Interleukin-6, interleukin-8, and a rapid and sensitive assay for calcitonin precursors for the determination of bacterial sepsis in febrile neutropenic children.
OBJECTIVE
Children with cancer often develop febrile illnesses after cytotoxic chemotherapy. Determining which children have serious bacterial infections in this vulnerable period would be valuable. We evaluated the ability of a rapid and sensitive assay for the concentration of calcitonin precursors (CTpr) as a sensitive diagnostic marker for bacterial sepsis in febrile, neutropenic children and determined the utility of measuring cytokines to improve the predictive value of this approach.


METHODS
Prospective cohort study.


METHODS
Academic children's hospital.


METHODS
Fifty-six children (aged 5 months to 17 yrs) with a known malignancy who presented with fever and neutropenia.


METHODS
Serial blood samples were obtained (admission, 24 hrs, and 48 hrs), and concentrations of CTpr, interleukin-6, and interleukin-8 were determined. Demographic and laboratory data from the patients were collected from the medical record.


RESULTS
Sixteen (29%) of the children met the criteria for bacterial sepsis. Plasma levels of CTpr and interleukin-8, but not interleukin-6, were increased at all time points in children with sepsis compared with those without sepsis. CTpr at 24 and 48 hrs after admission were reliable markers for sepsis (area under the curve = 0.92 and 0.908, respectively). Logistic regression using CTpr at 24 hrs in addition to interleukin-8 at 48 hrs produced the best-fit models associated with sepsis. Using cutoff values of CTpr >500 pg/mL and interleukin-8 >20 pg/mL produced a screening test for sepsis with 94% sensitivity and 90% specificity.


CONCLUSIONS
Our data show the utility of a rapid and sensitive assay for CTpr combined with interleukin-8 as a highly sensitive and specific diagnostic marker of bacterial sepsis in febrile, neutropenic children. The use of these markers as a clinical tool may allow for better prognostication for clinicians and may eventually lead to more targeted therapies for this heterogeneous population.
Stryjewski
Glenn R
GR
Department of Pediatrics and Critical Care Medicine, Children's National Medical Center, Washington, DC, USA. glenn.stryjewski@tenethealth.com
Nylen
Eric S
ES
Bell
Michael J
MJ
Snider
Richard H
RH
Becker
Kenneth L
KL
Wu
Amy
A
Lawlor
Christopher
C
Dalton
Heidi
H
D000293:Adolescent; D001424:Bacterial Infections / Q000150:complications / Q000175:diagnosis*; D002116:Calcitonin / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005334:Fever / Q000097:blood* / Q000209:etiology; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008163:Luminescent Measurements / Q000379:methods*; D008297:Male; D009369:Neoplasms / Q000150:complications; D009503:Neutropenia / Q000097:blood* / Q000209:etiology; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000150:complications / Q000175:diagnosis*
D015850:Interleukin-6; D016209:Interleukin-8; D011498:Protein Precursors; D002116:Calcitonin