G-CSF and IL-8 for early diagnosis of sepsis in neonates and critically ill children - safety and cost effectiveness of a new laboratory prediction model: study protocol of a randomized controlled trial [ISRCTN91123847].
BACKGROUND
Bacterial infection represents a serious risk in neonates and critically ill paediatric patients. Current clinical practice is characterized by frequent antibiotic treatment despite low incidence of true infection. However, some patients escape early diagnosis and progress to septic shock. Many new markers, including cytokines, have been suggested to improve decision making, but the clinical efficacy of these techniques remains uncertain. Therefore, we will test the clinical efficacy of a previously validated diagnostic strategy to reduce antibiotic usage and nosocomial infection related morbidity.


METHODS
All patients admitted to the multidisciplinary neonatal and paediatric intensive care unit of a university children's hospital will be included. Patients will be allocated either to routine sepsis work up or to the intervention strategy with additional cytokine measurements. Physicians will be requested to estimate the pre-test probability of sepsis and pneumonia at initial suspicion. In the treatment arm, physicians will receive raw cytokine results, the likelihood ratio and the updated post-test probability. A high post-test probability will suggest that immediate initiation of antibiotic treatment is appropriate, whereas a low post-test probability will be supportive of watchful waiting or discontinuing prophylactic empirical therapy. Physicians may overrule the suggestions resulting from the post-test probability.


CONCLUSIONS
This trial will ascertain the clinical efficacy of introducing new diagnostic strategies consisting of pre-test probability estimate, novel laboratory markers, and computer-generated post-test probability in infectious disease work up in critically ill newborns and children.
Horisberger
Thomas
T
Department of Neonatology and Intensive Care, University Children's Hospital, Zurich, Switzerland. thomas.horisberger@schweiz.ch <thomas.horisberger@schweiz.ch>
Harbarth
Stephan
S
Nadal
David
D
Baenziger
Oskar
O
Fischer
Joachim E
JE
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001431:Bacteriological Techniques; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003362:Cost-Benefit Analysis; D004363:Drug Utilization; D042241:Early Diagnosis; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood*; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data; D015278:Intensive Care Units, Pediatric / Q000706:statistics & numerical data; D016209:Interleukin-8 / Q000097:blood*; D015337:Multicenter Studies as Topic / Q000379:methods; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D018805:Sepsis / Q000175:diagnosis* / Q000188:drug therapy; D013557:Switzerland
D000900:Anti-Bacterial Agents; D015415:Biomarkers; D016209:Interleukin-8; D016179:Granulocyte Colony-Stimulating Factor