcus pneumoniae, one Streptococcus agalactiae), two had lobar pneumonia, 21 had pyelonephritis (90% Escherichia coli), one had mastoiditis, and one had retropharyngeal abscess. Benign infection was diagnosed in the remaining 70 (71%) children—52 with viral syndromes, 11 with cystitis, three with aseptic meningitis, and four with acute otitis media at 48-hour follow-up.
At a cutoff point of 0.5 ng/mL for detection of SBI, sensitivity (sens), specificity (spec), negative predictive value (NPV), and positive predictive value (PPV) of PCT were 93%, 74%, 96%, and 60%, respectively. For a CRP cutoff of 4 mg/dL, sens, spec, NPV, and PPV were 79%, 79%, 90%, and 61%, respectively. For WBC exceeding 15,000, sens was 52%, spec 74%, NPV 78%, and PPV 45%. For band counts greater than 1500, sens, spec, NPV, and PPV were 11%, 93%, 72%, and 38%, respectively. The probability of SBI in 54 children with PCT values less than 0.5 ng/mL was only 3%, vs. a 68% likelihood of SBI in 19 cases with PCT exceeding 2.0 ng/mL. The authors conclude that, in children younger than age 3 who have fever without source, a rapid assay for PCT is superior to measurement of WBC and band counts in detection (or exclusion) of SBI.
Commentary by Michael Felz, MD
I was unaware that PCT levels correlate with pediatric infectious syndromes, and that a new bedside device can measure this marker within 20 minutes. The statistical performance of this new infection predictor was as good as or better than CRP measurement, outperformed WBC in every parameter, and was superior to band counts in each measurement except specificity. The NPV of 96% for PCT is particularly noteworthy in excluding SBI, while the 93% sensitivity highlights this test’s strength in detecting cases of SBI. While the incidence of pyelonephritis in this study seems high, the authors acknowledge that prior studies reported similarly high rates when DMSA scanning was included.
Perhaps the PCT assay will ascend to pediatric prominence in this country, as it has in Switzerland. Another recent analysis1 of PCT in 445 febrile infants evaluated in a multicenter study in Spain demonstrated performance characteristics exceeding those of CRP for detection of SBI. The bottom line: PCT also could stand for "pretty convincing test."
Dr. Felz, Associate Professor, Department of Family Medicine, Medical College of Georgia, Augusta, is on the Editorial Board of Emergency Medicine Alert.
1. Lopez AF, et al. Procalcitonin in pediatric emergency departments for the early diagnosis of invasive bacterial infections in febrile infants: Results of a multicenter study and utility of a rapid qualitative test for this marker. Pediatr Infect Dis J 2003;22:895-903.