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






* Department of Pediatrics, Division of Neonatology and Pediatric Critical Care, University of Ulm, Ulm, Germany
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

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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