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PEDIATRICS Vol. 104 No. 3 September 1999, pp. 447-453

Reduction of Unnecessary Antibiotic Therapy in Newborn Infants Using Interleukin-8 and C-Reactive Protein as Markers of Bacterial Infections

Received Nov 17, 1998; accepted Mar 10, 1999.

Axel R. Franz*, Gerald SteinbachDagger , Martina Kron§, and Frank Pohlandt*

From the * Department of Pediatrics, Division of Neonatology and Pediatric Critical Care, the Dagger  Department of Clinical Chemistry, and the § Department of Biometry and Medical Documentation, University of Ulm, Ulm, Germany.

Objective.  To examine whether the determination of interleukin 8 (IL-8) and C-reactive protein (CRP) in neonates with suspected nosocomial bacterial infection (NBI) is feasible and cost-effective in reducing antibiotic therapy.

Methods.  Between April 1996 and May 1997, IL-8 was measured 260 times along with blood cultures, CRP, and immature-to-total-neutrophil (IT) ratio for suspected NBI in term and preterm neonates. All infants were retrospectively analyzed for NBI. Sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals were calculated for IL-8, CRP, and IT ratio. Receiver-operating characteristic curves were analyzed to determine optimal thresholds. Between June 1997 and June 1998, IL-8 was measured 215 times in newborn infants with suspected NBI and the decision to start antibiotic therapy was based on increased IL-8 and/or CRP values. A cost-effectiveness analysis was performed and sensitivity, specificity, and receiver-operating characteristic curves were reevaluated.

Results.  At the first suspicion of NBI, the combination of IL-8 >=  53 pg/mL and/or CRP >10 mg/L detected culture-proven NBI with 96% sensitivity. The combined culture-proven and clinical NBI were detected with 93% sensitivity and 80% specificity. The use of IL-8 reduced unnecessary antibiotic therapy for suspected NBI by 73% and was cost-effective when compared with initiating antibiotic therapy based on clinical signs alone or based on clinical signs and an increased IT ratio and/or CRP.

Conclusions.  The combination of IL-8 and/or CRP is a reliable and early test for the diagnosis of NBI in newborn infants. Using the combination of IL-8 and/or CRP to restrict antibiotic therapy to truly infected infants reduces unnecessary antibiotic therapy and is cost-effective.  Key words:  newborn infant, term, preterm, sepsis, nosocomial bacterial infection, interleukin 8, C-reactive protein, immature-to-total-neutrophil ratio, blood culture, costs.




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