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PEDIATRICS Vol. 114 No. 1 July 2004, pp. 1-8

Measurement of Interleukin 8 in Combination With C-Reactive Protein Reduced Unnecessary Antibiotic Therapy in Newborn Infants: A Multicenter, Randomized, Controlled Trial

Axel R. Franz, MD*, Karl Bauer, MD{ddagger}, Andreas Schalk, MD§, Suzanne M. Garland, MD||, Ellen D. Bowman, MD, Kerstin Rex, MD#,*, Calle Nyholm, MD**, Mikael Norman, MD{ddagger}{ddagger}, Adel Bougatef, MD§§, Martina Kron, PhD||, Walter Andreas Mihatsch, MD*, Frank Pohlandt, MD* for the International IL-8 Study Group

* Department of Pediatrics, Division of Neonatology and Pediatric Critical Care, University of Ulm, Ulm, Germany
{ddagger} Department of Pediatrics, Free University of Berlin, University Hospital Benjamin Franklin, Berlin, Germany
§ Department of Pediatrics, Landeskrankenhaus Villach, Villach, Austria
|| Department of Microbiology and Infectious Disease, Royal Women's Hospital, Women's and Children's Health, Carlton, Victoria, Australia
Department of Pediatrics, Royal Women's Hospital, Women's and Children's Health, Parkville, Victoria, Australia
# Department of Pediatrics, Kärnsjukhuset, Skövde, Sweden
** Department of Pediatrics, Länssjukhuset Ryhov, Jönköping, Sweden
{ddagger}{ddagger} Department of Woman and Child Health, Division of Neonatology, Karolinska Institutet and Hospital, Stockholm, Sweden
§§ Department of Neonatology, Academic Hospital, Brussels Free University, Brussels, Belgium
|| Department of Biometry and Medical Documentation, University of Ulm, Ulm, Germany

Objective. Neonatal bacterial infections carry a high mortality when diagnosed late. Early diagnosis is difficult because initial clinical signs are nonspecific. Consequently, physicians frequently prescribe antibiotic treatment to newborn infants for fear of missing a life-threatening infection. This study was designed to test the hypotheses that a diagnostic algorithm that includes measurements of interleukin 8 (IL-8) and C-reactive protein (CRP) 1) reduces antibiotic therapy and 2) does not result in more initially missed infections compared with standard management that does not include an IL-8 measurement.

Methods. Term and preterm infants who were <72 hours of age and had clinical signs or obstetric risk factors suggesting neonatal bacterial infection but stable enough to wait for results of diagnostic tests were enrolled into the study. A total of 1291 infants were randomly assigned to receive antibiotic therapy according to the guidelines of each center (standard group) or to receive antibiotic therapy when IL-8 was >70 pg/mL and/or CRP was >10 mg/L (IL-8 group). The primary outcome variables were 1) the number of infants treated with antibiotics and 2) the number of infants with infections missed at the initial evaluation.

Results. In the IL-8 group, fewer infants received antibiotic therapy than in the standard group (36.1% [237 of 656] vs 49.6% [315 of 635]). In the IL-8 group, 24 (14.5%) of 165 infants with infection were not detected at the initial evaluation, compared with 28 (17.3%) of 162 in the standard group.

Conclusions. The number of newborn infants who received postnatal antibiotic therapy can be reduced with a diagnostic algorithm that includes measurements of IL-8 and CRP. This diagnostic strategy seemed to be safe.


Key Words: cytokines • C-reactive protein • newborn infant • interleukin-8 • sepsis

Abbreviations: CRP, C-reactive protein • IL-8, interleukin 8 • CI, confidence interval


Received for publication Aug 25, 2003; Accepted Nov 13, 2003.


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