Published online October 31, 2008
PEDIATRICS Vol. 122 No. 5 November 2008, pp. 1117-1118 (doi:10.1542/peds.2008-2487)
This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tan, T. Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tan, T. Q.
Related Collections
Right arrow Infectious Disease & Immunity
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

COMMENTARY

Procalcitonin in Young Febrile Infants for the Detection of Serious Bacterial Infections: Is This the "Holy Grail"?

Tina Q. Tan, MD

Department of Pediatrics; Feinberg School of Medicine; Northwestern University; Chicago; Illinois; Division of Infectious Diseases; Children's Memorial Hospital; Chicago; Illinois

Abbreviations: SBI, serious bacterial infection • WBC, white blood cell • CRP, C-reactive protein • UTI, urinary tract infection

Over the last several decades, the search for an accurate and rapid diagnostic method of identifying young infants at high risk for serious bacterial infections (SBIs) who present with fever and no clear source of infection has been an ongoing and elusive challenge for clinicians. Published studies of infants who present with fever without an identifiable source have reported rates of SBIs of up to 12% in infants <28 days of age and up to 9% in infants 1 to 3 months of age.1–5 Previous guidelines that used clinical examination alone or in combination with laboratory investigation have been shown to be less than optimal at identifying young infants at high or low risk for SBIs.1,6,7

In an attempt to more accurately differentiate infants at higher risk for bacterial infections, various biomarkers have been studied. These biomarkers have included using a peripheral white blood cell (WBC) count cutoff of 15000/mm3 and absolute neutrophil count8,9 and C-reactive protein (CRP) level.10,11 Although a peripheral WBC cutoff of 15000/mm3 and absolute neutrophil count have been adopted for use in multiple guidelines and algorithms, these parameters have had variable performance in detecting those infants with bacteremia and have a decreased sensitivity for younger infants. Studies have shown that the use of CRP levels is superior to peripheral WBC counts as a screening tool for detecting infants with SBIs; however, CRP levels are not currently part of any of the published US guidelines for the evaluation and management of infants with SBIs.10,11

Procalcitonin is a relatively new biomarker that has been evaluated in critically ill and hospitalized infants and children and, to a lesser degree, in the outpatient emergency department setting as a diagnostic marker of bacterial infection.10,12–17 Published studies have examined the use of procalcitonin in a wide age range of infants and children. In this issue of Pediatrics Electronic Pages, Dauber et al18 evaluated an automated high-sensitivity assay for serum procalcitonin to study the performance of the test in identifying SBIs in febrile infants ≤90 days of age without an identifiable source of infection on examination. This age group was the focus of their study because of the difficulty in identifying young infants at risk for SBIs and because of the higher rate of associated morbidity and mortality. On the basis of the data from their study, the investigators concluded that a procalcitonin level of 0.12 ng/mL was the optimal cutoff value for identifying infants at low risk for SBI. The cutoff level chosen is interesting, given that the mean procalcitonin levels of the patients in their study who did not have an SBI were 0.4 and 0.38 ng/mL for those infants ≤28 and >28 days old, respectively. The results from their study are somewhat inconclusive, because there are several issues that seriously affect the interpretation of the assay's ability to detect infants with SBIs.

The first of the issues regards the definitions used as inclusion criteria for the infants with pneumonia in the definite-SBI group and those with urinary tract infection (UTI) in the possible-SBI groups. The use of sputum culture in infants and children has a very low sensitivity and specificity and should not be used as diagnostic criteria for pneumonia in this population. The finding of a positive radiograph in this population is adequate to make the diagnosis of pneumonia. Defining a possible UTI as one in which the patient has multiple organisms isolated, regardless of the results of the urinalysis, points much more strongly toward "dirty" urine and not a true infection. Inclusion of patients on the basis of these definitions would affect the accuracy of the assay being evaluated. The next issue regards the small number of patients with documented infections and the types of infections that were studied. The majority of the patients with definite SBIs had UTIs, with only a small number having bacteremia. There were no infants with more severe SBIs (eg, meningitis, bacterial pneumonia, sepsis). Because of the limited amount of data and the lack of inclusion of patients with more serious infections, it is difficult to draw any conclusions regarding the true accuracy of the procalcitonin assay being evaluated.

More disturbing are the significant differences in mean procalcitonin levels seen in infants with definite and definite plus possible infections who were ≤28 days of age (3.41 and 4.53 ng/mL, respectively) versus those >28 days of age (1.69 ng/mL and 1.45 ng/mL, respectively). An explanation that possibly accounts for the differences in the levels on the basis of age of the patient is not offered.

However, the most serious issue is one in which infants with culture-proven Escherichia coli bacteremia had a mean procalcitonin level of 0.44 ng/mL (a level similar to that of the patients with no SBIs) compared with infants with culture-proven group B streptococcal bacteremia who had a mean procalcitonin level of 3.56 ng/mL. This marked discrepancy in the procalcitonin levels of patients with proven infection leads to serious questions about the accuracy of the assay, a point that the authors downplay in their article.

The Dauber et al study raises many questions and provides few answers regarding the current sensitivity of the procalcitonin assay being evaluated as a screening method for the rapid identification of young infants at high risk for SBIs. Larger studies that include all types of serious infections are needed to evaluate the true sensitivity and specificity of this assay. On the basis of the data presented, the utility of this assay as a screening modality for infants at risk for SBIs remains unclear. However, in its current form it is not the "Holy Grail" that is being sought.


   FOOTNOTES
 
Accepted Aug 13, 2008.

Address correspondence to Tina Q. Tan, MD, Children's Memorial Hospital, Department of Pediatrics, 2300 Children's Plaza, Box 20, Chicago, IL 60614. E-mail: ttan{at}northwestern.edu or titan{at}childrensmemorial.org

The author has indicated she has no financial relationships relevant to this article to disclose.

Opinions expressed in these commentaries are those of the author and not necessarily those of the American Academy of Pediatrics or its Committees.


   REFERENCES
TOP
 REFERENCES
 

  1. Baker MD, Bell LM, Avner JR. Outpatient management without antibiotics of fever in selected infants. N Engl J Med. 1993;329 (20):1437 –1441[Abstract/Free Full Text]
  2. Baraff LJ, Bass JW, Fleisher GR, et al. Practice guidelines for the management of infants and children 0 to 36 months of age with fever without a source. Agency for Health Care Policy and Research [published correction appears in Ann Emerg Med. 1993;22(9):1490]. Ann Emerg Med. 1993;22 (7):1198 –1210[CrossRef][Web of Science][Medline]
  3. Baskin MN. The prevalence of serious bacterial infections by age in febrile infants during the first 3 months of life. Pediatr Ann. 1993;22 (8):462 –466[Web of Science][Medline]
  4. Bachur RG, Harper MB. Predictive model for serious bacterial infections among infants younger than 3 months of age. Pediatrics. 2001;108 (2):311 –316[Abstract/Free Full Text]
  5. Byington CL, Enriquez FR, Hoff C, et al. Serious bacterial infections in febrile infants 1 to 90 days old with and without viral infections. Pediatrics. 2004;113 (6):1662 –1666[Abstract/Free Full Text]
  6. Jaskiewicz JA, McCarthy CA, Richardson AC, et al. Febrile infants at low risk for serious bacterial infection: an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group. Pediatrics. 1994;94 (3):390 –396[Abstract/Free Full Text]
  7. Baskin MN, Fleisher GR, O'Rourke EJ. Identifying febrile infants at risk for a serious bacterial infection. J Pediatr. 1993;123 (3):489 –490[CrossRef][Web of Science][Medline]
  8. Bonadio WA, Smith D, Carmody J. Correlating CBC profile and infectious outcome: a study of febrile infants evaluated for sepsis. Clin Pediatr (Phila). 1992;31 (10):578 –582[Abstract/Free Full Text]
  9. Bonsu BK, Chb M, Harper MB. Identifying febrile young infants with bacteremia: is the peripheral white blood cell count an accurate screen? Ann Emerg Med. 2003;42 (2):216 –225[CrossRef][Web of Science][Medline]
  10. Galetto-Lacour A, Zamora SA, Gervaix A. Bedside procalcitonin and C-reactive protein tests in children with fever without localizing signs of infection seen in a referral center. Pediatrics. 2003;112 (5):1054 –1060[Abstract/Free Full Text]
  11. Pulliam PN, Attia MW, Cronan KM. C-reactive protein in febrile children 1 to 36 months of age with clinically undetectable serious bacterial infection. Pediatrics. 2001;108 (6):1275 –1279[Abstract/Free Full Text]
  12. Rey C, Los Arcos M, Concha A, et al. Procalcitonin and C-reactive protein as markers of systemic inflammatory response syndrome severity in critically ill children [published correction appears in Intensive Care Med. 2007;33(6):1108–1109]. Intensive Care Med. 2007;33 (3):477 –484[CrossRef][Web of Science][Medline]
  13. Nylen E, Muller B, Becker KL, Snider R. The future diagnostic role of procalcitonin levels: the need for improved sensitivity. Clin Infect Dis. 2003;36 (6):823 –824; author reply 826–827[CrossRef][Web of Science][Medline]
  14. van Rossum AM, Wulkan RW, Oudesluys-Murphy AM. Procalcitonin as an early marker of infection in neonates and children. Lancet Infect Dis. 2004;4 (10):620 –630[CrossRef][Web of Science][Medline]
  15. Fernández Lopez A, Luaces Cubells C, García García JJ, Fernández Pou J; Spanish Society of Pediatric Emergencies. 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 (10):895 –903[CrossRef][Web of Science][Medline]
  16. Lacour AG, Gervaix A, Zamora SA, et al. Procalcitonin, IL-6, IL-8, IL-1 receptor antagonist and C-reactive protein as identificators of serious bacterial infections in children with fever without localizing signs. Eur J Pediatr. 2001;160 (2):95 –100[CrossRef][Web of Science][Medline]
  17. Andreola B, Bressan S, Callegaro S, Liverani A, Plebani M, Da Dalt L. Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department. Pediatr Infect Dis J. 2007;26 (8):672 –677[CrossRef][Web of Science][Medline]
  18. Dauber A, Weiss S, Maniaci V, Nylen E, Becker KL, Bachur R. Procalcitonin levels in febrile infants after recent immunization. Pediatrics. 2008;122 (5). Available at: www.pediatrics.org/cgi/content/full/122/5/e1119–e1122
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tan, T. Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tan, T. Q.
Related Collections
Right arrow Infectious Disease & Immunity
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?